MEpedia - User contributions [en]

User talk:Sbrumfie

2019-02-27T21:48:35Z

Sbrumfie:/* Microglia Image */

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To see your contributions history, click Contributions in the top-right corner. To see recent contributions by others, click Recent Changes on the left. Not ready to edit pages, but want to suggest a change? On the page, just click Discussion, and write your suggestion there for others to see.|realName=|name=Sbrumfie}}

-- [[User:New user message|New user message]] ([[User talk:New user message|talk]]) 18:49, 8 June 2018 (PDT)

== Microglia Image ==

Hi Sbrumfie: Thanks for adding an image. You will need to put in the following:

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During the upload process, you can select the license. But you can still put the information in now.

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--[[User:MEcfsFMS|MEcfsFMS]] ([[User talk:MEcfsFMS|talk]]) 17:02, 25 October 2018 (EDT)

Added my name, timestamp won't be same as my original entry as just added now.

Yup, will do.

== Images Uploaded - Need License, Source, and Author ==

Please add to the image the LICENSE, SOURCE LINK, and AUTHOR for images you upload.

Images uploaded have the opportunity to select a license at the time of upload. If none is selected, you must add the license to the image.--[[User:MEandCFS|MEandCFS]] ([[User talk:MEandCFS|talk]]) 16:13, 27 February 2019 (EST)

Immune system

2019-02-27T21:31:27Z

Sbrumfie:Added text, pics and citations.

The '''immune system''' is a complex combination of organs, circulatory networks, and cells which work together to identify, target and eliminate harmful substances that enter the body. The immune system response has many steps. Once in full effect, different parts of the system move in parallel to restore health to the host. When the immune response is no longer needed, the immune system will suppress the reaction.<ref>{{Cite journal|last=Chaplin|first=David D.|date=2010-2|title=Overview of the Immune Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923430/|journal=The Journal of allergy and clinical immunology|volume=125|issue=2 Suppl 2|pages=S3–23|doi=10.1016/j.jaci.2009.12.980|issn=0091-6749|pmc=PMC2923430|pmid=20176265}}</ref><ref>{{Cite web|url=https://www.hopkinsmedicine.org/healthlibrary/conditions/infectious_diseases/immune_system_85,P00630|title=Immune System {{!}} Johns Hopkins Medicine Health Library|website=www.hopkinsmedicine.org|access-date=2019-02-27}}</ref>

[[Myalgic encephalomyelitis]] (ME) is a complex multi-systemic disorder which causes [[Nervous system|neurological]] impairments, [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] dysfunction, and immune, [[Gastrointestinal system|gastrointestinal]] and/or [[genitourinary]] symptoms.<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

==Types of Immune Response==
===Innate Immune System===
Prior to actually getting into the body, [[Pathogen|pathogens]] or toxicants have to pass the body’s most basic immune defense: the skin and mucous. Mucous especially plays an important role because it is present in all the places where infection is most likely to occur (e.g. the eyes, nose and mouth).

Innate immunity is the nonspecific method of eliminating pathogens from the body. The main agents that carry out this mass, undiscriminating disposal of pathogens and dead or defective cells are called [[Macrophage|macrophages]] and [[Neutrophil|neutrophils]].<ref>{{Cite journal|last=Walter|first=Peter|last2=Roberts|first2=Keith|last3=Raff|first3=Martin|last4=Lewis|first4=Julian|last5=Johnson|first5=Alexander|last6=Alberts|first6=Bruce|date=2002|title=Innate Immunity|url=https://www.ncbi.nlm.nih.gov/books/NBK26846/|journal=Molecular Biology of the Cell. 4th edition|language=en}}</ref> Macrophages are cells derived from monocytes which are made in the bone marrow. Initially, monocytes do not have a specific purpose. However, when these cells travel to and populate different tissues, those tissues emit signals for the type of immune cell that is needed in that area. Monocytes, therefore, alter their shape and function to satisfy work more effectively in their new location. These functions can vary from generalized (e.g. macrophages) to specific such as work done by [[B cell|B-]] and [[T cell|T-cells]].<ref>{{Cite web|url=https://www.sciencedirect.com/science/article/pii/S1369702115000206?via%3Dihub|title=ScienceDirect|website=www.sciencedirect.com|doi=10.1016/j.mattod.2015.01.019|access-date=2019-02-27}}</ref>

Macrophages are in almost every type of tissue and they are more abundant in tissue types that are especially susceptible to infection (e.g. lungs, stomach).<ref>{{Cite web|url=https://www.immunology.org/public-information/bitesized-immunology/cells/macrophages|title=Macrophages {{!}} British Society for Immunology|website=www.immunology.org|access-date=2019-02-27}}</ref> Because macrophages float around the body until needed, they are nearby and able to quickly migrate to the sight of infection. Within a span of hours they may be done neutralizing the pathogen.

Neutrophils are the most populous white blood cell and, like macrophages, they are phagocytic and come from the bone marrow. They differ from macrophages a couple of ways: they mature in the [[thymus]] despite being produced in the bone marrow<ref>{{Cite web|url=https://www.britannica.com/science/neutrophil|title=Neutrophil {{!}} leukocyte|website=Encyclopedia Britannica|language=en|access-date=2019-02-27}}</ref>, and also contain sacs inside them called granules that aid in the breakdown process. While macrophages are migratory and generally close by and can sense sites of infection, neutrophils need to be recruited to the sites.<ref>{{Cite web|url=https://www.news-medical.net/life-sciences/What-is-the-difference-Between-a-Phagocyte-Macrophage-Neutrophil-and-Eosinophil.aspx|title=What is the difference Between a Phagocyte, Macrophage, Neutrophil and Eosinophil?|date=2018-10-29|website=News-Medical.net|language=en|access-date=2019-02-27}}</ref>

If pathogens make it past the skin and mucous and the macrophages are unable to clear them, the body has a second method of removing infiltrators. After the initial exposure, the body “remembers” a specific signature on the infiltrator so that it can be identified and eliminated quickly during all subsequent exposures.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK279396/|title=The innate and adaptive immune systems|last=Information|first=National Center for Biotechnology|last2=Pike|first2=U. S. National Library of Medicine 8600 Rockville|last3=MD|first3=Bethesda|last4=Usa|first4=20894|date=2016-08-04|publisher=Institute for Quality and Efficiency in Health Care (IQWiG)|language=en}}</ref>

===Acquired or Adaptive Immunity===
Adaptive immunity is so named because the body must first experience an initial infection for this type of immunity to form against that specific contagion. The first time the body experiences an infection is the worst because it does not yet know how to best eliminate the infiltrating substance. After initial exposure, however, the body has several mechanisms to remember and quickly and aggressively neutralize the pathogen. Many times this system does its job so well that a person may not even realize they are symptomatic or have an infection.

The body needs to identify a pathogen prior to eliminating it. There are several cells that the immune system uses to recognize pathogens. Dendritic cells are antigen-presenting cells that help begin this secondary immune response. Dendritic cells (Greek: dendron, meaning tree) received their name because of the arm-like branches that spread out and grab antigens released by infectious agents.<ref name=":0">{{Cite web|url=https://www.immunology.org/public-information/bitesized-immunology/cells/dendritic-cells|title=Dendritic Cells {{!}} British Society for Immunology|website=www.immunology.org|access-date=2019-02-27}}</ref> The dendritic cells place the antigens, like flags, onto their surface for [[T helper cell|helper T-cells]] to recognize. After palpating a dendritic cell, white blood cells call helper T-cells (also called CD4 T-cells) which secrete lymphokines to direct other immune cells to target the infection. Helper T-cells also promote the production and release of proteins called antibodies.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK279397/|title=The defense mechanisms of the adaptive immune system|last=Information|first=National Center for Biotechnology|last2=Pike|first2=U. S. National Library of Medicine 8600 Rockville|last3=MD|first3=Bethesda|last4=Usa|first4=20894|date=2016-08-04|publisher=Institute for Quality and Efficiency in Health Care (IQWiG)|language=en}}</ref> Antibodies clump around pathogens neutralizing their infectious capabilities, perforate the surface of pathogens encouraging its deterioration, and signal to other cells to engulf and destroy the invader. B-cells are produced in the bone marrow and are the antibody factories of the body. They make specific antibodies for the specific pathogen(s) that the body is currently fighting.

Another type of T-cell, killer (cytotoxic) T-cells also must first be presented with antigens by one of the body’s antigen-presenting cells for it to activate. Once given a target, killer T-cells directly destroy infectious and defective material. Similar to antibodies, they punch holes in the membranes of bacteria, and infected or malfunctioning cells.<ref name=":0" />

The last kinds of T-cells are memory and regulatory. Memory T-cells engulfs the material from the infected or defective cells and store that information in case of a future infection by the same pathogen, or on locating a similar defect. This allows the immune system to react faster because it already knows what is needed to respond to that specific pathogen or defect. Regulatory T-cells keep helper and killer T-cells’ activity at higher levels only when they are necessary. These T-cells will reduce helper and killer T-cells and decrease their activity after the pathogen has been eliminated.<ref name=":0" />

==Components of the Immune System==
White blood cells, also called leukocytes, are the main defenders of the body. They circulate throughout the bloodstream (the circulatory system), surveying the body for possible threats.<ref>{{Cite journal|last=Shlomchik|first=Mark J.|last2=Walport|first2=Mark|last3=Travers|first3=Paul|last4=Charles A Janeway|first4=Jr|date=2001|title=The components of the immune system|url=https://www.ncbi.nlm.nih.gov/books/NBK27092/|journal=Immunobiology: The Immune System in Health and Disease. 5th edition|language=en}}</ref>[[File:White Blood Cell Types.jpg|thumb|795x795px|Variations in white blood cells and the immunity type they function within.<ref>{{Cite web|url=http://ib.bioninja.com.au/standard-level/topic-6-human-physiology/63-defence-against-infectio/types-of-leukocytes.html|title=Types of Leukocytes {{!}} BioNinja|website=ib.bioninja.com.au|access-date=2019-02-27}}</ref>]]
[[File:Granulocytes.jpg|thumb|The different types of granulocytes in humans. These immune cells contain sacs called granules and aid the body in fighting different harmful pathogens.<ref>{{Cite web|url=https://www.sinobiological.com/cluster-of-differentiation-in-granulocyte.html|title=Cluster of differentiation in granulocyte|website=www.sinobiological.com|access-date=2019-02-27}}</ref>]]

===Types and Functions of White Blood Cells (Leukocytes) ===
====Granulocytes====
Granulocytes are a type of white blood cell filled with double-membrane sacs called granules which contain a variety of substances. These substances aid in the immune response. The substances released include:
* histamine, a molecule that responds to injury, allergies and inflammation by inducing smooth muscle contraction and increased blood flow;
* cytokines, messenger proteins that induce other immune cells’ inflammatory functions;
* enzymes, metabolic proteins that decrease the amount of time it takes to carry out chemical reactions, and that activate other white blood cells.
The contents of granules can be released in two ways depending on the purpose of the substances that will be released. A granule can be ushered to the granulocyte’s membrane surface where the two will merge and the granule can dump its internal material into the area surrounding the cell. This method is helpful when the substances need to act directly on other tissues such as mast cells secreting histamine which act directly on the smooth muscle the mast cell in.

Alternately, granules can also release their internal material directly into the granulocyte. This process is helpful in cases where the granulocyte has engulfed a pathogen and the released elements from the granules can break it down. There are several types of granulocytes that perform functions related to both innate and adaptive immunity.

===== Basophils =====
Basophils, the least common granulocyte, help the body identify foreign substances. Once a pathogen is introduced to the body and consumed by a lymphocyte, such as a macrophage, the invader is broken down into smaller pieces. This eliminates it as a threat and makes disposal easier.

Additionally, in order for the immune cell to signal to the body that an invader was present (and that most likely there are other microbes nearby), the white blood cell will save some of the proteins from the pathogen and place it on its surface like a flag. These surface proteins are called antigens, and the process is called antigen presentation. Basophils are both capable of placing these antigens on themselves and onto other cells.

Now that the antigen can be identified, different white blood cells begin scanning cells’ surfaces in search of these markers. Helper T-cells (CD4 T-cells) are produced for this purpose. After sensing antigens, helper T-cells signal for the production of other while blood cell variants, which make inflammatory molecules that fight the infection. In addition, CD4 T-cells also help macrophages and killer T-cells perform their phagocytic and cytotoxic duties.

However, before a helper T-cell does all of this, they need to be: 1) told to function as these particular cells, and 2) stimulated to function in that manner. Basophils are the cells responsible for the programming and stimulation of these immune cells. It was initially hypothesized that basophils did not contain an essential component necessary to the differentiation of naive T-cells into helper T-cells. New evidence supports the idea that basophils do in fact possess all the necessary proteins, such as major histocompatibility complex II (see section below) and the cytokine IL-4, that stimulate the conversion of naive T-cells into helper T-cells.

Normal basophils amounts in the body range from 0-300/μL (0.000003L) of blood. Low levels are caused by afflictions such as hyperthyroidism or anaphylaxis. High levels are caused by hypothyroidism, and myeloproliferative disorders (blood disorders).

===== Eosinophils =====
Eosinophils are the next most common granulocyte. However, they store several enzymes and proteins with unidentified roles, so some the full extent of their purpose is unknown. Eosinophils inflict damage largely to parasites and to a smaller extent bacteria and viruses. These cells can also cause damage to the body’s own tissues during allergic reactions. Outside of the immune system, eosinophils help with organ development.

Eosinophils are typically less than 500/μL of blood. Infection by parasitic worms, ulcerative colitis, allergies are examples of maladies that can cause high levels of eosinophils, known as eosinophilia. Low levels may indicate alcohol intoxication, Cushing’s disease or problems with the bone marrow.
===== Neutrophils =====
Neutrophils are the most common immune cell and the first type of cell to arrive at the site of infection. These cells are flexible, bulbous, and multilobed. Normally, neutrophils travel through the blood and lymph systems but they have receptors that jut out of their surface like pins on a pincushion, that allow them to attach to cells stressed by damage or infection and perform their duty. With these receptors, neutrophils are also able to slip between cells if they’re needed in tissues outside of the blood and lymph systems.

Neutrophils are activated by chemical signals that stressed cells release. Cytokines, messenger proteins that induce different immune cell functions, can function in this capacity: switching migratory neutrophils to potent eradicator cells. Once operative, neutrophils working alongside macrophages in the innate immune system, engulfing and destroying pathogens non-specifically. This mechanism works because there are molecules present on pathogens that are not present on any of the cells in the body. These are called pathogen-associated molecular patterns (PAMPs). Cells in the body that have pattern-recognition receptors (PRRs), which neutrophils do, can identify the PAMPs and eliminate the non-self cells. Once ingested into the lumen on the neutrophil, the contents of the granules are released, which break down the microbe. Alternatively, the granules from a neutrophil can be released to the surrounding environment and break down pathogens outside of the cell.

Neutrophils are normally between 1500-8000 neutrophils/μL. High levels are caused by smoking, infection and non-infectious inflammation. Low levels appear with suppressed immune systems, autoimmune diseases and during drug treatments such as chemotherapy.

==== Monocytes ====
Monocytes are also white blood cells and are largely tasked with ingesting and eliminating microbial invaders, or identifying and presenting the proteins made by the infectious agent. They may also work in a restorative capacity to heal the affected area(s). Typically, monocytes become tissue macrophages or dendritic cells.

===== Macrophages =====
Macrophages are globular cells derived from monocytes that consume dysfunctional cells, cellular debris, and pathogens; they may be thought of as the garbage disposals of the immune system. They may be already present at sites where infection occurs, or they may migrate to the area of infection. As the name suggests, tissue macrophages exist in the different tissues in the body (e.g. liver or skin); they also are not necessarily derived from monocytes circulating in the blood and lymph system.

===== Dendritic cells =====
Dendritic cells are also monocyte-derived. They aid T-cell recognition of infectious material through the processing of antigens and production of proteins that major histocompatibility complexes (larger proteins on the surface of cells and tissues that allow the body to identify self from foreign) present to T-cells.

=== Production and Storage ===

==== Bone Marrow ====
White blood cells are produced in bone marrow. They begin as pluripotent hematopoietic stem cells (PSCs or HSCs) meaning they are capable of becoming any of the cells listed above, as well as red blood cells or platelets. T lymphocytes (T cells) are produced in the bone marrow while B lymphocytes (B cells) are both produced and develop to their full function in the bone marrow.

==== Thymus ====
The thymus is an immune organ that ceases having a functional capacity when puberty begins. During development, including during fetal development, the thymus stores T-cells (link to lower section maybe). The thymus is also a part of the endocrine system as it produces the hormone thymosin. This hormone initiates the maturation of T-cells. Once fully developed, the T-cells leave the thymus for the lymph nodes, where they enter active circulation and begin their immune duties.

==== The Lymph System ====
The lymph system, like the circulatory system, is comprised of vessels and nodes all throughout the body. Instead of blood, these vessels carry a slightly opaque, white fluid called lymph. This circulation system is responsible for removing toxins and infectious agents from tissues. Spread throughout the lymph tubes are small, grape-shaped compartments attached in clusters on the sides of vessels. These nodes, concentrated at the neck, upper chest, armpits and groin, constantly filter the lymph liquid of harmful substances. The lymph nodes contain B and T lymphocytes that specifically recognize dangerous material and make antibodies, which further help identify the pathogens, and eliminate them.

==== Spleen ====
The spleen filters the blood of dysfunctional or malformed red blood cells and platelets. It also clears away infectious agents from the blood. Macrophages neutralize all of these potential harms and recycle the products they can for further use by the body (e.g., hemoglobin from defective red blood cells can be put in new red blood cells). Lymphocytes are also stored in the spleen.

== Immune system symptoms ==

Symptoms related to M.E. include:
* [[Flu-like symptoms]] (sore throat, [[Sinusitis|sinus inflammation]], lymph node changes) that typically begin or worsens with [[exertion]], for instance as part of [[post-exertional malaise]] (PEM)
* Increased risk of contacting [[Viral infection|viruses]], which last for a prolonged time
* [[Gastrointestinal system|Gastro-intestinal]] problems, which may include [[nausea]], abdominal bloating, or [[irritable bowel syndrome]] (IBS)
* Needing to urinate either more urgently or [[Urinary frequency|more frequently]], sometimes at night ([[nocturia]])
* New sensitivities to smells, [[Chemical sensitivities|chemicals]], or [[Medicine sensitivities|medication]]; [[Food intolerance|food]] or [[Alcohol intolerance|alcohol intolerances]]<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
==Myalgic Encephalomyelitis==

There is evidence of immune dysregulation in [[Myalgic Encephalomyelitis]]:<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
* Reduced [[natural killer cell]] function.<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* Elevated [[regulatory T cell]]s<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* The [[Centers for Disease Control and Prevention]] ME/CFS page:
<blockquote>''Immune system abnormalities'' – some people with ME/CFS have impaired [[natural killer cell]] function and/or [[T cell]] function, chronic higher production of inflammatory [[Cytokine|cytokines]], and in some cases slight increase in some [[Autoantibody|autoantibodies]] ([[rheumatic factor]], [[Anti-thyroid antibody|anti-thyroid antibodies]], [[anti-gliadin]], [[Anti-smooth muscle antibody|anti-smooth muscle antibodies]], and [[Cold agglutinin|cold agglutinins]]).<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-19}}</ref></blockquote>

==Fibromyalgia==

In 2018, Zhang et al. research found inflammatory genes were involved in FM. Their paper ''SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study'' concluded: <blockquote>SNPs with significant TDTs were found in 36% of the cohort for ''CCL11'' and 12% for ''MEFV'', along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM.<ref>{{Cite journal|last=Zhang|first=Zhifang|last2=Feng|first2=Jinong|last3=Mao|first3=Allen|last4=Le|first4=Keith|last5=La Placa|first5=Deirdre|last6=Wu|first6=Xiwei|last7=Longmate|first7=Jeffrey|last8=Marek|first8=Claudia|last9=St. Amand|first9=R. Paul|date=2018-06-21|title=SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198625|doi=10.1371/journal.pone.0198625|issn=1932-6203|pmid=29927949|via=}}</ref></blockquote>There is ongoing [[Fibromyalgia#Immune_system_research|immune system research of fibromyalgia]].

==Learn more==

=== Further Reading ===
* [https://www.medicalnewstoday.com/articles/320101.php How the immune system works]

=== Videos ===
More on the immune system:
*[https://www.youtube.com/watch?v=GIJK3dwCWCw&feature=youtu.be Crash Course - The Immune System Part 1] ([[Adaptive immune system]])
*[https://www.youtube.com/watch?v=2DFN4IBZ3rI&feature=youtu.be Crash Course - The Immune System Part 2] ([[humoral immunity]] & [[B cell]]s)
*[https://www.youtube.com/watch?v=rd2cf5hValM&feature=youtu.be Crash Course - The Immune System Part 3] ([[cell-mediated immunity]] & [[T cell]]s)
More on neutrophils:
* [https://www.youtube.com/watch?v=FZxf1QDcEO0 Neutrophils and How White Blood Cells Work]
More on eosinophils
* [https://www.youtube.com/watch?v=3LNhUCLU3K8 Eosinophils]

==See also==
*[[Adaptive immune system]]
*[[Immune exhaustion hypothesis]]
*[[Innate immune system]]

==References==
<references />
[[Category:Body systems]]
[[Category:Immunology]]

Immune system

2019-02-27T20:47:35Z

Sbrumfie:added pics

The '''immune system''' is a complex combination of organs, circulatory networks, and cells which work together to identify, target and eliminate harmful substances that enter the body. The immune system response has many steps. Once in full effect, different parts of the system move in parallel to restore health to the host. When the immune response is no longer needed, the immune system will suppress the reaction.<ref>{{Cite journal|last=Chaplin|first=David D.|date=2010-2|title=Overview of the Immune Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923430/|journal=The Journal of allergy and clinical immunology|volume=125|issue=2 Suppl 2|pages=S3–23|doi=10.1016/j.jaci.2009.12.980|issn=0091-6749|pmc=PMC2923430|pmid=20176265}}</ref><ref>{{Cite web|url=https://www.hopkinsmedicine.org/healthlibrary/conditions/infectious_diseases/immune_system_85,P00630|title=Immune System {{!}} Johns Hopkins Medicine Health Library|website=www.hopkinsmedicine.org|access-date=2019-02-27}}</ref>

[[Myalgic encephalomyelitis]] (ME) is a complex multi-systemic disorder which causes [[Nervous system|neurological]] impairments, [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] dysfunction, and immune, [[Gastrointestinal system|gastrointestinal]] and/or [[genitourinary]] symptoms.<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

==Types of Immune Response==
===Innate Immune System===
Prior to actually getting into the body, [[Pathogen|pathogens]] or toxicants have to pass the body’s most basic immune defense: the skin and mucous. Mucous especially plays an important role because it is present in all the places where infection is most likely to occur (e.g. the eyes, nose and mouth).

Innate immunity is the nonspecific method of eliminating pathogens from the body. The main agents that carry out this mass, undiscriminating disposal of pathogens and dead or defective cells are called [[Macrophage|macrophages]] and [[Neutrophil|neutrophils]].<ref>{{Cite journal|last=Walter|first=Peter|last2=Roberts|first2=Keith|last3=Raff|first3=Martin|last4=Lewis|first4=Julian|last5=Johnson|first5=Alexander|last6=Alberts|first6=Bruce|date=2002|title=Innate Immunity|url=https://www.ncbi.nlm.nih.gov/books/NBK26846/|journal=Molecular Biology of the Cell. 4th edition|language=en}}</ref> Macrophages are cells derived from monocytes which are made in the bone marrow. Initially, monocytes do not have a specific purpose. However, when these cells travel to and populate different tissues, those tissues emit signals for the type of immune cell that is needed in that area. Monocytes, therefore, alter their shape and function to satisfy work more effectively in their new location. These functions can vary from generalized (e.g. macrophages) to specific such as work done by [[B cell|B-]] and [[T cell|T-cells]].<ref>{{Cite web|url=https://www.sciencedirect.com/science/article/pii/S1369702115000206?via%3Dihub|title=ScienceDirect|website=www.sciencedirect.com|doi=10.1016/j.mattod.2015.01.019|access-date=2019-02-27}}</ref>

Macrophages are in almost every type of tissue and they are more abundant in tissue types that are especially susceptible to infection (e.g. lungs, stomach).<ref>{{Cite web|url=https://www.immunology.org/public-information/bitesized-immunology/cells/macrophages|title=Macrophages {{!}} British Society for Immunology|website=www.immunology.org|access-date=2019-02-27}}</ref> Because macrophages float around the body until needed, they are nearby and able to quickly migrate to the sight of infection. Within a span of hours they may be done neutralizing the pathogen.

Neutrophils are the most populous white blood cell and, like macrophages, they are phagocytic and come from the bone marrow. They differ from macrophages a couple of ways: they mature in the [[thymus]] despite being produced in the bone marrow<ref>{{Cite web|url=https://www.britannica.com/science/neutrophil|title=Neutrophil {{!}} leukocyte|website=Encyclopedia Britannica|language=en|access-date=2019-02-27}}</ref>, and also contain sacs inside them called granules that aid in the breakdown process. While macrophages are migratory and generally close by and can sense sites of infection, neutrophils need to be recruited to the sites.<ref>{{Cite web|url=https://www.news-medical.net/life-sciences/What-is-the-difference-Between-a-Phagocyte-Macrophage-Neutrophil-and-Eosinophil.aspx|title=What is the difference Between a Phagocyte, Macrophage, Neutrophil and Eosinophil?|date=2018-10-29|website=News-Medical.net|language=en|access-date=2019-02-27}}</ref>

If pathogens make it past the skin and mucous and the macrophages are unable to clear them, the body has a second method of removing infiltrators. After the initial exposure, the body “remembers” a specific signature on the infiltrator so that it can be identified and eliminated quickly during all subsequent exposures.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK279396/|title=The innate and adaptive immune systems|last=Information|first=National Center for Biotechnology|last2=Pike|first2=U. S. National Library of Medicine 8600 Rockville|last3=MD|first3=Bethesda|last4=Usa|first4=20894|date=2016-08-04|publisher=Institute for Quality and Efficiency in Health Care (IQWiG)|language=en}}</ref>

===Acquired or Adaptive Immunity===
Adaptive immunity is so named because the body must first experience an initial infection for this type of immunity to form against that specific contagion. The first time the body experiences an infection is the worst because it does not yet know how to best eliminate the infiltrating substance. After initial exposure, however, the body has several mechanisms to remember and quickly and aggressively neutralize the pathogen. Many times this system does its job so well that a person may not even realize they are symptomatic or have an infection.

The body needs to identify a pathogen prior to eliminating it. There are several cells that the immune system uses to recognize pathogens. Dendritic cells are antigen-presenting cells that help begin this secondary immune response. Dendritic cells (Greek: dendron, meaning tree) received their name because of the arm-like branches that spread out and grab antigens released by infectious agents.<ref name=":0">{{Cite web|url=https://www.immunology.org/public-information/bitesized-immunology/cells/dendritic-cells|title=Dendritic Cells {{!}} British Society for Immunology|website=www.immunology.org|access-date=2019-02-27}}</ref> The dendritic cells place the antigens, like flags, onto their surface for [[T helper cell|helper T-cells]] to recognize. After palpating a dendritic cell, white blood cells call helper T-cells (also called CD4 T-cells) which secrete lymphokines to direct other immune cells to target the infection. Helper T-cells also promote the production and release of proteins called antibodies.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK279397/|title=The defense mechanisms of the adaptive immune system|last=Information|first=National Center for Biotechnology|last2=Pike|first2=U. S. National Library of Medicine 8600 Rockville|last3=MD|first3=Bethesda|last4=Usa|first4=20894|date=2016-08-04|publisher=Institute for Quality and Efficiency in Health Care (IQWiG)|language=en}}</ref> Antibodies clump around pathogens neutralizing their infectious capabilities, perforate the surface of pathogens encouraging its deterioration, and signal to other cells to engulf and destroy the invader. B-cells are produced in the bone marrow and are the antibody factories of the body. They make specific antibodies for the specific pathogen(s) that the body is currently fighting.

Another type of T-cell, killer (cytotoxic) T-cells also must first be presented with antigens by one of the body’s antigen-presenting cells for it to activate. Once given a target, killer T-cells directly destroy infectious and defective material. Similar to antibodies, they punch holes in the membranes of bacteria, and infected or malfunctioning cells.<ref name=":0" />

The last kinds of T-cells are memory and regulatory. Memory T-cells engulfs the material from the infected or defective cells and store that information in case of a future infection by the same pathogen, or on locating a similar defect. This allows the immune system to react faster because it already knows what is needed to respond to that specific pathogen or defect. Regulatory T-cells keep helper and killer T-cells’ activity at higher levels only when they are necessary. These T-cells will reduce helper and killer T-cells and decrease their activity after the pathogen has been eliminated.<ref name=":0" />

==Components of the Immune System==
White blood cells, also called leukocytes, are the main defenders of the body. They circulate throughout the bloodstream (the circulatory system), surveying the body for possible threats.<ref>{{Cite journal|last=Shlomchik|first=Mark J.|last2=Walport|first2=Mark|last3=Travers|first3=Paul|last4=Charles A Janeway|first4=Jr|date=2001|title=The components of the immune system|url=https://www.ncbi.nlm.nih.gov/books/NBK27092/|journal=Immunobiology: The Immune System in Health and Disease. 5th edition|language=en}}</ref>[[File:White Blood Cell Types.jpg|thumb|795x795px|Variations in white blood cells and the immunity type they function within.]]<ref>{{Cite web|url=http://ib.bioninja.com.au/standard-level/topic-6-human-physiology/63-defence-against-infectio/types-of-leukocytes.html|title=Types of Leukocytes {{!}} BioNinja|website=ib.bioninja.com.au|access-date=2019-02-27}}</ref>
[[File:Granulocytes.jpg|thumb|The different types of granulocytes in humans. These immune cells contain sacs called granules and aid the body in fighting different harmful pathogens.]]
<ref>{{Cite web|url=https://www.sinobiological.com/cluster-of-differentiation-in-granulocyte.html|title=Cluster of differentiation in granulocyte|website=www.sinobiological.com|access-date=2019-02-27}}</ref>

===Types and Functions of White Blood Cells (Leukocytes) ===
====Granulocytes====
Granulocytes are a type of white blood cell filled with double-membrane sacs called granules which contain a variety of substances. These substances aid in the immune response. The substances released include:
* histamine, a molecule that responds to injury, allergies and inflammation by inducing smooth muscle contraction and increased blood flow;
* cytokines, messenger proteins that induce other immune cells’ inflammatory functions;
* enzymes, metabolic proteins that decrease the amount of time it takes to carry out chemical reactions, and that activate other white blood cells.
The contents of granules can be released in two ways depending on the purpose of the substances that will be released. A granule can be ushered to the granulocyte’s membrane surface where the two will merge and the granule can dump its internal material into the area surrounding the cell. This method is helpful when the substances need to act directly on other tissues such as mast cells secreting histamine which act directly on the smooth muscle the mast cell in.

Alternately, granules can also release their internal material directly into the granulocyte. This process is helpful in cases where the granulocyte has engulfed a pathogen and the released elements from the granules can break it down. There are several types of granulocytes that perform functions related to both innate and adaptive immunity.

===== Basophils =====
Basophils, the least common granulocyte, help the body identify foreign substances. Once a pathogen is introduced to the body and consumed by a lymphocyte, such as a macrophage, the invader is broken down into smaller pieces. This eliminates it as a threat and makes disposal easier.

Additionally, in order for the immune cell to signal to the body that an invader was present (and that most likely there are other microbes nearby), the white blood cell will save some of the proteins from the pathogen and place it on its surface like a flag. These surface proteins are called antigens, and the process is called antigen presentation. Basophils are both capable of placing these antigens on themselves and onto other cells.

Now that the antigen can be identified, different white blood cells begin scanning cells’ surfaces in search of these markers. Helper T-cells (CD4 T-cells) are produced for this purpose. After sensing antigens, helper T-cells signal for the production of other while blood cell variants, which make inflammatory molecules that fight the infection. In addition, CD4 T-cells also help macrophages and killer T-cells perform their phagocytic and cytotoxic duties.

However, before a helper T-cell does all of this, they need to be: 1) told to function as these particular cells, and 2) stimulated to function in that manner. Basophils are the cells responsible for the programming and stimulation of these immune cells. It was initially hypothesized that basophils did not contain an essential component necessary to the differentiation of naive T-cells into helper T-cells. New evidence supports the idea that basophils do in fact possess all the necessary proteins, such as major histocompatibility complex II (see section below) and the cytokine IL-4, that stimulate the conversion of naive T-cells into helper T-cells.

Normal basophils amounts in the body range from 0-300/μL (0.000003L) of blood. Low levels are caused by afflictions such as hyperthyroidism or anaphylaxis. High levels are caused by hypothyroidism, and myeloproliferative disorders (blood disorders).

===== Eosinophils =====
Eosinophils are the next most common granulocyte. However, they store several enzymes and proteins with unidentified roles, so some the full extent of their purpose is unknown. Eosinophils inflict damage largely to parasites and to a smaller extent bacteria and viruses. These cells can also cause damage to the body’s own tissues during allergic reactions. Outside of the immune system, eosinophils help with organ development.

Eosinophils are typically less than 500/μL of blood. Infection by parasitic worms, ulcerative colitis, allergies are examples of maladies that can cause high levels of eosinophils, known as eosinophilia. Low levels may indicate alcohol intoxication, Cushing’s disease or problems with the bone marrow.
===== Neutrophils =====
Neutrophils are the most common immune cell and the first type of cell to arrive at the site of infection. These cells are flexible, bulbous, and multilobed. Normally, neutrophils travel through the blood and lymph systems but they have receptors that jut out of their surface like pins on a pincushion, that allow them to attach to cells stressed by damage or infection and perform their duty. With these receptors, neutrophils are also able to slip between cells if they’re needed in tissues outside of the blood and lymph systems.

Neutrophils are activated by chemical signals that stressed cells release. Cytokines, messenger proteins that induce different immune cell functions, can function in this capacity: switching migratory neutrophils to potent eradicator cells. Once operative, neutrophils working alongside macrophages in the innate immune system, engulfing and destroying pathogens non-specifically. This mechanism works because there are molecules present on pathogens that are not present on any of the cells in the body. These are called pathogen-associated molecular patterns (PAMPs). Cells in the body that have pattern-recognition receptors (PRRs), which neutrophils do, can identify the PAMPs and eliminate the non-self cells. Once ingested into the lumen on the neutrophil, the contents of the granules are released, which break down the microbe. Alternatively, the granules from a neutrophil can be released to the surrounding environment and break down pathogens outside of the cell.

Neutrophils are normally between 1500-8000 neutrophils/μL. High levels are caused by smoking, infection and non-infectious inflammation. Low levels appear with suppressed immune systems, autoimmune diseases and during drug treatments such as chemotherapy.

==== Monocytes ====
Monocytes are also white blood cells and are largely tasked with ingesting and eliminating microbial invaders, or identifying and presenting the proteins made by the infectious agent. They may also work in a restorative capacity to heal the affected area(s). Typically, monocytes become tissue macrophages or dendritic cells.

===== Macrophages =====
Macrophages are globular cells derived from monocytes that consume dysfunctional cells, cellular debris, and pathogens; they may be thought of as the garbage disposals of the immune system. They may be already present at sites where infection occurs, or they may migrate to the area of infection. As the name suggests, tissue macrophages exist in the different tissues in the body (e.g. liver or skin); they also are not necessarily derived from monocytes circulating in the blood and lymph system.

===== Dendritic cells =====
Dendritic cells are also monocyte-derived. They aid T-cell recognition of infectious material through the processing of antigens and production of proteins that major histocompatibility complexes (larger proteins on the surface of cells and tissues that allow the body to identify self from foreign) present to T-cells.

=== Production and Storage ===

==== Bone Marrow ====
White blood cells are produced in bone marrow. They begin as pluripotent hematopoietic stem cells (PSCs or HSCs) meaning they are capable of becoming any of the cells listed above, as well as red blood cells or platelets. T lymphocytes (T cells) are produced in the bone marrow while B lymphocytes (B cells) are both produced and develop to their full function in the bone marrow.

==== Thymus ====
The thymus is an immune organ that ceases having a functional capacity when puberty begins. During development, including during fetal development, the thymus stores T-cells (link to lower section maybe). The thymus is also a part of the endocrine system as it produces the hormone thymosin. This hormone initiates the maturation of T-cells. Once fully developed, the T-cells leave the thymus for the lymph nodes, where they enter active circulation and begin their immune duties.

==== The Lymph System ====
The lymph system, like the circulatory system, is comprised of vessels and nodes all throughout the body. Instead of blood, these vessels carry a slightly opaque, white fluid called lymph. This circulation system is responsible for removing toxins and infectious agents from tissues. Spread throughout the lymph tubes are small, grape-shaped compartments attached in clusters on the sides of vessels. These nodes, concentrated at the neck, upper chest, armpits and groin, constantly filter the lymph liquid of harmful substances. The lymph nodes contain B and T lymphocytes that specifically recognize dangerous material and make antibodies, which further help identify the pathogens, and eliminate them.

==== Spleen ====
The spleen filters the blood of dysfunctional or malformed red blood cells and platelets. It also clears away infectious agents from the blood. Macrophages neutralize all of these potential harms and recycle the products they can for further use by the body (e.g., hemoglobin from defective red blood cells can be put in new red blood cells). Lymphocytes are also stored in the spleen.

== Immune system symptoms ==

Symptoms related to M.E. include:
* [[Flu-like symptoms]] (sore throat, [[Sinusitis|sinus inflammation]], lymph node changes) that typically begin or worsens with [[exertion]], for instance as part of [[post-exertional malaise]] (PEM)
* Increased risk of contacting [[Viral infection|viruses]], which last for a prolonged time
* [[Gastrointestinal system|Gastro-intestinal]] problems, which may include [[nausea]], abdominal bloating, or [[irritable bowel syndrome]] (IBS)
* Needing to urinate either more urgently or [[Urinary frequency|more frequently]], sometimes at night ([[nocturia]])
* New sensitivities to smells, [[Chemical sensitivities|chemicals]], or [[Medicine sensitivities|medication]]; [[Food intolerance|food]] or [[Alcohol intolerance|alcohol intolerances]]<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
==Myalgic Encephalomyelitis==

There is evidence of immune dysregulation in [[Myalgic Encephalomyelitis]]:<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
* Reduced [[natural killer cell]] function.<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* Elevated [[regulatory T cell]]s<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* The [[Centers for Disease Control and Prevention]] ME/CFS page:
<blockquote>''Immune system abnormalities'' – some people with ME/CFS have impaired [[natural killer cell]] function and/or [[T cell]] function, chronic higher production of inflammatory [[Cytokine|cytokines]], and in some cases slight increase in some [[Autoantibody|autoantibodies]] ([[rheumatic factor]], [[Anti-thyroid antibody|anti-thyroid antibodies]], [[anti-gliadin]], [[Anti-smooth muscle antibody|anti-smooth muscle antibodies]], and [[Cold agglutinin|cold agglutinins]]).<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-19}}</ref></blockquote>

==Fibromyalgia==

In 2018, Zhang et al. research found inflammatory genes were involved in FM. Their paper ''SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study'' concluded: <blockquote>SNPs with significant TDTs were found in 36% of the cohort for ''CCL11'' and 12% for ''MEFV'', along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM.<ref>{{Cite journal|last=Zhang|first=Zhifang|last2=Feng|first2=Jinong|last3=Mao|first3=Allen|last4=Le|first4=Keith|last5=La Placa|first5=Deirdre|last6=Wu|first6=Xiwei|last7=Longmate|first7=Jeffrey|last8=Marek|first8=Claudia|last9=St. Amand|first9=R. Paul|date=2018-06-21|title=SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198625|doi=10.1371/journal.pone.0198625|issn=1932-6203|pmid=29927949|via=}}</ref></blockquote>There is ongoing [[Fibromyalgia#Immune_system_research|immune system research of fibromyalgia]].

==Learn more==

=== Further Reading ===
* [https://www.medicalnewstoday.com/articles/320101.php How the immune system works]

=== Videos ===
More on the immune system:
*[https://www.youtube.com/watch?v=GIJK3dwCWCw&feature=youtu.be Crash Course - The Immune System Part 1] ([[Adaptive immune system]])
*[https://www.youtube.com/watch?v=2DFN4IBZ3rI&feature=youtu.be Crash Course - The Immune System Part 2] ([[humoral immunity]] & [[B cell]]s)
*[https://www.youtube.com/watch?v=rd2cf5hValM&feature=youtu.be Crash Course - The Immune System Part 3] ([[cell-mediated immunity]] & [[T cell]]s)
More on neutrophils:
* [https://www.youtube.com/watch?v=FZxf1QDcEO0 Neutrophils and How White Blood Cells Work]
More on eosinophils
* [https://www.youtube.com/watch?v=3LNhUCLU3K8 Eosinophils]

==See also==
*[[Adaptive immune system]]
*[[Immune exhaustion hypothesis]]
*[[Innate immune system]]

==References==
<references />
[[Category:Body systems]]
[[Category:Immunology]]

Immune system

2019-02-27T20:40:00Z

Sbrumfie:Added citations

The '''immune system''' is a complex combination of organs, circulatory networks, and cells which work together to identify, target and eliminate harmful substances that enter the body. The immune system response has many steps. Once in full effect, different parts of the system move in parallel to restore health to the host. When the immune response is no longer needed, the immune system will suppress the reaction.<ref>{{Cite journal|last=Chaplin|first=David D.|date=2010-2|title=Overview of the Immune Response|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923430/|journal=The Journal of allergy and clinical immunology|volume=125|issue=2 Suppl 2|pages=S3–23|doi=10.1016/j.jaci.2009.12.980|issn=0091-6749|pmc=PMC2923430|pmid=20176265}}</ref><ref>{{Cite web|url=https://www.hopkinsmedicine.org/healthlibrary/conditions/infectious_diseases/immune_system_85,P00630|title=Immune System {{!}} Johns Hopkins Medicine Health Library|website=www.hopkinsmedicine.org|access-date=2019-02-27}}</ref>

[[Myalgic encephalomyelitis]] (ME) is a complex multi-systemic disorder which causes [[Nervous system|neurological]] impairments, [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] dysfunction, and immune, [[Gastrointestinal system|gastrointestinal]] and/or [[genitourinary]] symptoms.<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

== Immune system symptoms ==

Symptoms related to M.E. include:
* [[Flu-like symptoms]] (sore throat, [[Sinusitis|sinus inflammation]], lymph node changes) that typically begin or worsens with [[exertion]], for instance as part of [[post-exertional malaise]] (PEM)
* Increased risk of contacting [[Viral infection|viruses]], which last for a prolonged time
* [[Gastrointestinal system|Gastro-intestinal]] problems, which may include [[nausea]], abdominal bloating, or [[irritable bowel syndrome]] (IBS)
* Needing to urinate either more urgently or [[Urinary frequency|more frequently]], sometimes at night ([[nocturia]])
* New sensitivities to smells, [[Chemical sensitivities|chemicals]], or [[Medicine sensitivities|medication]]; [[Food intolerance|food]] or [[Alcohol intolerance|alcohol intolerances]]<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

==Types of Immune Response==
===Innate Immune System===
Prior to actually getting into the body, [[Pathogen|pathogens]] or toxicants have to pass the body’s most basic immune defense: the skin and mucous. Mucous especially plays an important role because it is present in all the places where infection is most likely to occur (e.g. the eyes, nose and mouth).

Innate immunity is the nonspecific method of eliminating pathogens from the body. The main agents that carry out this mass, undiscriminating disposal of pathogens and dead or defective cells are called [[Macrophage|macrophages]] and [[Neutrophil|neutrophils]].<ref>{{Cite journal|last=Walter|first=Peter|last2=Roberts|first2=Keith|last3=Raff|first3=Martin|last4=Lewis|first4=Julian|last5=Johnson|first5=Alexander|last6=Alberts|first6=Bruce|date=2002|title=Innate Immunity|url=https://www.ncbi.nlm.nih.gov/books/NBK26846/|journal=Molecular Biology of the Cell. 4th edition|language=en}}</ref> Macrophages are cells derived from monocytes which are made in the bone marrow. Initially, monocytes do not have a specific purpose. However, when these cells travel to and populate different tissues, those tissues emit signals for the type of immune cell that is needed in that area. Monocytes, therefore, alter their shape and function to satisfy work more effectively in their new location. These functions can vary from generalized (e.g. macrophages) to specific such as work done by [[B cell|B-]] and [[T cell|T-cells]].<ref>{{Cite web|url=https://www.sciencedirect.com/science/article/pii/S1369702115000206?via%3Dihub|title=ScienceDirect|website=www.sciencedirect.com|doi=10.1016/j.mattod.2015.01.019|access-date=2019-02-27}}</ref>

Macrophages are in almost every type of tissue and they are more abundant in tissue types that are especially susceptible to infection (e.g. lungs, stomach).<ref>{{Cite web|url=https://www.immunology.org/public-information/bitesized-immunology/cells/macrophages|title=Macrophages {{!}} British Society for Immunology|website=www.immunology.org|access-date=2019-02-27}}</ref> Because macrophages float around the body until needed, they are nearby and able to quickly migrate to the sight of infection. Within a span of hours they may be done neutralizing the pathogen.

Neutrophils are the most populous white blood cell and, like macrophages, they are phagocytic and come from the bone marrow. They differ from macrophages a couple of ways: they mature in the [[thymus]] despite being produced in the bone marrow<ref>{{Cite web|url=https://www.britannica.com/science/neutrophil|title=Neutrophil {{!}} leukocyte|website=Encyclopedia Britannica|language=en|access-date=2019-02-27}}</ref>, and also contain sacs inside them called granules that aid in the breakdown process. While macrophages are migratory and generally close by and can sense sites of infection, neutrophils need to be recruited to the sites.<ref>{{Cite web|url=https://www.news-medical.net/life-sciences/What-is-the-difference-Between-a-Phagocyte-Macrophage-Neutrophil-and-Eosinophil.aspx|title=What is the difference Between a Phagocyte, Macrophage, Neutrophil and Eosinophil?|date=2018-10-29|website=News-Medical.net|language=en|access-date=2019-02-27}}</ref>

If pathogens make it past the skin and mucous and the macrophages are unable to clear them, the body has a second method of removing infiltrators. After the initial exposure, the body “remembers” a specific signature on the infiltrator so that it can be identified and eliminated quickly during all subsequent exposures.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK279396/|title=The innate and adaptive immune systems|last=Information|first=National Center for Biotechnology|last2=Pike|first2=U. S. National Library of Medicine 8600 Rockville|last3=MD|first3=Bethesda|last4=Usa|first4=20894|date=2016-08-04|publisher=Institute for Quality and Efficiency in Health Care (IQWiG)|language=en}}</ref>

===Acquired or Adaptive Immunity===
Adaptive immunity is so named because the body must first experience an initial infection for this type of immunity to form against that specific contagion. The first time the body experiences an infection is the worst because it does not yet know how to best eliminate the infiltrating substance. After initial exposure, however, the body has several mechanisms to remember and quickly and aggressively neutralize the pathogen. Many times this system does its job so well that a person may not even realize they are symptomatic or have an infection.

The body needs to identify a pathogen prior to eliminating it. There are several cells that the immune system uses to recognize pathogens. Dendritic cells are antigen-presenting cells that help begin this secondary immune response. Dendritic cells (Greek: dendron, meaning tree) received their name because of the arm-like branches that spread out and grab antigens released by infectious agents.<ref name=":0">{{Cite web|url=https://www.immunology.org/public-information/bitesized-immunology/cells/dendritic-cells|title=Dendritic Cells {{!}} British Society for Immunology|website=www.immunology.org|access-date=2019-02-27}}</ref> The dendritic cells place the antigens, like flags, onto their surface for [[T helper cell|helper T-cells]] to recognize. After palpating a dendritic cell, white blood cells call helper T-cells (also called CD4 T-cells) which secrete lymphokines to direct other immune cells to target the infection. Helper T-cells also promote the production and release of proteins called antibodies.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK279397/|title=The defense mechanisms of the adaptive immune system|last=Information|first=National Center for Biotechnology|last2=Pike|first2=U. S. National Library of Medicine 8600 Rockville|last3=MD|first3=Bethesda|last4=Usa|first4=20894|date=2016-08-04|publisher=Institute for Quality and Efficiency in Health Care (IQWiG)|language=en}}</ref> Antibodies clump around pathogens neutralizing their infectious capabilities, perforate the surface of pathogens encouraging its deterioration, and signal to other cells to engulf and destroy the invader. B-cells are produced in the bone marrow and are the antibody factories of the body. They make specific antibodies for the specific pathogen(s) that the body is currently fighting.

Another type of T-cell, killer (cytotoxic) T-cells also must first be presented with antigens by one of the body’s antigen-presenting cells for it to activate. Once given a target, killer T-cells directly destroy infectious and defective material. Similar to antibodies, they punch holes in the membranes of bacteria, and infected or malfunctioning cells.<ref name=":0" />

The last kinds of T-cells are memory and regulatory. Memory T-cells engulfs the material from the infected or defective cells and store that information in case of a future infection by the same pathogen, or on locating a similar defect. This allows the immune system to react faster because it already knows what is needed to respond to that specific pathogen or defect. Regulatory T-cells keep helper and killer T-cells’ activity at higher levels only when they are necessary. These T-cells will reduce helper and killer T-cells and decrease their activity after the pathogen has been eliminated.<ref name=":0" />

==Components of the Immune System==
White blood cells, also called leukocytes, are the main defenders of the body. They circulate throughout the bloodstream (the circulatory system), surveying the body for possible threats.<ref>{{Cite journal|last=Shlomchik|first=Mark J.|last2=Walport|first2=Mark|last3=Travers|first3=Paul|last4=Charles A Janeway|first4=Jr|date=2001|title=The components of the immune system|url=https://www.ncbi.nlm.nih.gov/books/NBK27092/|journal=Immunobiology: The Immune System in Health and Disease. 5th edition|language=en}}</ref>

=== Types and Functions of White Blood Cells (Leukocytes) ===
[[File:White Blood Cell Types.jpg|thumb|795x795px|Variations in white blood cells and the immunity type they function within.]]

====Granulocytes====
Granulocytes are a type of white blood cell filled with double-membrane sacs called granules which contain a variety of substances. These substances aid in the immune response. The substances released include:
* histamine, a molecule that responds to injury, allergies and inflammation by inducing smooth muscle contraction and increased blood flow;
* cytokines, messenger proteins that induce other immune cells’ inflammatory functions;
* enzymes, metabolic proteins that decrease the amount of time it takes to carry out chemical reactions, and that activate other white blood cells.
The contents of granules can be released in two ways depending on the purpose of the substances that will be released. A granule can be ushered to the granulocyte’s membrane surface where the two will merge and the granule can dump its internal material into the area surrounding the cell. This method is helpful when the substances need to act directly on other tissues such as mast cells secreting histamine which act directly on the smooth muscle the mast cell in.

Alternately, granules can also release their internal material directly into the granulocyte. This process is helpful in cases where the granulocyte has engulfed a pathogen and the released elements from the granules can break it down. There are several types of granulocytes that perform functions related to both innate and adaptive immunity.

===== Basophils =====
Basophils, the least common granulocyte, help the body identify foreign substances. Once a pathogen is introduced to the body and consumed by a lymphocyte, such as a macrophage, the invader is broken down into smaller pieces. This eliminates it as a threat and makes disposal easier.

Additionally, in order for the immune cell to signal to the body that an invader was present (and that most likely there are other microbes nearby), the white blood cell will save some of the proteins from the pathogen and place it on its surface like a flag. These surface proteins are called antigens, and the process is called antigen presentation. Basophils are both capable of placing these antigens on themselves and onto other cells.

Now that the antigen can be identified, different white blood cells begin scanning cells’ surfaces in search of these markers. Helper T-cells (CD4 T-cells) are produced for this purpose. After sensing antigens, helper T-cells signal for the production of other while blood cell variants, which make inflammatory molecules that fight the infection. In addition, CD4 T-cells also help macrophages and killer T-cells perform their phagocytic and cytotoxic duties.

However, before a helper T-cell does all of this, they need to be: 1) told to function as these particular cells, and 2) stimulated to function in that manner. Basophils are the cells responsible for the programming and stimulation of these immune cells. It was initially hypothesized that basophils did not contain an essential component necessary to the differentiation of naive T-cells into helper T-cells. New evidence supports the idea that basophils do in fact possess all the necessary proteins, such as major histocompatibility complex II (see section below) and the cytokine IL-4, that stimulate the conversion of naive T-cells into helper T-cells.

Normal basophils amounts in the body range from 0-300/μL (0.000003L) of blood. Low levels are caused by afflictions such as hyperthyroidism or anaphylaxis. High levels are caused by hypothyroidism, and myeloproliferative disorders (blood disorders).

===== Eosinophils =====
Eosinophils are the next most common granulocyte. However, they store several enzymes and proteins with unidentified roles, so some the full extent of their purpose is unknown. Eosinophils inflict damage largely to parasites and to a smaller extent bacteria and viruses. These cells can also cause damage to the body’s own tissues during allergic reactions. Outside of the immune system, eosinophils help with organ development.

Eosinophils are typically less than 500/μL of blood. Infection by parasitic worms, ulcerative colitis, allergies are examples of maladies that can cause high levels of eosinophils, known as eosinophilia. Low levels may indicate alcohol intoxication, Cushing’s disease or problems with the bone marrow.
===== Neutrophils =====
Neutrophils are the most common immune cell and the first type of cell to arrive at the site of infection. These cells are flexible, bulbous, and multilobed. Normally, neutrophils travel through the blood and lymph systems but they have receptors that jut out of their surface like pins on a pincushion, that allow them to attach to cells stressed by damage or infection and perform their duty. With these receptors, neutrophils are also able to slip between cells if they’re needed in tissues outside of the blood and lymph systems.

Neutrophils are activated by chemical signals that stressed cells release. Cytokines, messenger proteins that induce different immune cell functions, can function in this capacity: switching migratory neutrophils to potent eradicator cells. Once operative, neutrophils working alongside macrophages in the innate immune system, engulfing and destroying pathogens non-specifically. This mechanism works because there are molecules present on pathogens that are not present on any of the cells in the body. These are called pathogen-associated molecular patterns (PAMPs). Cells in the body that have pattern-recognition receptors (PRRs), which neutrophils do, can identify the PAMPs and eliminate the non-self cells. Once ingested into the lumen on the neutrophil, the contents of the granules are released, which break down the microbe. Alternatively, the granules from a neutrophil can be released to the surrounding environment and break down pathogens outside of the cell.

Neutrophils are normally between 1500-8000 neutrophils/μL. High levels are caused by smoking, infection and non-infectious inflammation. Low levels appear with suppressed immune systems, autoimmune diseases and during drug treatments such as chemotherapy.

==== Monocytes ====
Monocytes are also white blood cells and are largely tasked with ingesting and eliminating microbial invaders, or identifying and presenting the proteins made by the infectious agent. They may also work in a restorative capacity to heal the affected area(s). Typically, monocytes become tissue macrophages or dendritic cells.

===== Macrophages =====
Macrophages are globular cells derived from monocytes that consume dysfunctional cells, cellular debris, and pathogens; they may be thought of as the garbage disposals of the immune system. They may be already present at sites where infection occurs, or they may migrate to the area of infection. As the name suggests, tissue macrophages exist in the different tissues in the body (e.g. liver or skin); they also are not necessarily derived from monocytes circulating in the blood and lymph system.

===== Dendritic cells =====
Dendritic cells are also monocyte-derived. They aid T-cell recognition of infectious material through the processing of antigens and production of proteins that major histocompatibility complexes (larger proteins on the surface of cells and tissues that allow the body to identify self from foreign) present to T-cells.

=== Production and Storage ===

==== Bone Marrow ====
White blood cells are produced in bone marrow. They begin as pluripotent hematopoietic stem cells (PSCs or HSCs) meaning they are capable of becoming any of the cells listed above, as well as red blood cells or platelets. T lymphocytes (T cells) are produced in the bone marrow while B lymphocytes (B cells) are both produced and develop to their full function in the bone marrow.

==== Thymus ====
The thymus is an immune organ that ceases having a functional capacity when puberty begins. During development, including during fetal development, the thymus stores T-cells (link to lower section maybe). The thymus is also a part of the endocrine system as it produces the hormone thymosin. This hormone initiates the maturation of T-cells. Once fully developed, the T-cells leave the thymus for the lymph nodes, where they enter active circulation and begin their immune duties.

==== The Lymph System ====
The lymph system, like the circulatory system, is comprised of vessels and nodes all throughout the body. Instead of blood, these vessels carry a slightly opaque, white fluid called lymph. This circulation system is responsible for removing toxins and infectious agents from tissues. Spread throughout the lymph tubes are small, grape-shaped compartments attached in clusters on the sides of vessels. These nodes, concentrated at the neck, upper chest, armpits and groin, constantly filter the lymph liquid of harmful substances. The lymph nodes contain B and T lymphocytes that specifically recognize dangerous material and make antibodies, which further help identify the pathogens, and eliminate them.

==== Spleen ====
The spleen filters the blood of dysfunctional or malformed red blood cells and platelets. It also clears away infectious agents from the blood. Macrophages neutralize all of these potential harms and recycle the products they can for further use by the body (e.g., hemoglobin from defective red blood cells can be put in new red blood cells). Lymphocytes are also stored in the spleen.

==Myalgic Encephalomyelitis==

There is evidence of immune dysregulation in [[Myalgic Encephalomyelitis]]:<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
* Reduced [[natural killer cell]] function.<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* Elevated [[regulatory T cell]]s<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* The [[Centers for Disease Control and Prevention]] ME/CFS page:
<blockquote>''Immune system abnormalities'' – some people with ME/CFS have impaired [[natural killer cell]] function and/or [[T cell]] function, chronic higher production of inflammatory [[Cytokine|cytokines]], and in some cases slight increase in some [[Autoantibody|autoantibodies]] ([[rheumatic factor]], [[Anti-thyroid antibody|anti-thyroid antibodies]], [[anti-gliadin]], [[Anti-smooth muscle antibody|anti-smooth muscle antibodies]], and [[Cold agglutinin|cold agglutinins]]).<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-19}}</ref></blockquote>

==Fibromyalgia==

In 2018, Zhang et al. research found inflammatory genes were involved in FM. Their paper ''SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study'' concluded: <blockquote>SNPs with significant TDTs were found in 36% of the cohort for ''CCL11'' and 12% for ''MEFV'', along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM.<ref>{{Cite journal|last=Zhang|first=Zhifang|last2=Feng|first2=Jinong|last3=Mao|first3=Allen|last4=Le|first4=Keith|last5=La Placa|first5=Deirdre|last6=Wu|first6=Xiwei|last7=Longmate|first7=Jeffrey|last8=Marek|first8=Claudia|last9=St. Amand|first9=R. Paul|date=2018-06-21|title=SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198625|doi=10.1371/journal.pone.0198625|issn=1932-6203|pmid=29927949|via=}}</ref></blockquote>There is ongoing [[Fibromyalgia#Immune_system_research|immune system research of fibromyalgia]].

==Learn more==

=== Further Reading ===
* [https://www.medicalnewstoday.com/articles/320101.php How the immune system works]

=== Videos ===
More on the immune system:
*[https://www.youtube.com/watch?v=GIJK3dwCWCw&feature=youtu.be Crash Course - The Immune System Part 1] ([[Adaptive immune system]])
*[https://www.youtube.com/watch?v=2DFN4IBZ3rI&feature=youtu.be Crash Course - The Immune System Part 2] ([[humoral immunity]] & [[B cell]]s)
*[https://www.youtube.com/watch?v=rd2cf5hValM&feature=youtu.be Crash Course - The Immune System Part 3] ([[cell-mediated immunity]] & [[T cell]]s)
More on neutrophils:
* [https://www.youtube.com/watch?v=FZxf1QDcEO0 Neutrophils and How White Blood Cells Work]
More on eosinophils
* [https://www.youtube.com/watch?v=3LNhUCLU3K8 Eosinophils]

==See also==
*[[Adaptive immune system]]
*[[Immune exhaustion hypothesis]]
*[[Innate immune system]]

==References==
<references />
[[Category:Body systems]]
[[Category:Immunology]]

Immune system

2019-02-26T21:03:38Z

Sbrumfie:Adding content

The '''immune system''' is a complex combination of organs, circulatory networks, and cells which work together to identify, target and eliminate harmful substances that enter the body. The immune system response has many steps. Once in full effect, different parts of the system move in parallel to restore health to the host. When the immune response is no longer needed, the immune system will suppress the reaction.

[[Myalgic encephalomyelitis]] (ME) is a complex multi-systemic disorder which causes [[Nervous system|neurological]] impairments, [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] dysfunction, and immune, [[Gastrointestinal system|gastrointestinal]] and/or [[genitourinary]] symptoms.<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

== Immune system symptoms ==

Symptoms related to M.E. include:
* [[Flu-like symptoms]] (sore throat, [[Sinusitis|sinus inflammation]], lymph node changes) that typically begin or worsens with [[exertion]], for instance as part of [[post-exertional malaise]] (PEM)
* Increased risk of contacting [[Viral infection|viruses]], which last for a prolonged time
* [[Gastrointestinal system|Gastro-intestinal]] problems, which may include [[nausea]], abdominal bloating, or [[irritable bowel syndrome]] (IBS)
* Needing to urinate either more urgently or [[Urinary frequency|more frequently]], sometimes at night ([[nocturia]])
* New sensitivities to smells, [[Chemical sensitivities|chemicals]], or [[Medicine sensitivities|medication]]; [[Food intolerance|food]] or [[Alcohol intolerance|alcohol intolerances]]<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

==Types of Immune Response==
===Innate Immune System===
Prior to actually getting into the body, [[Pathogen|pathogens]] or toxicants have to pass the body’s most basic immune defense: the skin and mucous. Mucous especially plays an important role because it is present in all the places where infection is most likely to occur (e.g. the eyes, nose and mouth).

Innate immunity is the nonspecific method of eliminating pathogens from the body. The main agents that carry out this mass, undiscriminating disposal of pathogens and dead or defective cells are called [[Macrophage|macrophages]] and [[Neutrophil|neutrophils]]. Macrophages are cells derived from monocytes which are made in the bone marrow. Initially, monocytes do not have a specific purpose. However, when these cells travel to and populate different tissues, those tissues emit signals for the type of immune cell that is needed in that area. Monocytes, therefore, alter their shape and function to satisfy work more effectively in their new location. These functions can vary from generalized (e.g. macrophages) to specific such as work done by [[B cell|B-]] and [[T cell|T-cells]].

Macrophages are in almost every type of tissue and they are more abundant in tissue types that are especially susceptible to infection (e.g. lungs, stomach). Because macrophages float around the body until needed, they are nearby and able to quickly migrate to the sight of infection. Within a span of hours they may be done neutralizing the pathogen.

Neutrophils are the most populous white blood cell and, like macrophages, they are phagocytic and come from the bone marrow. They differ from macrophages a couple of ways: they mature in the [[thymus]] despite being produced in the bone marrow, and also contain sacs inside them called granules that aid in the breakdown process. While macrophages are migratory and generally close by and can sense sites of infection, neutrophils need to be recruited to the sites.

If pathogens make it past the skin and mucous and the macrophages are unable to clear them, the body has a second method of removing infiltrators. After the initial exposure, the body “remembers” a specific signature on the infiltrator so that it can be identified and eliminated quickly during all subsequent exposures.

===Acquired or Adaptive Immunity===
Adaptive immunity is so named because the body must first experience an initial infection for this type of immunity to form against that specific contagion. The first time the body experiences an infection is the worst because it does not yet know how to best eliminate the infiltrating substance. After initial exposure, however, the body has several mechanisms to remember and quickly and aggressively neutralize the pathogen. Many times this system does its job so well that a person may not even realize they are symptomatic or have an infection.

The body needs to identify a pathogen prior to eliminating it. There are several cells that the immune system uses to recognize pathogens. Dendritic cells are antigen-presenting cells that help begin this secondary immune response. Dendritic cells (Greek: dendron, meaning tree) received their name because of the arm-like branches that spread out and grab antigens released by infectious agents. The dendritic cells place the antigens, like flags, onto their surface for [[T helper cell|helper T-cells]] to recognize. In response to identifying an antigen on a dendritic cell, white blood cells called helper T-cells (also called CD4 T-cells) will secrete lymphokines which direct other immune cells to target the infection. Helper T-cells also promote the production and release of proteins called antibodies. Antibodies clump around pathogens neutralizing their infectious capabilities, perforate the surface of pathogens encouraging its decay, and signal to other cells to engulf and destroy the invader. B-cells are produced in the bone marrow and are the antibody factories of the body. They make specific antibodies for the specific pathogen(s) that the body is currently fighting.

Another type of T-cell, killer (cytotoxic) T-cells also must first be presented with antigens by one of the body’s antigen-presenting cells for it to activate. Once given a target, killer T-cells directly destroy infectious and defective material. Similar to antibodies, they punch holes in the membranes of bacteria, and infected or malfunctioning cells.

The last kinds of T-cells are memory and regulatory. Memory T-cells engulfs the material from the infected or defective cells and store that information in case of a future infection by the same pathogen, or on locating a similar defect. This allows the immune system to react faster because it already knows what is needed to respond to that specific pathogen or defect. Regulatory T-cells keep helper and killer T-cells’ activity at higher levels only when they are necessary. These T-cells will reduce helper and killer T-cells and decrease their activity after the pathogen has been eliminated.

==Components of the Immune System==
White blood cells, also called leukocytes, are the main defenders of the body. They circulate throughout the bloodstream (the circulatory system), surveying the body for possible threats.

=== Types and Functions of White Blood Cells (Leukocytes) ===
[[File:White Blood Cell Types.jpg|thumb|795x795px|Variations in white blood cells and the immunity type they function within.]]

==== g ====

====Hypersensitivity====
====Granulocytes====
Granulocytes are a type of white blood cell filled with double-membrane sacs called granules which contain a variety of substances. These substances aid in the immune response. The substances released include:
* histamine, a molecule that responds to injury, allergies and inflammation by inducing smooth muscle contraction and increased blood flow;
* cytokines, messenger proteins that induce other immune cells’ inflammatory functions;
* enzymes, metabolic proteins that decrease the amount of time it takes to carry out chemical reactions, and that activate other white blood cells.
The contents of granules can be released in two ways depending on the purpose of the substances that will be released. A granule can be ushered to the granulocyte’s membrane surface where the two will merge and the granule can dump its internal material into the area surrounding the cell. This method is helpful when the substances need to act directly on other tissues such as mast cells secreting histamine which act directly on the smooth muscle the mast cell in.

Alternately, granules can also release their internal material directly into the granulocyte. This process is helpful in cases where the granulocyte has engulfed a pathogen and the released elements from the granules can break it down. There are several types of granulocytes that perform functions related to both innate and adaptive immunity.

===== Basophils =====
Basophils, the least common granulocyte, help the body identify foreign substances. Once a pathogen is introduced to the body and consumed by a lymphocyte, such as a macrophage, the invader is broken down into smaller pieces. This eliminates it as a threat and makes disposal easier.

Additionally, in order for the immune cell to signal to the body that an invader was present (and that most likely there are other microbes nearby), the white blood cell will save some of the proteins from the pathogen and place it on its surface like a flag. These surface proteins are called antigens, and the process is called antigen presentation. Basophils are both capable of placing these antigens on themselves and onto other cells.

Now that the antigen can be identified, different white blood cells begin scanning cells’ surfaces in search of these markers. Helper T-cells (CD4 T-cells) are produced for this purpose. After sensing antigens, helper T-cells signal for the production of other while blood cell variants, which make inflammatory molecules that fight the infection. In addition, CD4 T-cells also help macrophages and killer T-cells perform their phagocytic and cytotoxic duties.

However, before a helper T-cell does all of this, they need to be: 1) told to function as these particular cells, and 2) stimulated to function in that manner. Basophils are the cells responsible for the programming and stimulation of these immune cells. It was initially hypothesized that basophils did not contain an essential component necessary to the differentiation of naive T-cells into helper T-cells. New evidence supports the idea that basophils do in fact possess all the necessary proteins, such as major histocompatibility complex II (see section below) and the cytokine IL-4, that stimulate the conversion of naive T-cells into helper T-cells.

Normal basophils amounts in the body range from 0-300/μL (0.000003L) of blood. Low levels are caused by afflictions such as hyperthyroidism or anaphylaxis. High levels are caused by hypothyroidism, and myeloproliferative disorders (blood disorders).

===== Eosinophils =====
Eosinophils are the next most common granulocyte. However, they store several enzymes and proteins with unidentified roles, so some the full extent of their purpose is unknown. Eosinophils inflict damage largely to parasites and to a smaller extent bacteria and viruses. These cells can also cause damage to the body’s own tissues during allergic reactions. Outside of the immune system, eosinophils help with organ development.

Eosinophils are typically less than 500/μL of blood. Infection by parasitic worms, ulcerative colitis, allergies are examples of maladies that can cause high levels of eosinophils, known as eosinophilia. Low levels may indicate alcohol intoxication, Cushing’s disease or problems with the bone marrow.
===== Neutrophils =====
Neutrophils are the most common immune cell and the first type of cell to arrive at the site of infection. These cells are flexible, bulbous, and multilobed. Normally, neutrophils travel through the blood and lymph systems but they have receptors that jut out of their surface like pins on a pincushion, that allow them to attach to cells stressed by damage or infection and perform their duty. With these receptors, neutrophils are also able to slip between cells if they’re needed in tissues outside of the blood and lymph systems.

Neutrophils are activated by chemical signals that stressed cells release. Cytokines, messenger proteins that induce different immune cell functions, can function in this capacity: switching migratory neutrophils to potent eradicator cells. Once operative, neutrophils working alongside macrophages in the innate immune system, engulfing and destroying pathogens non-specifically. This mechanism works because there are molecules present on pathogens that are not present on any of the cells in the body. These are called pathogen-associated molecular patterns (PAMPs). Cells in the body that have pattern-recognition receptors (PRRs), which neutrophils do, can identify the PAMPs and eliminate the non-self cells. Once ingested into the lumen on the neutrophil, the contents of the granules are released, which break down the microbe. Alternatively, the granules from a neutrophil can be released to the surrounding environment and break down pathogens outside of the cell.

Neutrophils are normally between 1500-8000 neutrophils/μL. High levels are caused by smoking, infection and non-infectious inflammation. Low levels appear with suppressed immune systems, autoimmune diseases and during drug treatments such as chemotherapy.

==== Monocytes ====
Monocytes are also white blood cells and are largely tasked with ingesting and eliminating microbial invaders, or identifying and presenting the proteins made by the infectious agent. They may also work in a restorative capacity to heal the affected area(s). Typically, monocytes become tissue macrophages or dendritic cells.

===== Macrophages =====
Macrophages are globular cells derived from monocytes that consume dysfunctional cells, cellular debris, and pathogens; they may be thought of as the garbage disposals of the immune system. They may be already present at sites where infection occurs, or they may migrate to the area of infection. As the name suggests, tissue macrophages exist in the different tissues in the body (e.g. liver or skin); they also are not necessarily derived from monocytes circulating in the blood and lymph system.

===== Dendritic cells =====
Dendritic cells are also monocyte-derived. They aid T-cell recognition of infectious material through the processing of antigens and production of proteins that major histocompatibility complexes (larger proteins on the surface of cells and tissues that allow the body to identify self from foreign) present to T-cells.

=== Production and Storage ===

==== Bone Marrow ====
White blood cells are produced in bone marrow. They begin as pluripotent hematopoietic stem cells (PSCs or HSCs) meaning they are capable of becoming any of the cells listed above, as well as red blood cells or platelets. T lymphocytes (T cells) are produced in the bone marrow while B lymphocytes (B cells) are both produced and develop to their full function in the bone marrow.

==== Thymus ====
The thymus is an immune organ that ceases having a functional capacity when puberty begins. During development, including during fetal development, the thymus stores T-cells (link to lower section maybe). The thymus is also a part of the endocrine system as it produces the hormone thymosin. This hormone initiates the maturation of T-cells. Once fully developed, the T-cells leave the thymus for the lymph nodes, where they enter active circulation and begin their immune duties.

==== The Lymph System ====
The lymph system, like the circulatory system, is comprised of vessels and nodes all throughout the body. Instead of blood, these vessels carry a slightly opaque, white fluid called lymph. This circulation system is responsible for removing toxins and infectious agents from tissues. Spread throughout the lymph tubes are small, grape-shaped compartments attached in clusters on the sides of vessels. These nodes, concentrated at the neck, upper chest, armpits and groin, constantly filter the lymph liquid of harmful substances. The lymph nodes contain B and T lymphocytes that specifically recognize dangerous material and make antibodies, which further help identify the pathogens, and eliminate them.

==== Spleen ====
The spleen filters the blood of dysfunctional or malformed red blood cells and platelets. It also clears away infectious agents from the blood. Macrophages neutralize all of these potential harms and recycle the products they can for further use by the body (e.g., hemoglobin from defective red blood cells can be put in new red blood cells). Lymphocytes are also stored in the spleen.

==Myalgic Encephalomyelitis==

There is evidence of immune dysregulation in [[Myalgic Encephalomyelitis]]:<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
* Reduced [[natural killer cell]] function.<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* Elevated [[regulatory T cell]]s<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* The [[Centers for Disease Control and Prevention]] ME/CFS page:
<blockquote>''Immune system abnormalities'' – some people with ME/CFS have impaired [[natural killer cell]] function and/or [[T cell]] function, chronic higher production of inflammatory [[Cytokine|cytokines]], and in some cases slight increase in some [[Autoantibody|autoantibodies]] ([[rheumatic factor]], [[Anti-thyroid antibody|anti-thyroid antibodies]], [[anti-gliadin]], [[Anti-smooth muscle antibody|anti-smooth muscle antibodies]], and [[Cold agglutinin|cold agglutinins]]).<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-19}}</ref></blockquote>

==Fibromyalgia==

In 2018, Zhang et al. research found inflammatory genes were involved in FM. Their paper ''SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study'' concluded: <blockquote>SNPs with significant TDTs were found in 36% of the cohort for ''CCL11'' and 12% for ''MEFV'', along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM.<ref>{{Cite journal|last=Zhang|first=Zhifang|last2=Feng|first2=Jinong|last3=Mao|first3=Allen|last4=Le|first4=Keith|last5=La Placa|first5=Deirdre|last6=Wu|first6=Xiwei|last7=Longmate|first7=Jeffrey|last8=Marek|first8=Claudia|last9=St. Amand|first9=R. Paul|date=2018-06-21|title=SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198625|doi=10.1371/journal.pone.0198625|issn=1932-6203|pmid=29927949|via=}}</ref></blockquote>There is ongoing [[Fibromyalgia#Immune_system_research|immune system research of fibromyalgia]].

==Learn more==

=== Further Reading ===
* [https://www.medicalnewstoday.com/articles/320101.php How the immune system works]

=== Videos ===
More on the immune system:
*[https://www.youtube.com/watch?v=GIJK3dwCWCw&feature=youtu.be Crash Course - The Immune System Part 1] ([[Adaptive immune system]])
*[https://www.youtube.com/watch?v=2DFN4IBZ3rI&feature=youtu.be Crash Course - The Immune System Part 2] ([[humoral immunity]] & [[B cell]]s)
*[https://www.youtube.com/watch?v=rd2cf5hValM&feature=youtu.be Crash Course - The Immune System Part 3] ([[cell-mediated immunity]] & [[T cell]]s)
More on neutrophils:
* [https://www.youtube.com/watch?v=FZxf1QDcEO0 Neutrophils and How White Blood Cells Work]
More on eosinophils
* [https://www.youtube.com/watch?v=3LNhUCLU3K8 Eosinophils]

==See also==
*[[Adaptive immune system]]
*[[Immune exhaustion hypothesis]]
*[[Innate immune system]]

==References==
<references />
[[Category:Body systems]]
[[Category:Immunology]]

Immune system

2019-02-26T21:01:17Z

Sbrumfie:Adding content

The '''immune system''' is a complex combination of organs, circulatory networks, and cells which work together to identify, target and eliminate harmful substances that enter the body. The immune system response has many steps. Once in full effect, different parts of the system move in parallel to restore health to the host. When the immune response is no longer needed, the immune system will suppress the reaction.

[[Myalgic encephalomyelitis]] (ME) is a complex multi-systemic disorder which causes [[Nervous system|neurological]] impairments, [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] dysfunction, and immune, [[Gastrointestinal system|gastrointestinal]] and/or [[genitourinary]] symptoms.<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

== Immune system symptoms ==

Symptoms related to M.E. include:
* [[Flu-like symptoms]] (sore throat, [[Sinusitis|sinus inflammation]], lymph node changes) that typically begin or worsens with [[exertion]], for instance as part of [[post-exertional malaise]] (PEM)
* Increased risk of contacting [[Viral infection|viruses]], which last for a prolonged time
* [[Gastrointestinal system|Gastro-intestinal]] problems, which may include [[nausea]], abdominal bloating, or [[irritable bowel syndrome]] (IBS)
* Needing to urinate either more urgently or [[Urinary frequency|more frequently]], sometimes at night ([[nocturia]])
* New sensitivities to smells, [[Chemical sensitivities|chemicals]], or [[Medicine sensitivities|medication]]; [[Food intolerance|food]] or [[Alcohol intolerance|alcohol intolerances]]<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

==Types of Immune Response==
===Innate Immune System===
Prior to actually getting into the body, [[Pathogen|pathogens]] or toxicants have to pass the body’s most basic immune defense: the skin and mucous. Mucous especially plays an important role because it is present in all the places where infection is most likely to occur (e.g. the eyes, nose and mouth).

Innate immunity is the nonspecific method of eliminating pathogens from the body. The main agents that carry out this mass, undiscriminating disposal of pathogens and dead or defective cells are called [[Macrophage|macrophages]] and [[Neutrophil|neutrophils]]. Macrophages are cells derived from monocytes which are made in the bone marrow. Initially, monocytes do not have a specific purpose. However, when these cells travel to and populate different tissues, those tissues emit signals for the type of immune cell that is needed in that area. Monocytes, therefore, alter their shape and function to satisfy work more effectively in their new location. These functions can vary from generalized (e.g. macrophages) to specific such as work done by [[B cell|B-]] and [[T cell|T-cells]].

Macrophages are in almost every type of tissue and they are more abundant in tissue types that are especially susceptible to infection (e.g. lungs, stomach). Because macrophages float around the body until needed, they are nearby and able to quickly migrate to the sight of infection. Within a span of hours they may be done neutralizing the pathogen.

Neutrophils are the most populous white blood cell and, like macrophages, they are phagocytic and come from the bone marrow. They differ from macrophages a couple of ways: they mature in the [[thymus]] despite being produced in the bone marrow, and also contain sacs inside them called granules that aid in the breakdown process. While macrophages are migratory and generally close by and can sense sites of infection, neutrophils need to be recruited to the sites.

If pathogens make it past the skin and mucous and the macrophages are unable to clear them, the body has a second method of removing infiltrators. After the initial exposure, the body “remembers” a specific signature on the infiltrator so that it can be identified and eliminated quickly during all subsequent exposures.

===Acquired or Adaptive Immunity===
Adaptive immunity is so named because the body must first experience an initial infection for this type of immunity to form against that specific contagion. The first time the body experiences an infection is the worst because it does not yet know how to best eliminate the infiltrating substance. After initial exposure, however, the body has several mechanisms to remember and quickly and aggressively neutralize the pathogen. Many times this system does its job so well that a person may not even realize they are symptomatic or have an infection.

The body needs to identify a pathogen prior to eliminating it. There are several cells that the immune system uses to recognize pathogens. Dendritic cells are antigen-presenting cells that help begin this secondary immune response. Dendritic cells (Greek: dendron, meaning tree) received their name because of the arm-like branches that spread out and grab antigens released by infectious agents. The dendritic cells place the antigens, like flags, onto their surface for [[T helper cell|helper T-cells]] to recognize. In response to identifying an antigen on a dendritic cell, white blood cells called helper T-cells (also called CD4 T-cells) will secrete lymphokines which direct other immune cells to target the infection. Helper T-cells also promote the production and release of proteins called antibodies. Antibodies clump around pathogens neutralizing their infectious capabilities, perforate the surface of pathogens encouraging its decay, and signal to other cells to engulf and destroy the invader. B-cells are produced in the bone marrow and are the antibody factories of the body. They make specific antibodies for the specific pathogen(s) that the body is currently fighting.

Another type of T-cell, killer (cytotoxic) T-cells also must first be presented with antigens by one of the body’s antigen-presenting cells for it to activate. Once given a target, killer T-cells directly destroy infectious and defective material. Similar to antibodies, they punch holes in the membranes of bacteria, and infected or malfunctioning cells.

The last kinds of T-cells are memory and regulatory. Memory T-cells engulfs the material from the infected or defective cells and store that information in case of a future infection by the same pathogen, or on locating a similar defect. This allows the immune system to react faster because it already knows what is needed to respond to that specific pathogen or defect. Regulatory T-cells keep helper and killer T-cells’ activity at higher levels only when they are necessary. These T-cells will reduce helper and killer T-cells and decrease their activity after the pathogen has been eliminated.

==Components of the Immune System==
White blood cells, also called leukocytes, are the main defenders of the body. They circulate throughout the bloodstream (the circulatory system), surveying the body for possible threats.

=== Types and Functions of White Blood Cells (Leukocytes) ===
[[File:White Blood Cell Types.jpg|thumb|795x795px|Variations in white blood cells and the immunity type they function within.]]

==== g ====

====Hypersensitivity====
====Granulocytes====
Granulocytes are a type of white blood cell filled with double-membrane sacs called granules which contain a variety of substances. These substances aid in the immune response. The substances released include:
* histamine, a molecule that responds to injury, allergies and inflammation by inducing smooth muscle contraction and increased blood flow;
* cytokines, messenger proteins that induce other immune cells’ inflammatory functions;
* enzymes, metabolic proteins that decrease the amount of time it takes to carry out chemical reactions, and that activate other white blood cells.
The contents of granules can be released in two ways depending on the purpose of the substances that will be released. A granule can be ushered to the granulocyte’s membrane surface where the two will merge and the granule can dump its internal material into the area surrounding the cell. This method is helpful when the substances need to act directly on other tissues such as mast cells secreting histamine which act directly on the smooth muscle the mast cell in.

Alternately, granules can also release their internal material directly into the granulocyte. This process is helpful in cases where the granulocyte has engulfed a pathogen and the released elements from the granules can break it down. There are several types of granulocytes that perform functions related to both innate and adaptive immunity.

===== Basophils =====
Basophils, the least common granulocyte, help the body identify foreign substances. Once a pathogen is introduced to the body and consumed by a lymphocyte, such as a macrophage, the invader is broken down into smaller pieces. This eliminates it as a threat and makes disposal easier.

Additionally, in order for the immune cell to signal to the body that an invader was present (and that most likely there are other microbes nearby), the white blood cell will save some of the proteins from the pathogen and place it on its surface like a flag. These surface proteins are called antigens, and the process is called antigen presentation. Basophils are both capable of placing these antigens on themselves and onto other cells.

Now that the antigen can be identified, different white blood cells begin scanning cells’ surfaces in search of these markers. Helper T-cells (CD4 T-cells) are produced for this purpose. After sensing antigens, helper T-cells signal for the production of other while blood cell variants, which make inflammatory molecules that fight the infection. In addition, CD4 T-cells also help macrophages and killer T-cells perform their phagocytic and cytotoxic duties.

However, before a helper T-cell does all of this, they need to be: 1) told to function as these particular cells, and 2) stimulated to function in that manner. Basophils are the cells responsible for the programming and stimulation of these immune cells. It was initially hypothesized that basophils did not contain an essential component necessary to the differentiation of naive T-cells into helper T-cells. New evidence supports the idea that basophils do in fact possess all the necessary proteins, such as major histocompatibility complex II (see section below) and the cytokine IL-4, that stimulate the conversion of naive T-cells into helper T-cells.

Normal basophils amounts in the body range from 0-300/μL (0.000003L) of blood. Low levels are caused by afflictions such as hyperthyroidism or anaphylaxis. High levels are caused by hypothyroidism, and myeloproliferative disorders (blood disorders).

===== Eosinophils =====
Eosinophils are the next most common granulocyte. However, they store several enzymes and proteins with unidentified roles, so some the full extent of their purpose is unknown. Eosinophils inflict damage largely to parasites and to a smaller extent bacteria and viruses. These cells can also cause damage to the body’s own tissues during allergic reactions. Outside of the immune system, eosinophils help with organ development.

Eosinophils are typically less than 500/μL of blood. Infection by parasitic worms, ulcerative colitis, allergies are examples of maladies that can cause high levels of eosinophils, known as eosinophilia. Low levels may indicate alcohol intoxication, Cushing’s disease or problems with the bone marrow.
[[File:Eosinophils attack parasite vid.mp4|thumb|Eosinophils eliminating a parasite that threatens the body.]]

===== Neutrophils =====
Neutrophils are the most common immune cell and the first type of cell to arrive at the site of infection. These cells are flexible, bulbous, and multilobed. Normally, neutrophils travel through the blood and lymph systems but they have receptors that jut out of their surface like pins on a pincushion, that allow them to attach to cells stressed by damage or infection and perform their duty. With these receptors, neutrophils are also able to slip between cells if they’re needed in tissues outside of the blood and lymph systems.

Neutrophils are activated by chemical signals that stressed cells release. Cytokines, messenger proteins that induce different immune cell functions, can function in this capacity: switching migratory neutrophils to potent eradicator cells. Once operative, neutrophils working alongside macrophages in the innate immune system, engulfing and destroying pathogens non-specifically. This mechanism works because there are molecules present on pathogens that are not present on any of the cells in the body. These are called pathogen-associated molecular patterns (PAMPs). Cells in the body that have pattern-recognition receptors (PRRs), which neutrophils do, can identify the PAMPs and eliminate the non-self cells. Once ingested into the lumen on the neutrophil, the contents of the granules are released, which break down the microbe. Alternatively, the granules from a neutrophil can be released to the surrounding environment and break down pathogens outside of the cell.

Neutrophils are normally between 1500-8000 neutrophils/μL. High levels are caused by smoking, infection and non-infectious inflammation. Low levels appear with suppressed immune systems, autoimmune diseases and during drug treatments such as chemotherapy.

==== Monocytes ====
Monocytes are also white blood cells and are largely tasked with ingesting and eliminating microbial invaders, or identifying and presenting the proteins made by the infectious agent. They may also work in a restorative capacity to heal the affected area(s). Typically, monocytes become tissue macrophages or dendritic cells.

===== Macrophages =====
Macrophages are globular cells derived from monocytes that consume dysfunctional cells, cellular debris, and pathogens; they may be thought of as the garbage disposals of the immune system. They may be already present at sites where infection occurs, or they may migrate to the area of infection. As the name suggests, tissue macrophages exist in the different tissues in the body (e.g. liver or skin); they also are not necessarily derived from monocytes circulating in the blood and lymph system.

===== Dendritic cells =====
Dendritic cells are also monocyte-derived. They aid T-cell recognition of infectious material through the processing of antigens and production of proteins that major histocompatibility complexes (larger proteins on the surface of cells and tissues that allow the body to identify self from foreign) present to T-cells.

=== Production and Storage ===

==== Bone Marrow ====
White blood cells are produced in bone marrow. They begin as pluripotent hematopoietic stem cells (PSCs or HSCs) meaning they are capable of becoming any of the cells listed above, as well as red blood cells or platelets. T lymphocytes (T cells) are produced in the bone marrow while B lymphocytes (B cells) are both produced and develop to their full function in the bone marrow.

==== Thymus ====
The thymus is an immune organ that ceases having a functional capacity when puberty begins. During development, including during fetal development, the thymus stores T-cells (link to lower section maybe). The thymus is also a part of the endocrine system as it produces the hormone thymosin. This hormone initiates the maturation of T-cells. Once fully developed, the T-cells leave the thymus for the lymph nodes, where they enter active circulation and begin their immune duties.

==== The Lymph System ====
The lymph system, like the circulatory system, is comprised of vessels and nodes all throughout the body. Instead of blood, these vessels carry a slightly opaque, white fluid called lymph. This circulation system is responsible for removing toxins and infectious agents from tissues. Spread throughout the lymph tubes are small, grape-shaped compartments attached in clusters on the sides of vessels. These nodes, concentrated at the neck, upper chest, armpits and groin, constantly filter the lymph liquid of harmful substances. The lymph nodes contain B and T lymphocytes that specifically recognize dangerous material and make antibodies, which further help identify the pathogens, and eliminate them.

==== Spleen ====
The spleen filters the blood of dysfunctional or malformed red blood cells and platelets. It also clears away infectious agents from the blood. Macrophages neutralize all of these potential harms and recycle the products they can for further use by the body (e.g., hemoglobin from defective red blood cells can be put in new red blood cells). Lymphocytes are also stored in the spleen.

==Myalgic Encephalomyelitis==

There is evidence of immune dysregulation in [[Myalgic Encephalomyelitis]]:<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
* Reduced [[natural killer cell]] function.<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* Elevated [[regulatory T cell]]s<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* The [[Centers for Disease Control and Prevention]] ME/CFS page:
<blockquote>''Immune system abnormalities'' – some people with ME/CFS have impaired [[natural killer cell]] function and/or [[T cell]] function, chronic higher production of inflammatory [[Cytokine|cytokines]], and in some cases slight increase in some [[Autoantibody|autoantibodies]] ([[rheumatic factor]], [[Anti-thyroid antibody|anti-thyroid antibodies]], [[anti-gliadin]], [[Anti-smooth muscle antibody|anti-smooth muscle antibodies]], and [[Cold agglutinin|cold agglutinins]]).<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-19}}</ref></blockquote>

==Fibromyalgia==

In 2018, Zhang et al. research found inflammatory genes were involved in FM. Their paper ''SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study'' concluded: <blockquote>SNPs with significant TDTs were found in 36% of the cohort for ''CCL11'' and 12% for ''MEFV'', along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM.<ref>{{Cite journal|last=Zhang|first=Zhifang|last2=Feng|first2=Jinong|last3=Mao|first3=Allen|last4=Le|first4=Keith|last5=La Placa|first5=Deirdre|last6=Wu|first6=Xiwei|last7=Longmate|first7=Jeffrey|last8=Marek|first8=Claudia|last9=St. Amand|first9=R. Paul|date=2018-06-21|title=SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198625|doi=10.1371/journal.pone.0198625|issn=1932-6203|pmid=29927949|via=}}</ref></blockquote>There is ongoing [[Fibromyalgia#Immune_system_research|immune system research of fibromyalgia]].

==Learn more==

=== Further Reading ===
* [https://www.medicalnewstoday.com/articles/320101.php How the immune system works]

=== Videos ===
More on the immune system:
*[https://www.youtube.com/watch?v=GIJK3dwCWCw&feature=youtu.be Crash Course - The Immune System Part 1] ([[Adaptive immune system]])
*[https://www.youtube.com/watch?v=2DFN4IBZ3rI&feature=youtu.be Crash Course - The Immune System Part 2] ([[humoral immunity]] & [[B cell]]s)
*[https://www.youtube.com/watch?v=rd2cf5hValM&feature=youtu.be Crash Course - The Immune System Part 3] ([[cell-mediated immunity]] & [[T cell]]s)
More on neutrophils:
* [https://www.youtube.com/watch?v=FZxf1QDcEO0 Neutrophils and How White Blood Cells Work]
More on eosinophils
* [https://www.youtube.com/watch?v=3LNhUCLU3K8 Eosinophils]

==See also==
*[[Adaptive immune system]]
*[[Immune exhaustion hypothesis]]
*[[Innate immune system]]

==References==
<references />
[[Category:Body systems]]
[[Category:Immunology]]

File:Eosinophils attack parasite vid.mp4

2019-02-26T20:51:42Z

Sbrumfie:

Eosinophils eliminating a parasite in the body

Immune system

2019-02-26T20:23:11Z

Sbrumfie:Added content.

The '''immune system''' is a complex combination of organs, circulatory networks, and cells which work together to identify, target and eliminate harmful substances that enter the body. The immune system response has many steps. Once in full effect, different parts of the system move in parallel to restore health to the host. When the immune response is no longer needed, the immune system will suppress the reaction.

[[Myalgic encephalomyelitis]] (ME) is a complex multi-systemic disorder which causes [[Nervous system|neurological]] impairments, [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] dysfunction, and immune, [[Gastrointestinal system|gastrointestinal]] and/or [[genitourinary]] symptoms.<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

== Immune system symptoms ==

Symptoms related to M.E. include:
* [[Flu-like symptoms]] (sore throat, [[Sinusitis|sinus inflammation]], lymph node changes) that typically begin or worsens with [[exertion]], for instance as part of [[post-exertional malaise]] (PEM)
* Increased risk of contacting [[Viral infection|viruses]], which last for a prolonged time
* [[Gastrointestinal system|Gastro-intestinal]] problems, which may include [[nausea]], abdominal bloating, or [[irritable bowel syndrome]] (IBS)
* Needing to urinate either more urgently or [[Urinary frequency|more frequently]], sometimes at night ([[nocturia]])
* New sensitivities to smells, [[Chemical sensitivities|chemicals]], or [[Medicine sensitivities|medication]]; [[Food intolerance|food]] or [[Alcohol intolerance|alcohol intolerances]]<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

==Types of Immune Response==
===Innate Immune System===
Prior to actually getting into the body, [[Pathogen|pathogens]] or toxicants have to pass the body’s most basic immune defense: the skin and mucous. Mucous especially plays an important role because it is present in all the places where infection is most likely to occur (e.g. the eyes, nose and mouth).

Innate immunity is the nonspecific method of eliminating pathogens from the body. The main agents that carry out this mass, undiscriminating disposal of pathogens and dead or defective cells are called [[Macrophage|macrophages]] and [[Neutrophil|neutrophils]]. Macrophages are cells derived from monocytes which are made in the bone marrow. Initially, monocytes do not have a specific purpose. However, when these cells travel to and populate different tissues, those tissues emit signals for the type of immune cell that is needed in that area. Monocytes, therefore, alter their shape and function to satisfy work more effectively in their new location. These functions can vary from generalized (e.g. macrophages) to specific such as work done by [[B cell|B-]] and [[T cell|T-cells]].

Macrophages are in almost every type of tissue and they are more abundant in tissue types that are especially susceptible to infection (e.g. lungs, stomach). Because macrophages float around the body until needed, they are nearby and able to quickly migrate to the sight of infection. Within a span of hours they may be done neutralizing the pathogen.

Neutrophils are the most populous white blood cell and, like macrophages, they are phagocytic and come from the bone marrow. They differ from macrophages a couple of ways: they mature in the [[thymus]] despite being produced in the bone marrow, and also contain sacs inside them called granules that aid in the breakdown process. While macrophages are migratory and generally close by and can sense sites of infection, neutrophils need to be recruited to the sites.

If pathogens make it past the skin and mucous and the macrophages are unable to clear them, the body has a second method of removing infiltrators. After the initial exposure, the body “remembers” a specific signature on the infiltrator so that it can be identified and eliminated quickly during all subsequent exposures.

===Acquired or Adaptive Immunity===
Adaptive immunity is so named because the body must first experience an initial infection for this type of immunity to form against that specific contagion. The first time the body experiences an infection is the worst because it does not yet know how to best eliminate the infiltrating substance. After initial exposure, however, the body has several mechanisms to remember and quickly and aggressively neutralize the pathogen. Many times this system does its job so well that a person may not even realize they are symptomatic or have an infection.

The body needs to identify a pathogen prior to eliminating it. There are several cells that the immune system uses to recognize pathogens. Dendritic cells are antigen-presenting cells that help begin this secondary immune response. Dendritic cells (Greek: dendron, meaning tree) received their name because of the arm-like branches that spread out and grab antigens released by infectious agents. The dendritic cells place the antigens, like flags, onto their surface for [[T helper cell|helper T-cells]] to recognize. In response to identifying an antigen on a dendritic cell, white blood cells called helper T-cells (also called CD4 T-cells) will secrete lymphokines which direct other immune cells to target the infection. Helper T-cells also promote the production and release of proteins called antibodies. Antibodies clump around pathogens neutralizing their infectious capabilities, perforate the surface of pathogens encouraging its decay, and signal to other cells to engulf and destroy the invader. B-cells are produced in the bone marrow and are the antibody factories of the body. They make specific antibodies for the specific pathogen(s) that the body is currently fighting.

Another type of T-cell, killer (cytotoxic) T-cells also must first be presented with antigens by one of the body’s antigen-presenting cells for it to activate. Once given a target, killer T-cells directly destroy infectious and defective material. Similar to antibodies, they punch holes in the membranes of bacteria, and infected or malfunctioning cells.

The last kinds of T-cells are memory and regulatory. Memory T-cells engulfs the material from the infected or defective cells and store that information in case of a future infection by the same pathogen, or on locating a similar defect. This allows the immune system to react faster because it already knows what is needed to respond to that specific pathogen or defect. Regulatory T-cells keep helper and killer T-cells’ activity at higher levels only when they are necessary. These T-cells will reduce helper and killer T-cells and decrease their activity after the pathogen has been eliminated.

==Components of the Immune System==
White blood cells, also called leukocytes, are the main defenders of the body. They circulate throughout the bloodstream (the circulatory system), surveying the body for possible threats.

=== Types and Functions of White Blood Cells (Leukocytes) ===
[[File:White Blood Cell Types.jpg|thumb|795x795px|Variations in white blood cells and the immunity type they function within.]]

==== g ====

====Hypersensitivity====
====Granulocytes====
Granulocytes are a type of white blood cell filled with double-membrane sacs called granules which contain a variety of substances. These substances aid in the immune response. The substances released include:
* histamine, a molecule that responds to injury, allergies and inflammation by inducing smooth muscle contraction and increased blood flow;
* cytokines, messenger proteins that induce other immune cells’ inflammatory functions;
* enzymes, metabolic proteins that decrease the amount of time it takes to carry out chemical reactions, and that activate other white blood cells.
The contents of granules can be released in two ways depending on the purpose of the substances that will be released. A granule can be ushered to the granulocyte’s membrane surface where the two will merge and the granule can dump its internal material into the area surrounding the cell. This method is helpful when the substances need to act directly on other tissues such as mast cells secreting histamine which act directly on the smooth muscle the mast cell in.

Alternately, granules can also release their internal material directly into the granulocyte. This process is helpful in cases where the granulocyte has engulfed a pathogen and the released elements from the granules can break it down. There are several types of granulocytes that perform functions related to both innate and adaptive immunity.

===== Basophils =====
Basophils, the least common granulocyte, help the body identify foreign substances. Once a pathogen is introduced to the body and consumed by a lymphocyte, such as a macrophage, the invader is broken down into smaller pieces. This eliminates it as a threat and makes disposal easier.

Additionally, in order for the immune cell to signal to the body that an invader was present (and that most likely there are other microbes nearby), the white blood cell will save some of the proteins from the pathogen and place it on its surface like a flag. These surface proteins are called antigens, and the process is called antigen presentation. Basophils are both capable of placing these antigens on themselves and onto other cells.

Now that the antigen can be identified, different white blood cells begin scanning cells’ surfaces in search of these markers. Helper T-cells (CD4 T-cells) are produced for this purpose. After sensing antigens, helper T-cells signal for the production of other while blood cell variants, which make inflammatory molecules that fight the infection. In addition, CD4 T-cells also help macrophages and killer T-cells perform their phagocytic and cytotoxic duties.

However, before a helper T-cell does all of this, they need to be: 1) told to function as these particular cells, and 2) stimulated to function in that manner. Basophils are the cells responsible for the programming and stimulation of these immune cells. It was initially hypothesized that basophils did not contain an essential component necessary to the differentiation of naive T-cells into helper T-cells. New evidence supports the idea that basophils do in fact possess all the necessary proteins, such as major histocompatibility complex II (see section below) and the cytokine IL-4, that stimulate the conversion of naive T-cells into helper T-cells.

Normal basophils amounts in the body range from 0-300/μL (0.000003L) of blood. Low levels are caused by afflictions such as hyperthyroidism or anaphylaxis. High levels are caused by hypothyroidism, and myeloproliferative disorders (blood disorders).

===== Eosinophils =====
Eosinophils are the next most common granulocyte. However, they store several enzymes and proteins with unidentified roles, so some the full extent of their purpose is unknown. Eosinophils inflict damage largely to parasites and to a smaller extent bacteria and viruses. These cells can also cause damage to the body’s own tissues during allergic reactions. Outside of the immune system, eosinophils help with organ development.

Eosinophils are typically less than 500/μL of blood. Infection by parasitic worms, ulcerative colitis, allergies are examples of maladies that can cause high levels of eosinophils, known as eosinophilia. Low levels may indicate alcohol intoxication, Cushing’s disease or problems with the bone marrow.

===== Neutrophils =====
Neutrophils are the most common immune cell and the first type of cell to arrive at the site of infection. These cells are flexible, bulbous, and multilobed. Normally, neutrophils travel through the blood and lymph systems but they have receptors that jut out of their surface like pins on a pincushion, that allow them to attach to cells stressed by damage or infection and perform their duty. With these receptors, neutrophils are also able to slip between cells if they’re needed in tissues outside of the blood and lymph systems.

Neutrophils are activated by chemical signals that stressed cells release. Cytokines, messenger proteins that induce different immune cell functions, can function in this capacity: switching migratory neutrophils to potent eradicator cells. Once operative, neutrophils working alongside macrophages in the innate immune system, engulfing and destroying pathogens non-specifically. This mechanism works because there are molecules present on pathogens that are not present on any of the cells in the body. These are called pathogen-associated molecular patterns (PAMPs). Cells in the body that have pattern-recognition receptors (PRRs), which neutrophils do, can identify the PAMPs and eliminate the non-self cells. Once ingested into the lumen on the neutrophil, the contents of the granules are released, which break down the microbe. Alternatively, the granules from a neutrophil can be released to the surrounding environment and break down pathogens outside of the cell.

Neutrophils are normally between 1500-8000 neutrophils/μL. High levels are caused by smoking, infection and non-infectious inflammation. Low levels appear with suppressed immune systems, autoimmune diseases and during drug treatments such as chemotherapy.

==== Monocytes ====
Monocytes are also white blood cells and are largely tasked with ingesting and eliminating microbial invaders, or identifying and presenting the proteins made by the infectious agent. They may also work in a restorative capacity to heal the affected area(s). Typically, monocytes become tissue macrophages or dendritic cells.

===== Macrophages =====
Macrophages are globular cells derived from monocytes that consume dysfunctional cells, cellular debris, and pathogens; they may be thought of as the garbage disposals of the immune system. They may be already present at sites where infection occurs, or they may migrate to the area of infection. As the name suggests, tissue macrophages exist in the different tissues in the body (e.g. liver or skin); they also are not necessarily derived from monocytes circulating in the blood and lymph system.

===== Dendritic cells =====
Dendritic cells are also monocyte-derived. They aid T-cell recognition of infectious material through the processing of antigens and production of proteins that major histocompatibility complexes (larger proteins on the surface of cells and tissues that allow the body to identify self from foreign) present to T-cells.

=== Production and Storage ===

==== Bone Marrow ====
White blood cells are produced in bone marrow. They begin as pluripotent hematopoietic stem cells (PSCs or HSCs) meaning they are capable of becoming any of the cells listed above, as well as red blood cells or platelets. T lymphocytes (T cells) are produced in the bone marrow while B lymphocytes (B cells) are both produced and develop to their full function in the bone marrow.

==== Thymus ====
The thymus is an immune organ that ceases having a functional capacity when puberty begins. During development, including during fetal development, the thymus stores T-cells (link to lower section maybe). The thymus is also a part of the endocrine system as it produces the hormone thymosin. This hormone initiates the maturation of T-cells. Once fully developed, the T-cells leave the thymus for the lymph nodes, where they enter active circulation and begin their immune duties.

==== The Lymph System ====
The lymph system, like the circulatory system, is comprised of vessels and nodes all throughout the body. Instead of blood, these vessels carry a slightly opaque, white fluid called lymph. This circulation system is responsible for removing toxins and infectious agents from tissues. Spread throughout the lymph tubes are small, grape-shaped compartments attached in clusters on the sides of vessels. These nodes, concentrated at the neck, upper chest, armpits and groin, constantly filter the lymph liquid of harmful substances. The lymph nodes contain B and T lymphocytes that specifically recognize dangerous material and make antibodies, which further help identify the pathogens, and eliminate them.

==== Spleen ====
The spleen filters the blood of dysfunctional or malformed red blood cells and platelets. It also clears away infectious agents from the blood. Macrophages neutralize all of these potential harms and recycle the products they can for further use by the body (e.g., hemoglobin from defective red blood cells can be put in new red blood cells). Lymphocytes are also stored in the spleen.

==Myalgic Encephalomyelitis==

There is evidence of immune dysregulation in [[Myalgic Encephalomyelitis]]:<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
* Reduced [[natural killer cell]] function.<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* Elevated [[regulatory T cell]]s<ref>{{Cite journal|last=Brenu|first=Ekua Weba|last2=Huth|first2=Teilah K.|last3=Hardcastle|first3=Sharni L.|last4=Fuller|first4=Kirsty|last5=Kaur|first5=Manprit|last6=Johnston|first6=Samantha|last7=Ramos|first7=Sandra B.|last8=Staines|first8=Don R.|last9=Marshall-Gradisnik|first9=Sonya M.|date=Apr 2014|title=Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref>

* The [[Centers for Disease Control and Prevention]] ME/CFS page:
<blockquote>''Immune system abnormalities'' – some people with ME/CFS have impaired [[natural killer cell]] function and/or [[T cell]] function, chronic higher production of inflammatory [[Cytokine|cytokines]], and in some cases slight increase in some [[Autoantibody|autoantibodies]] ([[rheumatic factor]], [[Anti-thyroid antibody|anti-thyroid antibodies]], [[anti-gliadin]], [[Anti-smooth muscle antibody|anti-smooth muscle antibodies]], and [[Cold agglutinin|cold agglutinins]]).<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-19}}</ref></blockquote>

==Fibromyalgia==

In 2018, Zhang et al. research found inflammatory genes were involved in FM. Their paper ''SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study'' concluded: <blockquote>SNPs with significant TDTs were found in 36% of the cohort for ''CCL11'' and 12% for ''MEFV'', along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM.<ref>{{Cite journal|last=Zhang|first=Zhifang|last2=Feng|first2=Jinong|last3=Mao|first3=Allen|last4=Le|first4=Keith|last5=La Placa|first5=Deirdre|last6=Wu|first6=Xiwei|last7=Longmate|first7=Jeffrey|last8=Marek|first8=Claudia|last9=St. Amand|first9=R. Paul|date=2018-06-21|title=SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198625|doi=10.1371/journal.pone.0198625|issn=1932-6203|pmid=29927949|via=}}</ref></blockquote>There is ongoing [[Fibromyalgia#Immune_system_research|immune system research of fibromyalgia]].

==Learn more==
*[https://www.youtube.com/watch?v=GIJK3dwCWCw&feature=youtu.be Crash Course - The Immune System Part 1] ([[Adaptive immune system]])
*[https://www.youtube.com/watch?v=2DFN4IBZ3rI&feature=youtu.be Crash Course - The Immune System Part 2] ([[humoral immunity]] & [[B cell]]s)
*[https://www.youtube.com/watch?v=rd2cf5hValM&feature=youtu.be Crash Course - The Immune System Part 3] ([[cell-mediated immunity]] & [[T cell]]s)

==See also==
*[[Adaptive immune system]]
*[[Immune exhaustion hypothesis]]
*[[Innate immune system]]

==References==
<references />
[[Category:Body systems]]
[[Category:Immunology]]

Immune system

2019-02-26T17:16:35Z

Sbrumfie:Added content and deleted some of the unnecessary bits.

File:Microglia MEpedia.jpg

2019-02-26T16:56:35Z

Sbrumfie:Added citations and licensing details for this picture.

This picture depicts different types of glia.<ref>{{Cite web|url=http://cnx.org/content/m44747/latest/Figure_35_01_06.jpg|title=Neurons and Glial Cells|last=|first=OpenStax College|authorlink=|last2=|first2=|authorlink2=|date=October 17, 2013|website=http://cnx.org/content/m44747/latest/Figure_35_01_06.jpg|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

Licence: ''[https://creativecommons.org/licenses/by/4.0/ CC BY: Attribution]''

Microglia

2018-10-25T01:57:41Z

Sbrumfie:i bolded a word

[[File:Microglia MEpedia.jpg|thumb|This is an image of cells in the brain including microglia.]]
'''Microglia''' are small glial cells in the brain that act as immune cells in the brain, support other brain cells structurally and nutritionally, and survey their environment for abnormalities. They are considered the resident macrophages and become activated when foreign molecules or cells enter the or when brain cells are damaged or defective.

== Microglia Activity ==
Microglia function in multiple capacities:

=== Apoptosis ===
One of their functions is to clean up the remains of a cell after it has apoptosed (self induction of cell death). This is important because the contents of a cell can be harmful when not contained by cell or organelle membranes. The microglia when activated takes on a blob-like structure and ingests the dead cell and its contents. Microglia can also prompt cells to become apoptotic.

=== Neural Pruning ===
Microglia also prune neurons at the synapses, which are the spaces between neurons across which neurotransmitters travel. If these are damaged, dysfunctional or underused microglia will repair or remove the problem area. This function of microglia is important to development but may become harmful during neuroinflammatory events. During inflammation of the brain, the microglia may prune too much causing a loss of synaptic integrity.

=== Priming and Microglia Activation ===
Several events can cause microglia to become primed. Priming means that microglia will respond more aggressively and more easily to activating factors, and occurs when the microglia are over-exposed to harmful events or stimuli. One of the events that can prime microglia is aging. Usually, cells in the body are continuously recycled and regenerated so that they function like new. Microglia are not replaced often, however, and can wear from use.

Infections can also cause microglial priming. During an infection, immune molecules called cytokines circulate throughout the body. Some of these molecules can get directly into the brain and activate microglia, or they can indirectly activate microglia through neural signaling of the vagus nerve. If an infection persists for an extended period of time, microglia will continuously be activated and may become damaged from use.

Traumatic brain injuries also prime microglia. Direct damage to the brain (e.g. concussion, stroke or blunt force trauma) causes the microglia to work continuously to resolve the damage. The damage itself also causes the release of inflammatory markers that activate the microglia. Continued functioning can cause persistent symptoms of the initial damage.

==Chronic fatigue syndrome==
== Notable studies ==
* 2015, [https://www.sciencedirect.com/science/article/pii/S0028390814004031?via%3Dihub Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease]<ref>{{Cite journal|date=2015-09-01|title=Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease|url=https://www.sciencedirect.com/science/article/pii/S0028390814004031|journal=Neuropharmacology|language=en|volume=96|pages=29–41|doi=10.1016/j.neuropharm.2014.10.028|issn=0028-3908}}</ref>

== Learn more ==
*[https://www.youtube.com/watch?v=JmQIaOp4vKs Cell Motility of Microglia Cultured in TIC] by Cell Press via YouTube
*[https://www.youtube.com/watch?v=1LeqiLuah6A Depletion of microglia and inhibition of exosome synthesis halt tau propagation] by Research Square via YouTube
*[https://www.youtube.com/watch?v=fBfrT_WXBQA 2-Minute Neuroscience: Glial Cells] by Neuroscientifically Challenged via YouTube
*February 21, 2018 - [https://www.verywellhealth.com/microglia-in-fibromyalgia-chronic-fatigue-syndrome-3862780 Microglia in Fibromyalgia and Chronic Fatigue Syndrome] by Adrienne Dellwo for Very Well Health

==See also==
*[[Alzheimer's]]
*[[Dorsal root ganglia]]
*[[Glial cell]]
*[[Low-dose naltrexone]]
*[[Nervous system]]
*[[Jarred Younger]]

==References==
<references />
[[Category:Body systems]]
[[Category:Neurology]]

Microglia

2018-10-25T01:55:45Z

Sbrumfie:I added a pic

[[File:Microglia MEpedia.jpg|thumb|This is an image of cells in the brain including microglia.]]
Microglia are small glial cells in the brain that act as immune cells in the brain, support other brain cells structurally and nutritionally, and survey their environment for abnormalities. They are considered the resident macrophages and become activated when foreign molecules or cells enter the or when brain cells are damaged or defective.

== Microglia Activity ==
Microglia function in multiple capacities:

=== Apoptosis ===
One of their functions is to clean up the remains of a cell after it has apoptosed (self induction of cell death). This is important because the contents of a cell can be harmful when not contained by cell or organelle membranes. The microglia when activated takes on a blob-like structure and ingests the dead cell and its contents. Microglia can also prompt cells to become apoptotic.

=== Neural Pruning ===
Microglia also prune neurons at the synapses, which are the spaces between neurons across which neurotransmitters travel. If these are damaged, dysfunctional or underused microglia will repair or remove the problem area. This function of microglia is important to development but may become harmful during neuroinflammatory events. During inflammation of the brain, the microglia may prune too much causing a loss of synaptic integrity.

=== Priming and Microglia Activation ===
Several events can cause microglia to become primed. Priming means that microglia will respond more aggressively and more easily to activating factors, and occurs when the microglia are over-exposed to harmful events or stimuli. One of the events that can prime microglia is aging. Usually, cells in the body are continuously recycled and regenerated so that they function like new. Microglia are not replaced often, however, and can wear from use.

Infections can also cause microglial priming. During an infection, immune molecules called cytokines circulate throughout the body. Some of these molecules can get directly into the brain and activate microglia, or they can indirectly activate microglia through neural signaling of the vagus nerve. If an infection persists for an extended period of time, microglia will continuously be activated and may become damaged from use.

Traumatic brain injuries also prime microglia. Direct damage to the brain (e.g. concussion, stroke or blunt force trauma) causes the microglia to work continuously to resolve the damage. The damage itself also causes the release of inflammatory markers that activate the microglia. Continued functioning can cause persistent symptoms of the initial damage.

==Chronic fatigue syndrome==
== Notable studies ==
* 2015, [https://www.sciencedirect.com/science/article/pii/S0028390814004031?via%3Dihub Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease]<ref>{{Cite journal|date=2015-09-01|title=Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease|url=https://www.sciencedirect.com/science/article/pii/S0028390814004031|journal=Neuropharmacology|language=en|volume=96|pages=29–41|doi=10.1016/j.neuropharm.2014.10.028|issn=0028-3908}}</ref>

== Learn more ==
*[https://www.youtube.com/watch?v=JmQIaOp4vKs Cell Motility of Microglia Cultured in TIC] by Cell Press via YouTube
*[https://www.youtube.com/watch?v=1LeqiLuah6A Depletion of microglia and inhibition of exosome synthesis halt tau propagation] by Research Square via YouTube
*[https://www.youtube.com/watch?v=fBfrT_WXBQA 2-Minute Neuroscience: Glial Cells] by Neuroscientifically Challenged via YouTube
*February 21, 2018 - [https://www.verywellhealth.com/microglia-in-fibromyalgia-chronic-fatigue-syndrome-3862780 Microglia in Fibromyalgia and Chronic Fatigue Syndrome] by Adrienne Dellwo for Very Well Health

==See also==
*[[Alzheimer's]]
*[[Dorsal root ganglia]]
*[[Glial cell]]
*[[Low-dose naltrexone]]
*[[Nervous system]]
*[[Jarred Younger]]

==References==
<references />
[[Category:Body systems]]
[[Category:Neurology]]

File:Microglia MEpedia.jpg

2018-10-25T01:55:03Z

Sbrumfie:

It shows microglia

Microglia

2018-10-25T01:49:12Z

Sbrumfie:i added text

[[File:Microglia.JPG|320px|thumb|right|Microglia (green) act as support cells for neurons (red)]]

Microglia are small glial cells in the brain that act as immune cells in the brain, support other brain cells structurally and nutritionally, and survey their environment for abnormalities. They are considered the resident macrophages and become activated when foreign molecules or cells enter the or when brain cells are damaged or defective.

i

==Chronic fatigue syndrome==
== Notable studies ==
* 2015, [https://www.sciencedirect.com/science/article/pii/S0028390814004031?via%3Dihub Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease]<ref>{{Cite journal|date=2015-09-01|title=Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease|url=https://www.sciencedirect.com/science/article/pii/S0028390814004031|journal=Neuropharmacology|language=en|volume=96|pages=29–41|doi=10.1016/j.neuropharm.2014.10.028|issn=0028-3908}}</ref>

== Learn more ==
*[https://www.youtube.com/watch?v=JmQIaOp4vKs Cell Motility of Microglia Cultured in TIC] by Cell Press via YouTube
*[https://www.youtube.com/watch?v=1LeqiLuah6A Depletion of microglia and inhibition of exosome synthesis halt tau propagation] by Research Square via YouTube
*[https://www.youtube.com/watch?v=fBfrT_WXBQA 2-Minute Neuroscience: Glial Cells] by Neuroscientifically Challenged via YouTube
*February 21, 2018 - [https://www.verywellhealth.com/microglia-in-fibromyalgia-chronic-fatigue-syndrome-3862780 Microglia in Fibromyalgia and Chronic Fatigue Syndrome] by Adrienne Dellwo for Very Well Health

==See also==
*[[Alzheimer's]]
*[[Dorsal root ganglia]]
*[[Glial cell]]
*[[Low-dose naltrexone]]
*[[Nervous system]]
*[[Jarred Younger]]

==References==
<references />
[[Category:Body systems]]
[[Category:Neurology]]

Hypothalamus

2018-10-25T01:24:27Z

Sbrumfie:added a ref section

[[File:Hypothalamus small.gif|thumb|The hypothalamus (pictured in red) is the body's hormone controller.]]
The body has standard levels where it is best able to function. If these levels change for any reason, the '''hypothalamus''' detects the change and sends out neural signals or hormonal messaging to the affected tissues. For example, when temperature is increased or decreased, the hypothalamus initiates the process to get the body to sweat (which cools the body back to its standard temperature) or shiver (which warms the body back to its standard temperature), respectively.<ref name=":0">{{Cite journal|last=Thomas|first=Nihal|last2=Kapoor|first2=Nitin|last3=Naik|first3=Dukhabandhu|date=2015-12-18|title=55 Chapter Hypothalamus and Hypothalamic Disorders HYPOTHALAMUS AND HYPOTHALAMIC DISORDERS ANATOMY AND DEVELOPMENT OF THE HYPOTHALAMUS Gross Anatomy|url=https://www.researchgate.net/publication/299436898_55_Chapter_Hypothalamus_and_Hypothalamic_Disorders_HYPOTHALAMUS_AND_HYPOTHALAMIC_DISORDERS_ANATOMY_AND_DEVELOPMENT_OF_THE_HYPOTHALAMUS_Gross_Anatomy}}</ref>
[[Category:Endocrine system]]

== Functions ==
* Controls the pituitary
* Balancing fluids in the body (useful to blood pressure, dehydration, overhydration)
** '''Vasopressin/antidiuretic hormone''' - a hormone that causes the kidneys to retain more water.<ref>{{Cite news|url=https://www.healthline.com/human-body-maps/hypothalamus#hypothalamus-diagram|title=Hypothalamus: Anatomy, Function, Diagram, Conditions, Health Tips|work=Healthline|access-date=2018-10-25|language=en}}</ref>
* Sex organ processes, birthing, breast milk production
** '''Oxytocin''' - released by the hypothalamus, has general function on moderating emotion and behaviors such as bonding, sexual arousal and recognition, and also sends hormones to the reproductive organs during childbirth.
** '''Gonadotropin-releasing hormone''' - causes the pituitary to produce '''follicle stimulating hormone''' (FSH; causes ovaries to produce estradiol and start ovulation, and causes the testes to both start the process of creating sperm and send signals back to the pituitary to stop sending FSH), and '''luteinizing hormone''' (LH; causes the ovaries to produce steroids such as progesterone, and causes the testes to produces steroids such as testosterone).<ref>{{Cite news|url=https://www.healthline.com/human-body-maps/hypothalamus#hypothalamus-diagram|title=Hypothalamus: Anatomy, Function, Diagram, Conditions, Health Tips|work=Healthline|access-date=2018-10-25|language=en}}</ref><ref>{{Cite web|url=https://mcb.berkeley.edu/courses/mcb135e/fsh-lh.html|title=FSH and LH|website=mcb.berkeley.edu|access-date=2018-10-25}}</ref>
* Metabolism
** '''Thyroid stimulating hormone''' - released by the hypothalamus acts on the thyroid to regulate breathing, heart rate, body temperature, some feeding and drinking behaviors etc.<ref>{{Cite news|url=https://www.endocrineweb.com/conditions/thyroid-nodules/thyroid-gland-controls-bodys-metabolism-how-it-works-symptoms-hyperthyroi|title=Thyroid Gland: Overview|work=EndocrineWeb|access-date=2018-10-25|language=en}}</ref>
* Circadian Rhythm
Once the hormones have performed the desired function, the tissues produce chemicals that are sent back to hypothalamus telling it to stop producing the hormones. This loop of signaling ensures that the hypothalamus does not overproduce hormones, maintaining order in the body.<ref name=":0" />

== Hypothalamic Dysfunction ==

=== General Dysfunction ===
Dysfunction of the pituitary can be caused by a number of events: damage to the brain, genetic predisposition, tumors, eating disorders, and autoimmune disorders. This dysfunction can lead to under- or overproduction of hormones which can lead to problems such as low body water (underproduction of vasopressin), inability to sense satiety, and insomnia.<ref>{{Cite news|url=https://www.healthline.com/human-body-maps/hypothalamus#symptoms|title=Hypothalamus: Anatomy, Function, Diagram, Conditions, Health Tips|work=Healthline|access-date=2018-10-25|language=en}}</ref>

=== Sleep Dysfunction in ME/CFS ===
A common symptom of ME/CFS is sleep disturbances. These perturbations in the regular sleeping cycle may have deleterious effects on biological processes and the progression of a condition such as ME/CFS. During sleep deprivation, studies show that there is dysregulation of enzyme complexes in the hypothalamus among other brain structures. These enzymes complexes play a role in the oxidative and nitrosative stress pathways, which if disrupted, can lead to blood brain barrier perforation and neuroinflammation (See Oxidative Stress under [[Neuroinflammation]]).<ref>{{Cite journal|date=2018-10-01|title=The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis|url=https://www.sciencedirect.com/science/article/pii/S1087079217301521|journal=Sleep Medicine Reviews|language=en|volume=41|pages=255–265|doi=10.1016/j.smrv.2018.03.007|issn=1087-0792}}</ref>

Another study found that ME/CFS patients have altered circadian rhythms and skin temperatures that do not follow normal patterns (e.g. temperature decreasing in the evening near bedtime). These functions are related to the hypothalamus and suggest that there may be hypothalamic dysfunction.<ref>{{Cite journal|last=Cambras|first=Trinitat|last2=Castro-Marrero|first2=Jesús|last3=Zaragoza|first3=Maria Cleofé|last4=Díez-Noguera|first4=Antoni|last5=Alegre|first5=José|date=2018-06-06|title=Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198106|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198106|doi=10.1371/journal.pone.0198106|issn=1932-6203|pmc=PMC5991397|pmid=29874259}}</ref>

== References ==
<references />

Hypothalamus

2018-10-25T01:21:34Z

Sbrumfie:I added a pic

File:Hypothalamus small.gif

2018-10-25T01:17:51Z

Sbrumfie:

It shows the hypothalamus.

Hypothalamus

2018-10-25T01:14:08Z

Sbrumfie:Added to page

The body has standard levels where it is best able to function. If these levels change for any reason, the '''hypothalamus''' detects the change and sends out neural signals or hormonal messaging to the affected tissues. For example, when temperature is increased or decreased, the hypothalamus initiates the process to get the body to sweat (which cools the body back to its standard temperature) or shiver (which warms the body back to its standard temperature), respectively.<ref name=":0">{{Cite journal|last=Thomas|first=Nihal|last2=Kapoor|first2=Nitin|last3=Naik|first3=Dukhabandhu|date=2015-12-18|title=55 Chapter Hypothalamus and Hypothalamic Disorders HYPOTHALAMUS AND HYPOTHALAMIC DISORDERS ANATOMY AND DEVELOPMENT OF THE HYPOTHALAMUS Gross Anatomy|url=https://www.researchgate.net/publication/299436898_55_Chapter_Hypothalamus_and_Hypothalamic_Disorders_HYPOTHALAMUS_AND_HYPOTHALAMIC_DISORDERS_ANATOMY_AND_DEVELOPMENT_OF_THE_HYPOTHALAMUS_Gross_Anatomy}}</ref>
[[Category:Endocrine system]]

== Functions ==
* Controls the pituitary
* Balancing fluids in the body (useful to blood pressure, dehydration, overhydration)
** '''Vasopressin/antidiuretic hormone''' - a hormone that causes the kidneys to retain more water.<ref>{{Cite news|url=https://www.healthline.com/human-body-maps/hypothalamus#hypothalamus-diagram|title=Hypothalamus: Anatomy, Function, Diagram, Conditions, Health Tips|work=Healthline|access-date=2018-10-25|language=en}}</ref>
* Sex organ processes, birthing, breast milk production
** '''Oxytocin''' - released by the hypothalamus, has general function on moderating emotion and behaviors such as bonding, sexual arousal and recognition, and also sends hormones to the reproductive organs during childbirth.
** '''Gonadotropin-releasing hormone''' - causes the pituitary to produce '''follicle stimulating hormone''' (FSH; causes ovaries to produce estradiol and start ovulation, and causes the testes to both start the process of creating sperm and send signals back to the pituitary to stop sending FSH), and '''luteinizing hormone''' (LH; causes the ovaries to produce steroids such as progesterone, and causes the testes to produces steroids such as testosterone).<ref>{{Cite news|url=https://www.healthline.com/human-body-maps/hypothalamus#hypothalamus-diagram|title=Hypothalamus: Anatomy, Function, Diagram, Conditions, Health Tips|work=Healthline|access-date=2018-10-25|language=en}}</ref><ref>{{Cite web|url=https://mcb.berkeley.edu/courses/mcb135e/fsh-lh.html|title=FSH and LH|website=mcb.berkeley.edu|access-date=2018-10-25}}</ref>
* Metabolism
** '''Thyroid stimulating hormone''' - released by the hypothalamus acts on the thyroid to regulate breathing, heart rate, body temperature, some feeding and drinking behaviors etc.<ref>{{Cite news|url=https://www.endocrineweb.com/conditions/thyroid-nodules/thyroid-gland-controls-bodys-metabolism-how-it-works-symptoms-hyperthyroi|title=Thyroid Gland: Overview|work=EndocrineWeb|access-date=2018-10-25|language=en}}</ref>
* Circadian Rhythm
Once the hormones have performed the desired function, the tissues produce chemicals that are sent back to hypothalamus telling it to stop producing the hormones. This loop of signaling ensures that the hypothalamus does not overproduce hormones, maintaining order in the body.<ref name=":0" />

== Hypothalamic Dysfunction ==

=== General Dysfunction ===
Dysfunction of the pituitary can be caused by a number of events: damage to the brain, genetic predisposition, tumors, eating disorders, and autoimmune disorders. This dysfunction can lead to under- or overproduction of hormones which can lead to problems such as low body water (underproduction of vasopressin), inability to sense satiety, and insomnia.<ref>{{Cite news|url=https://www.healthline.com/human-body-maps/hypothalamus#symptoms|title=Hypothalamus: Anatomy, Function, Diagram, Conditions, Health Tips|work=Healthline|access-date=2018-10-25|language=en}}</ref>

=== Sleep Dysfunction in ME/CFS ===
A common symptom of ME/CFS is sleep disturbances. These perturbations in the regular sleeping cycle may have deleterious effects on biological processes and the progression of a condition such as ME/CFS. During sleep deprivation, studies show that there is dysregulation of enzyme complexes in the hypothalamus among other brain structures. These enzymes complexes play a role in the oxidative and nitrosative stress pathways, which if disrupted, can lead to blood brain barrier perforation and neuroinflammation (See Oxidative Stress under [[Neuroinflammation]]).<ref>{{Cite journal|date=2018-10-01|title=The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis|url=https://www.sciencedirect.com/science/article/pii/S1087079217301521|journal=Sleep Medicine Reviews|language=en|volume=41|pages=255–265|doi=10.1016/j.smrv.2018.03.007|issn=1087-0792}}</ref>

Another study found that ME/CFS patients have altered circadian rhythms and skin temperatures that do not follow normal patterns (e.g. temperature decreasing in the evening near bedtime). These functions are related to the hypothalamus and suggest that there may be hypothalamic dysfunction.<ref>{{Cite journal|last=Cambras|first=Trinitat|last2=Castro-Marrero|first2=Jesús|last3=Zaragoza|first3=Maria Cleofé|last4=Díez-Noguera|first4=Antoni|last5=Alegre|first5=José|date=2018-06-06|title=Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198106|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198106|doi=10.1371/journal.pone.0198106|issn=1932-6203|pmc=PMC5991397|pmid=29874259}}</ref>

Endocrine system

2018-10-18T16:23:16Z

Sbrumfie:I added pics

[[File:Overview of the Endocrine System.jpg|thumb|Overview of the Endocrine System]]
The '''endocrine system''' uses a combination of glands and hormones to send signals to the nervous system and control functions in the body.

Several different glands exist in the body which release hormones. These hormones travel through either the blood or the lymph circuitry to their designated site of action, and produce biochemical changes<ref name=":0">{{Cite web|url=https://www.lamission.edu/lifesciences/lecturenote/AliPhysio1/Endrocrine%20System.pdf|title=The Endocrine System|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref>{{Cite web|url=https://web.duke.edu/pathology/siteParts/avaps/06.06.4_Pathology_of_the_Endocrine_System_I_final_.pdf|title=Pathology of Endocrine System|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>.

== Function ==
Two types of hormones may be released: steroid and protein. Steroid hormones permeate tissues and can directly enter the nucleus to trigger DNA to start protein production. Protein hormones do not share this mechanism because they are unable to enter the nucleus due to their membranes being incompatible with the nuclear membrane. Instead, protein hormones attach to messenger receptor cell on the outside of the target tissues’ cells. Based on the hormone that attaches, a different cascade of cellular processes will occur ending in tissue response (which could be increased enzymatic activity, cellular secretion, and ion channel opening or closing)<ref name=":0" />.

== Glands and Hormone ==

=== Pituitary ===
The [[pituitary gland]] is a small bulb situated at the base of the brain and both releases hormones and controls other glands which release hormones. It is under direct control of the hypothalamus, a section of the brain right above the pituitary<ref>{{Cite news|url=https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/pituitary-gland-disorders/overview-of-the-pituitary-gland|title=Overview of the Pituitary Gland - Hormonal and Metabolic Disorders - Merck Manuals Consumer Version|work=Merck Manuals Consumer Version|access-date=2018-10-18|language=en-US}}</ref>. The hypothalamus receives input about hormonal and homeostatic states in the body, processes that information, then relays instructions to the pituitary gland to respond with certain hormones<ref>{{Cite web|url=https://nba.uth.tmc.edu/neuroscience/m/s4/chapter01.html|title=Hypothalamus: Structural Organization (Section 4, Chapter 1) Neuroscience Online: An Electronic Textbook for the Neurosciences {{!}} Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston|website=nba.uth.tmc.edu|access-date=2018-10-18}}</ref>. For example, osmoreceptors, water-level sensing cells, in the hypothalamus detect when you are dehydrated. The hypothalamus tells the pituitary to release antidiuretic hormone, which notifies the bladder to retain water. Water levels in the body will increase and once at an adequate level the osmoreceptors stop their signaling to have ADH released<ref name=":1">{{Cite web|url=https://courses.lumenlearning.com/suny-ap2/chapter/the-pituitary-gland-and-hypothalamus/|title=The Pituitary Gland and Hypothalamus {{!}} Anatomy and Physiology II|website=courses.lumenlearning.com|access-date=2018-10-18}}</ref>.

{| class="wikitable"
|Anterior Lobe Hormones<ref>{{Cite web|url=http://www.yourhormones.info/glands/pituitary-gland/|title=Pituitary gland {{!}} You and Your Hormones from the Society for Endocrinology|website=www.yourhormones.info|language=en|access-date=2018-10-18}}</ref><ref name=":1" />
|
|-
|
* Growth hormone
* Thyroid-stimulating hormone
* Adrenocorticotropic hormone
* Follicle-stimulating hormone
* Prolactin
|
* Controls the growth and development of the body
* Activates thyroid hormone production
* Activates the adrenal glands (on the kidneys) which produce hormones like stress
* Activates sperm and testosterone production in the testes and egg and estrogen production in the ovaries
* Activates milk production in the breasts
|}
[[File:Glands and Hormonse.jpg|thumb|Glands and Related Hormones]]
Pituitary dysfunction can lead to several disorders, including:
* Acromegaly - an overproduction of growth hormone which can cause gigantism in children and oversized limbs in adults.
* Cushing’s Disease - usually caused by a tumor on the pituitary, it is an overproduction of ACTH, the hormone that stimulates the production of cortisol. It leads to consistent high levels of cortisol in the bloodstream leading to symptoms such as increased fat around the neck, memory and cognitive dysfunction, and osteoporosis.
* Hypopituitarism - when the pituitary doesn’t produce enough hormones; can cause anemia, decreased appetite, weight changes, joint stiffness, and developmental problems (in children).

=== Hypothalamus ===
The [[hypothalamus]] maintains homeostasis in the body. It receives input from sources such as the vagus nerve (which can relay information about blood pressure and stomach fullness), the optic nerve (which relays levels of light), receptors in the body and skin (which relay temperature), and even has its own receptors which inform about the amount of molecules in the blood<ref>{{Cite web|url=http://webspace.ship.edu/cgboer/limbicsystem.html|title=The Limbic System|last=Boeree|first=George|website=webspace.ship.edu|access-date=2018-10-18}}</ref> (which relays if there is an unbalanced ratio of fluid to molecules).

When the hypothalamus is not functioning properly, many systems become dysregulated. This dysfunction can be caused by a number of different triggers such as an eating disorder, a tumor, brain injury or genetic mutations<ref>{{Cite web|url=https://rarediseases.info.nih.gov/diseases/2932/hypothalamic-dysfunction|title=Hypothalamic dysfunction {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|language=en|access-date=2018-10-18}}</ref>. A malfunctioning hypothalamus alters motivations to drink, eat and copulate which can lead to malnutrition or overeating, dehydration or overhydration and decreased or increased sexual behavior. Sleep patterns, activity levels, and menstruation may also change<ref>{{Cite web|url=https://www.braininjury-explanation.com/consequences/impact-by-brain-area/hypothalamus|title=Hypothalamus / Impact per brain area / Consequences {{!}} Braininjury-explanation.com|website=www.braininjury-explanation.com|language=nl|access-date=2018-10-18}}</ref>.

=== Thyroid ===
The thyroid is a gland located in the throat. It is necessary in proper brain functioning and health, and is important to the development of children and fetus’s brains. The gland also plays a role in controlling the breakdown and use of proteins, carbohydrates and fats<ref>{{Cite news|url=https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/thyroid-disorders/overview-of-thyroid-function|title=Overview of Thyroid Function - Endocrine and Metabolic Disorders - Merck Manuals Professional Edition|work=Merck Manuals Professional Edition|access-date=2018-10-18|language=en-US}}</ref>. The thyroid has cells that absorb iodine. The cells use iodine to produce T3 and T4, thyroid hormones that can moderate the body’s temperature, and vitals (e.g. blood pressure and heart rate), and the breakdown of various biomolecules such as fat<ref>{{Cite news|url=https://www.healthline.com/health/t3|title=T3 Test: Purpose, Procedure & Risks|work=Healthline|access-date=2018-10-18|language=en}}</ref>.

Dysfunction of this gland can mean an overproduction or underproduction of its hormones. Malfunction can lead symptoms such as to hair loss, muscle fatigue and weakness, sensitivity to environmental temperature changes<ref>{{Cite news|url=https://www.healthline.com/health/t3#uses-amp-symptoms|title=T3 Test: Purpose, Procedure & Risks|work=Healthline|access-date=2018-10-18|language=en}}</ref>.

== Relationship to ME/CFS ==
Hypothalamo-pituitary-adrenal axis (HPA) is the collaborative functioning between the hypothalamus and the pituitary gland. These tissues work together to regulate hormone production and release, and also moderate bodily functions such as temperature regulation, fluid balance, appetite and thirst detection. Hypofunction of the HPA has been identified as a problem experienced in ME/CFS patients. Lower cortisol levels were identified in ME/CFS patients than in healthy controls, and has been shown to be connected to decreased sleep<ref>{{Cite journal|last=Nijhof|first=Sanne L.|last2=Rutten|first2=Juliette M. T. M.|last3=Uiterwaal|first3=Cuno S. P. M.|last4=Bleijenberg|first4=Gijs|last5=Kimpen|first5=Jan L. L.|last6=Putte|first6=Elise M. van de|date=2014-4|title=The role of hypocortisolism in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/24636516|journal=Psychoneuroendocrinology|volume=42|pages=199–206|doi=10.1016/j.psyneuen.2014.01.017|issn=1873-3360|pmid=24636516}}</ref>. Exogenous cortisol administration was tested as a possible treatment however these results should be replicated due to the group’s use of solely the Fukuda Assessment of ME/CFS (which may allow for error in diagnosis of the condition). Furthermore, several journals suggested CBT as a feasible treatment option to increase cortisol levels, however due to the extensive literature questioning and undermining the utility of CBT in ME/CFS in overall treatment, other options should be explored in this research<ref>{{Cite journal|last=Twisk|first=Frank N. M.|last2=Maes|first2=Michael|date=2009|title=A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS|url=https://www.ncbi.nlm.nih.gov/pubmed/19855350|journal=Neuro Endocrinology Letters|volume=30|issue=3|pages=284–299|issn=0172-780X|pmid=19855350}}</ref><ref>{{Cite journal|last=Núñez|first=Montserrat|last2=Fernández-Solà|first2=Joaquim|last3=Nuñez|first3=Esther|last4=Fernández-Huerta|first4=José-Manuel|last5=Godás-Sieso|first5=Teresa|last6=Gomez-Gil|first6=Esther|date=2011-01-15|title=Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up|url=https://link.springer.com/article/10.1007/s10067-010-1677-y|journal=Clinical Rheumatology|language=en|volume=30|issue=3|pages=381–389|doi=10.1007/s10067-010-1677-y|issn=0770-3198}}</ref>.

== References ==

[[Category:Body systems]]
<references />

File:Overview of the Endocrine System.jpg

2018-10-18T16:16:42Z

Sbrumfie:

Retrieved from Creative Commons: https://upload.wikimedia.org/wikipedia/commons/1/15/1801_The_Endocrine_System.jpg

Neuroinflammation

2018-08-31T15:39:15Z

Sbrumfie:Edits

[[File:Microglia and Astrocyte Dysfunction.png|thumb|Possible mechanism showing the decline of microglia and astrocyte function and structure.]]
'''Neuroinflammation''' takes place when the central nervous system (CNS), which consists of the brain and spinal cord, undergoes an immune response. This may be due to microglial cell activation.[[File:ME-CFS Brain Images.jpg|500px|thumb|right|Top Scans: Control Patient, Bottom Scans: ME/CFS Patient]]

Neuroinflammation is thought to occur when immune cells from the body infiltrate the [[central nervous system]] (CNS) (links to CNS page), which consists of the brain and spinal cord. Infiltration of these immune cells can occur both when the brain is damaged and when there is infection in the body. <ref name=":0">{{Cite journal|last=Graeber|first=Manuel B.|last2=Li|first2=Wei|last3=Rodriguez|first3=Michael L.|date=2011-12-01|title=Role of microglia in CNS inflammation|url=https://www.ncbi.nlm.nih.gov/pubmed/21889505|journal=FEBS letters|volume=585|issue=23|pages=3798–3805|doi=10.1016/j.febslet.2011.08.033|issn=1873-3468|pmid=21889505}}</ref>

Microglia, the primary defense mechanisms for the CNS, activate in response to the immune cells and respond to repair the damage in the brain or fight the infection. <ref name=":0" /><ref name=":1">{{Cite journal|last=DiSabato|first=Damon J.|last2=Quan|first2=Ning|last3=Godbout|first3=Jonathan P.|date=2016-10|title=Neuroinflammation: the devil is in the details|url=https://www.ncbi.nlm.nih.gov/pubmed/26990767|journal=Journal of Neurochemistry|volume=139 Suppl 2|pages=136–153|doi=10.1111/jnc.13607|issn=1471-4159|pmc=PMC5025335|pmid=26990767}}</ref> As microglia work to restore damaged tissues by activating T-cells leading to further inflammation. Consistent microglia activation and release of these cells lead to the chronic damage that perpetuate neuroinflammation. <ref name=":1" />

==Diseases Associated with Neuroinflammation==
Neuroinflammation is a symptom of many diseases and thought to be a part of ME. Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are illnesses where the brain experiences decline in structure and function, and also where it shows clear signs of neuroinflammation. Inflammation of the brain is linked to activated microglia, cytokine presence in the brain<ref>{{Cite journal|last=CHEN|first=WEI-WEI|last2=ZHANG|first2=XIA|last3=HUANG|first3=WEN-JUAN|date=2016-4|title=Role of neuroinflammation in neurodegenerative diseases (Review)|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805095/|journal=Molecular Medicine Reports|volume=13|issue=4|pages=3391–3396|doi=10.3892/mmr.2016.4948|issn=1791-2997|pmc=PMC4805095|pmid=26935478}}</ref>, and changes in the neurochemicals produced by the brain<ref name=":2">{{Cite journal|last=Albrecht|first=Daniel S.|last2=Granziera|first2=Cristina|last3=Hooker|first3=Jacob M.|last4=Loggia|first4=Marco L.|date=2016-04-20|title=In Vivo Imaging of Human Neuroinflammation|url=https://www.ncbi.nlm.nih.gov/pubmed/26985861|journal=ACS chemical neuroscience|volume=7|issue=4|pages=470–483|doi=10.1021/acschemneuro.6b00056|issn=1948-7193|pmc=PMC5433433|pmid=26985861}}</ref>. These effects also occur in ME which is why researchers are searching to more strongly show neuroinflammation in these patients.

==Causes==

=== Microglia Activation ===
The blood brain barrier (BBB), a membrane that separates the brain from the rest of the body, may become compromised in ME patients. If there are cytokines circulating in the bloodstream, they may get into the brain through opened sections of the BBB<ref name=":3">{{Cite journal|last=Morris|first=Gerwyn|last2=Maes|first2=Michael|date=2013-12|title=A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/22718491|journal=Metabolic Brain Disease|volume=28|issue=4|pages=523–540|doi=10.1007/s11011-012-9324-8|issn=1573-7365|pmid=22718491}}</ref>. While this initially starts as a normal brain response so that the brain can get the body back to normal, healthy functioning, this process can be predisposed to dysfunction and activation may be sustained longer than usual.

Microglia are cells that can act as the brain’s primary immune response. If cytokines or immune cells from outside the CNS enter the brain through the BBB, the microglia will respond to the immune threat and attempt to clear the infiltrators out. However, this process increases neuron activation and the release of more cytokines potentially leading to a cycle of neuroinflammation<ref name=":3" />.

One study used a radioligand, a tracer that lights up in the presence of a specific molecule, in a positron emission tomography (PET) scanner in search of activated microglia in ME patients’ brains. Activated microglia cells are believed to be correlated to neuroinflammation. Increased radioligand presence in ME subjects’ brains was observed; however, further analysis of these data and replication of their results are needed<ref>{{Cite journal|last=Nakatomi|first=Yasuhito|last2=Mizuno|first2=Kei|last3=Ishii|first3=Akira|last4=Wada|first4=Yasuhiro|last5=Tanaka|first5=Masaaki|last6=Tazawa|first6=Shusaku|last7=Onoe|first7=Kayo|last8=Fukuda|first8=Sanae|last9=Kawabe|first9=Joji|date=2014-6|title=Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study|url=https://www.ncbi.nlm.nih.gov/pubmed/24665088|journal=Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine|volume=55|issue=6|pages=945–950|doi=10.2967/jnumed.113.131045|issn=1535-5667|pmid=24665088}}</ref>.

===Oxidative and Nitrosative Stress===
Neuroinflammation may also be related to excess oxygen and nitrogen molecules in tissues. This can cause oxidative or nitrosative stress (O&NS), leading to tissue damage. The O&NS pathway helps maintain the blood brain barrier, an important membrane keeping the brain protected from harmful substances present in the blood. When the pathway is dysfunctional, the blood-brain barrier becomes less effective at keeping out particles. Breakdown of this barrier could lead to immune cells entering the brain and trigger an immune response, leading to neuroinflammation. Researchers propose a link between the dysfunction of brain tissues in ME/ and the breakdown of the oxidative and nitrosative stress pathway<ref name=":3" />.

=== Activation of cyclical neuroinflammation: A self-perpetuating cycle ===
When a patient gets an infection, the body attempts to return homeostasis. The immune system has regulatory structures called toll-like receptors (TLRs). High amounts of stress or a previous injury can predispose an individual’s TLRs to be more sensitive, releasing inflammatory molecules more readily in response to an immune stressor<ref>{{Cite journal|last=Gárate|first=Iciar|last2=Garcia-Bueno|first2=Borja|last3=Madrigal|first3=Jose Luis Muñoz|last4=Caso|first4=Javier Rubén|last5=Alou|first5=Luis|last6=Gomez-Lus|first6=Marisa L.|last7=Micó|first7=Juan Antonio|last8=Leza|first8=Juan Carlos|date=2013-01-01|title=Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway|url=https://www.ncbi.nlm.nih.gov/pubmed/22906518|journal=Biological Psychiatry|volume=73|issue=1|pages=32–43|doi=10.1016/j.biopsych.2012.07.005|issn=1873-2402|pmid=22906518}}</ref>. One of the downstream pathways of TLRs, the oxidative and nitrosative stress pathway (O&NS) can get activated. If this pathway is overstimulated, the body will produce a larger-scale response in an effort to return to normal<ref>{{Cite journal|last=Liu|first=JiaJun|last2=Buisman-Pijlman|first2=Femke|last3=Hutchinson|first3=Mark R.|date=2014|title=Toll-like receptor 4: innate immune regulator of neuroimmune and neuroendocrine interactions in stress and major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/25324715|journal=Frontiers in Neuroscience|volume=8|pages=309|doi=10.3389/fnins.2014.00309|issn=1662-4548|pmc=PMC4179746|pmid=25324715}}</ref>. In this attempt, a chemical called damage-associated molecular patterns (DAMPs) triggers the release of more inflammatory molecules, some of which activate the TLRs<ref>{{Cite journal|last=Morris|first=Gerwyn|last2=Berk|first2=Michael|last3=Walder|first3=Ken|last4=Maes|first4=Michael|date=2015-02-06|title=Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses|url=https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0259-2|journal=BMC Medicine|language=En|volume=13|issue=1|doi=10.1186/s12916-014-0259-2|issn=1741-7015|pmc=PMC4320458|pmid=25856766}}</ref> (Morris et al., 2015). The process of activation from TLRs to the O&NS pathway to the production of more inflammatory molecules then becom<ref name=":4">{{Cite journal|last=Chaudhuri|first=A.|last2=Condon|first2=B. R.|last3=Gow|first3=J. W.|last4=Brennan|first4=D.|last5=Hadley|first5=D. M.|date=2003-02-10|title=Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12598734|journal=Neuroreport|volume=14|issue=2|pages=225–228|doi=10.1097/01.wnr.0000054960.21656.64|issn=0959-4965|pmid=12598734}}</ref>es a cycle.

== Possible Neurological Biomarkers of ME ==
When the brain is going through challenges such as neuroinflammation or neurodegeneration, several chemicals become dysregulated. These changes are able to be recorded using a special function of magnetic resonance (MR) scanners. Because each chemical has a distinct molecular structure, the magnetic field formed by the scanner will bounce off of each chemical in unique ways. This allows the technician to measure the amounts of these chemicals in the brain.

Several neurochemicals have been studied in relation to ME patients. Myo-inositol is thought to be involved in astrocyte function (Albrecht et al. 2016) and trended to be higher in ME patients compared to controls<ref name=":5">{{Cite journal|last=Brooks|first=J. C.|last2=Roberts|first2=N.|last3=Whitehouse|first3=G.|last4=Majeed|first4=T.|date=2000-11|title=Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11144799|journal=The British Journal of Radiology|volume=73|issue=875|pages=1206–1208|doi=10.1259/bjr.73.875.11144799|issn=0007-1285|pmid=11144799}}</ref>.

N-acetylacetate (NAA) shows neuron density, which has been found in other neurological disorders<ref name=":2" /> and has been shown to be lower in ME patients<ref name=":4" /><ref name=":5" />, but this was not found in all studies<ref>{{Cite journal|last=Puri|first=B. K.|last2=Counsell|first2=S. J.|last3=Zaman|first3=R.|last4=Main|first4=J.|last5=Collins|first5=A. G.|last6=Hajnal|first6=J. V.|last7=Davey|first7=N. J.|date=2002-9|title=Relative increase in choline in the occipital cortex in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12197861|journal=Acta Psychiatrica Scandinavica|volume=106|issue=3|pages=224–226|issn=0001-690X|pmid=12197861}}</ref><ref name=":6">{{Cite journal|last=Tomoda|first=A.|last2=Miike|first2=T.|last3=Yamada|first3=E.|last4=Honda|first4=H.|last5=Moroi|first5=T.|last6=Ogawa|first6=M.|last7=Ohtani|first7=Y.|last8=Morishita|first8=S.|date=2000-1|title=Chronic fatigue syndrome in childhood|url=https://www.ncbi.nlm.nih.gov/pubmed/10761837|journal=Brain & Development|volume=22|issue=1|pages=60–64|issn=0387-7604|pmid=10761837}}</ref>.

Choline is linked to activation of glia, loss of energy and expression of macrophages in the brain<ref name=":2" /> and has been shown to change compared to controls<ref name=":4" /><ref name=":5" /><ref name=":6" /> <ref>{{Cite journal|last=Puri|first=B. K.|last2=Agour|first2=M.|last3=Gunatilake|first3=K. D. R.|last4=Fernando|first4=K. a. C.|last5=Gurusinghe|first5=A. I.|last6=Treasaden|first6=I. H.|date=2009-11|title=An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)|url=https://www.ncbi.nlm.nih.gov/pubmed/19906518|journal=Prostaglandins, Leukotrienes, and Essential Fatty Acids|volume=81|issue=5-6|pages=303–305|doi=10.1016/j.plefa.2009.10.002|issn=1532-2823|pmid=19906518}}</ref>.

Lactate increases when more energy is being expended and has been shown to be higher than controls<ref name=":7">{{Cite journal|last=Mathew|first=Sanjay J.|last2=Mao|first2=Xiangling|last3=Keegan|first3=Kathryn A.|last4=Levine|first4=Susan M.|last5=Smith|first5=Eric L. P.|last6=Heier|first6=Linda A.|last7=Otcheretko|first7=Viktor|last8=Coplan|first8=Jeremy D.|last9=Shungu|first9=Dikoma C.|date=2009-4|title=Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study|url=https://www.ncbi.nlm.nih.gov/pubmed/18942064|journal=NMR in biomedicine|volume=22|issue=3|pages=251–258|doi=10.1002/nbm.1315|issn=0952-3480|pmid=18942064}}</ref><ref>{{Cite journal|last=Shungu|first=Dikoma C.|last2=Weiduschat|first2=Nora|last3=Murrough|first3=James W.|last4=Mao|first4=Xiangling|last5=Pillemer|first5=Sarah|last6=Dyke|first6=Jonathan P.|last7=Medow|first7=Marvin S.|last8=Natelson|first8=Benjamin H.|last9=Stewart|first9=Julian M.|date=2012-9|title=Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology|url=https://www.ncbi.nlm.nih.gov/pubmed/22281935|journal=NMR in biomedicine|volume=25|issue=9|pages=1073–1087|doi=10.1002/nbm.2772|issn=1099-1492|pmc=PMC3896084|pmid=22281935}}</ref><ref name=":8">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Vu|first2=Diana|last3=Coplan|first3=Jeremy D.|last4=Mao|first4=Xiangling|last5=Blate|first5=Michelle|last6=Kang|first6=Guoxin|last7=Soto|first7=Eli|last8=Kapusuz|first8=Tolga|last9=Shungu|first9=Dikoma C.|date=2017|title=Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pubmed/29308330|journal=Fatigue: Biomedicine, Health & Behavior|volume=5|issue=1|pages=15–20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=PMC5754037|pmid=29308330}}</ref><ref name=":9">{{Cite journal|last=Murrough|first=James W.|last2=Mao|first2=Xiangling|last3=Collins|first3=Katherine A.|last4=Kelly|first4=Chris|last5=Andrade|first5=Gizely|last6=Nestadt|first6=Paul|last7=Levine|first7=Susan M.|last8=Mathew|first8=Sanjay J.|last9=Shungu|first9=Dikoma C.|date=2010-7|title=Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/20661876|journal=NMR in biomedicine|volume=23|issue=6|pages=643–650|doi=10.1002/nbm.1512|issn=1099-1492|pmid=20661876}}</ref>, and significantly differs from lactate levels in people with psychological disorders<ref name=":7" /><ref name=":9" />. Both ME patients and fibromyalgia patients were found to have similar levels of elevated lactate, so more tests would be needed to differentiate the two<ref name=":8" />.

Though contrasts were found between ME people and controls in many of these biomarker studies, researchers are not sure what the changes mean specifically because the metabolites are used in multiple brain processes. Furthermore, the results shown by these papers has not been largely replicated. However, if repeated, these biomarkers could potentially become an objective measure for diagnosing ME.

==Notable studies==
*2010, Autopsies of four deceased ME patients showed various pathological phenomena in the central and [[peripheral nervous system]]s. <ref>{{Cite web|url=https://www.meassociation.org.uk/2011/01/pathology-of-mecfs-pilot-study-of-four-autopsy-reports/|title=Pathology of ME/CFS: pilot study of four autopsy reports|last=|first=|date=Jan 2011|website=www.meassociation.org.uk|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-10}}</ref>
*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder]]'. NY Times Well article by [[David Tuller]] on the [[brain scans]] of [[ME/CFS]] patient's researched by [[Stanford ME/CFS Initiative]]. (2014)<ref>{{Cite news|url=http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chronic-fatigue-syndrome-offer-clues-about-disorder/?_r=0|title=Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder|last=Tuller|first=David|date=Nov 24, 2014|work=Well|access-date=2018-08-10|archive-url=|archive-date=|dead-url=|language=en}}</ref>

==Talks & interviews==
*2016, [https://www.youtube.com/watch?v=1p6UojKL010 Do you have a hot brain?]<ref>{{Cite web|url=https://www.youtube.com/watch?v=1p6UojKL010|title=Do you have a hot brain?|last=Younger|first=Jarred|date=Apr 25, 2016|website=YouTube|via=Younger Lab|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
*2016, [https://www.youtube.com/watch?v=_ijlkRwORfM What is neuroinflammation?]<ref>{{Cite web|url=https://www.youtube.com/watch?v=_ijlkRwORfM|title=What is neuroinflammation?|last=Younger|first=Jarred|date=Apr 4, 2016|website=YouTube|via=Younger Lab|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

==Learn more==
*[https://en.wikipedia.org/wiki/Neuroinflammation Wikipedia]

== See also ==
*[[Brain imaging]]
*[[Jarred Younger]]

==References==
<references />

[[Category:Body systems]]

File:Microglia and Astrocyte Dysfunction.png

2018-08-31T15:36:17Z

Sbrumfie:

Possible mechanism of microglia and astrocyte decline.

Neuroinflammation

2018-08-31T14:41:23Z

Sbrumfie:Edits

'''Neuroinflammation''' takes place when the central nervous system (CNS), which consists of the brain and spinal cord, undergoes an immune response. This may be due to microglial cell activation.[[File:ME-CFS Brain Images.jpg|500px|thumb|right|Top Scans: Control Patient, Bottom Scans: ME/CFS Patient]]

Neuroinflammation is thought to occur when immune cells from the body infiltrate the [[central nervous system]] (CNS) (links to CNS page), which consists of the brain and spinal cord. Infiltration of these immune cells can occur both when the brain is damaged and when there is infection in the body. <ref name=":0">{{Cite journal|last=Graeber|first=Manuel B.|last2=Li|first2=Wei|last3=Rodriguez|first3=Michael L.|date=2011-12-01|title=Role of microglia in CNS inflammation|url=https://www.ncbi.nlm.nih.gov/pubmed/21889505|journal=FEBS letters|volume=585|issue=23|pages=3798–3805|doi=10.1016/j.febslet.2011.08.033|issn=1873-3468|pmid=21889505}}</ref>

Microglia, the primary defense mechanisms for the CNS, activate in response to the immune cells and respond to repair the damage in the brain or fight the infection. <ref name=":0" /><ref name=":1">{{Cite journal|last=DiSabato|first=Damon J.|last2=Quan|first2=Ning|last3=Godbout|first3=Jonathan P.|date=2016-10|title=Neuroinflammation: the devil is in the details|url=https://www.ncbi.nlm.nih.gov/pubmed/26990767|journal=Journal of Neurochemistry|volume=139 Suppl 2|pages=136–153|doi=10.1111/jnc.13607|issn=1471-4159|pmc=PMC5025335|pmid=26990767}}</ref> As microglia work to restore damaged tissues by activating T-cells leading to further inflammation. Consistent microglia activation and release of these cells lead to the chronic damage that perpetuate neuroinflammation. <ref name=":1" />

==Diseases Associated with Neuroinflammation==
Neuroinflammation is a symptom of many diseases and thought to be a part of ME. Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are illnesses where the brain experiences decline in structure and function, and also where it shows clear signs of neuroinflammation. Inflammation of the brain is linked to activated microglia, cytokine presence in the brain<ref>{{Cite journal|last=CHEN|first=WEI-WEI|last2=ZHANG|first2=XIA|last3=HUANG|first3=WEN-JUAN|date=2016-4|title=Role of neuroinflammation in neurodegenerative diseases (Review)|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805095/|journal=Molecular Medicine Reports|volume=13|issue=4|pages=3391–3396|doi=10.3892/mmr.2016.4948|issn=1791-2997|pmc=PMC4805095|pmid=26935478}}</ref>, and changes in the neurochemicals produced by the brain<ref name=":2">{{Cite journal|last=Albrecht|first=Daniel S.|last2=Granziera|first2=Cristina|last3=Hooker|first3=Jacob M.|last4=Loggia|first4=Marco L.|date=2016-04-20|title=In Vivo Imaging of Human Neuroinflammation|url=https://www.ncbi.nlm.nih.gov/pubmed/26985861|journal=ACS chemical neuroscience|volume=7|issue=4|pages=470–483|doi=10.1021/acschemneuro.6b00056|issn=1948-7193|pmc=PMC5433433|pmid=26985861}}</ref>. These effects also occur in ME which is why researchers are searching to more strongly show neuroinflammation in these patients.

==Causes==

=== Microglia Activation ===
The blood brain barrier (BBB), a membrane that separates the brain from the rest of the body, may become compromised in ME patients. If there are cytokines circulating in the bloodstream, they may get into the brain through opened sections of the BBB<ref name=":3">{{Cite journal|last=Morris|first=Gerwyn|last2=Maes|first2=Michael|date=2013-12|title=A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/22718491|journal=Metabolic Brain Disease|volume=28|issue=4|pages=523–540|doi=10.1007/s11011-012-9324-8|issn=1573-7365|pmid=22718491}}</ref>. While this initially starts as a normal brain response so that the brain can get the body back to normal, healthy functioning, this process can be predisposed to dysfunction and activation may be sustained longer than usual.

Microglia are cells that can act as the brain’s primary immune response. If cytokines or immune cells from outside the CNS enter the brain through the BBB, the microglia will respond to the immune threat and attempt to clear the infiltrators out. However, this process increases neuron activation and the release of more cytokines potentially leading to a cycle of neuroinflammation<ref name=":3" />.

One study used a radioligand, a tracer that lights up in the presence of a specific molecule, in a positron emission tomography (PET) scanner in search of activated microglia in ME patients’ brains. Activated microglia cells are believed to be correlated to neuroinflammation. Increased radioligand presence in ME subjects’ brains was observed; however, further analysis of these data and replication of their results are needed<ref>{{Cite journal|last=Nakatomi|first=Yasuhito|last2=Mizuno|first2=Kei|last3=Ishii|first3=Akira|last4=Wada|first4=Yasuhiro|last5=Tanaka|first5=Masaaki|last6=Tazawa|first6=Shusaku|last7=Onoe|first7=Kayo|last8=Fukuda|first8=Sanae|last9=Kawabe|first9=Joji|date=2014-6|title=Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study|url=https://www.ncbi.nlm.nih.gov/pubmed/24665088|journal=Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine|volume=55|issue=6|pages=945–950|doi=10.2967/jnumed.113.131045|issn=1535-5667|pmid=24665088}}</ref>.

===Oxidative and Nitrosative Stress===
Neuroinflammation may also be related to excess oxygen and nitrogen molecules in tissues. This can cause oxidative or nitrosative stress (O&NS), leading to tissue damage. The O&NS pathway helps maintain the blood brain barrier, an important membrane keeping the brain protected from harmful substances present in the blood. When the pathway is dysfunctional, the blood-brain barrier becomes less effective at keeping out particles. Breakdown of this barrier could lead to immune cells entering the brain and trigger an immune response, leading to neuroinflammation. Researchers propose a link between the dysfunction of brain tissues in ME/ and the breakdown of the oxidative and nitrosative stress pathway<ref name=":3" />.

=== Activation of cyclical neuroinflammation: A self-perpetuating cycle ===
When a patient gets an infection, the body attempts to return homeostasis. The immune system has regulatory structures called toll-like receptors (TLRs). High amounts of stress or a previous injury can predispose an individual’s TLRs to be more sensitive, releasing inflammatory molecules more readily in response to an immune stressor<ref>{{Cite journal|last=Gárate|first=Iciar|last2=Garcia-Bueno|first2=Borja|last3=Madrigal|first3=Jose Luis Muñoz|last4=Caso|first4=Javier Rubén|last5=Alou|first5=Luis|last6=Gomez-Lus|first6=Marisa L.|last7=Micó|first7=Juan Antonio|last8=Leza|first8=Juan Carlos|date=2013-01-01|title=Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway|url=https://www.ncbi.nlm.nih.gov/pubmed/22906518|journal=Biological Psychiatry|volume=73|issue=1|pages=32–43|doi=10.1016/j.biopsych.2012.07.005|issn=1873-2402|pmid=22906518}}</ref>. One of the downstream pathways of TLRs, the oxidative and nitrosative stress pathway (O&NS) can get activated. If this pathway is overstimulated, the body will produce a larger-scale response in an effort to return to normal<ref>{{Cite journal|last=Liu|first=JiaJun|last2=Buisman-Pijlman|first2=Femke|last3=Hutchinson|first3=Mark R.|date=2014|title=Toll-like receptor 4: innate immune regulator of neuroimmune and neuroendocrine interactions in stress and major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/25324715|journal=Frontiers in Neuroscience|volume=8|pages=309|doi=10.3389/fnins.2014.00309|issn=1662-4548|pmc=PMC4179746|pmid=25324715}}</ref>. In this attempt, a chemical called damage-associated molecular patterns (DAMPs) triggers the release of more inflammatory molecules, some of which activate the TLRs<ref>{{Cite journal|last=Morris|first=Gerwyn|last2=Berk|first2=Michael|last3=Walder|first3=Ken|last4=Maes|first4=Michael|date=2015-02-06|title=Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses|url=https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0259-2|journal=BMC Medicine|language=En|volume=13|issue=1|doi=10.1186/s12916-014-0259-2|issn=1741-7015|pmc=PMC4320458|pmid=25856766}}</ref> (Morris et al., 2015). The process of activation from TLRs to the O&NS pathway to the production of more inflammatory molecules then becom<ref name=":4">{{Cite journal|last=Chaudhuri|first=A.|last2=Condon|first2=B. R.|last3=Gow|first3=J. W.|last4=Brennan|first4=D.|last5=Hadley|first5=D. M.|date=2003-02-10|title=Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12598734|journal=Neuroreport|volume=14|issue=2|pages=225–228|doi=10.1097/01.wnr.0000054960.21656.64|issn=0959-4965|pmid=12598734}}</ref>es a cycle.

== Possible Neurological Biomarkers of ME ==
When the brain is going through challenges such as neuroinflammation or neurodegeneration, several chemicals become dysregulated. These changes are able to be recorded using a special function of magnetic resonance (MR) scanners. Because each chemical has a distinct molecular structure, the magnetic field formed by the scanner will bounce off of each chemical in unique ways. This allows the technician to measure the amounts of these chemicals in the brain.

Several neurochemicals have been studied in relation to ME patients. Myo-inositol is thought to be involved in astrocyte function (Albrecht et al. 2016) and trended to be higher in ME patients compared to controls<ref name=":5">{{Cite journal|last=Brooks|first=J. C.|last2=Roberts|first2=N.|last3=Whitehouse|first3=G.|last4=Majeed|first4=T.|date=2000-11|title=Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11144799|journal=The British Journal of Radiology|volume=73|issue=875|pages=1206–1208|doi=10.1259/bjr.73.875.11144799|issn=0007-1285|pmid=11144799}}</ref>.

N-acetylacetate (NAA) shows neuron density, which has been found in other neurological disorders<ref name=":2" /> and has been shown to be lower in ME patients<ref name=":4" /><ref name=":5" />, but this was not found in all studies<ref>{{Cite journal|last=Puri|first=B. K.|last2=Counsell|first2=S. J.|last3=Zaman|first3=R.|last4=Main|first4=J.|last5=Collins|first5=A. G.|last6=Hajnal|first6=J. V.|last7=Davey|first7=N. J.|date=2002-9|title=Relative increase in choline in the occipital cortex in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12197861|journal=Acta Psychiatrica Scandinavica|volume=106|issue=3|pages=224–226|issn=0001-690X|pmid=12197861}}</ref><ref name=":6">{{Cite journal|last=Tomoda|first=A.|last2=Miike|first2=T.|last3=Yamada|first3=E.|last4=Honda|first4=H.|last5=Moroi|first5=T.|last6=Ogawa|first6=M.|last7=Ohtani|first7=Y.|last8=Morishita|first8=S.|date=2000-1|title=Chronic fatigue syndrome in childhood|url=https://www.ncbi.nlm.nih.gov/pubmed/10761837|journal=Brain & Development|volume=22|issue=1|pages=60–64|issn=0387-7604|pmid=10761837}}</ref>.

Choline is linked to activation of glia, loss of energy and expression of macrophages in the brain<ref name=":2" /> and has been shown to change compared to controls<ref name=":4" /><ref name=":5" /><ref name=":6" /> <ref>{{Cite journal|last=Puri|first=B. K.|last2=Agour|first2=M.|last3=Gunatilake|first3=K. D. R.|last4=Fernando|first4=K. a. C.|last5=Gurusinghe|first5=A. I.|last6=Treasaden|first6=I. H.|date=2009-11|title=An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)|url=https://www.ncbi.nlm.nih.gov/pubmed/19906518|journal=Prostaglandins, Leukotrienes, and Essential Fatty Acids|volume=81|issue=5-6|pages=303–305|doi=10.1016/j.plefa.2009.10.002|issn=1532-2823|pmid=19906518}}</ref>.

Lactate increases when more energy is being expended and has been shown to be higher than controls<ref name=":7">{{Cite journal|last=Mathew|first=Sanjay J.|last2=Mao|first2=Xiangling|last3=Keegan|first3=Kathryn A.|last4=Levine|first4=Susan M.|last5=Smith|first5=Eric L. P.|last6=Heier|first6=Linda A.|last7=Otcheretko|first7=Viktor|last8=Coplan|first8=Jeremy D.|last9=Shungu|first9=Dikoma C.|date=2009-4|title=Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study|url=https://www.ncbi.nlm.nih.gov/pubmed/18942064|journal=NMR in biomedicine|volume=22|issue=3|pages=251–258|doi=10.1002/nbm.1315|issn=0952-3480|pmid=18942064}}</ref><ref>{{Cite journal|last=Shungu|first=Dikoma C.|last2=Weiduschat|first2=Nora|last3=Murrough|first3=James W.|last4=Mao|first4=Xiangling|last5=Pillemer|first5=Sarah|last6=Dyke|first6=Jonathan P.|last7=Medow|first7=Marvin S.|last8=Natelson|first8=Benjamin H.|last9=Stewart|first9=Julian M.|date=2012-9|title=Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology|url=https://www.ncbi.nlm.nih.gov/pubmed/22281935|journal=NMR in biomedicine|volume=25|issue=9|pages=1073–1087|doi=10.1002/nbm.2772|issn=1099-1492|pmc=PMC3896084|pmid=22281935}}</ref><ref name=":8">{{Cite journal|last=Natelson|first=Benjamin H.|last2=Vu|first2=Diana|last3=Coplan|first3=Jeremy D.|last4=Mao|first4=Xiangling|last5=Blate|first5=Michelle|last6=Kang|first6=Guoxin|last7=Soto|first7=Eli|last8=Kapusuz|first8=Tolga|last9=Shungu|first9=Dikoma C.|date=2017|title=Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pubmed/29308330|journal=Fatigue: Biomedicine, Health & Behavior|volume=5|issue=1|pages=15–20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=PMC5754037|pmid=29308330}}</ref><ref name=":9">{{Cite journal|last=Murrough|first=James W.|last2=Mao|first2=Xiangling|last3=Collins|first3=Katherine A.|last4=Kelly|first4=Chris|last5=Andrade|first5=Gizely|last6=Nestadt|first6=Paul|last7=Levine|first7=Susan M.|last8=Mathew|first8=Sanjay J.|last9=Shungu|first9=Dikoma C.|date=2010-7|title=Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/20661876|journal=NMR in biomedicine|volume=23|issue=6|pages=643–650|doi=10.1002/nbm.1512|issn=1099-1492|pmid=20661876}}</ref>, and significantly differs from lactate levels in people with psychological disorders<ref name=":7" /><ref name=":9" />. Both ME patients and fibromyalgia patients were found to have similar levels of elevated lactate, so more tests would be needed to differentiate the two<ref name=":8" />.

Though contrasts were found between ME people and controls in many of these biomarker studies, researchers are not sure what the changes mean specifically because the metabolites are used in multiple brain processes. Furthermore, the results shown by these papers has not been largely replicated. However, if repeated, these biomarkers could potentially become an objective measure for diagnosing ME.

==Notable studies==
*2010, Autopsies of four deceased ME patients showed various pathological phenomena in the central and [[peripheral nervous system]]s. <ref>{{Cite web|url=https://www.meassociation.org.uk/2011/01/pathology-of-mecfs-pilot-study-of-four-autopsy-reports/|title=Pathology of ME/CFS: pilot study of four autopsy reports|last=|first=|date=Jan 2011|website=www.meassociation.org.uk|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-10}}</ref>
*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder]]'. NY Times Well article by [[David Tuller]] on the [[brain scans]] of [[ME/CFS]] patient's researched by [[Stanford ME/CFS Initiative]]. (2014)<ref>{{Cite news|url=http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chronic-fatigue-syndrome-offer-clues-about-disorder/?_r=0|title=Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder|last=Tuller|first=David|date=Nov 24, 2014|work=Well|access-date=2018-08-10|archive-url=|archive-date=|dead-url=|language=en}}</ref>

==Talks & interviews==
*2016, [https://www.youtube.com/watch?v=1p6UojKL010 Do you have a hot brain?]<ref>{{Cite web|url=https://www.youtube.com/watch?v=1p6UojKL010|title=Do you have a hot brain?|last=Younger|first=Jarred|date=Apr 25, 2016|website=YouTube|via=Younger Lab|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
*2016, [https://www.youtube.com/watch?v=_ijlkRwORfM What is neuroinflammation?]<ref>{{Cite web|url=https://www.youtube.com/watch?v=_ijlkRwORfM|title=What is neuroinflammation?|last=Younger|first=Jarred|date=Apr 4, 2016|website=YouTube|via=Younger Lab|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

==Learn more==
*[https://en.wikipedia.org/wiki/Neuroinflammation Wikipedia]

== See also ==
*[[Brain imaging]]
*[[Jarred Younger]]

==References==
<references />

[[Category:Body systems]]

Neuroinflammation

2018-06-25T06:28:22Z

Sbrumfie:I am updating this page

A concrete definition for neuroinflammation is not fully agreed on in the scientific world yet, but it is thought to follow similar patterns that inflammation in the rest of the body follows. Inflammation, in general, occurs when a pathogen, or something foreign to the body, gets into the body. The body detects the toxin with immune cells which then signal other immune cells to help eliminate the pathogen. The response and build-up of these immune cells is what is referred to as inflammation. The central nervous system (brain and spinal cord; CNS) are believed to do the same sort action with different types of cells. One of the main immune cells in the CNS is microglia, a type of brain cell that, when activated, signals other immune cells to help the brain fight diseases. This action is similar to how the body fights infection. Therefore, '''neuroinflammation''' is described as a combination of microglial activation and its response.<ref>Graeber, M. B., Li, W., & Rodriguez, M. L. (2011). Role of microglia in CNS inflammation. FEBS letters, 585(23), 3798-3805.</ref>

==Evidence==
===Immune and Brain Interaction===
Research has shown that the brain and the immune system communicate through the vagus nerve<ref name="Goehler et al. 1997">Goehler, L. E., Relton, J. K., Dripps, D., Kiechle, R., Tartaglia, N., Maier, S. F., & Watkins, L. R. (1997). Vagal paraganglia bind biotinylated interleukin-1 receptor antagonist: a possible mechanism for immune-to-brain communication. Brain research bulletin, 43(3), 357-364</ref>. , a highly branched nerve that controls several systems of the body including sensory information to and from the heart, lungs and stomach, muscle movement including speech, homeostatic control of the heart, lungs and stomach, in addition to its effects in the immune system<ref>https://www.medicalnewstoday.com/articles/318128.php</ref>. When the body is infected by a foreign substance such as bacteria or a virus, the blood has sensors called macrophages floating around to detect the contaminate. The macrophages release the protein interleukin-1 beta (IL-1B) to start signaling the brain that there is a contagion present. This protein attaches to nearby vagus nerve protein receptors and upon connection, the vagus nerve alerts the brain to begin fighting off the bacteria or virus at this location. Activation of the vagus nerve in this manner causes the body to experience typical behaviors of a sick person such as sensitivity to pain stimuli, decreased appetite, and fever, all of which are regulated by the nerve<ref name="Goehler et al. 1997">Goehler, L. E., Relton, J. K., Dripps, D., Kiechle, R., Tartaglia, N., Maier, S. F., & Watkins, L. R. (1997). Vagal paraganglia bind biotinylated interleukin-1 receptor antagonist: a possible mechanism for immune-to-brain communication. Brain research bulletin, 43(3), 357-364</ref>.

Signaling along the vagus nerve pathway does not occur in isolation; when the nerve is firing in the brain, other neuronal cells also start to function in coordination. Glia, a different type of brain cell that lie adjacent to nerves and neurons in the brain, also becomes activated. The problem with activating the glial is that it can also trigger more cells to start functioning<ref>Ren, K., and Dubner, R. (2008). Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr. Opin. Anaesthesiol. 21, 570–579.</ref>. Continued activation of this pathway could cause dysfunction leading to symptoms present in chronic fatigue syndrome, including neuroinflammation<ref>VanElzakker, M. B. (2013). Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis. Medical hypotheses, 81(3), 414-423.</ref>.

==Causes==
===Oxidative and Nitrosative Stress===
One possible for what may cause the inflamed cells in the brain follows a oxygen and nitrogen molecules. An overabundance of oxygen and nitrogen molecules in tissues can cause oxidative and nitrosative stress. The build-up causes negative chemical reaction between the tissues and the molecules leading to tissue damage. This relates to neuroinflammation because researchers propose a link between the dysfunction of brain tissues in ME/CFS and the breakdown of the oxidative and nitrosative stress pathway. This pathway helps maintain the blood brain barrier, an important membrane keeping the brain protected from harmful substances present in the blood.When the pathway is dysfunctional, the blood-brain barrier becomes less effective at keeping out particles. This loss of efficacy could lead to immune cells entering the brain and beginning an immune response that leads to inflammation (e.g. neuroinflammation). <ref>Morris, G., and Maes, M. (2014). Oxidative and nitrosative stress and immune-inflammatory pathways in patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Current neuropharmacology, 12(2), 168-185.</ref>

==Notable studies==
*Autopsies of four deceased ME patients showed various pathological phenomena in the central and peripheral nervous systems. <ref>[http://www.meassociation.org.uk/research2015/current-research2015/pathology-of-cfs205/ Pathology of CFS: Pilot Study of Four Autopsy Cases - Dec. 2010]</ref>
*Brain Scans of [[ME/CFS]] from [[Stanford ME/CFS Initiative]] show inflammation. The New York Times article "Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder" has startling color images.<ref>[http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chronic-fatigue-syndrome-offer-clues-about-disorder/?_r=0 Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder]</ref>

==Talks & interviews==
*2016, [https://www.youtube.com/watch?v=1p6UojKL010 Do you have a hot brain?]
*2016, [https://www.youtube.com/watch?v=_ijlkRwORfM&feature=youtu.be What is neuroinflammation?] ([[Jarred Younger]])

==Learn more==
*[https://en.wikipedia.org/wiki/Neuroinflammation Wikipedia - Neuroinflammation]

== See also ==
*[[Jarred Younger]]
*[[Brain imaging]]

==References==
<references />

[[Category:Body systems]]

Neuroinflammation

2018-06-25T05:32:42Z

Sbrumfie:I am updating this page

A concrete definition for neuroinflammation is not fully agreed on in the scientific world yet, but it is thought to follow similar patterns that inflammation in the rest of the body follows. Inflammation, in general, occurs when a pathogen, or something foreign to the body, gets into the body. The body detects the toxin with immune cells which then signal other immune cells to help eliminate the pathogen. The response and build-up of these immune cells is what is referred to as inflammation. The central nervous system (brain and spinal cord; CNS) are believed to do the same sort action with different types of cells. One of the main immune cells in the CNS is microglia, a type of brain cell that, when activated, signals other immune cells to help the brain fight diseases. This action is similar to how the body fights infection. Therefore, '''neuroinflammation''' is described as a combination of microglial activation and its response.<ref>Graeber, M. B., Li, W., & Rodriguez, M. L. (2011). Role of microglia in CNS inflammation. FEBS letters, 585(23), 3798-3805.</ref>

==Evidence==
===Immune and Brain Interaction===
Research has shown that the brain and the immune system communicate through the vagus nerve<ref name="Goehler et al. 1997">Goehler, L. E., Relton, J. K., Dripps, D., Kiechle, R., Tartaglia, N., Maier, S. F., & Watkins, L. R. (1997). Vagal paraganglia bind biotinylated interleukin-1 receptor antagonist: a possible mechanism for immune-to-brain communication. Brain research bulletin, 43(3), 357-364</ref>. , a highly branched nerve that controls several systems of the body including sensory information to and from the heart, lungs and stomach, muscle movement including speech, homeostatic control of the heart, lungs and stomach, in addition to its effects in the immune system<ref>https://www.medicalnewstoday.com/articles/318128.php</ref>. When the body is infected by a foreign substance such as bacteria or a virus, the blood has sensors called macrophages floating around to detect the contaminate. The macrophages release the protein interleukin-1 beta (IL-1B) to start signaling the brain that there is a contagion present. This protein attaches to nearby vagus nerve protein receptors and upon connection, the vagus nerve alerts the brain to begin fighting off the bacteria or virus at this location. Activation of the vagus nerve in this manner causes the body to experience typical behaviors of a sick person such as sensitivity to pain stimuli, decreased appetite, and fever, all of which are regulated by the nerve<ref name="Goehler et al. 1997">Goehler, L. E., Relton, J. K., Dripps, D., Kiechle, R., Tartaglia, N., Maier, S. F., & Watkins, L. R. (1997). Vagal paraganglia bind biotinylated interleukin-1 receptor antagonist: a possible mechanism for immune-to-brain communication. Brain research bulletin, 43(3), 357-364</ref>.

Signaling along the vagus nerve pathway does not occur in isolation; when the nerve is firing in the brain, other neuronal cells also start to function in coordination. Glia, a different type of brain cell that lie adjacent to nerves and neurons in the brain, also becomes activated. The problem with activating the glial is that it can also trigger more cells to start functioning<ref>Ren, K., and Dubner, R. (2008). Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr. Opin. Anaesthesiol. 21, 570–579.</ref>. Continued activation of this pathway could cause dysfunction leading to symptoms present in chronic fatigue syndrome, including neuroinflammation<ref>VanElzakker, M. B. (2013). Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis. Medical hypotheses, 81(3), 414-423.</ref>.

Neuroinflammation is inflammation of the nervous tissue, particularly the brain. Inflammation has been found in autopsies of [[ME/CFS]] patients. ME/CFS patients also have [[microglia]] activation.<ref>http://www.ncbi.nlm.nih.gov/pubmed/24665088</ref>

==Notable studies==
*Autopsies of four deceased ME patients showed various pathological phenomena in the central and peripheral nervous systems. <ref>[http://www.meassociation.org.uk/research2015/current-research2015/pathology-of-cfs205/ Pathology of CFS: Pilot Study of Four Autopsy Cases - Dec. 2010]</ref>
*Brain Scans of [[ME/CFS]] from [[Stanford ME/CFS Initiative]] show inflammation. The New York Times article "Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder" has startling color images.<ref>[http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chronic-fatigue-syndrome-offer-clues-about-disorder/?_r=0 Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder]</ref>

==Talks & interviews==
*2016, [https://www.youtube.com/watch?v=1p6UojKL010 Do you have a hot brain?]
*2016, [https://www.youtube.com/watch?v=_ijlkRwORfM&feature=youtu.be What is neuroinflammation?] ([[Jarred Younger]])

==Learn more==
*[https://en.wikipedia.org/wiki/Neuroinflammation Wikipedia - Neuroinflammation]

== See also ==
*[[Jarred Younger]]
*[[Brain imaging]]

==References==
<references />

[[Category:Body systems]]

Neuroinflammation

2018-06-25T03:51:07Z

Sbrumfie:I am updating this page

Neuroinflammation

2018-06-25T03:45:21Z

Sbrumfie:I am updating this page

Neuroinflammation

2018-06-25T03:42:22Z

Sbrumfie:I am updating this page

Neuroinflammation

2018-06-25T03:39:41Z

Sbrumfie:I am inputting more information about what neuroinflammation is and how it works in chronic fatigue syndrom

'''A concrete definition for neuroinflammation is not fully agreed on in the scientific world yet, but it is thought to follow similar patterns that inflammation in the rest of the body follows. Inflammation, in general, occurs when a pathogen, or something foreign to the body, gets into the body. The body detects the toxin with immune cells which then signal other immune cells to help eliminate the pathogen. The response and build-up of these immune cells is what is referred to as inflammation. The central nervous system (brain and spinal cord; CNS) are believed to do the same sort action with different types of cells. One of the main immune cells in the CNS is microglia, a type of brain cell that, when activated, signals other immune cells to help the brain fight diseases. This action is similar to how the body fights infection. Therefore, neuroinflammation is described as a combination of microglial activation and its response.

Neuroinflammation''' is inflammation of the nervous tissue, particularly the brain. Inflammation has been found in autopsies of [[ME/CFS]] patients. ME/CFS patients also have [[microglia]] activation.<ref>http://www.ncbi.nlm.nih.gov/pubmed/24665088</ref>

==Notable studies==
*Autopsies of four deceased ME patients showed various pathological phenomena in the central and peripheral nervous systems. <ref>[http://www.meassociation.org.uk/research2015/current-research2015/pathology-of-cfs205/ Pathology of CFS: Pilot Study of Four Autopsy Cases - Dec. 2010]</ref>
*Brain Scans of [[ME/CFS]] from [[Stanford ME/CFS Initiative]] show inflammation. The New York Times article "Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder" has startling color images.<ref>[http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chronic-fatigue-syndrome-offer-clues-about-disorder/?_r=0 Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder]</ref>

==Talks & interviews==
*2016, [https://www.youtube.com/watch?v=1p6UojKL010 Do you have a hot brain?]
*2016, [https://www.youtube.com/watch?v=_ijlkRwORfM&feature=youtu.be What is neuroinflammation?] ([[Jarred Younger]])

==Learn more==
*[https://en.wikipedia.org/wiki/Neuroinflammation Wikipedia - Neuroinflammation]

== See also ==
*[[Jarred Younger]]
*[[Brain imaging]]

==References==
<references />

[[Category:Body systems]]