Immune system

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 neurological impairments, energy metabolism/ion transport dysfunction, and immune, gastrointestinal and/or genitourinary symptoms.

Immune system symptoms
Symptoms related to M.E. include:
 * Flu-like symptoms (sore throat, 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 viruses, which last for a prolonged time
 * Gastro-intestinal problems, which may include nausea, abdominal bloating, or irritable bowel syndrome (IBS)
 * Needing to urinate either more urgently or more frequently, sometimes at night (nocturia)
 * New sensitivities to smells, chemicals, or medication; food or alcohol intolerances

Innate Immune System
Prior to actually getting into the body, 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 macrophages and 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- and 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 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.

Autoimmunity
ME/CFS patients have anti-cholinergic muscarinic, Β-adrenergic, phosphatidylinositol and serotonin antibodies when compared to healthy controls.

Myalgic Encephalomyelitis
There is evidence of immune dysregulation in Myalgic Encephalomyelitis.

Reduced natural killer cell function.

Elevated regulatory T cells

The Centers for Disease Control and Prevention ME/CFS page: "Immune system abnormalities – some people with ME/CFS have impaired natural killer cell function and/or T cell function, chronic higher production of inflammatory cytokines, and in some cases slight increase in some autoantibodies (rheumatic factor, anti-thyroid antibodies, anti-gliadin, anti-smooth muscle antibodies, and cold agglutinins)."

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: "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."There is ongoing immune system research of fibromyalgia.

Learn more

 * Crash Course - The Immune System Part 1 (Adaptive immune system)
 * Crash Course - The Immune System Part 2 (humoral immunity & B cells)
 * Crash Course - The Immune System Part 3 (cell-mediated immunity & T cells)