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{{Cleanup | date = February 2019|reason=Citations are needed for much of the information}} 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 name="Chaplin2010">{{Cite journal | last = Chaplin | first = David D. | date = Feb 2010 | 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=2923430|pmid=20176265}}</ref><ref>{{Cite web | url = https://www.hopkinsmedicine.org/healthlibrary/conditions/infectious_diseases/immune_system_85,P00630 | title = Immune System | website = Johns Hopkins Medicine Health Library|access-date=2019-02-27}}</ref> The [[brain]] and [[spinal cord]] have their own immune system.<ref name="SCI-immune">{{Cite journal | title = Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution | date = Feb 2019|url=https://www.nature.com/articles/s41586-019-0924-x|journal=Nature|volume=566|issue=7744|pages=388–392|last=Masuda | first = Takahiro|author-link=|last2=Sankowski | first2 = Roman | author-link2 = |last3=Staszewski | first3 = Ori|author-link3=|last4=Böttcher | first4 = Chotima|author-link4=|last5=Amann | first5 = Lukas|author-link5=|last6=Sagar | first6 = |author-link6=|last7=Scheiwe | first7 = Christian|last8=Nessler | first8 = Stefan|last9=Kunz | first9 = Patrik|last10=van Loo|first10=Geert|last11=Coenen|first11=Volker Arnd|language=en|doi=10.1038/s41586-019-0924-x|pmc=|pmid=|access-date=|issn=1476-4687|quote=|via=}}</ref><ref name="Ampie2022">{{Cite journal | title = Immunological defense of CNS barriers against infections | date = 2022-05-10|url=https://www.sciencedirect.com/science/article/pii/S1074761322001832|journal=Immunity|volume=55|issue=5|pages=781–799|last=Ampie | first = Leonel|last2=McGavern | first2 = Dorian B.|language=en|doi=10.1016/j.immuni.2022.04.012|issn=1074-7613}}</ref> [[Microglia]] cells are a part of that immune system.<ref name="Pruss2017">{{Cite journal | title = Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex | date = Nov 2017|url=https://www.nature.com/articles/nn.4643|journal=Nature Neuroscience|volume=20|issue=11|pages=1549–1559|last=Prüss | first = Harald|author-link=|last2=Tedeschi | first2 = Andrea | author-link2 = |last3=Thiriot | first3 = Aude|author-link3=|last4=Lynch | first4 = Lydia|author-link4=|last5=Loughhead | first5 = Scott M.|author-link5=|last6=Stutte | first6 = Susanne|author-link6=|last7=Mazo | first7 = Irina B.|last8=Kopp | first8 = Marcel A.|last9=Brommer | first9 = Benedikt|last10=Blex|first10=Christian|last11=Geurtz|first11=Laura-Christin|language=en|doi=10.1038/nn.4643|pmc=|pmid=|access-date=|issn=1546-1726|quote=|via=}}</ref><ref name="Ampie2022" /> Injury to the [[brain]] or [[spinal cord]], such as those caused by stroke or physical [[trauma]], result in a considerable weakening of the immune system.<ref name="Pruss2017" /> [[Myalgic encephalomyelitis]] (ME) is a complex multi-systemic disorder which causes [[Nervous system|neurological]] impairments, [[Portal:Energy metabolism|energy metabolism]]/[[ion transportation]] dysfunction, immune symptoms, [[Gastrointestinal system|gastrointestinal]] and/or genitourinary symptoms.<ref name="ICC">{{Cite journal | last = Carruthers | first = Bruce M. | authorlink = Bruce Carruthers | last2 = van de Sande | first2 = Marjorie I. | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Klimas | first4 = Nancy G. | author-link4 = Nancy Klimas | last5 = Broderick | first5 = Gordon | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = Terry | authorlink6 = Terry Mitchell | last7 = Staines | first7 = Donald | authorlink7 = Donald Staines | last8 = Powles | first8 = A.C. Peter | authorlink8 = A C Peter Powles | last9 = Speight | first9 = Nigel | author-link9 = Nigel Speight | last10 = Vallings | first10 = Rosamund | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = Lucinda | authorlink11 = Lucinda Bateman | last12 = Baumgarten-Austrheim | first12 = Barbara | authorlink12 = 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 = Jo Daehyun | 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> The [[Centers for Disease Control and Prevention]] (CDC) notes that [[ME/CFS]] impacts multiple body systems. These include the immune system, [[Metabolic|cellular metabolism]] abnormalities, [[neuroendocrine symptoms|neuroendocrine disturbances]], and [[blood pressure]] or heart rate regulation abnormalities.<ref name="etiology">{{Cite web | title = Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | url = https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=[[Centers for Disease Control and Prevention]] | date = 2018-11-08|access-date=2019-01-22|language=en-us|last=Centers for Disease Control and Prevention | first = |authorlink=Centers for Disease Control and Prevention|last2= | first2 = |authorlink2=|archive-url=|archive-date=|url-status=}}</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]]s and [[neutrophil]]s.<ref name="Walter2002">{{Cite book | 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 | chapter = Innate Immunity | url = https://www.ncbi.nlm.nih.gov/books/NBK26846/ | title = Molecular Biology of the Cell |edition=4th | editor-last = Alberts | editor-first = B | editor-last2 = Johnson | editor-first2 = A | editor-last3 = Lewis | editor-first3 = J | location = New York | publisher = Garland Science |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]]s.<ref>{{Cite journal | url = https://doi.org/10.1016/j.mattod.2015.01.019 | title = Biomaterial based modulation of macrophage polarization: a review and suggested design principles | journal = Materials Today | volume = 18 | issue = 6 | date = July–August 2015 | pages = 313-325 | first = Rukmani | last = Sridharan | first2 = Andrew R. | last2 = Cameron | first3 = Daniel J. | last3 = Kelly | first4 = Cathal J. | last4 = Kearney | first5 = Fergal J. | last5 = O'Brien |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 name="macrophages">{{Cite web | url = https://www.immunology.org/public-information/bitesized-immunology/cells/macrophages | title = Macrophages|website = British Society for Immunology|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 name="britannica">{{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 uses its [[adaptive immune system]] to attack the germs. After the initial exposure, the body's adaptive immune system "remembers" a specific signature on the germs so that it can be identified and eliminated quickly during all subsequent exposures.<ref name="NBK279396">{{Cite book | url =https://www.ncbi.nlm.nih.gov/books/NBK279396/ | title = The innate and adaptive immune systems | last = National Center for Biotechnology Information|location=|url-status=dead|archive-date=|archive-url= | date = 2016-08-04|publisher=Institute for Quality and Efficiency in Health Care|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.<ref name="NBK279396" /> 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="dendritic">{{Cite web | url = https://www.immunology.org/public-information/bitesized-immunology/cells/dendritic-cells | title = Dendritic Cells | website = British Society for Immunology|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 name="NBK279397">{{Cite book | url =https://www.ncbi.nlm.nih.gov/books/NBK279397/ | title = The defense mechanisms of the adaptive immune system | last = National Center for Biotechnology Information|location=Cologne, Germany | date = 2016-08-04|publisher=Institute for Quality and Efficiency in Health Care|language=en}}</ref>{{citation needed | date = 2021}} 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 cell|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, [[Cytotoxic 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="dendritic" /> 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 cell]]s 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="dendritic" /> ==Components of the Immune System== [[leukocyte|White blood cell]]s, 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 name="Shlomchik2001">{{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) === ====[[Granulocyte]]s==== [[Granulocyte]]s 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. ===== [[Basophil granulocyte|Basophils]] ===== [[Basophil granulocyte|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 [[Hashimoto's thyroiditis (hypothyroidism)|hypothyroidism]], and myeloproliferative disorders (blood disorders).{{citation needed | date = 2023}} ===== [[Eosinophil|Eosinophils]] ===== [[Eosinophil]]s 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. ===== [[Neutrophil|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 [[Tel:1500-8000|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. ==== [[Monocyte]]s ==== [[Monocyte]]s 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. ===== [[Macrophage]]s ===== [[Macrophage]]s 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 [[macrophage]]s exist in the different tissues in the body (e.g. liver or skin); they also are not necessarily derived from [[monocyte]]s circulating in the [[blood]]and lymph system. ===== Dendritic cells===== [[Dendritic cell]]s 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-cell]]s. 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 node]]s, 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 ME/CFS 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 sensitivities|food]] or [[Alcohol intolerance|alcohol intolerances]]<ref name="ICC" /> ==Myalgic encephalomyelitis== There is evidence of immune dysregulation in [[myalgic encephalomyelitis|Myalgic Encephalomyelitis]]:<ref name="ICC" /> * 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 states: <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 antibodies, anti-gliadin, anti-smooth muscle antibodies, and 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 | date = 2018-07-10 | website = [[Centers for Disease Control and Prevention]]|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 name="Zhang2018">{{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] - Medical News Today === Videos === More on the immune system: *[https://www.youtube.com/watch?v=GIJK3dwCWCw Crash Course - The Immune System Part 1] ([[Adaptive immune system]]) *[https://www.youtube.com/watch?v=2DFN4IBZ3rI Crash Course - The Immune System Part 2] ([[humoral immunity]] & [[B cell]]s) *[https://www.youtube.com/watch?v=rd2cf5hValM Crash Course - The Immune System Part 3] ([[cell-mediated immunity]] & [[T cell]]s) * [https://www.youtube.com/watch?v=FZxf1QDcEO0 Neutrophils and How White Blood Cells Work] - Neutrphils * [https://www.youtube.com/watch?v=3LNhUCLU3K8 Eosinophils] ==See also== *[[Adaptive immune system]] *[[Immune exhaustion hypothesis]] *[[Innate immune system]] *[[Major histocompatibility complex]] ==References== {{Reflist}} [[Category:Body systems]] [[Category:Immunology]]
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