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Autoimmunity

Aka: Autoimmunity, Autoimmune Condition, Autoimmune Disease, Self-Tolerance, Central Tolerance to Self Antigen, Peripheral Tolerance to Self Antigen, Regulatory T-Cell, Autoreactive Lymphocyte, Tolerance Induction to Self Antigen, Autosensitivity
  1. Epidemiology
    1. Women account for 75% of Autoimmunity
    2. Age of onset is most common in young adult women
  2. Physiology: Self-Tolerance
    1. Background
      1. Self-Tolerance prevents immune response to self-Antigens (body fighting itself)
    2. Central Tolerance (eliminate autoreactive cells that attack self)
      1. T-Cells (Thymus)
        1. Autoreactive T-Cells are eliminated (apoptosis) before release into peripheral circulation (negative selection)
        2. Lower affinity autoreactive T-Cells are released into circulation as Regulatory T Cells for peripheral tolerance
      2. B-Cells (Bone Marrow)
        1. Autoreactive B-Cells are eliminated (apoptosis) before release into peripheral circulation (negative selection) OR
        2. Receptor Editing allows B Cells to redefine Ig Light chain, and therefore no longer self-reactive
    3. Peripheral Tolerance (immunologically deactive autoreactive cells)
      1. T-Cells
        1. Deletion: Autoreactive cells are killed (apoptosis)
        2. Anergy: Autoreactive T-Cells become inactive, unresponsive to Antigen stimulation
        3. Suppression: Regulatory T-Cells inhibit autoreactive T-Cells, preventing self-Antigen reaction
      2. B-Cells
        1. T-Helper Cells are typically absent for self-Antigen, and the autoreactive B-Cells remain inactive or die
  3. Risk Factors
    1. Genetic Predisposition to Autoimmunity
      1. Major Histocompatibility Complex (MHC) Defects - Human Leukocyte Antigen (HLA) I and II specific allotypes
        1. Example: Type 1 Diabetes Mellitus is associated with DR3 and DR4 HLA types
      2. Non-MHC Genetic Defects
        1. Example: Autoimmune Lymphoproliferative Syndrome is associated with Fas Gene Mutation
    2. Environmental Predisposition to Autoimmunity
      1. Infectious Disease (e.g. Coxsackie Virus B and Type 1 Diabetes Mellitus)
  4. Mechanism
    1. Mediators of Autoimmunity
      1. T-Cell mediated self tissue destruction
        1. Autoreactive CD4+ T Cells (with or without CD8+ T Cells)
      2. Autoantibody
        1. IgG Antibody produced in autoreactive B Cells and facilitated by autoreactive Autoreactive CD4+ T Cells
    2. Mechanisms
      1. Molecular mimicry
        1. Microbes (Strep. pyogenes) presents Antigen similar to human organ Antigens (e.g. Heart Valves)
        2. T-Cells and B-Cells respond to microbe Antigens, but also respond to other host tissue Antigens
      2. Polyclonal Lymphocyte activation
        1. Polyclonal activators (e.g. EBV, CMV) non-specifically activate B-Cells including autoreactive cells
        2. Other polyclonal activators (e.g. lectin plant protein including PHA) activate T Cells
      3. Sequestered Antigen Release
        1. Non-exposed tissue Antigens (e.g. behind blood-brain barrier) may be exposed with injury (e.g. Head Injury)
      4. Antigen Spreading
        1. Initial auoreactive B-Cells and T-Cells respond to a single host tissue Antigen
        2. With injury and inflammation, additional host Antigens are exposed and become targets of Autoimmunity
    3. Predisposing factors
      1. Autoimmunity increases with age: lower self tolerance
      2. Genetic predisposition
    4. Protective factors
      1. Autoimmunity less common where high Antigen exposure
      2. Protective exposures in first year of life
        1. Eating dirt
        2. Living on a farm
        3. House pet
        4. Day care
      3. References
        1. Weiss (2002) N Engl J Med 347:930 [PubMed]
  5. Associated Conditions: Dermatologic Autoimmune Conditions
    1. Psoriasis
    2. Dermatitis herpeteformis
    3. Pemphigus Vulgaris
    4. Vitiligo
    5. Alopecia Areata
  6. Associated Conditions: Endocrine Autoimmune Conditions
    1. Insulin Dependent Diabetes Mellitus
      1. Autoantibody to Pancreatic Beta Cell Antigens
    2. Grave's Disease
      1. Autoantibody: TSH Receptor Antibody (Thyroid Stimulating Immunoglobulin)
    3. Hashimoto's Thyroiditis
      1. Autoantibody: Antithyroid Peroxidase Antibody (TPO Antibody) and Antithyroglobulin Antibody (TgAb)
      2. Thyroid tissue infiltration and destruction by B-Cells and CD4+ T Cells
    4. Addison's Disease
      1. Autoantibody to Adrenal cytoplasmic P450 Antigens
  7. Associated Conditions: Gastrointestinal Autoimmune Conditions
    1. Crohn's Disease
    2. Ulcerative Colitis
    3. Primary Biliary Cirrhosis
      1. Autoantibody to Centromere
    4. Autoimmune Hepatitis
      1. Autoantibody to hepatocyte Antigens
  8. Associated Conditions: Hematologic Autoimmune Conditions
    1. Autoimmune Hemolytic Anemia
    2. Autoimmune Thrombocytopenia
    3. Pernicious Anemia
      1. Autoantibody to Gastrointestinal Intrinsic Factor and parietal cells
  9. Associated Conditions: Musculoskeletal Autoimmune Conditions
    1. Ankylosing Spondylitis
    2. Systemic Lupus Erythematosus
      1. Autoantibody to nuclear and ribosomal Antigens (dsDNA, SS-A or Ro, SS-B or La, Smith, DNA-Histone)
    3. Drug-induced Lupus
      1. Autoantibody to nuclear Antigens (dsDNA, DNA-Histone)
    4. Rheumatoid Arthritis
      1. Predisposition in patients with HLA-DR4 haplotypes (MHC Class 2)
      2. Autoantibody to nuclear Antigens (rheumatoid-associated nuclear Antigen, Ribonucleoprotein, DNA-Histone)
      3. Autoantibodies to IgG as well as IgM and IgA (Rheumatoid Factors)
        1. Autoantibody binding to Fc region of IgG results in Complement Activation and host tissue destruction
    5. Scleroderma (Systemic Sclerosis, also part of CREST Syndrome)
      1. Autoantibody to nucleolar Antigens (nucleolar-specific RNA, centromere, Ribonucleoprotein, Scl-70/Topisomerase)
    6. Polymyositis
      1. Autoantibody to nuclear Antigens (PM-Scl, Jo-1, Ribonucleoprotein)
    7. Dermatomyositis
      1. Autoantibody to nuclear Antigens (Jo-1, Mi-2)
    8. Sjogren's Syndrome
      1. Autoantibody to nuclear Antigens and cytoplasmic Antigens
  10. Associated Conditions: Neurologic Autoimmune Conditions
    1. Guillain-Barre Syndrome
    2. Multiple Sclerosis
      1. Autoantibody to brain and spinal cord myelin proteins
    3. Myasthenia Gravis
      1. Autoantibody to acetylcholine receptor on Muscle Cells
  11. Associated Conditions: Vascular Autoimmune Conditions
    1. Temporal Arteritis
    2. Anti-phospholipid Syndrome
    3. Granulomatosis with Polyangiitis (previously known as Wegener's Granulomatosis)
    4. Behcet's Syndrome
    5. Rheumatic Fever
      1. Autoantibody to myocardial and valvular Antigens (cross reactive to Group A Streptococcal Antigens)
  12. Associated Conditions: Miscellaneous
    1. Goodpasture Syndrome
      1. Autoantibody to Renal and Lung Type IV Collagen
  13. References
    1. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL, p. 32-40
    2. Zuber (2003) AAFP Board Review, Seattle

Autoimmune Diseases (C0004364)

Definition (MEDLINEPLUS)

Your body's immune system protects you from disease and infection. But if you have an autoimmune disease, your immune system attacks healthy cells in your body by mistake. Autoimmune diseases can affect many parts of the body.

No one is sure what causes autoimmune diseases. They do tend to run in families. Women - particularly African-American, Hispanic-American, and Native-American women - have a higher risk for some autoimmune diseases.

There are more than 80 types of autoimmune diseases, and some have similar symptoms. This makes it hard for your health care provider to know if you really have one of these diseases, and if so, which one. Getting a diagnosis can be frustrating and stressful. Often, the first symptoms are fatigue, muscle aches and a low fever. The classic sign of an autoimmune disease is inflammation, which can cause redness, heat, pain and swelling.

The diseases may also have flare-ups, when they get worse, and remissions, when symptoms get better or disappear. Treatment depends on the disease, but in most cases one important goal is to reduce inflammation. Sometimes doctors prescribe corticosteroids or other drugs that reduce your immune response.
Definition (NCI_CTCAE) A disorder resulting from loss of function or tissue destruction of an organ or multiple organs, arising from humoral or cellular immune responses of the individual to his own tissue constituents.
Definition (NCI) A disorder resulting from loss of function or tissue destruction of an organ or multiple organs, arising from humoral or cellular immune responses of the individual to his own tissue constituents. It may be systemic (e.g., systemic lupus erythematosus), or organ specific, (e.g., thyroiditis).
Definition (NCI_NCI-GLOSS) A condition in which the body recognizes its own tissues as foreign and directs an immune response against them.
Definition (MSH) Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
Definition (CSP) heading term for a diverse group of disorders characterized by pathologenic immune reactions to autologous (self) tissue; for nonnpatholgical, developmental, or phenomenological aspects of autoimmunity, use AUTOIMMUNITY.
Concepts Disease or Syndrome (T047)
MSH D001327
ICD10 M30-M36
SnomedCT 191006002, 85828009
LNC LP128504-0, LP130888-3, MTHU040269, MTHU040494
English Autoimmune Diseases, Disease, Autoimmune, Diseases, Autoimmune, autoimmune disorder, AUTOIMMUNE DISEASE, AUTOIMMUNE DISORDER NOS, AUTOIMMUNE DIS, autoimmune disease (diagnosis), autoimmune disease, Autoimmune disorder NOS, Autoimmune disorders, Autoimmune disease NOS, autoimmune disease NOS, Autoimmune Diseases [Disease/Finding], autoimmune diseases, autoimmune disorders, Autoimmune Disease, Autoimmune disease NOS (disorder), Autoimmune diseases, DISEASE, AUTOIMMUNE, Autoimmune disease, Autoimmune disorder, Autoimmune disease (disorder), Autoimmune disease, NOS, Autoimmune disorder, NOS, Autoimmune Disorders, Autoimmune Disorder
Italian Patologia autoimmune, Patologie autoimmuni, Patologia autoimmune NAS, Malattie autoimmuni
Dutch auto-immuunziekte NAO, auto-immuunziekten, auto-immuunziekte, Auto-immuunziekte, Auto-immuunziekten, Immuunziekte, auto-, Ziekte, auto-immuun-, Ziekten, auto-immuun-
French Troubles auto-immuns SAI, DESORDRES AUTO-IMMUNS SAI, Trouble auto-immun, Troubles auto-immuns, Maladies autoimmunes, Maladies auto-immunes
German Autoimmunerkrankung NNB, Autoimmunerkrankung, Autoimmunstoerungen, Autoimmunkrankheiten, Krankheiten, Autoimmun-
Portuguese Doença auto-imune NE, DOENCA AUTOIMUNE, Doenças Autoimunes, Afecções auto-imunes, Doença auto-imune
Spanish Trastorno autoinmune NEOM, enfermedad autoinmune, enfermedad autoinmunitaria, SAI (trastorno), enfermedad autoinmunológica, SAI, enfermedad autoinmunitaria, SAI, Trastornos autoinmunes, Trastorno autoinmune, enfermedad autoinmune (trastorno), enfermedad autoinmunológica, SAI (trastorno), trastorno autoinmune, enfermedad autoinmunitaria (trastorno), enfermedad autoinmunitaria, Enfermedades Autoinmunes
Japanese 自己免疫障害, 自己免疫障害ＮＯＳ, ｼﾞｺﾒﾝｴｷｼｮｳｶﾞｲNOS, ｼﾞｺﾒﾝｴｷｼｮｳｶﾞｲ
Swedish Autoimmuna sjukdomar
Czech autoimunitní nemoci, Autoimunitní onemocnění NOS, Poruchy autoimunity, Autoimunitní onemocnění
Finnish Autoimmuunitaudit
Russian AUTOIMMUNNYE BOLEZNI, АУТОИММУННЫЕ БОЛЕЗНИ
Croatian AUTOIMUNOSNE BOLESTI
Polish Choroby autoimmunizacyjne, Choroby z autoagresji
Hungarian Autoimmun betegség, Autoimmun betegségek, Autoimmun betegség k.m.n.
Norwegian Autoimmune sykdommer, Autoimmun sykdom
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Autoimmunity (C0004368)

Definition (NCI) Autoimmune Status; the state of a person's health in regard to autoimmune disease or antibody presence.
Definition (MSH) Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
Definition (CSP) developmentally complex, not necessarily pathological, possibly pervasive, cell or humoral immune system reactivity toward autologous (self) antigens; do not confuse with AUTOIMMUNE DISORDER.
Concepts Pathologic Function (T046)
MSH D015551
SnomedCT 4301008
English Autoimmunities, Autoimmunity, self recognition (immune), autoimmunity, autoimmunities, Autoimmune state (finding), Autoimmune state, Autoimmune state, NOS, Autoimmunity, NOS, Autoimmune Status
Swedish Autoimmunitet
Czech autoimunita
Finnish Autoimmuniteetti
French Auto-immunité, Autoimmunité
Russian AUTOIMMUNITET, АУТОИММУНИТЕТ
Spanish estado autoinmunitario (hallazgo), estado autoinmune (hallazgo), estado autoinmunitario, estado autoinmune, autoinmunidad, Autoinmunidad
Portuguese Autoimunidade, Reação Autoimune
Croatian AUTOIMUNOST
Polish Odpowiedź autoimmunizacyjna, Autoodporność, Odpowiedź autoodpornościowa
Norwegian Autoimmunitet
German Autoimmunisierung
Dutch Auto-immuniteit
Italian Autoimmunità
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Regulatory T-Lymphocytes (C0039198)

Definition (MSH) CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Concepts Cell (T025)
MSH D050378
Russian T-ЛИМФОЦИТЫ РЕГУЛЯТОРНЫЕ, СУПРЕССОРЫ-ЭФФЕКТОРЫ T-ЛИМФОЦИТЫ, SUPRESSORY-EFFEKTORY T-LIMFOTSITY, T-KLETKI, SUPRESSORY-INDUKTORY, T-LIMFOTSITY, SUPRESSORY-EFFEKTORY, T-KLETKI, SUPRESSORY-EFFEKTORY, T-KLETKI REGULIATORNYE, T-LIMFOTSITY, SUPRESSORY-INDUKTORY, REGULIATORNYE T-LIMFOTSITY, T-LIMFOTSITY REGULIATORNYE, KLETKI SUPRESSORY, T-KLETKI-SUPRESSORY, TH3 KLETKI, T-LIMFOTSITY-SUPRESSORY, T-КЛЕТКИ, СУПРЕССОРЫ-ИНДУКТОРЫ, T-КЛЕТКИ, СУПРЕССОРЫ-ЭФФЕКТОРЫ, T-ЛИМФОЦИТЫ-СУПРЕССОРЫ, T-ЛИМФОЦИТЫ, СУПРЕССОРЫ-ИНДУКТОРЫ, T-ЛИМФОЦИТЫ, СУПРЕССОРЫ-ЭФФЕКТОРЫ, T-КЛЕТКИ-СУПРЕССОРЫ, TH3 КЛЕТКИ, КЛЕТКИ СУПРЕССОРЫ, РЕГУЛЯТОРНЫЕ Т-ЛИМФОЦИТЫ, Т-КЛЕТКИ РЕГУЛЯТОРНЫЕ
English REG T LYMPHOCYTES, T LYMPHOCYTES REG, LYMPHOCYTES J REGULATORY, T CELLS REG, REG T CELLS, Treg Cells, Cells, Treg, Treg Cell, Cell, Treg, T-Lymphocytes, Regulatory, Regulatory T-Lymphocyte, T Lymphocytes, Regulatory, T-Lymphocyte, Regulatory, Regulatory T Cells, Regulatory T Lymphocytes, Regulatory T-Cells, T Cells, Regulatory, T-Cells, Regulatory, Regulatory T-Lymphocytes
Czech supresorové buňky, T-lymfocyty regulační, regulační T-buňky
Portuguese Células T Reguladoras, Células T Regulatórias, Linfócitos T Reguladores
Spanish Células T Regulatorias, Linfocitos Th3, Linfocitos T Supresores de Ocurrencia Natural, Linfocitos T Reguladores, Células T Reguladoras
Finnish Säätelevät T-imusolut
French Thymocytes régulateurs, Cellules T régulatrices, Lymphocytes T régulateurs
German Treg-Zellen, LYMPHOZYTEN J REGULATORISCHE, T-Lymphozyten, regulatorische, Regulatorische T-Lymphozyten, Regulatorische T-Zellen, T-Zellen, regulatorische
Japanese サプレッサー細胞, T細胞-サプレッサーインデューサー, サプレッサーエフェクターTリンパ球, サプレッサーインデューサーT細胞, T細胞-サプレッサーエフェクタ, Tリンパ球-サプレッサーエフェクタ, Tリンパ球-調節, T細胞-サプレッサーインデューサ, Tリンパ球-サプレッサーエフェクター, 制御性T細胞, リンパ球-T-サプレッサーインデューサー, リンパ球-T-調節, サプレッサ細胞, T細胞-サプレッサーエフェクター, T細胞-調節, サプレッサーエフェクターT細胞, サプレッサーインデューサーTリンパ球, 抑制T細胞, サプレッサーT細胞, サプレッサーインデューサTリンパ球, サプレッサーエフェクタT細胞, 調節Tリンパ球, T細胞-サプレッサー, Tリンパ球-サプレッサーインデューサー, サプレッサーインデューサT細胞, サプレッサーエフェクタTリンパ球, 調節T細胞, Suppressor T細胞
Swedish T-lymfocyter, regulatoriska
Italian Cellule Treg, Cellute T regolatrici, Linfociti T regolatori
Croatian T-LIMFOCITI, REGULACIJSKI
Polish Limfocyt T supresorowy, Limfocyt T regulatorowy, Limfocyty T supresorowe, Limfocyty Treg, Limfocyty T regulatorowe
Norwegian T-celler, regulatoriske, Regulatoriske T-lymfocytter, Regulatoriske T-celler, Treg-celler, T-lymfocytter, regulatoriske
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Autosensitivity (C0301927)

Concepts Pathologic Function (T046)
SnomedCT 62978008
English Autosensitivity, Autosensitivity (finding), Autosensitivity, NOS
Spanish autosensibilidad (hallazgo), autosensibilidad, isosensibilidad
Sources
Derived from the NIH UMLS (Unified Medical Language System)


peripheral tolerance induction to self antigen (C1817918)

Definition (GO) Tolerance induction to self antigens in the peripheral lymphoid tissues: blood, lymph nodes, spleen, and mucosal-associated lymphoid tissues. [GOC:jal, ISBN:0781735149]
Concepts Organism Function (T040)
English peripheral tolerance induction to self antigen
Sources
Derived from the NIH UMLS (Unified Medical Language System)


tolerance induction (C1817959)

Definition (GO) A process that directly activates any of the steps required for tolerance, a physiologic state in which the immune system does not react destructively against the components of an organism that harbors it or against antigens that are introduced to it. [GO_REF:0000022, GOC:jal, GOC:mtg_15nov05, ISBN:0781735149]
Concepts Biologic Function (T038)
English tolerance induction
Sources
Derived from the NIH UMLS (Unified Medical Language System)


central tolerance induction to self antigen (C1817961)

Definition (GO) Tolerance induction in the central lymphoid organs directed at self antigens. [GOC:jal, ISBN:0781735149, PMID:16460922]
Concepts Biologic Function (T038)
English central tolerance induction to self antigen
Sources
Derived from the NIH UMLS (Unified Medical Language System)


tolerance induction to self antigen (C1817965)

Definition (GO) Tolerance induction directed at self antigens. [GO_REF:0000022, GOC:jal, GOC:mtg_15nov05, ISBN:0781735149]
Concepts Biologic Function (T038)
English tolerance induction to self antigen
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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