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