Autoimmune Diseases Autoimmune Diseases Presented By Dr. Manal Yassin

Self Tolerance (natural tolerance): It is a physiological mechanism through which the immune system is unable to react against self antigens. Thousands of autoreactive T &. B cell clones are continuously generated by body that if they have the chance they are capable to react against self antigens. However, the cells are prevented from doing so by two main mechanisms:

Central tolerance (clonal deletion): Any immature self reactive T and B cell clones once generated are deleted by apoptosis. This mechanism takes place in the central lymphoid organs i.e. thymus and bone marrow. Peripheral tolerance (clonal anergy): Peripheral tolerance is induced when mature autoreactive lymphocytes recognized self-antigens in the peripheral tissues.

Etiology of Autoimmune diseases: Cytokine imbalance due to a defect in regulating Thl/Th2 response. Reveal of hidden or sequestered antigens as a result of trauma, surgery or infection. Alteration of self antigens which could result from: Physical agents as radiation Chemical agents or drugs as penicillin (hapten) that binds to tissue antigens, and causes hemolytic anemia Infections as TB. or viral infections which may “break” T cell anergy.

Cross reactive antigens, e. g Cross reactive antigens, e.g., an antibody (heterophile Ab) formed to a foreign antigen reacts with self antigen that shares some antigenic determinants with the foreign antigen as in rheumatic fever or glomerulonephritis following streptococcal sore throat. Some foreign antigens may share determinants with self HLA molecules. This is called (molecular mimicry). Deficiency of complement, congenital or acquired, impairs clearance of immune complexes which may be deposited in various organs or tissues.

Genetically inherited defects: This is evident as autoimmune diseases run in families and are associated with particular HLA types, e.g.: B27 in ankylosing spondylitis DR3 in insulin dependent diabetes DR4 in rheumatoid arthritis Personal factors: Age: The frequency of autoimmune diseases increase in old age. Sex: Autoimmune diseases tend to be frequent in females.

Mechanisms of tissue damage in autoimmunity: Type II hypersensitivity e.g. (autoimmune hemolytic anemia, drug induced hemolytic anemia, thrombocytopenia and agranulocytopenia) Type III hypersensitivity reaction e.g. systemic lupus erythematosus (SLE). Type IV (cell mediated) e.g., autoimmune thyroiditis (Hashimoto's disease).

Types of Autoimmune diseases: Organ confined: e.g. hemolytic anemia, Graves disease. Systemic disease: Abnormal immune response occurs against antigen not- localized in one organ as SLE (auto Ab against DNA) and rheumatoid arthritis (auto-Ab IgM against FC of IgG).

Diagnosis of Autoimmune diseases: General diagnosis: Elevated serum Igs. Decreased serum complement Detection of circulatory ICs. Decreased levels of Ts cells. Specific diagnosis: Detection of specific auto Abs e.g., anti DNA in SLE. Detection of ICs deposition in tissues by biopsy. Treatment: Metabolic control may be effective in certain organ-specific diseases, e.g., antithyroid drugs in Graves’disease. Immunosuppressive therapy and anti-inflammatory drugs.

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