Tolerence and autoimmun diseases

Tolerence and autoimmun diseases - ‫بسم اللة...

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Unformatted text preview: ‫بسم اللة الرحمن‬ ‫الرحيم‬ Tolerance Tolerance And Autoimmune Diseases Tolerence Tolerence * It is a specific immunologic unresponsiveness i.e. the absence of specific immunoresponses to a particular antigen in a fully immunocomptent person * Unresponsiveness to self antigens is known as auto tolerance * Both B­cells and T­cells participate in tolerence * But T­cells play the primary role Central Tolerance Central Clonal–deletion: * The process by which T­cells acquire the ability to distinguish self from non self, in fetal thymus * This involves the killing of T­cells that react against antigens present in the fetus at that time Peripheral Tolerance Peripheral * T­cell tolerance (clonal anergy): * Some self­reactive T cells are not killed in thymus * Functional inactivation of surviving self­ reactive T cells Tolerance Tolerance * B­cells become tolerant to self by two mechanisms: 1) Clonal deletion Probably while B­cell precursors are in bon marrow 2) Clonal anergy B cells in the periphery * Tolerance in B­cells is less complete than in T­cells * The most autoimmune diseases are mediated by antibodies Factors Influencing The Induction Tolerance Factors 1) Immunologic maturity of the host: Neonates are immunologically immature and well accept allograft that would be rejected by mature host 2) Structure and dose of antigen: a­ Simple molecules induce tolerance more readily than complex ones b­ Very high and very low doses of antigen may result in tolerance Factors Influencing The Induction Tolerance Factors 3) T­cells become tolerant more readily and remain tolerant longer than B­cells 4) The continuous presence of antigen helps to maintain tolerance 5) Administration of immunosuppressive drugs enhances tolerance as in transplantation Clinical Importance of Tolerance Clinical 1) Organ transplantation: Introduction of tolerance may help in prevention of rejection 2) Tumor development: Tolerance to tumor antigen results in growth of the tumor without being detected by the immune mechanisms 3) Autoimmune disorders: Disturbance of self­tolerance results in autoimmune disease Autoimmune Diseases Autoimmune Diseases Autoimmune Diseases Autoimmune * Autoimmune diseases occur due to breakdown of the mechanisms that maintain auto tolerance * Auto­antibodies and self reactive T­cells are produced, resulting in tissue damage by several mechanisms Etiology Of Autoimmune Diseases Etiology 1) Genetic predisposition: ­ Familial incidence of autoimmune diseases ­ Most of them appear to be associated with certain MHC genes, specially MHC II genes e.g. Rheumatoid arthritis is associated with DR4 Thyroditis with DR5 Multiple sclerosis with DR2 SLE with DR2/DR3 Type I diabetes with DR3/DR4 Ankylosing spondylitis with B27 Rheumatoid Arthritis Etiology Of Autoimmune Diseases Etiology 2) Exposure to infectious antigens that cross react with self antigens ­ An immune response to these antigen will result in immune attack against self antigens e.g. Antibodies against M protein of Streptococcus pyogens may react with heart valves and cause Rheumatic fever 3) Alteration of self antigens or the appearance of new antigens under the effect of drugs, chemicals, or viral infections 4) Hormonal influences play a role e.g. SLE affects women 10 times more than men Mechanisms Of Disease Production Mechanisms * The disease may be organ specific e.g Hashimoto thyroditis * The disease may be systemic e.g. SLE or rheumatoid arthritis 1) Binding of an autoantibody to host cells result in complement fixation and tissue destruction e.g. Haemolytic anemia (Type II hypersensitivity) Mechanisms Of Disease Production Mechanisms 2) Formation of immune complexes and their deposition in tissues, joints, kidney and skin The immune complexes fix complement resulting in tissue damage e.g. SLE and rheumatoid arthritis (Type III hyper.) 3) DTH reactions (Type IV)) due to auto reactive T­cells e.g. Ulcerative colitis, multiple sclerosis and type I diabetes Laboratory Diagnosis Laboratory 1­ There is elevated serum immunoglobulins 2­ Complement levels may be decreased 3­ Immune complexe detected in serum or organ biopsy 4­ Auto antibodies can be detected in serum e.g. anti­nuclear, anti­smooth muscles, Rh factor and anti­mitochondrial Ab 5­ Testing for antibodies specific to particular Ag, involved in organ specific diseases (anti­thyroid Ab) Thanks Thanks ...
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This note was uploaded on 12/21/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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