Autoimmunity

Autoimmunity - BIO/MI 494 AUTOIMMUNITY Fall 2008 I. II....

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BIO/MI 494 AUTOIMMUNITY Fall 2008 I. Definition of autoimmunity or autoimmune disease II. Tolerance 1. Definition III. Mechanisms of self-tolerance 1. Introduction 2. Central tolerance 3. Peripheral tolerance a. Clonal anergy b. Clonal deletion c. Regulatory cells IV. Effector mechanisms of autoimmune disease 1. Introduction 2. Classification of immunologic diseases a. Type II hypersensitivity b. Type III hypersensitivity c. Type IV hypersensitivity 3. Diseases caused by anti-tissue antibodies (Type II) a. Autoimmune hemolytic anemia b. Myasthenia gravis c. Graves’ disease 4. Diseases caused by immune complexes (Type III) a. Systemic lupus erythematous 5. Diseases caused by delayed-type hypersensitivity (Type IV) a. Insulin-dependent diabetes mellitus V. Possible etiologies of autoimmune diseases 1. Immunologic factors 2. Genetic factors 3. Hormonal factors 4. Virus and bacterial infection 5. Aging
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~+ ======> Anergy (functional unresponsiveness) Figure 10-1 Fates of lymphocytes after enc()unter with antigens. In a normal immune response, an immunogenic antigen stimulates the proliferation and differen- tiation of antigen-specific lymphocytes. (Immunogenic antigens are recognize<J by lymphocytes in the presence of second signals, or costimulators, which are not shown.) Tolerogenic antigens may induce functional unresponsiveness or death of antigen-specific lymphocytes, making these cells incapable of responding to the antigen (tolerance). Some antigens elicit no response (ignorance), but the lym- phocytes are able to respond to subsequent antigen challenge (not shown). This illustration depicts T lymphocytes; the same principles apply to B lymphocytes. Note that T lymphocytes recognize anti- gens presented by antigen-presenting cells, which are not shown.
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II l "\j 'I ~ \ A~~:;O'SiS Chan;e ~n \ (deletion) receptors ,~ nil D~velopment /1 of regulatory \\ (receptor n T lymphocytes __ \ ~d~~~~\ -1 ' (~~~~~yI~I~S_ 11 . ~~ Mature FIGURE 11-2 Central and peripheral toler- ance to self antigens. Immature lymphocytes specific for self antigens may encounter these antigens in the generative lymphoid organs and Recognition of self antigen \\ <\ I I are deleted, change their specificity (B cells v only), or (in the case of C04+ T cells) develop into ~~ regulatory lymphocytes (central tolerance). Some self-reactive lymphocytes may mature ~o and enter peripheral tissues and may be inacti- vated or deleted by encounter with self antigens .... ~ CI> in these tissues, or are suppressed by the regu- a.. L I latory T cells (peripheral tolerance). (Note that T I Anergy I Apoptosis cells recognize antigens presented by antigen- ~_eletiOn) Suppression presenting cells, which are not shown.) J Thymus Periphery Lymphoid precursor n ! Recognition of self antigen / ~I ~ Negative selection: deletion Immature' T cells specific for self antigen 11-3 Central T cell tolerance.
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Autoimmunity - BIO/MI 494 AUTOIMMUNITY Fall 2008 I. II....

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