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Autoimmunity

Autoimmunity. Autoimmunity. Loss of self tolerace leading to immune response to self tissues May be organ-specific, localized or systemic Genetic background plays a role in extent & severity of diseases. Virtually all autoimmune responses are T-dep. Formation of new or altered epitopes

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Autoimmunity

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  1. Autoimmunity

  2. Autoimmunity • Loss of self tolerace leading to immune response to self tissues • May be organ-specific, localized or systemic • Genetic background plays a role in extent & severity of diseases. • Virtually all autoimmune responses are T-dep. • Formation of new or altered epitopes • Sharing epitopes between tissues & agents (molecular mimicry) • Exposure of hidden antigens • Viral infections • Loss of control of lymphocyte responses

  3. Assumption of NO autoimmunity- T cell unresponsiveness because of : • Clonal deletion • T-suppression • Clonal anergy • Inadequate anto-antigen presentation

  4. Criteria for autoimmune disease • Direct proof • Transferring autoantibodies or self-reactive lymphocytes to healthy individuals & reproduce the disease (for ethical reason, use scid mice) • Indirect proof • Identify target antigen & reproduce the disease in the experimental animals • Study genetically predisposed animal models • Circumstantial evidence • Familial tendency • Lymphocyte infiltration or MHC association • Clinical improvement with immune suppressive drugs

  5. Figure 17.1Possible mechanisms of induction of autoimmunity.

  6. Normal thyroid gland Gland in Hashimoto’s thyroiditis

  7. Figure 17.2``Lumpy-bumpy'' staining pattern of fluorescent antibody specific for human Ig: immune aggregate deposits in glomerular basement membrane. [Courtesy of Dr. Angelo Ucci, Tufts University School of Medicine.]

  8. Islet of Langerhans in pacreas from a normal mouse (a) and from a mouse with a disease resembling insulin-dependent diabetes mellitus (b)

  9. “Butterfly” rash over the cheeks of a young girl with systemic lupus erythematosus

  10. Rheumatoid arthirtis

  11. Proposed mechanisms for induction of autoimmunity • Release of sequestered antigens • Molecular mimicry • Inappropriate expression of class II MHC molecules • Polyclonal B cell activation

  12. Treatment of autoimmune diseases • Current therapies • Immunosuppressive drugs • Removal of target tissues • Experimental therapeutic approaches • T cell vaccination • Peptide blockade of MHC molecules • Monoclonal-antibody treatment • Tolerance induction by oral antigens

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