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Autoimmunity Tolerance sometimes is broken self reactive cells do form, but are usually

Autoimmunity Tolerance sometimes is broken self reactive cells do form, but are usually inactivated or suppressed Damage can be antibody- or T-cell mediated Some disease are systemic, others organ- specific. Organ-specific target is a molecule unique to that organ

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Autoimmunity Tolerance sometimes is broken self reactive cells do form, but are usually

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  1. Autoimmunity Tolerance sometimes is broken self reactive cells do form, but are usually inactivated or suppressed Damage can be antibody- or T-cell mediated Some disease are systemic, others organ- specific

  2. Organ-specific target is a molecule unique to that organ Hashimoto’s thyroiditis T cell and antibody mediated inflammation leads to goiter antibodies to thyroid protein interfere with iodine uptake Graves’ disease (TSH receptor) MS- myelin

  3. Goodpasture’s syndrome Antibodies to membrane antigens in kidney and alveoli Complement activation, cell damage, inflammation IDDM (insulin-dependent diabetes mellitus) both T and B cells involved CTLs, autoantibodies subsequent DTH response kills beta cells

  4. Antibodies to receptors Graves- disease Autoantibody mimics TSH, leads to constant thyroid stimulation Myasthenia gravis Autoantibody blocks Ach receptor, eventually destroys it

  5. Multiple sclerosis- T cell mediated Rheumatoid arthritis: IgM autoantibodies that react with IgG Fc

  6. Systemic diseases- damage is widespread Systemic lupus erythematosis autoantibodies to everything anti-nuclear antibodies are diagnostic Type II, III and inflammatory damage

  7. p. 466

  8. How does autoimmunity occur? Transferred by T cells (CD4+ cells specifically) TH1 cells transfer disease TH2 cells protect against it

  9. Role for mast cells? (Lee et al., Science, 9/6/02) Inflammatory arthritis Complement Fc receptors Cytokines (esp. TNF-) Mast cells produce lots of cytokines Activated by immune complexes?

  10. “Adoptive transfer” p. 467

  11. Autoantibody can be transferred from patient to recipient Graves’ disease can be transferred from human to rat Also from mother to fetus child is born with Graves’disease treated by plasmapheresis

  12. Why does autoimmunity occur? “sequestered antigens”- normally not seen, so not deleted, in T cell development MBP heart muscle proteins nuclear antigens sperm Avoid by injection of antigen into thymus?

  13. p. 469

  14. Hormonal status of patient Many autoimmune diseases are more frequent in one sex than the other (Ankylosing spondylitis in men; MS, SLE, Graves’ disease, RA in women) Onset during reproductive years (RA- remission during pregnancy?)

  15. p. 510

  16. “Wrong” cells induced to express MHC Class II antigen (and act as APCs) maybe additional signals, such as IL-1 and TNF Polyclonal B cell activation T cell independent Large amounts of IgM produced

  17. Treatment of autoimmune disease Immunosuppression Removal of thymus Plasmapheresis

  18. Experimental approaches p. 475

  19. T cell vaccines (Ag-specific T cells) Interfere with antigen presentation Monoclonal antibodies variety of target antigens Oral induction of tolerance So far, efforts have been more successful in mice than humans

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