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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 - PowerPoint PPT Presentation
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Autoimmunity
Tolerance sometimes is brokenself 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-specifictarget is a molecule unique to that organ
Hashimoto’s thyroiditisT cell and antibody mediatedinflammation leads to goiter
antibodies to thyroid protein interfere withiodine uptake
Graves’ disease (TSH receptor)MS- myelin
Goodpasture’s syndrome
Antibodies to membrane antigens in kidney andalveoli
Complement activation, cell damage, inflammation
IDDM (insulin-dependent diabetes mellitus)both T and B cells involvedCTLs, autoantibodies
subsequent DTH response kills beta cells
Antibodies to receptors
Graves- disease
Autoantibody mimics TSH, leads to constantthyroid stimulation
Myasthenia gravis
Autoantibody blocks Ach receptor, eventuallydestroys it
Multiple sclerosis- T cell mediated
Rheumatoid arthritis: IgM autoantibodies thatreact with IgG Fc
Systemic diseases- damage is widespread
Systemic lupus erythematosis
autoantibodies to everythinganti-nuclear antibodies are diagnostic
Type II, III and inflammatory damage
p. 466
How does autoimmunity occur?
Transferred by T cells (CD4+ cells specifically)
TH1 cells transfer disease
TH2 cells protect against it
Role for mast cells? (Lee et al., Science, 9/6/02)Inflammatory arthritisComplementFc receptorsCytokines (esp. TNF-)
Mast cells produce lots of cytokinesActivated by immune complexes?
“Adoptive transfer” p. 467
Autoantibody can be transferred from patientto recipient
Graves’ disease can be transferred from humanto rat
Also from mother to fetuschild is born with Graves’diseasetreated by plasmapheresis
Why does autoimmunity occur?
“sequestered antigens”- normally not seen, sonot deleted, in T cell development
MBPheart muscle proteinsnuclear antigenssperm
Avoid by injection of antigen into thymus?
p. 469
Hormonal status of patient
Many autoimmune diseases are more frequentin one sex than the other
(Ankylosing spondylitis in men; MS, SLE, Graves’disease, RA in women)
Onset during reproductive years
(RA- remission during pregnancy?)
p. 510
“Wrong” cells induced to express MHC Class IIantigen (and act as APCs)maybe additional signals, such as IL-1and TNF
Polyclonal B cell activationT cell independentLarge amounts of IgM produced
Treatment of autoimmune disease
Immunosuppression
Removal of thymus
Plasmapheresis
Experimental approaches p. 475
T cell vaccines (Ag-specific T cells)
Interfere with antigen presentation
Monoclonal antibodiesvariety of target antigens
Oral induction of tolerance
So far, efforts have been more successfulin mice than humans