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Flashcards in Autoimmunity Deck (18):

4 immune privileged areas

brain, eye, testes, uterus (fetus)


what is backup to central tolerance

peripheral tolerance


3 mechs of peripheral tolerance

1. regulatory cytokines (IL-10, TGF)
2. immunoinhibitory molecules (CTLA-4)
3. Treg cells


2 main classes of autoimmune diseases

1. systemic - SLE, RA, systemic sclerosis
2. organ specific - Type 1 diabetes, MS, thyroiditis


why are autoimmune disorders chronic

can rarely eliminate autoantigens, so keep reacting to them


3 ways to know disease is autoimmine

1. clear evidence of autoantibodies or autoaggresive Tcells
2. may be transmitted from mother to fetus through IgG
3. in animals the disease can be transfered by Tcells or antibodies


8 postulated etiologies of autoimmune disorders

1. molecular mimicry with infections (rheumatic fever)
2. failure of Treg cells - mutated FoxP3
3. B-cell or T-cell polyclonal activation - esp. SLE - many autoantibodies released
4. mutations to key regulatory molecules (AIRE) - can't show self in thymus
5. tissue damage releasing hidden antigen (eye, testes)
6. vit. D def. - ADs more common at high latitiudes
7. drugs and toxins
8. Cancer


evidence for hormonal influence

ADs 10x more common in women


3 main types of Treg

1. natural foxP3+ - from thymus (nTreg)
2. induced foxP3+ in periphery - (iTreg)
3. Type 1 regulatory T cells - release IL-10 and TGF-B


what is IPEX syndrome

caused by foxP3 mutations and cause rapidly lethal widespread autoimmune disease


what is lupus

antinulear antibodies ANA, but others can exist
- causes immune complex disease
- can be induced by drugs and made worse by UV light


what is systemic sclerosis (scleroderma)

- progressive fibrosis of skin and internal organs
- raynaud - vasoconstriction to cold
- occlusive vascular disease
- ANAs


what is rheumatoid arthritis

- inflammation of the synovium with pannus formation causes cartiledge destruction
- not just a joint disease, may attack lungs, heart


what is rheumatoid factor

autoantibodies reactive to Fc region of IgG


2 examples of authimmune diseases mainly mediated by T cells

1. MS
2. Types 1 diabetes


how does cancer initiate autoimmunity

- mutated tumor antigens may mimic
- tumors may express antigen that is normally only present in embryo
- tumors can secrete mediators that alter immune tolerance


what is anti-NMDA-r encephalitis

teratoma that has abnormal neural tissue that activates the immune system


therapy for autoimmune disorders

1. corticosteroids and immunosupressive drugs
2. TNFa and IL-6 blockade
3. IVIg
4. mABs against B-cells
5. interferons

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