Autoimmunity

Question 1

4 immune privileged areas

Answer 1

brain, eye, testes, uterus (fetus)

Question 2

what is backup to central tolerance

Answer 2

peripheral tolerance

Question 3

3 mechs of peripheral tolerance

Answer 3

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

Question 4

2 main classes of autoimmune diseases

Answer 4

1. systemic - SLE, RA, systemic sclerosis

2. organ specific - Type 1 diabetes, MS, thyroiditis

Question 5

why are autoimmune disorders chronic

Answer 5

can rarely eliminate autoantigens, so keep reacting to them

Question 6

3 ways to know disease is autoimmine

Answer 6

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

Question 7

8 postulated etiologies of autoimmune disorders

Answer 7

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

Question 8

evidence for hormonal influence

Answer 8

ADs 10x more common in women

Question 9

3 main types of Treg

Answer 9

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

Question 10

what is IPEX syndrome

Answer 10

caused by foxP3 mutations and cause rapidly lethal widespread autoimmune disease

Question 11

what is lupus

Answer 11

antinulear antibodies ANA, but others can exist

• causes immune complex disease
• can be induced by drugs and made worse by UV light

Question 12

what is systemic sclerosis (scleroderma)

Answer 12

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

Question 13

what is rheumatoid arthritis

Answer 13

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

Question 14

what is rheumatoid factor

Answer 14

autoantibodies reactive to Fc region of IgG

Question 15

2 examples of authimmune diseases mainly mediated by T cells

Answer 15

1. MS

2. Types 1 diabetes

Question 16

how does cancer initiate autoimmunity

Answer 16

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

Question 17

what is anti-NMDA-r encephalitis

Answer 17

teratoma that has abnormal neural tissue that activates the immune system

Question 18

therapy for autoimmune disorders

Answer 18

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