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Flashcards in Autoimmunity Deck (20):
1

List the immunologically privileged sites:

-brain
-eye
-testis
-uterus (fetus)
-hamster cheek pouch

2

What constitutes peripheral tolerance?

-regulatory cytokines (IL-10, TGF-beta)
-immunoinhibitory molecules molecules (CTLA-4, PD-1)
-Tregs

3

What are the two main classes of autoimmune disease and give examples of each:

1. Systemic: SLE, rheumatoid arthritis, systemic sclerosis, mixed connective tissue disease

2. Organ specific: T1DM, multiple sclerosis, thyroiditis, Goodpasture, Guillain-Barre syndrome

4

What are the characteristics of autoimmune disease?

-evidence of autoantibodies and/or autoreactive Tcells
-some AI diseases are transmitted from mother to fetus by passage of IgG autoantibodies through placenta
-in animals the disease can be transferred by T cells or antibodies (adoptive or passive transfer)

5

List the postulated etiologies of ADs:

1. molecular mimicry with infectious agents --> rheumatic fever, Guillain-Barre

2. failure of Tregs

3. B cell or T cell polyclonal activation (especially SLE)

4. mutations to key regulatory molecules (AIRE, Foxp3) ex. PTPN-22 polymorphisms

5. tissue damage releasing hidden antigens (ex. sympathetic opthalmia, orchitis)

6. vitamin D deficiency ex. AD more common at high altitudes

7. Drugs and toxins (ex. autoimmune hemolytic anemia, SLE)

6

Name one reason we believe hormones influence ADs?

ADs are more common in females (estrogen related?). ex. SLE 10x more common in Females

7

List the 3 major types of Tregs:

-thymic derived (natural) Foxp3+ (nTreg)
-induced (adaptive) Foxp3+ (iTreg)
-Type 1 regulatory T cells (Tr1); produce IL-10 and TGF-beta

8

What lethal autoimmune/inflammatory condition do Foxp3+ mutations result in?

IPEX Syndrome

9

What Abs are present in SLE?

anti-nuclear antibodies (ANA)

10

What is more specific than ANA for diagnosing SLE?

anti-dsDNA

11

what immune complex diseases are characteristic of SLE?

-skin rash
-glomerulonephritis
-arthritis
-vasculitis
-endocarditis

12

Can SLE be induced by drugs? What drugs?

Yes. By hydralazine and procainamide.

13

What are possible mechanisms of SLE?

-autoantibodies
-immune-complex disease
-deficiency of compliment (ex. C2, C4, C1q)
-exposure to UV light exacerbates SLE

14

What is scleroderma (systemic sclerosis)?

-progressive fibrosis of skin and internal organs
-Raynaud's phenomenon
-occlusive vascular disease
-renal disease with HTN
-ANAs
-can overlap with other ADs

15

Describe Rheumatoid Arthritis (RA):

-inflammation of synovium with pannus formation and destruction of cartilage
-not just about joints--> inflammation of lungs, heart, m etc possible
-vasculitis
-characterized by RF= rheumatoid factors ie autoantibodies reactive to the Fc segment of IgG.

16

What are two examples of organ-specific ADs caused by T cell activity?

-MS (in mice model= EAE- experimental autoimmune encephalomyelitis)
-T1DM

17

What cells attack pancreatic beta cells in T1DM?

-CD4+ (Th cells)
-CD8+ (CTLs)

18

What autoimmune conditions associated with cancer (PNS)

-neurological diseases: sensory neuropathy, Eaton-Lambert myesthenia syndrome
-systemic diseases (dermatomyositis/polymyositis)
-cancer-associated retinopathy
-skin diseases (paraneoplastic pemphigus)

19

How do tumours initiate autoimmunity?

-anti-cancer immunity is often autoimmune
-mutated tumour antigens break tolerance
-tumours express antigens expressed during embryonic period or in immune-privileged sites
-tumours can secrete mediators that alter immune tolerance

20

What therapies are used in autoimmune disease?

-corticosteroids and immunosuppressive drugs (SLE)
-TNF-alpha or IL-6 cytokine blockade (RA)
-immunomodulatory agents (interferon-beta-MS, IVIG-many ADs)
-mAbs against B cells ex. anti-CD20 (RA)
-mAb against B cell lymphocyte stimulator BLyS (SLE)