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Flashcards in Autoimmunity Deck (20)
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1
Q

List the immunologically privileged sites:

A
  • brain
  • eye
  • testis
  • uterus (fetus)
  • hamster cheek pouch
2
Q

What constitutes peripheral tolerance?

A
  • regulatory cytokines (IL-10, TGF-beta)
  • immunoinhibitory molecules molecules (CTLA-4, PD-1)
  • Tregs
3
Q

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

A
  1. Systemic: SLE, rheumatoid arthritis, systemic sclerosis, mixed connective tissue disease
  2. Organ specific: T1DM, multiple sclerosis, thyroiditis, Goodpasture, Guillain-Barre syndrome
4
Q

What are the characteristics of autoimmune disease?

A
  • 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
Q

List the postulated etiologies of ADs:

A
  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
Q

Name one reason we believe hormones influence ADs?

A

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

7
Q

List the 3 major types of Tregs:

A
  • thymic derived (natural) Foxp3+ (nTreg)
  • induced (adaptive) Foxp3+ (iTreg)
  • Type 1 regulatory T cells (Tr1); produce IL-10 and TGF-beta
8
Q

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

A

IPEX Syndrome

9
Q

What Abs are present in SLE?

A

anti-nuclear antibodies (ANA)

10
Q

What is more specific than ANA for diagnosing SLE?

A

anti-dsDNA

11
Q

what immune complex diseases are characteristic of SLE?

A
  • skin rash
  • glomerulonephritis
  • arthritis
  • vasculitis
  • endocarditis
12
Q

Can SLE be induced by drugs? What drugs?

A

Yes. By hydralazine and procainamide.

13
Q

What are possible mechanisms of SLE?

A
  • autoantibodies
  • immune-complex disease
  • deficiency of compliment (ex. C2, C4, C1q)
  • exposure to UV light exacerbates SLE
14
Q

What is scleroderma (systemic sclerosis)?

A
  • progressive fibrosis of skin and internal organs
  • Raynaud’s phenomenon
  • occlusive vascular disease
  • renal disease with HTN
  • ANAs
  • can overlap with other ADs
15
Q

Describe Rheumatoid Arthritis (RA):

A
  • 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
Q

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

A
  • MS (in mice model= EAE- experimental autoimmune encephalomyelitis)
  • T1DM
17
Q

What cells attack pancreatic beta cells in T1DM?

A
  • CD4+ (Th cells)

- CD8+ (CTLs)

18
Q

What autoimmune conditions associated with cancer (PNS)

A
  • neurological diseases: sensory neuropathy, Eaton-Lambert myesthenia syndrome
  • systemic diseases (dermatomyositis/polymyositis)
  • cancer-associated retinopathy
  • skin diseases (paraneoplastic pemphigus)
19
Q

How do tumours initiate autoimmunity?

A
  • 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
Q

What therapies are used in autoimmune disease?

A
  • 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)