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HDM Exam #2 > Autoimmunity > Flashcards

Autoimmunity Flashcards

1
Q

Central tolerance

A

Induced in immature self-reactive lymphocytes in primary lymphoid organs.

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2
Q

Peripheral tolerance

A

Induced in mature self-reactive lymphocytes in peripheral sites.

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3
Q

Fate of cells w/ central tolerance

A

Apoptosis
Develop into Treg cells
B cells can attempt a change in BCR specificity

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4
Q

Fate of cells w/ peripheral tolerance

A

Anergy
Apoptosis
Suppressed by Treg cells

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5
Q

AIRE

A

Found in the thymus and exposes T cells to antigens from all kinds of cell types.
Helps to protect against autoimmunity.

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6
Q

Central tolerance curve explanation

A

Cells with weak avidity undergo apoptosis (nonfunctional)
Cells with high self- reactivity are deleted.
Thymocytes activated below a threshold are postively selected to become mature T cells.
A small percentage express FOXp3 and develop into Treg cells.

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7
Q

Mechanism of anergy

A

T cells engage inhibitory receptors CTLA-4 or PD-1 that block activation.

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8
Q

Checkpoint blockade

A

Treatment of cancer patients with anti-CTLA-4 and anti-PD-1. This can also cause autoimmune reactions.

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9
Q

Cytokines affecting Treg

A 
Generation of Treg requires TGF-beta
Express FOXp3 and are CD4+CD25+.
Express high levels of CTLA-4.
Cells are long-lived.
IL-2 IS CRITICAL FOR THEIR SURVIVAL.
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10
Q

Inducible Treg cells (iTreg)

A

FOXp3 can be induced in mature T cells by presence of TGF-beta IF IL-6 is not present (hence a strong relationship between Th17 and iTreg).

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11
Q

Retinoic acid receptor (RAR)

A

Inhibits formation of Th17 but promotes FOXp3 expression.

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12
Q

Basic mechanisms for Treg cells (4)

A

Secrete inhibitory cytokines (TGF-beta and IL-10)
Cell-to-cell contact to block DC function
Metabolic disruption (death of target by deprivation of cytokines, specifically IL-22)
Cytolysis via granzyme and perforin

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13
Q

Targeting of DCs by Treg mechanism

A

Binding of CTLA-4 and B7 inhibits DC maturation AND induction of IDO, which degrades Trp (an essential AA).

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14
Q

B cell Central Tolerance

A

Immature B cells that recognize self-ags undergo receptor editing (further rearrangement and replacement of IgL-chain genes). If this fails, cells undergo apoptosis.
Weak recognition leads to anergy.

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15
Q

Retinoic acid in Treg development

A

DCs secrete RA which stimulates developmento of Treg cells from naive CD4+CD25- T cells.

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16
Q

CD22 receptor

A

An inhibitory receptor that is phosphorylated by Lyn and recruits SHP-1 to inhibit BCR signaling.
Defects in Lyn, SHP-1, and CD22 inhibitory receptor can lead to autoimmunity.

17
Q

AIRE gene causes a failure of what?

A

Central tolerance. All others cause failure of peripheral tolerance.

18
Q

AIRE Deficiency causes:

A

Autoimmune polyendocrine syndrome

19
Q

FOXp3 causes

A

IPEX Syndrome

20
Q

Mutations in AIRE are associated with:

A

Decreased expression of self-Ags in the thymus.

21
Q

Diseases associated with polymorphisms in CTLA-4 (know 2)

A

Type I Diabetes

Grave’s Disease

22
Q

2 improtant properties of CTLA-4

A

CTLA-4 expression is low on resting T cellls until activated by Ag.
CTLA-4 terminates continuing activation of responding T cells (the brakes of the system).

23
Q

CTLA-4 has both intrinsic and extrinsic actions. Explain.

A

Engagement of CTLA-4 can deliver inhibitory signals that terminate activation (intrinsic).
CTLA-4 on Treg (or any responding T cell) can bind to B7 molecules and make them unavailable to CD28.

24
Q

Polymorphisms of what genes has the strongest association with autoimmunity?

A

MHC/HLA genes

Non-HLA genes can also play a role.

25
Q

3 ways microbial Ags can elicit autoimmunity:

A
  1. Molecular mimicry (Rheumatic fever, MS)
  2. Polyclonal (bystander) activation to actiavte autoreactive lymphocytes (create cytokine field).
  3. Release of previously sequestered Ags.
26
Q

MS molecular mimicry by microbial Ag

A

T cells react w/ myelin basic protein and peptides from EBV, influenza A and HPV

27
Q

Rheumatic fever

A

Triggered by Streptococcal infection and mediated by cross-reactivity between strep Ags and cardiac myosin.

28
Q

Estrogens exacerbate:

A

Systemic lupus erythematosus by altering B-cell repitoire in absence of inflammation.

29
Q

Penicillins can bind RBCs and:

A

Generate a neoantigen and cause hemolytic anemia.

30
Q

Immune privileged sites (7)

A 
Eye
Brain
Pregnant uterus
Ovary
Testes
Adrenal cortex
Hair follicle
31
Q

Immune privilege

A

These tissues are able to tolerate the introduction of antigens without eliciting an inflammatory immune response.

32
Q

Strongest associations with MHC genes 1-4

ATRP

A

Ankylosing spondylitis (MHC I)
Type I DM (MHC II)
RA (MHC II)
Pemphigus vulgaris (MHC II)

HDM Exam #2 (7 decks)

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