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Inflammation and Immunity > 2.2.1 Tolerance and Autoimmunity > Flashcards

2.2.1 Tolerance and Autoimmunity Flashcards

1
Q

Define immunogenic.

A

Elicits proliferation, differentiation, and effector function from lymphocytes

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2
Q

Define tolerogenic.

A

does not elicit a functional lymphocyte response (lymphocyte killed, inactivated, or no reaction at all)

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3
Q

Distinguish b/t central and peripheral tolerance. Where do they occur?

A

Central: occurs during lymphocyte development in primary lymphoid organs (Thymus and BM) Peripheral: occurs in the periphery (SLOs or non-lymphoid tissues)

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4
Q

What is the term for the promoting survival of T cells that recognize MHC molecules with low affinity for self-peptides?

A

Positive Selection

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5
Q

What happens to T cells that have a strong affinity for self-peptides in the thymus? Is this a perfect process?

A

Negative selection, not 100% effective

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6
Q

If cells don’t recognize MHC at all, what happens?

A

Death by neglect

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7
Q

If cells recognize MHC with strong affinity for self-peptides but survive thymic development, what is their mature cellular form? What do they contibute to?

A

Treg; peripheral tolerance

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8
Q

How do T cells specific for Ag not expressed in the thymus get negatively selected?

A

AIRE gene (autoimmune regulator) - induces the expression of peripheral tissue Ag by cells in the thymus

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9
Q

What happens if there is a mutation in AIRE?

A

APECED (autoimmune polyendocrineopathy-candidiasis-ectodermal dystrophy syndrome): a multi-organ autoimmunity

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10
Q

What are the four peripheral responses to an autoreactive T cell?

A
  1. Functional inactivation (anergy)
  2. Treg-mediated suppression
  3. Death (apoptosis)
  4. Ignorance
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11
Q

What type of signal leads to anergy?

A

Naive T cells recognize MHC/peptide complex (signal 1) in the absence of costimulation (signal 2) or in the presence of inhibitory signals

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12
Q

What is the main co-receptor on T cells involved in the signal 2 of the 2-signal theory?

A

CD28 (on T cell) binds B7-1/2 of APC

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13
Q

What are two inhibitory recepors-lignand interactions responsible for angery?

A

PD-1 (T cell)/PDL (APC)

CTLA-4 (T cell)/B7 (APC) blocks binding of CD28 to B7 and can deliver inhibitory signals

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14
Q

What are the targets of ipilimumab and nivolumab?

A

ipilimumab: anti-CTLA-4 Ab
nivolumab: anti-PD-1 Ab

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15
Q

What transcription factor is important in Treg development and function?

A

FoxP3

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16
Q

A mutation in FoxP3 leads to a lack of functional Treg, which yields mulitorgan autoimmunity. What is the acronym for this disorder?

A

IPEX

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17
Q

What interaction is responsible for lymphocyte activation induced cell death that clears effector lymphocytes?

A

Fas-FasL

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18
Q

What is the genetic cause of autoimmune lymphoproliferative syndrome (ALPS)? What are the two results of this mutation?

A

Mutated Fas signaling; autoimmunity and lymphocyte accumulation

19
Q

What is receptor editing?

A

Immature B cells that recognize self Ag reexpress RAG genes, resume Ig light recombination and express a new Ig light chain

20
Q

What are the three mechanisms of peripheral tolerance?

A

Anergy, Death (apoptosis), Ignorance

21
Q

How is Ig concentration related to Ig half-life?

A

Higher concentration, decreased half-life

22
Q

Which receptors on B cells and macrophages have an immunoregulatory function?

A

Fc receptors

23
Q

Co-cross linking of what turns off the effector B cell?

A

BCR and FcgammaRII

24
Q

What is Rhogam? When is it administered?

A

Immune gammaglobulin (IgG Ab) to Rh Ag; given to Rh neg mothers during pregnancy and at parturition

25
Q

What is the mechanism of rhogam?

A

Eliminates fetal Rh pos RBCs from maternal circulation

Turns off maternal B cells by cross-linking BCR and FcgammaRII

26
Q

Which three cytokines are secreted by macrophages to aid in the return to homeostasis after infection? What do they inhibit?

A

IL-10: inhibits Th1

TGF-beta: inhibits macrophage activation and T cells

PGE2: inhibits lymphocyte proliferation

27
Q

What are the three types of autoimmunity tissue damage?

A

Ab-mediated (Type II)

Immune complex-mediated (Type III)

T cell-mediated (Type IV)

[No Type I]

28
Q

What is the autoimmune receptor Ab present in Graves dz (Type II)? What can lead to the diagnosis of Graves dz?

A

Anti-TSH receptor Ab;

Agonistic thyroid-stimulating Ab

29
Q

In Graves Dz, what is the resulting effect on the thyroid?

A

Thyroid hyperplasia (goiter) and hyperthyroidism - due to constitutive activation of TSH receptor by auto-antibody.

30
Q

What type of autoimmunity dz is Goodpasture’s Dz?

A

Type II

31
Q

What is the Ab directed against in Goodpasture’s Dz?

A

Non-collagenous domains of type IV collagen of glomerular basement membrane (GBM)

32
Q

What is enough to diagnose Goodpasture’s Dz?

A

Linear IgG in kidney GBM and anti-GBM Ab

33
Q

What type of toxicity is present in goodpasture’s dz? What are the clinical symptoms of goodpasture’s?

A

Neutrophil-mediated cytotoxicity; bleeding in lungs and progressive kidney failure

34
Q

What type of autoimmune dz is systemic lupus erythematosus? What are some associated symptoms?

A

Type III

fever, arthritis, myalgia, skin involvement, photosensitivity, anemia, IC desposition in kidneyand joints

35
Q

What is an ANA test?

A

Cells fixed on slide, patient serum added, antinuclear antibodies bind, secondary antibody against human antibodies tagged with a fluorescent dye

36
Q

What type of AI dz is multiple sclerosis? Pathogenesis?

A

Type IV

Immune attack of the myelin sheath that covers nerve fibers

37
Q

What are some of the autoantigens present in MS? What immune cells are involved in this AI distruction?

A

myelin basic protein, myelin oligodendrocyte glycoprotein, proteolipoprotein

CD4+ Th1 (IFN-gamma) and Th17 (IL-17)

38
Q

What occurs in Type I DM, a type IV AI dz? Which cells are involved?

A

Destruction of beta cells in pancreatic islets

CD4+ and CD8+ T cells

39
Q

What are 5 genes that affect a person’s genetic susceptibility to an AI dz? What dz’s are they associated with?

A

PTPN22: involved in B and T cell signaling – RA, SLE, TIDM

NOD-2: involved in NLR (innate) – 25% of Crohn’s dz

high affinity chain of IL-2 receptor (CD25): effector Treg balance – multiple AI dz

IL-23R: involved in Th17 differentiation – multiple AI dz

CTLA-4: multiple AI dz

40
Q

What is abatacept?

A

CTLA-4-Ig

41
Q

Name an anit-CD20 Ab.

A

Rituximab

42
Q

Name 3 Anti-TNF Ab

A

Infliximab, Adalimumab, Certolizumab pegol

43
Q

Name an Anti-IL-6 Ab.

A

Tocilizumab

44
Q
A

Inflammation and Immunity (51 decks)

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