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PHS 932 > Block 2 Lecture 6/7 -- Transplant > Flashcards

Block 2 Lecture 6/7 -- Transplant Flashcards

1
Q

MoA of OKT3

A

Anti-TCR (anti-CD3)

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2
Q

MoA of CTLA4-Ig

A

anti-costimulatory

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3
Q

MoA of basiliximab

A

anti-IL-2R

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4
Q

MoA of daclizumab

A

anti-IL-2R

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5
Q

MoA of rapamycin

A

interferes with mTOR signaling

– reduces proliferation

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6
Q

MoA of cyclosporine

A

inhibits calcineurin

– interferes with NF-AT mediated cytokine transcription (IL-2)

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7
Q

MoA of FK506/tacrolimus

A

inhibits calcineurin

– interferes with NF-AT mediated cytokine transcription (IL-2)

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8
Q

MoA of azathioprine

A

anti-proliferator blocks B/T cell synthesis

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9
Q

MoA of mycophenolate

A

anti-proliferator blocks B/T cell synthesis

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10
Q

MoA of corticosteroids

A

1) anti-inflammatory: inhibit m0 cytokine synthesis

2) blocks T cell activation

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11
Q

MoA of thymoglobulin

A

anti-tcr

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12
Q

MoA of atgam

A

anti-tcr

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13
Q

What agents are used in induction immunosuppression?

A

1) anti-TCR
2) anti-IL-2R
3) alemtuzumab

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14
Q

MoA of alemtuzumab

A

targets CD52

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15
Q

What drugs are used in maintenance immunosuppression?

A

1) calcineurin inhibitors
2) anti-proliferators
3) +/- corticosteroids

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16
Q

How is hyperacute rejection mediated?

A

self-Ab-mediated (against blood or graft)

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17
Q

How is acute rejection mediated?

A

allo-Ag-specific CD4/8 T-cell-mediated

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18
Q

How is chronic rejection mediated?

A

CD4-cytokine mediated

endothelium recognizes cytokines

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19
Q

Results of hyperacute rejection:

A

1) complement activation
2) endothelial damage
3) inflammation
4) thrombosis

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20
Q

Results of acute rejection:

A

1) parenchymal cell damage
2) interstitial inflammation
3) endothelialitis

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21
Q

Results of chronic rejection:

A

1) chronic inflammatory reaction in vasculature walls
2) intimal smooth muscle cell proliferation
3) vessel occlusion

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22
Q

What is direct antigen presentation?

A

allo/donor-APC presents self-Ag to T-cell

– T cell recognizes allo-MHC as foreign

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23
Q

What is indirect antigen presentation?

A

self-APC presents peptide of donor-MHC as Ag to T cell

24
Q

How does sensitization occur?

A

direct- or indirect-antigen recognition

25
Q

What is the role of T-cells in rejection?

A

1) sensitization
2) IL-2 release
3) rejection

26
Q

What occurs in the rejection phase after sensitization?

A

effector CD4/8’s migrate to periphery

27
Q

What are the reagents in mixed lymphocyte reaction?

A

donor and recipient’s mononuclear leukocytes

    • (DCs, NK, B, T)
    • one set may be inactivated
28
Q

What are the reagents in cross matching test?

A
    • recipient serum + donor lymphocytes

- - add complement

29
Q

What is measured in the MLR?

A

B/T proliferation

30
Q

What is measured in cross-matching?

A

cell lysis

31
Q

What are the reagents in a PRA test?

A

1) fluorescent-MHC-labeled coated beads

2) patient’s serum

32
Q

What is measured in a PRA?

A

% of MHC bound by patient’s MHC

33
Q

What does the PRA result represent?

A

risk for hyperacute and acute rejection

34
Q

How might MHC-Abs be pre-formed?

A

1) past transfusion
2) past transplant
3) pregnancy

35
Q

How many HLA alleles must be matched for a “perfect match”?

A

6

36
Q

Where are HLA alleles located?

A

chromosome 6

37
Q

Why are PRA’s performed multiple times?

A

serum titers change over time

38
Q

What are tests run to determine pre-formed Abs and HLA matching?

A

PRA
cross-matching
MLR

39
Q

What backbone is common to all blood antigens?

A

4-sugar backbone

1) galactose
2) NAG (glucosamine)
3) galactose
4) fucose

40
Q

Describe A blood Ag structure

A

backbone + N-acetyl-galactosamine

41
Q

Describe B blood Ag structure

A

backbone + galactose

42
Q

Describe O blood Ag structure

A

backbone only

43
Q

What is the result of IL-2 production in sensitization?

A

1) T-cell proliferation
2) clonal expansion
3) cytokine production

44
Q

What is the signaling cascade of the IL-2R?

A

1) production of mTOR

results in proliferation

45
Q

What is the signaling cascade of the TCR?

A

1) calcineurin activation
2) NFAT activation
- - results in IL-2 production

3) also produces mTOR
- - results in proliferation

46
Q

What is the signaling cascade of CD28?

A

results in IL-2 production

47
Q

What interactions are involved in the immunological synapse?

A

1) pMHC - TCR
2) B7 - CD28
3) IL2 - IL2R

48
Q

What are the goals of immunosuppressive therapy?

A

prevent acute rejection and minimize toxicity

49
Q

What are non-T-cell depleting induction agents?

A

1) anti-IL2R

2) basiliximab

50
Q

What are T-cell depleting induction agents?

A

1) antithymocyte globulin

2) alemtuzumab

51
Q

What is the role of CD52?

A

on T-cells, leads to ADCC

52
Q

How is cytokine release syndrome prevented?

A

1) APAP
2) benadryl
3) methylprednisolone

53
Q

What agent is prone to provoking cytokine release syndrome?

A

OKT3

54
Q

What is the induction cocktail?

A

1) T-cell depleting/non-depleting
2) cytokine prophylaxis
3) steroid taper

55
Q

MoA of sirolimus

A

mTOR inhibitor

56
Q

MoA of everolimus

A

mTOR inhibitor

57
Q

What is the immunosuppressive maintenance cocktail?

A

2-3 meds from different classes +/- steroids

    • calcineurin
    • mTOR inhibitors
    • antiproliferatives

PHS 932 (23 decks)

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