Block 2 Lecture 6/7 -- Transplant

Question 1

MoA of OKT3

Answer 1

Anti-TCR (anti-CD3)

Question 2

MoA of CTLA4-Ig

Answer 2

anti-costimulatory

Question 3

MoA of basiliximab

Answer 3

anti-IL-2R

Question 4

MoA of daclizumab

Answer 4

anti-IL-2R

Question 5

MoA of rapamycin

Answer 5

interferes with mTOR signaling

– reduces proliferation

Question 6

MoA of cyclosporine

Answer 6

inhibits calcineurin

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

Question 7

MoA of FK506/tacrolimus

Answer 7

inhibits calcineurin

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

Question 8

MoA of azathioprine

Answer 8

anti-proliferator blocks B/T cell synthesis

Question 9

MoA of mycophenolate

Answer 9

anti-proliferator blocks B/T cell synthesis

Question 10

MoA of corticosteroids

Answer 10

1) anti-inflammatory: inhibit m0 cytokine synthesis

2) blocks T cell activation

Question 11

MoA of thymoglobulin

Answer 11

anti-tcr

Question 12

MoA of atgam

Answer 12

anti-tcr

Question 13

What agents are used in induction immunosuppression?

Answer 13

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

Question 14

MoA of alemtuzumab

Answer 14

targets CD52

Question 15

What drugs are used in maintenance immunosuppression?

Answer 15

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

Question 16

How is hyperacute rejection mediated?

Answer 16

self-Ab-mediated (against blood or graft)

Question 17

How is acute rejection mediated?

Answer 17

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

Question 18

How is chronic rejection mediated?

Answer 18

CD4-cytokine mediated

endothelium recognizes cytokines

Question 19

Results of hyperacute rejection:

Answer 19

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

Question 20

Results of acute rejection:

Answer 20

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

Question 21

Results of chronic rejection:

Answer 21

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

Question 22

What is direct antigen presentation?

Answer 22

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

– T cell recognizes allo-MHC as foreign

Question 23

What is indirect antigen presentation?

Answer 23

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

Question 24

How does sensitization occur?

Answer 24

direct- or indirect-antigen recognition

Question 25

What is the role of T-cells in rejection?

Answer 25

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

Question 26

What occurs in the rejection phase after sensitization?

Answer 26

effector CD4/8's migrate to periphery

Question 27

What are the reagents in mixed lymphocyte reaction?

Answer 27

donor and recipient's mononuclear leukocytes - - (DCs, NK, B, T) - - one set may be inactivated

Question 28

What are the reagents in cross matching test?

Answer 28

- - recipient serum + donor lymphocytes | - - add complement

Question 29

What is measured in the MLR?

Answer 29

B/T proliferation

Question 30

What is measured in cross-matching?

Answer 30

cell lysis

Question 31

What are the reagents in a PRA test?

Answer 31

1) fluorescent-MHC-labeled coated beads | 2) patient's serum

Question 32

What is measured in a PRA?

Answer 32

% of MHC bound by patient's MHC

Question 33

What does the PRA result represent?

Answer 33

risk for hyperacute and acute rejection

Question 34

How might MHC-Abs be pre-formed?

Answer 34

1) past transfusion 2) past transplant 3) pregnancy

Question 35

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

Answer 35

6

Question 36

Where are HLA alleles located?

Answer 36

chromosome 6

Question 37

Why are PRA's performed multiple times?

Answer 37

serum titers change over time

Question 38

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

Answer 38

PRA cross-matching MLR

Question 39

What backbone is common to all blood antigens?

Answer 39

4-sugar backbone 1) galactose 2) NAG (glucosamine) 3) galactose 4) fucose

Question 40

Describe A blood Ag structure

Answer 40

backbone + N-acetyl-galactosamine

Question 41

Describe B blood Ag structure

Answer 41

backbone + galactose

Question 42

Describe O blood Ag structure

Answer 42

backbone only

Question 43

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

Answer 43

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

Question 44

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

Answer 44

1) production of mTOR | results in proliferation

Question 45

What is the signaling cascade of the TCR?

Answer 45

1) calcineurin activation 2) NFAT activation - - results in IL-2 production 3) also produces mTOR - - results in proliferation

Question 46

What is the signaling cascade of CD28?

Answer 46

results in IL-2 production

Question 47

What interactions are involved in the immunological synapse?

Answer 47

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

Question 48

What are the goals of immunosuppressive therapy?

Answer 48

prevent acute rejection and minimize toxicity

Question 49

What are non-T-cell depleting induction agents?

Answer 49

1) anti-IL2R | 2) basiliximab

Question 50

What are T-cell depleting induction agents?

Answer 50

1) antithymocyte globulin | 2) alemtuzumab

Question 51

What is the role of CD52?

Answer 51

on T-cells, leads to ADCC

Question 52

How is cytokine release syndrome prevented?

Answer 52

1) APAP 2) benadryl 3) methylprednisolone

Question 53

What agent is prone to provoking cytokine release syndrome?

Answer 53

OKT3

Question 54

What is the induction cocktail?

Answer 54

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

Question 55

MoA of sirolimus

Answer 55

mTOR inhibitor

Question 56

MoA of everolimus

Answer 56

mTOR inhibitor

Question 57

What is the immunosuppressive maintenance cocktail?

Answer 57

2-3 meds from different classes +/- steroids - - calcineurin - - mTOR inhibitors - - antiproliferatives