Transplant Pharmacology

Question 1

What is an autologous transplant?

Answer 1

transplant between same individual

Question 2

What is an allogeneic transplant?

Answer 2

transplant within species

Question 3

What is a xenogeneic trnasplant

Answer 3

transplant between species

Question 4

What is the purpose of matching tissue antigens in allogenic transplantation?

Answer 4

minimize genetic variation (blood type, MHC) to minimize rejection

Question 5

What is the principal role of passenger antigen presenting cells in triggering transplant rejection?

Answer 5

1. donor dendritic cells (APCs) migrate to host lymph nodes and induce host T cell activation
2. activated host T cells destroy allograft tissues

Question 6

What is the role of IL-2 in acute rejection?

Answer 6

Drives actions and proliferation of host T cell as a result of donor dendritic cells inducing host T cells

Question 7

Describe the two signal model of T cell activation in acute rejection

Answer 7

signal 1: The donor dentritic cell with the mismatched MHC binds to the host T cell receptor
signal 2: donor dendritic cells express costimulatory molecules which lead to inflammation and determines amount of IL-2

Question 7

What are the main classes of drugs used in anti-rejection therapy?

Answer 7

1. Corticosteroids
2. Antiproliferatives
3. T cell inhibitors (CNIs, IL-2 antagonists, mTOR inhibitor)
4. costimulatory blockade

Question 8

What is the phosphatase being inhibited by Tacrolimus?

Answer 8

inhibits calcineurin phosphatase; decreases IL-2 and supresses T cell activation/ proliferation

Question 9

What is the role of NFAT in T cell activation and how is it affected by Tacrolimus and Cyclosporine?

Answer 9

1. NFAT is a transcriptional regulator of IL-2 gene expression, calcinuerin dephosphorylates NFAT so it can translocate into the nucleus and induce transcription of the IL-2 gene
2. cyclosporine and tacrolimus prevent this process from happening

Question 10

How do modified and non-modified forms of cyclosporine affect bioavalability?

Answer 10

modified micro-ionized drug have increased bioavalibility compare to non-modified

Question 11

What decreases absorption of cyclosporine?

Answer 11

reduced biliary flow

Question 12

What is the role of antiproliferatives in preventing rejection?

Answer 12

inhibits inosine monophosphate dehydrogenase–> inhibits purine synthesis –> inhibits lymphocyte proliferation –> indices apoptosis of proliferating T cells

Question 13

Why should live vaccines be avoided when using immunosuppressants?

Answer 13

vaccine efficacy may diminish

Question 14

How do IL-2 receptor antagonists supress activated T cells specifically?

Answer 14

igG1 agonist CD25 (IL-2 R-alpha) expressed on activated T cells blocking paracrine effect of IL-2

Question 15

How do mTOR inhibitors effect T cell responses?

Answer 15

mTOR kinase inhibitors block IL-2 signaling, blocking paracrine effect of IL-2 –> suppresses T cell proliferation

Question 16

Compare mTOR inhibitors and antithymocyte gobulin

Answer 16

mTOR inhibitors are selective for ACTIVE T cells; antothymocyte gobulin is a CD45 -pan leukocyte marker and results in trasnient depletion of ALL Tmcells