Immunosuppressant Drugs

Question 1

What are the 4 main classes of immunosuppressants?

Answer 1

T cell suppressants
Antibody reagents
Cytotoxic drugs
Glucocorticoids

Question 2

What are the 2 common pathways in T-cell inactivation for immunosuppression?

Answer 2

Protein kinase C –> AP1 –> cell nucleus

Calcineurin –> NFAT

Question 3

What is the key signaling pathway for gene transcription in the T-cell model?

Answer 3

NFAT + AP1 leads to gene transcription.

Both factors must be present.

Question 4

What 2 immunosuppressant drugs:

prevent the activation of NFAT
acts on calcineurin

Answer 4

Cyclosporine A

Tacrolimus (FK506)

Question 5

What are significant side effects of calcineurin inhibitors such as Cyclosporine A, Tacrolimus? (3)

Answer 5

HTN
renal dysfunction
gingival hyperplasia

Question 6

What is the new drug approach to immunosuppression?

Answer 6

NFAT inhibition w/out affect calcineurin activity to minimize side effects.

Question 7

What new immunosuppressant drug:

mTOR inhibitor (mammalian target of r)
 blocks cytokine signaling in CD8

Answer 7

Sirolimus (rapamycin)

Question 8

What drugs target calcineurin which affect the NFAT molecule?

Answer 8

Cyclophiline A

Tacrolimus

Question 9

What drugs work on the immunophilin FKBP12?

Answer 9

Tacrolimus (FK506)

Sirolimus (Rapamycin)

Question 10

What drug targets mTOR and affects p70s6 kinase?

Answer 10

Sirolimus (Rapamycin)

Question 11

What antibody reagent:

depletes T-helper cells
used before organ transplant
kills cells at CD3 site
is a mouse monoclonal antibody

Answer 11

Muromonab CD3

Question 12

What antibody reagent:

blocks cytokine signaling
is a genetically engineered reagent
is a humanized anti-IL2R antibody

Answer 12

Daclizumab (Zenapax)

Question 13

What antibody reagent:

human IgG globulin
blocks formation of maternal antibody against Rh+ fetus
used in Rh- female during pregnancy and after birth to prevent hemolytic disease of the newborn

Answer 13

RhoGAM

Question 14

What class of drugs:

used at lower doses than in cancer therapy

interfere with nucleic acid metabolism

prevent clonal expansion of T and B cells

Answer 14

cytotoxic drugs

Question 15

What drug:

inhibits inosine monophosphate dehydrogenase (IMPDH)

Answer 15

Mycophenolate mofetil (MMF)

Question 16

What drug:

Pro-drug: active metabolite is mycophenolic acid (MPA)

Answer 16

Mycophenolate mofetil (MMF)

Question 17

What drug:

lymphocytes rely on de novo (from the beginning) pathway to greater extent than other cell types

Answer 17

Mycophenolate mofetil (MMF)

Question 18

What drug:

prevents clonal expansion of immune cells

Answer 18

Mycophenolate mofetil (MMF)

Question 19

What drug:

affects lymphocyte trafficking (anti- adhesion)
inhibit T cell proliferation
inhibit function of macrophages and lymphocytes

Answer 19

Glucocorticoids: Prednisone

Question 20

Does prednisone inhibit the expression of cytokines?

Answer 20

Yes

Question 21

What do glucocorticoids stimulate the production of?

Answer 21

IKB, NF-KB

Question 22

What are the primary mechanisms of immunosuppressant drugs? (5)

Answer 22

1= Antigen recognition
2= T cell depletion
3= T cell activation
4= Cytokines (synthesis, signaling)
5= Proliferation