03/20a Immunosuppression

Question 1

What are the three broad categories of agent that can be used to modulate the immune system?

Answer 1

Anti-inflammatory agents
Immunosuppressive agents
Immunostimulatory agents

Question 2

Why is it important to reduce or block inflammation in immunosuppression?

Answer 2

Most immune-mediated diseases have a strong inflammatory component
Reducing inflammation, and thus reducing tissue injury and allowing effective action, is key for long term therapy with immunosuppressives

Question 3

What is the mechanism of NSAIDs?

Answer 3

Block production of inflammatory mediators

Question 4

How do glucocorticoids and methotrexate work?

Answer 4

By killing inflammatory cells

Question 5

How do antimalarials work?

Answer 5

By inhibiting endosomal function and autophagy

Question 6

Which drugs inhibit lymphocyte signaling?

Answer 6

Cyclosporin
Rapamycin
JAK kinase inhibitors

Question 7

What are the four classes of immunosuppressive drugs?

Answer 7

Class 1 - nucleic acid synthesis inhibitors
Class 2 - nonspecific or unknown mechanism of action
Class 3 - immune system-derived
Class 4 - T cell-specific

Question 8

What are the two main immunosuppressive functions of steroids?

Answer 8

1) Induce expression of pro-apoptotic genes to lead to apoptosis of lymphocytes
2) Bind to and inhibit NF-kappa-B-mediated transcription via the glucocorticoid receptor

Question 9

Which drug is the gold standard against which all other immunsuppressants are measured?

Answer 9

Cyclosporin A

Question 10

What is the mechanism of action of Cyclosporin A?

Answer 10

It blocks a specific step required for T cell activation - antigen presentation via the antigen receptor

Question 11

What does it mean that Cyclosporin A is a ‘prodrug?’

Answer 11

It only forms an active drug as a drug-protein complex with cyclophilin

Question 12

What is the target of the active drug-protein complex of Cyclosporin A?

Answer 12

Calcineurin

Question 13

What is the major complication of Cyclosporin A therapy?

Answer 13

Nephrotoxicity, which includes vasoconstriction, glomerular sclerosis, and tubular effects

Question 14

What other drug besides Cyclosporin A targets calcineurin?

Answer 14

FK506 (tacrolimus)

Question 15

What do all three T cell-specific drugs have in common?

Answer 15

They are prodrugs that must bind to a cellular protein to be active