Immunopharmacology

Question 1

What are the three antibody induction reagants?

Answer 1

rATG, alemtuzumab, basiliximab

Question 2

Rabbit anti-thymovcyte globulins

Answer 2

anti-t cell, reacts with CD2,3,4,8,11a etc. Depletes lymphocytes from blood and lymphoid organs. Takes immune system several months to recover

Question 3

Alemtuzumab

Answer 3

humanized anti cd52, depletes T cells by triggering antibody mediated lymphocyte lysis

Question 4

Basiliximab

Answer 4

Humanized antibodiy cd25, acts as an IL-2r antagonist that inhibits t cell proliferation. well tolerated but not as effective

Question 5

What is the mechanism of action for glucocorticoids?

Answer 5

They diffuse into cells, bind receptors, promote receptor dimerization and nuclear translocation. The active receptors bind ot target genes and influence their expression, inhibiting critical immunoregulatory genes

Question 6

What are some serious side effects of glucocorticoids?

Answer 6

hyperglycemia, hypertension, hyperlipidemia, obesity, osteopenia, cataracts, growth retardion in children, poor wound healing, mania and psychosis, increased risk of infection

Question 7

Azathioprine

Answer 7

inhibits de novo purine biosynthesis, lymphocyte proliferation, and cd28/rac1 t cell costimulation

Question 8

What drugs does axathioprine interact with?

Answer 8

allopurinol and februxostat because they are xanthine oxidase inhibitors and you get a build up of thiouric acid

Question 9

Mucophenolate mofetil (MMF)

Answer 9

non competitive, reversible inhibitor of inosine monophosphate dehydrogenase type II, the rate limiting enzyme in the de novo synthesis of prine neucleotides. IMPDHII is selectively expressed in lymphocytes.

Question 10

What is a rare but potentially fatal AE of MMF?

Answer 10

progressive multifocal leukoencephalopathy caused by reactivation of JC virus

Question 11

What are the other antiproliferative drugs used for immunosuppression?

Answer 11

methotrexate, cyclophosphamide, chlorambucil

Question 12

What are the immunophilin binding drugs?

Answer 12

Inhibitors of T cell signaling pathways

Calcineurin inhibitors: cyclosporine and tacrolimusmTOR inhibitors: sirolimus and everolimus

Question 13

What does cyclosporine bind to?

Answer 13

cyclophilin

Question 14

What does tacrolimus bind to?

Answer 14

FKBP(FK506 binding protein)

Question 15

What is the critical mechanism for clycosporine and tacrolimus?

Answer 15

They form inhibitory complexes that bind and inhibit calcineurin, which is involved in the activation of NFAT tf, critical for IL2

Question 16

What are the important adverse effects of tacrolimus and cyclosporine?

Answer 16

Nephrotoxicity and hypertension. drugs that inhibit CYP3a4 increase toxicity.

Question 17

What are the mtor inhibitors?

Answer 17

Sirolimus and everolimus

Question 18

How do mTOR inhibitors work?

Answer 18

they inhibit the mTOR kinase complex which inhibits Il2 mediated signals in T cells

Question 19

What are the contraindications for mtor inhibitors?

Answer 19

liver transplant: hepatic artery thrombosis

lung transplant: anastomotic dehiscence

Question 20

Ipilumumab

Answer 20

mAb specific for the ctla4 protein expressed on t cells, binds to CTLA4 and prevents CTLA4 from delivering a negative signal, leaving cd28 co stimulation intact, and leading to enhanced CD28 co stimulation

Question 21

Pembrolizumab and nivolumab

Answer 21

antibodies specific for negative regulatory PD1 protein expressed on t cells. leads to enhanced t cell immune responses against the cancer cell

Question 22

What medications are used for treatment of relapsing remitting MS?

Answer 22

fingolimod, natalizumab, interferon beta, glatiramer acetate