Immunology

Question 1

Cyclosporin

Answer 1

Cyclosporin

Binds to cyclophilins, inhibits calcineurin

Blocks T cell activation by preventing IL-2 Transcription.

USE: Transplant rejection prophylaxis, psoriasis, RA
TOX: Nephrotoxicity and HTN ( causes vasoconstriction of efferent and afferent renal arteries)

Question 2

Tacrolimus (FK506)

Answer 2

Tacrolimus

Binds FK506BP, inhibits calcineurin. Blocks T cell activation by preventing IL-2 transcription.

USE: Transplant rejection prophylaxis.
TOX: Neurotoxicity (HA, paraesthesias), nephrotoxicity and HTN

Question 3

Sirolimus

Answer 3

Sirolimus

mTOR inhibitor that binds FKBP. Blocks T-cell activation and B cell differentiation by preventing response at IL-2.

USE: Kidney transplant and rejection prophylaxis.

TOX: NOT NEPHROTOXIC. (causes anemia, etc)

Used in drug-eluting stents, synergistic w cyclosporine.

Question 4

Daclizumab, basiliximab

Answer 4

Daclizumab

Monoclonal Abs that block IL-2R (CD25)

USE: Kidney transplant rejection prophylaxis.

TOX: Edema, HTN, tremor

Question 5

Azothioprine

Answer 5

Azothioprine

Antimetabolite precursor of 6MP, inhibits lymphocyte proliferation by blocking nucleotide synthesis (dec proliferation of cells)

USE: Transplant rejection prophylaxis, RA, crohn, glomerulonephritis, autoimmune conditions

TOX: Leukopenia, anemia, thrombocytopenia.

6MP degraded by XO (6MP is a metabolite of Azothioprine) Therefore increased toxicity by allopurinol.

Question 6

Glucocorticoids

Answer 6

Inhibit NFKB, suppress B and T cell function by decreasing transcription of cytokines.

Transplant prophylaxis, autoimmune DO, inflammation

Can cause many SE including iatrogenic Cushing syndrome.

Question 7

Mycophenylate

Answer 7

Blocks IMP-Dehydrogenase, preventing synthesis of guanine nucleotide.

Decreases cell proliferation of T cells and B cells

USed in transplant PTS, SLE Nephritis

Question 8

Muromunab (OKT3)

Answer 8

Muromunab

monoclonal Ab that binds CD3 on surface of T cells, interferes with T cell signal transduction. USed for transplants

Question 9

Thalidamide

Answer 9

Thalidamide

USed for immunosuppresion, antiangiogenic

MECH: affects TNFalpha

TOX: Phocomelia (prior use as sedative in pregnancy)

Question 10

Alemtuzumab

Answer 10

Alemtuzumab

Targets CD52, Used for CLL

(Alymtuzumab, for chronic lymphocytic leukemia

Question 11

Bevacizumab

Answer 11

Bevacizumab

Target VEGF, used in colorectal cancer and renal cell carcinoma

Question 12

Cetuximab

Answer 12

Cetuximab

Blocks EGFR, used in stage IV colorectal cancer, head and neck cancer

Question 13

Rituximab

Answer 13

Rituximab blocks CD20, used in B-cell non hodgkin lymphoma, CLL, rhuematoid arthritis, ITP

Question 14

Adalimumab, infliximab

Answer 14

Adalimumab blocks soluble TNF-alpha

Used in IBD, RA, ankylosing spondylitis, psoriasis

Entercept is a decoy TNF alpha receptor (not a monoclonal Ab)

Question 15

Eculizumab

Answer 15

Eculizumab blocks complement protein C5

USE: paroxysmal nocturnal hemoglobinuria

Question 16

Natalizumab

Answer 16

Natalizumab blocks alpha4-integrin, used in MS, crohns
alpha 4 integrin is involved in WBC adhesion. Risk of PML in patients with JC virus

Question 17

Denosumab

Answer 17

Denosumab blocks RANKL

USE- osteoporosis, inhibits osteoclast maturation (mimics osteoprotegerin)

Denosumab affects osteoclasts

Question 18

Abciximab

Answer 18

Abciximab blocks platelet glycoproteins IIB/IIIa.

USE: Antiplatelet agent for prevention of ischemic complications in patients undergoing coronary intervention (unstable angina)

IIb times IIIa = ab”six”umab

Question 19

Digoxin immune Fab

Answer 19

Targets Digoxin, antidote for digoxin toxicity

Question 20

Omalizumab

Answer 20

Omalizumab blocks IgE,

USE: allergic asthma, prevents IGE from binding FCERI. Very expensive, rarely used

Question 21

Palivizumab

Answer 21

Palivizumab blocks RSV F protein

USE: RSV prophylaxis for high risk infants

PaliVIzumab - virus

Question 22

Ranibizumab, bevacizumab

Answer 22

Ranibizumab and bevacizumab target VEGF

Used in neovascular age-related macular degeneration