Immunomodulators

Question 1

Azathioprine

Answer 1

• General growth inhibitor
• Metabolized to G-mercaptopurine then 6-thioguanine – inhibit purine synthesis and incorporated in DNA causing DNA damage
• Myelosuppression, nausea, vomiting
• Renal and other tissue transplantation, auto-immune disease

Question 2

Cyclophosphamide

Answer 2

• General growth inhibitor
• Very effective by cross-linking DNA and killing proliferative cells (prevents expansion of antigen-specific lymphocytes)
• Myelosuppression, nausea, vomiting, infertility
• Auto-immune diseases and bone marrow transplant

Question 3

Leflunomide

Answer 3

• General growth inhibitor
• Metabolized to A77-1726 – inhibits dihydroorotate dehydrogenase – decreased pyrmidine synthesis
• Diarrhea, modest hepatotoxicity, less myelosuppression
• Rheumatoid arthritis (drug of choice), some auto-immune

Question 4

Methotrexate

Answer 4

• General growth inhibitor
• Inhibits dihydrofolate reductase – direct/ indirect inhibition - prevent thymidine
• Nausea, mucosal ulcers, hepatotoxicity, less myelosuppression
• Rheumatoid arthritis (drug of choice), some auto-immune

Question 5

Mycophenolate mofetil

Answer 5

• General growth inhibitor
• Hydrolyzed to mycophenolic acid – prevents purine synthesis
• Myelosuppression, nausea, vomiting
• Solid organ transplant, some auto-immune disease

Question 6

Prednisone

Answer 6

• Glucocorticoid
• Induced and repressed gene transcription of various inflammatory mediators – both anti-inflammatory and immunosuppressive effects
• Cushing’s syndrome, glucose intolerance, susceptible to infection, osteoporosis, hypertension
• First-line for solid organ and hematopoietic stem cell transplant, management of various immune-disorders

Question 7

Sirolimus

Answer 7

• mTOR inhibitor
• Binds to FKBP12 and prevents cytokine-induced growth
• Myelosuppression, hyperlipidemia, hypertension, edema, hepatotoxicity
• Preserve solid organ transplants, steroid-resistant graft-versus-host disease in hematopoietic stem cell transplants

Question 8

Cyclosporine

Answer 8

• Calcineurin inhibitor
• Prevent TCR-induced cytokine expression by preventing activation of NF-AT – binds to cyclophilin
• Nephrotoxicity, hypertension, hyperglycemia, liver dysfunction
• Kidney, liver, and cardiac transplants – autoimmune disorders and inflammatory diseases (often combined with another drug)

Question 9

Tacrolimus (FK506)

Answer 9

• Calcineurin inhibitor
• Prevent TCR-induced cytokine expression by preventing activation of NF-AT – binds to FKBP12 (10-100 times more potent than cyclosporine)
• Nephrotoxicity, hypertension, hyperglycemia, liver dysfunction
• Kidney, liver, and cardiac transplants – autoimmune disorders and inflammatory diseases (often combined with another drug)

Question 10

Anti-T cell globulin

Answer 10

• Antibodies and fusion proteins
• Purified serum IgG from repeated injection of human T cells into aminmals – blocks T cell surface receptors and opsonizes T cells
• Cytokine release syndrome, serum sickness, anaphylaxis potential
• Prolonged T cell depletion (more than 1 year) – late rejection as lymphoid system recovers

Question 11

Alemtuzumab

Answer 11

• Antibodies and fusion proteins
• Anti-CD52 (surface protein expressed on immune cells) – depletes cells involved in adaptive/innate immunity
• Myelosuppression, flu-like symptoms
• Produces prolonged depletion of T cell and other cells of immune system (1 year)

Question 12

Basiliximab

Answer 12

• Antibodies and fusion proteins
• Blocks and opsonizes the alpha-chain of IL-2 receptor (CD25) present on activated T cells
• None
• Depletes only antigen-activated T cells so reduced incidence of infection and malignancy

Question 13

Rh (D) immune globulin

Answer 13

• Antibodies and fusion proteins
• Concentrated solution of human IgG with high titer of Rh(D) antibodies – prevents maternal immune response to fetal Rh(D) antigen
• Rh hemolytic disease

Question 14

Belatacept

Answer 14

• Antibodies and fusion proteins
• High affinity for B7 – prevents interaction between B7 and CD28 – anergic T cells (no proliferation/cytokine production)
• Anemia, neutropenia, peripheral edema, increased infection and malignancy, PTLD
• Anemia, neutropenia, peripheral edema, increased infection and malignancy, PTLD
• Kidney transplantation to prevent rejection

Question 15

Interleukin-2

Answer 15

• Cytokine
• Increased proliferation of activated T cells, production of IFNy, and CK cells
• Serious capillary leak syndrome, hypotension, reduced organ perfusion
• Metastatic melanoma and renal cell carcinoma

Question 16

IFN-y

Answer 16

• Cytokine

* Stimulate cell mediated cytotoxic immune response

Question 17

BCG

Answer 17

• Adjuvant
• Surface antigens interact directly with PRRs on APCs and increase APC activity
• Direct activation of leukocytes can lead to septic shock
• Cancer therapies