immunopharmacology

Question 1

Vaccines

Answer 1

active immunization with attenuated organism synthetic antigenic peptides

Question 2

antisera or antibodies

Answer 2

passive immunization with antisera or monoclonal antibodies

Question 3

immunopotentiation

Answer 3

enhance the immune response
BCG- attenuated strain of mycobacterium bovis
stimulates NK T cells, may cross react immunologically with tumor cell Ags, used as an adjuvant in immunotherapy of certain cancers
Levamisole- anthelmintic drug

Question 4

IL1

Answer 4

produced by M@ in response to viruses, bacteria, Ag, inflammatory agents
Activates lymphocytes
Promotes differentiation of Ab forming cells
Endogenous pyrogen

Question 5

IL2

Answer 5

produced by T cells, GF for T cells and promotes proliferation, enhances tumoricytic activity of lymphocytes

Question 6

IFN

Answer 6

a-IFN and B-IFN produced by leukocytes, y-IFN produced by lymphocytes

inhibit replication of viruses, enhance phagocytosis and cytotoxicity

Tested (B-IFN = viral infection, y-IFN)

Question 7

TNF

Answer 7

mediator of inflammation: stimulates IL1 synthesis, activates neutrophils, stimulates PGs synthesis, stimulates collagenase production, elevated in rheumatoid arthritis

Question 8

Cell mediated cytotoxicity

Answer 8

1. Macrophage (M@) processing of Ag
2. presentation of Ag to T cell
3. Expression of IL 1 and IL2 receptors on T cell
4. Secretion of IL 1 M@
5. IL promotes IL 2 release from helper T cells
6. IL2 acts on lymphocytes to promote replication of cytotoxic cells

Question 9

uses of immunosuppressants

Answer 9

prvention of allograft rejection

treatment of autoimmune diseases

Question 10

prednisolone

Answer 10

cell trafic accumulation: reduce access of cells to target tissue (lymphocytopenia and monocytopenia), prevects neutrophil adherence to endothelium, inhibit action of chemotactic factors

cell function: interferes with M@ Ag processing, blocks the action of lymphokines, inhibits binding to Fc receptors

used in combo with other drugs in Auto immune diesease dnd to prevent graft rejection

toxicity: supression of HPA axis, acute adrenal insufficiency with abrupt withdrawal, Cushings syndrome

Contraindicated in presense of exisiting infection

Question 11

cytotoxic agents

Answer 11

in response to antigen, immune cells proliferate in a synchronized manner with a burst of mitotic division. These drugs kill these rapidly proliferating cells

best used at time of intial exposure to exposure, kills a high precentage of precursor cells

Relevant clone stimulated by Ag will be killed. other immune cells and clones not stimulated by Ag are spared

usually administered in a low dosage daily to block immunoproliferation continually

Question 12

Azathioprine

Answer 12

Metabolized to 6 Mercaptopurine, orally active, purine anti metabolite that inhibits purine biosynthesis and thereby inhibits DNA synthesis (de novo and salvage paths)
inhibits rejection of transplanted organs and in some diseases as rheumatoid arthritis
bonemarrow depression is a major side effect, GI and hepatic toxicity may occur

Question 13

Cyclophosphamide

Answer 13

an alkylating agent that results in agent that results cross linking of DNA to kill replicating and non replicating cells
Toxic effect more pronounced on B cells so more effective in suppressing humoral immunity
Orally active
used in the treatment of autimmune diseases not effective in preventing graft rejections
bone marrow depression as a SE

Question 14

Methotrexate

Answer 14

inhibitor of dihydrofolate reductase- inhibit folate dependent steps in purine synthesis- inhibits DNA synthesis

Used to treat autoimmune disease, hepatic toxicity

Question 15

Mycophenolate Mofetil

Answer 15

Metabolized to the active mycophenolic acid
MOA: lymphocyte selective immunosuppressant:
1. inhibits IMP dehydrogenase (IMP->GMP) necessary for de novo purine synthesis, no effect on salvage pathway
2. lymphocytes cant make GMP via slavage pathway, must use denovo so selective for lymphocytes
3. inhibits lymphocyte proliferation and expression of cell surface adhesion molecules
4. more selective than azathioprine and methotrexate but equally effective

Orally active
used w/ cyclosporine and corticosteroids to prevent renal allograft rejection. allows for lower dose of cyclosporine to be used so less toxicity

used to treat autoimmune diseases–rheumatoid arthritis and refractory psoriasis
should be used with caution in pts with active GI disease, reduced renal function and infections

SE: infection, leukopenia, anemia

contraind: in pregnancy (malformation and spon abortions)

Question 16

Cyclosporine

Answer 16

lipophilic peptide antibiotic
MOA: binds to cellular receptor and inhibits Ca-dependent phosphatase. Blocks activation of transcription factor (NFAT) necessary for IL2 production
inhibits mRNA synthesis that codes for lymphokines as IL2. By blocking IL2 synthesis, it blocks T cell helper function so inhibits T cell proliferation and cytotoxicity. Does not alter T cell response to IL2. since it is not lymphotoxic, its more selective in its action

orally active
Used to prevent rejection , more effective than other agents with fewer SEs, and used in some auto immune diseases

Nephrotoxicicty is a major side effect, reversible with discont. hepatotoxicicty

Question 17

Tracolimus

Answer 17

binds to FK binding protein, a cyclophilin-related protein. Same MOA as cyclosporine
Spectrum of action is the same as cyclosporine but 50-100 times more potent. less toxic

Question 18

sirolimus

Answer 18

inhibits T cell activation and proliferation downstream of IL 2. binds FKBP-12.
no binding to calcineurin
binds to mTOR blocks G1–> s transition

Uses same for cyclosporine, coating of cardiac stents

Question 19

basiliximab

Answer 19

MOA: Recombinant monoclonal antibodies against a-subunit of IL2 receptor
Blocks IL2 receptor- inhibits binding of IL2 to its receptor, inhibits T cell activation and proliferation
must be given IV
Prophylactically treats allograft rejection. Not used for acute rejection. used in combo with calcineurin inhibitor and corticosteroid
CX: pregnancy, breastfeeding infection and murine hypersensitivity

Question 20

alemtuzumab

Answer 20

MOA: CD52 is a glycoprotein expressed on B- and T lymphocytes, monocytes and NK cells

drug binds to CD52 causing lympholysis via ADCC, causes B and T cell depletion

must be given IV

Used as an immuno suppressant in renal transplants. avoids high dose corticosteroids. Used to treat chronic lymphocytic leukemia and MS.

SE: neutropenia, thrombocytopenia anemia can occur

Question 21

Belatacept

Answer 21

MOA: a fusion protein of the Fc fragment of the IgG1 and extracellular domain of CD152 found on T cells. CD 152 binds CD80 and CD84 on antigen presenting cells

Selective T cell co stimulation inhibitor. It binds to cell surface co stimulation ligands CD80 CD86 on T cells. inhibits T cell activation

Must be given IV

Used prophylactic organ rejeection of kidney. alternative to calcineurin inhibitors to reduce long term toxicity of the drugs. Used in combo with mycophenolate mofetil, corticosteroids and basiliximab

Toxicity- infusion related reactions are infrequent, typically well tolerated