06- Immunomodulators

Question 1

adaptive immune response

Answer 1

immune response mediated by T-cells and B-cells

• immune response that responds to a specific antigen (not a generalized response seen with innate immunity)
• aka– antigen specific immunity

Question 2

adjuvant

Answer 2

a substance that enhances the body’s immune response to an antigen
-e.g.- Alum, BCG (ImmuCyst)

Question 3

anti-inflammatory

Answer 3

drugs that inhibit elements of INNATE immunity (generalized immune response)

Question 4

B-Cell

Answer 4

immune cells that make up part of ADAPTIVE immunity

• activated by cytokines secreted by T-cells
• produce antibodies to “foreign” antigens
• antibodies bind to antigens and activate complement system and cells that secrete inflammatory mediators (Innate Immunity)
• special type can be antigen presenting cell, that reveals antigens to T-cells and activates them
• targeted by immuno-modulatory agents

Question 5

cytokine

Answer 5

secreted by activated T-cells

• effect the development and activity of B-cells, cytotoxic cells (NK cells, cytotoxic T-cells or leukocytes mediating inflammatory reactions (macrophages, neutrophils, etc.)
• e.g. Interleukin-2, interferons

Question 6

cytoxic

Answer 6

something that is toxic to a living cell

Question 7

humoral response

Answer 7

the aspect of immunity that is mediated by macromolecules (as opposed to cell-mediated immunity) found in extracellular fluids such as secreted antibodies, complement proteins and certain antimicrobial peptides.

Question 8

immunostimulant

Answer 8

use of normal agonists of immune system activation to enhance developing immune response
-promote systemic activation of immune system
-stimulate increased release of cytokines and inflammatory mediators “downstream”
-adverse effects reflect systemic inflammatory reactions
Limitations: does not promote specific immune response, alt. therapies generally work better, expensive

Question 9

immunosuppressive

Answer 9

a drug that suppresses the immune response in an individual

Question 10

opsonization

Answer 10

an immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte
-generally marked by an antibody then destroyed by phagocyte

Question 11

T-cell

Answer 11

immune cells make up part of ADAPTIVE immunity

• activated by Antigen Presenting Cells and then secrete cytokines to activate other B-Cells (to produce antibodies), cytotoxic cells, or leukocytes mediating inflammatory reactions (macrophages, neutrophils, etc)
• subsets include helper T-cells (secrete cytokines when activated by APC) and Memory T-cells (can be reactivated more quickly with repeated infection by same antigen)

Question 12

Azathioprine

Answer 12

General growth inhibitor
-inhibits purine synthesis (prodrug)
-incorporates into DNA as thio-guanine (leading to DNA damage).
inactivated by xanthine oxidase.
use: renal and other txp, some autoimmune (SLE, RA).
S/E: myelosuppression, NV

Question 13

cyclophosphamide

Answer 13

General growth inhibitor

• cross linkage of DNA leading to destruction of proliferating T-cells and decreased colonal expansion.
• Use: autoimmune disease, bone marrow txp
• S/E: myelosuppression, NV, infertility.

Question 14

leflunomide

Answer 14

General growth inhibitor
-inhibits dihyroorolate dehydrogenase resulting in decreased pyridimine synthesis.
-Use: RA and some autoimmune diseases.
S/E: hepatoxicity, diarrhea, myelosuppression.

Question 15

methotrexate

Answer 15

General growth inhibitor
-inhibits dihydrofolate reductase (DHFR) resulting in prevention of synthesis of thymidine and purine nucleotides.
Use: RA and some autoimmune diseases
S/E: hepatotoxicity, nausea, myelosuppression, mucosal ulcers.

Question 16

mycophenolate mofetil

Answer 16

General growth inhibitor

• metabolized to mycophenolic acid (prodrug)
• inhibits ionsine monophosphate dehydrogenase resulting in decreased purine synthesis
• Use: solid organ txp (alternate to cyclosporine) and some autoimmune disease.
• S/E: myelosuppression, NV

Question 17

prednisone

Answer 17

Glucocorticoid

• increased transcription of annexins resulting in decreased production of PLA2 (decreased prostanoid and leukotriene production).
• represses cytokine transcription resulting in a decrease in T-cell proliferation.
• use: solid organ txp and hematopoietic stem cell txp
• S/E: with greater than 2 wks use: cushing syndrome, diabetes, glucose intolerance, ocular disturbances, HTN, osteoporosis, psychiatric disturbances, GI ulceration.

Question 18

cyclosporine

Answer 18

Calcineurin Inhibitor
-prevention of TCR induced cytokine expression by inhibiting calcineurin activity.
-binds with cyclophillin to prevent calcineurin from removing phosphate groups from NF-AT. This prevents cytokine transcription.
-Uses: kidney, liver, and cardiac txp.
S/E: Nephrotoxicity, HTN, hyperglycemia, liver dysfunction (possible increased risk of CA).

Question 19

tacrolimus (FK-506)

Answer 19

Calcineurin Inhibitor
-prevention of TCR induced cytokine expression by inhibiting calcineurin activity.
-binds with FKBP12 to prevent calcineurin from removing phosphate groups from NF-AT. This prevents cytokine transcription.
-Uses: kidney, liver, and cardiac txp.
S/E: Nephrotoxicity, HTN, hyperglycemia, liver dysfunction (possible increased risk of CA).
-10-100x more potent than cyclosporine

Question 20

Anti-T Cell globulin (ATG)

Answer 20

animal antibody

• blocks T-Cell surface receptors and opsinizes them.
• Results in cytokine release syndrome (fever, chills, etc) and can be prevented my pre-Tx with acetaminophen and anthistamine.
• serum sickness may occur

Question 21

alemtuzumab

Answer 21

Chimeric (humanized antibody)

• Anti CD-52 (located on T cells, B cells, monocytes, macros, and NK cells).
• S/E: myelosuppression, flu-like Sx, and possible depletion of T-cells for up to 1 yr.

Question 22

basiliximab

Answer 22

Chimeric (humanized antibody)

• Anti-CD-25 (IL-2 receptor) present on activated T-cells.
• depletes only activated T-cells
• minimal adverse effects.
• good for people at decreased risk for rejection.

Question 23

RH (D) immune globulin

Answer 23

Human antibody

• used for Rh negative mother giving birth the Rh positive baby to prevent antibody production against Rh positive fetus with subsequent pregnancies (resulting in hemolytic anemia).
• concentrated human IgG with high titre of Rh-D antibodies
• Must be given when exposure of mother the Rh-D from baby (i.e. ROM, bleed, etc).

Question 24

belatacept

Answer 24

Fc fushion Protein
-blocks binding of B7 (Antigen Presenting Cell) with CD-28 (T-Cell).
-prevents proliferation of T-cells and cytokine production
-T Cells become “anergic” and some may die
Use: Kidney txp
S/E: neutropenia, anemia, peripheral edema, increased risk for infections, PLTD (contrindicated in EBV neg patients).

Question 25

INF-ɣ

Answer 25

Cytokine

-stimulates cell-mediated cytotoxic killer cell activity (TH-1 like response)

Question 26

INL-2

Answer 26

Cytokine

• increased proliferation of activated T-cells, production of INF-ɣ, and cell-mediated cytotoxicity.
• Associated with serious capillary leak syndrome, HOTN, and decreased organ perfusion.

Question 27

BCG

Answer 27

Adjuvant

• live attenuated bacillus calmete-guerin
• increases APC activity
• useful for bladder CA
• direct activation of leukocytes can lead to SIRS and possibly sepsis