06- Immunomodulators Flashcards
adaptive immune response
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
adjuvant
a substance that enhances the body’s immune response to an antigen
-e.g.- Alum, BCG (ImmuCyst)
anti-inflammatory
drugs that inhibit elements of INNATE immunity (generalized immune response)
B-Cell
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
cytokine
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
cytoxic
something that is toxic to a living cell
humoral response
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.
immunostimulant
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
immunosuppressive
a drug that suppresses the immune response in an individual
opsonization
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
T-cell
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)
Azathioprine
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
cyclophosphamide
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.
leflunomide
General growth inhibitor
-inhibits dihyroorolate dehydrogenase resulting in decreased pyridimine synthesis.
-Use: RA and some autoimmune diseases.
S/E: hepatoxicity, diarrhea, myelosuppression.
methotrexate
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.
mycophenolate mofetil
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
prednisone
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.
cyclosporine
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).
tacrolimus (FK-506)
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
Anti-T Cell globulin (ATG)
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
alemtuzumab
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.
basiliximab
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.
RH (D) immune globulin
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).
belatacept
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).
INF-ɣ
Cytokine
-stimulates cell-mediated cytotoxic killer cell activity (TH-1 like response)
INL-2
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.
BCG
Adjuvant
- live attenuated bacillus calmete-guerin
- increases APC activity
- useful for bladder CA
- direct activation of leukocytes can lead to SIRS and possibly sepsis
