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18 Cards in this Set

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T Cell Suppressants
Mechanism: either block the calcineurin (NFAT) pathway or the PKC pathway of gene expression

Cyclosporine A(Sandimmune)
Tacrolimus (Prograf)
Sirolimus (Rapamune/rapamycin)
Abatacept (Orencia)
Cyclosporine A
(Sandimmune)
T cell suppressant

calcineurin inhibitor (at an intracellular receptor cyclophilin)- blocks the activation of T cells via blocking NFAT gene expression

Side Effects- renal, HTN, overgrowth of gum tissues
Tacrolimus (Prograf)- FK506
T cell Suppressant

calcineurin inhibitor (by binding a different intracellular receptor FKBP12)- blocks the activation of T cells via blocking NFAT gene expression

Side Effects- renal, HTN, overgrowth of gum tissues
Sirolimus (Rapamune/ rapamycin)
T-Cell Suppressant

binds FKBP12 (like Tacrolimus) but acts as an mTOR inhibitor to decreases DNA synthesis and cell proliferation in response to cytokines binding their receptors-interrupts cytokine signaling in B- and T-cells.
Abatacept (Orencia)
T- cell suppressor- but used for rheumatoid arthritis, not for organ transplantation

a homologue of CD28- binds CD80 or CD86 to interrupt the costimulatory signal and block T-cell activation- results in T-cell Anergy
Antibody Reagents
Uses-
1. Prior to transplantation to deplete certain cell populations that could mount a rejection response to a transplanted organ (Atgam, OKT3)
2. Acute rejection in somebody already immunosuppressed on the triple regimen (Daclizumab)
3. To prevent hemolytic disease of the newborn (RhoGAM)


Antithymocyte globulin (Atgam)
Muromonab-CD3 (OKT3)
Daclizumab (Zenapax)
Rho(D)Ig (RhoGAM)
Antithymocyte globulin (Atgam)
Antibody derived from horses injected with human lymphocytes- purified IgG is isolated and injected into the patient to deplete T cells very rapidly
Muromonab-CD3 (OKT3)
Mouse monoclonal antibody that specifically targets the CD3 molecule on the helper T cell- as a big molecule, it can prevent interaction between helper T cells and APCs, but most importantly induces lysis of helper T cells
Daclizumab (Zenapax)
Antibody against the IL-2 receptor thereby blocking IL-2 from meeting its target on the CD8 cell- blocks downstream signaling.

Used for acute rejection episodes
Rho(D)Ig (RhoGAM)
Human product isolated from the serum of people with antibodies against the Rh antigen- given to Rh- women during pregnancy to prevent sensitization- does not cause lysis of those cells, just coats them to block their interaction with APCs

Used to prevent Hemolytic disease of newborn (+ kid with - mom)
Cytotoxic Drugs
interfere with the metabolism of nucleic acids- prevents clonal expansion of T and B cells

Mycophenolate mofetil (Celicept)
Azathioprine(Imuran)

also used (at higher doses) in cancer chemotherapy to kill rapidly dividing cells
Azathioprine (Imuran)
Cytotoxic

a pro-drug and is metabolized to mercaptopurine- Its metabolite is incorporated into the DNA strand during replication- it is bulky and stalls the DNA polymerase to interrupt chain elongation
Mycophenolate mofetil (Celicept)
Cytotoxic

a pro-drug that is metabolized to mycophenolic acid- the enzyme (IMP dehydrogenase) inhibitor that prevents the production of one of the nucleotides vital to DNA synthesis.
*Lymphocytes are more reliant on the de novo pathway than they are on the salvage pathway- drug specificity for immune cells over other rapidly proliferating cells
Glucocorticoids
multiple sites of action via binding of steroid receptors to initiate transcription of I_B (the inhibitory subunit of NF-_B):
1. Prevent lymphocyte trafficking by blocking adhesion
2. Inhibit T cell proliferation
3. Inhibit expression of cytokines
4. Inhibit macrophage and lymphocyte function

Prednisone(Prednisolone)
Methylprednisolone
Methylprednisolone
Glucocorticoid
Prednisone (Prednisolone)
Glucocorticoid

prevents lymphocyte tracking by blocking the adhesion of lymphocytes to the endothelium in order to leave the circulatory system
Risks of long term immunosupression
Immediate risk of infection

Long-term risk of malignancy
Organ transplants regimen
triple regimen:
T-cell suppressant
a cytotoxic drug
a glucocorticoid

antibody agents are used pre-transplant to prepare the immune system