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16 Cards in this Set

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  • Back
What enzyme converts Prednisone to Prednisolone?
11-beta-hydroxysteroid dehydrogenase
What is the MOA of Prednisone/Prednisolone?
1. Leukocytopenia
2. Reduced size and lymphoid content of the lymph nodes & spleen
3. Interferes w/ function of Macrophages/Monocytes
4. Prevents activation of helper T cells
5. Prevents proliferation of T & B cells
6. Suppresses the production of Ab by B cells
7. Interferes w/ the function of helper T cells
8. Interference with lymphokine synthesis
The Leukocytopenia caused by Prednisone leads to what changes in the numbers of circulating Lymphocytes, Monocytes, Eosinophils, Basophils, and Neutrophils?
All cells are decreased in number except Neutrophils

Increased circulating cells due to release of mature cells from bone marrow & decreased movement from blood into vascular tissue
Corticosteroids interfere with the function of Macrophages/Monocytes by blocking the expression of the genes for _______ & _______.
IL-1: activates Th0 helper T-cells

IL-6: activates Th2 helper cells, B-cells, plasma cells
Corticosteroids interfere with the function of helper T cells by blocking the expression of the genes for: ????
IL-2 : T-cell proliferation; further activation of IL-2 production from the Th0 cell secreting IL-2

IL-4: stimulates the proliferation of B-cells and the development of Ab-secreting plasma cells

TNF-beta: activates macrophages, NK cells, and CTLs

IFN-gamma: (same as TNF-beta)
What are the net effects of Corticosteroids on helper T cell function?
1. No activation of Th1 & Th2 helper T cells
2. No activation of CTLs
3. No synthesis of TNFbeta & IFNy by helper T cells
4. Reverses the increased expression of MHC II proteins & adhesion molecules by allograft cells
Corticosteroid inhibit the expression of what Lymphokines?
IL-1, 2, 4, 6

IFN-y

TNF
What is the MOA of Cyclosporine?
1. Blocks helper T-cell activation

2. Prevents clonal expansion of T cells and B cells

3. Prevents activation of CTLs
Cyclosporine prevents the transcription of the genes for ?
IL-2
TNF-beta
IFN-y
IL-2 receptors (on T-cell surface)
What enzyme dephosphorylates cytosolic NFATC in activated T-cells?
Calcineurin
What is the function of dephosphorylated NFATC?
Migrates to the nucleus where it activates the genes which code for IL-2, IL-2 receptors, TNF-beta, IFN-y
How does Cyclosporine interfere with signal transduction mechanism that culminates in txn of genes for IL-2, IL-2 receptors, TNFbeta, and IFN-y?
Cyclosporine binds to a cytoplasmic protein called Cyclophilin and the Cyclosporine-Cyclophilin complex inhibits the enzymatic activity of Calcineurin
What is the MOA of Tacrolimus?
Binds to the cytosolic protein FKBP of helper T cells

Tacrolimus-FKBP complex inhibits Calcineurin and thus prevents the production of IL-2, IL-2 receptors, IFN-y by helper T-cells
What is the MOA of Mycophenolate?
Inhibits Inosine Monophosphate Dehydrogenase, an enzyme critical in the de novo synthesis of Guanine by T & B lymphocytes
Why does Mycophenolic acid act specifically on Lymphocytes?
These cells, unlike others derived from the bone marrow, lack HGPRT and thus have no alternate pathway for purine biosynthesis
What is the MOA of Muromonab-CD3 (OKT-3)?
Antibody directed against the CD3 complex of helper T-cells and CTLs

Binding of OKT3 to the CD3 complex blocks the binding of the foreign antigen presented by the APC; helper T-cell cannot be activated

Deactivation of the CD3 complex causes the T-cell receptor antigen recognition site to undergo endocytosis

T-cells become inactive and are removed from the circulation by the reticuloendothelial system