Immune modulators Flashcards
What is IL-2 and what does it do?
A cytokine that stimulates the cell-mediated immune response.
What can recombinant IL-2 be used to treat?
Metastatic melanoma and renal cell carcinoma.
How does CsA and FK-506 work to suppress the cell mediated immune response?
IL-2 modulator.
CsA and FK-506 (Tacrolimus) enter the T cell.
Bind to immunophillins (CyP A and B and FKBP 12).
Complex binds to calcineurin.
Calcineurin cannot bind to and de-phosphorylate NF-AT.
NF-AT cannot enter nucleus and bind to IL-2 promoter. Therefore, IL-2 not synthesised.
How does Rapamycin work to suppress the cell mediated immune response?
IL-2 modulator.
Rapamycin (sirolimus) binds to FKBP.
Complex binds to mTOR.
Causes cell cycle arrest at G1.
Therefore, inhibits signalling of IL-2.
Clinical use of CsA and FK-506/Tacrolimus?
To prevent rejection in organ transplants/allografts.
Clinical uses of rapamycin/sirolimus?
- To prevent rejection in organ transplants/allografts.
- To treat cancer.
- To prevent stent-induced intimal hyperplasia by using coated stents.
Toxicity of IL-2 modulators?
Nephrotoxicity.
Rapamycin less toxic but tends to cause dyslipidemia.
Examples of IL-1 modulators?
Anakinra and Canakinumab.
Clinical use of IL-1 modulators?
RA.
Key actions of TNF a?
Increase inflammation Increase cell infiltration Increase angiogenesis Increase CRP in serum Articular cartilage degradation.
Examples of TNFa modulators?
Etanercept Infliximab Adalimumab Golimumab Certolizumab. Thalidomide.
(Refer to cytokine lecture slide 38 on nomenclature and the drug document.)
Examples of stimulatory cytokines?
IL-1, 2 and TNF
Examples of inhibitory cytokines?
IL-4, 10, 13.
What is cyclophoshamide and what does it do?
Alkylating cytotoxic immunosuppressant.
Causes leucopenia (granulocytes, lymphocytes, monocytes, and inhibit NK cells.)
SE’s: Alopecia and nausea.
What are integrins?
Cell adhesion molecules. Usually proteins.
e.g, GPIIb/IIa ( alpha IIb/ beta3) on platelets.
Beta2 on lymphocytes.