Immunomodulators for NEET/AIIMS/USMLE/FMGE/PLAB скачать в хорошем качестве

Immunomodulators for NEET/AIIMS/USMLE/FMGE/PLAB

Immunomodulators for NEET/AIIMS/USMLE/FMGE/PLAB PATHOPHYSIOLOGY OF GRAFT REJECTION • When a solid organ is transplanted for e.g. kidney, a foreign protein present in the organ for the recipient’s body is recognized by the MHC receptors and brought out and presented to the local immune cells. • The local immune cells produce inflammatory mediators like IL-1, IL-6 and TNF-α, which stimulate a phosphatase calcineurin present in the CD-4 cells of central lymphoid organs like lymph node and spleen. • Calcineurin being a phosphatase, dephosphorylates cytoplasmic nuclear factor for activation of T lymphocytes (NFATC), which can enter in to the nucleus and combines with NFATN and increases transcription actor for synthesis of IL-2. • IL-2 acts on the IL-2 receptors present in resting CD-8 cells and pushes it in to cell cycle of proliferation; G1-S phase being mediated by a protein called as m-tor. • These CD-8 lymphocytes once released in to systemic circulation attack the foreign protein in the kidney and cause inflammatory damage leading to graft rejection. This process can be inhibited by various drugs as given below. 1. Steroids - Inhibit synthesis of inflammatory mediators/induce apoptosis of lymphocytes 2. Cyclosporine/Tacrolimus - Block calcineurin and decrease transcription of IL-2 3. Basailiximab/Daclizumab - Block CD-25 4. Sirolimus/Everolimus - Block m-TOR and thus inhibit lymphocyte proliferation at G1-S phase 5. Azathioprine - Block lymhocyte proliferation at S phase