62. | Principles of Surgery, Companion Handbook

Principles of Surgery Companion Handbook

FIGURE 10-1 T-cell receptor activation through its interaction with MHC and adhesion molecules and the mechanism of action of selected immunosuppressants. The TCR binds to an MHC molecule (class II is shown). This event is stabilized by an accessory molecule (CD4 or CD8, depending on the MHC class). The costimulatory molecule gp39 upregulates the expression of the APC costimulation molecules B7, shifting the balance of negative regulation by CTLa4 to positive regulation by CD28. This potentiates signal transduction and activation of NF-AT, which in turn induces IL-2 synthesis. IL-2 works in an autocrine loop to force the cell into a division cycle. Cyclosporine (CyA) and tacrolimus (FK506) both block this signal transduction by blocking the calcineurin/calmodulin-potentiating proteins cyclophilin and FK-binding protein, respectively. Rapamycin (RAP) blocks the IL-2 receptor signal transduction by blocking the interaction of RAFT and FK-binding protein.