Allorecognition

Two types of recognition: Direct recognition occurs when the recipients T c ells recognize allogenic antigens presented by the donor antigen presenting cells. indirect recognition occurs when donor antigens on recipient antige n presenting cells are recognized. Direct recognition: Direct recognition occurs during the first days or week s after transplantation when naive recipient cells recognize donor dendriti c cells that have migrated to secondary lymphoid organs. This explains why acute rejection occurs mainly during the first weeks after transplantation. Indirect recognition: This is certainly a less intense mechanism than direc t recognition. It probably is involved in acute rejection but is known to p lay a major role in chronic rejection. CD4 cells that have been activated b y indirect recognition play an essential role in activating B cells, leadin g to the formation of anti-HLA antibodies as well as in activating macropha ges and monocytes, endothelial cells and smooth muscle cells. Induction of tolerance: Three mechanisms of action for regulating the allo- immune response leading to graft tolerance have been put forward: consumpti on of interleukin-2, production of suppressive cytokins, direct or indirect suppressive contact. T cell activation: Knowledge of the intracellular signals induced by T cell receptor activation makes it possible to target key proteins that could be blocked leading to better immunosuppression than with calcineurin inhibiti on.