graft rejection

Graft rejection, transplant rejection, or allograft rejection is a normal process in which the functional immune system of a transplant recipient attacks the transplanted organ or tissue. Immunosuppressive drugs are administered to recipients in order to minimize the risk of rejection. Rarely, the donor stem cells of an allogeneic stem cell transplant will not survive because of their attack by the recipient's lymphocytes. Conditioning of patients with cytotoxic therapy prior to transplantation is intended to suppress the recipient's immune system sufficiently to avoid graft rejection. In occasional recipients, a graft may be unsuccessful because too few donor cells have been infused.

An emerging body of evidence suggests that innate immunity, providing the first line of host defence against invading pathogens or their components (PAMPs), also plays a critical role in acute and chronic allograft rejection. Donor organ injury induces an inflammatory milieu in the allograft, and this appears to be the initial key event for activation of the innate immune system. Injury-induced generation of putative endogenous molecular ligand, in terms of damage/danger-associated molecular patterns (DAMPs) such as heat shock proteins, are recognized by toll-like receptors (TLRs). Acute allograft injury such as oxidative stress during donor brain-death condition and post-ischemic reperfusion injury in the recipient could induce DAMPs, which may activate innate TLR-bearing dendritic cells, which could initiate the recipient´s adaptive alloimmune response by way of direct allo-recognition through donor-derived DCs and indirect allo-recognition through recipient-derived DCs, leading to acute allograft rejection. Chronic injurious events in the allograft induce the generation of DAMPs, which may interact with and activate innate TLR-bearing vascular cells (endothelial cells, smooth muscle cells), contributing to the development of atherosclerosis of donor organ vessels and promoting chronic allograft rejection.[from]

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. . . since 10/06/06