Overview
In the clinical situation the vast majority of transplants are allografts, organs transplanted between genetically different individuals of the same species. These will be the focus of this chapter. However, the future may hold the option of xenografting where organs are transplanted from one species to another. Commercial and other considerations have dictated the choice of the pig as a potential donor for humans. Where appropriate, mention will be made of xenotransplantation.
Graft rejection is often categorized according to the tempo at which it happens. The terms hyperacute, acute and chronic rejection are used to describe graft damage that occurs in minutes to hours, days to weeks, or months to years after transplantation, respectively [1]. However, the mechanisms responsible for acute rejection may be activated late after transplantation, while the changes characteristic of chronic rejection may be seen very early after transplantation in some recipients. Hence it is generally better to think in terms of the underlying mechanisms and accept that the immune system will do its utmost, using almost every specific and nonspecific mechanism it can muster, to destroy the transplanted tissue. In general, if steps were not taken to overcome the mechanisms of rejection then the majority of grafts would be lost very quickly.
To complicate matters, the graft itself responds to the transplantation procedure and to its new and often hostile environment. The period of cold ischaemia during the transplantation procedure elicits the expression of a range of new molecules, including adhesion molecules, proinflammatory cytokines and chemokines. These serve to promote the infiltration of the graft by recipient leukocytes, first by neutrophils, followed by monocytes and macrophages then ultimately by lymphocytes.