Excerpt from Immunosuppression

Synonyms, Key Words, and Related Terms: immunosuppression, immunosuppressive therapy, organ transplantation, graft rejection

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Organ transplantation elicits a complex series of immunologic processes. These processes are generally categorized as inflammation, immunity, and tissue repair and structural reinforcement of damaged tissues. Inflammation in the transplantation site is mediated by macrophages and T cells and proinflammatory mediators (eg, interleukin 2 [IL-2]). Activation of biochemical cascades (eg, classic complement cascade) results in elaboration of bioactive intermediates such as C3a and C5a. After antigens have been effectively controlled by the immune system, macrophages, endothelial cells, smooth muscle cells, and fibroblasts begin to promote repair and structural reinforcement of damaged cells.

Rejection results when a pathologic and intense inflammatory response develops or when repair and remodeling of tissues fails. In hyperacute rejection, transplant patients are serologically presensitized to alloantigens (ie, graft antigens are recognized as foreign). Hyperacute rejection may develop within minutes to hours of graft implantation.

In acute rejection, graft alloantigens are encountered by T cells, with resulting cytokine (and possibly antibody) release that then leads to tissue distortion, vascular insufficiency, and cell destruction. These processes can occur within 24 hours after graft implantation and continue over a period of days to weeks.

In chronic rejection, pathologic tissue remodeling and reinforcement occurs. Blood flow is reduced, which leads to regional tissue ischemia, fibrosis, and cell death.

The introduction of routine pretransplant screening of graft recipients for antidonor antibodies has made hyperacute rejection rare nowadays. No accepted therapeutic strategy currently exists to treat chronic rejection.

The control of acute rejection has been the primary aim of immunosuppression, thereby allowing tissue repair to progress. The use of combination immunosuppressive therapy has evolved over a number of years.

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