Transplantation involves the ability to replace damaged or diseased body parts by transplanting organs from one individual to another. Unfortunately, the immune system is exquisitely adept at recognizing nonself and rejecting transplanted organs from donors differing genetically from the recipient ( 89). The genetically encoded molecules that trigger the rejection response are termed histcccmpatibility antigens and are divided into two primary categories: major (encoded by class I and II MHC genes) and minor (scores, possibly hundreds, of antigens encoded by widely diverse genes scattered across the chromosomes). Because a genetically perfect match between host and donor in humans exists only between identical twins, transplantation surgeons are forced to minimize or eliminate the recipient immune response against the transplanted organ. Some of these responses can be minimized by using the closest possible genetic match between donor and recipient by tissue typing, but in humans, this is possible only for the HLA system. The alternative is the use of drugs to reduce immune responsiveness. Ideally, only the ability of the immune system to react to the antigens on the transplanted organ would be diminished (i.e., induction of antigen-specific immunologic tolerance), leaving the rest of the immune system intact. However, we currently must rely on drugs that depress the immune system in a relatively nonspecific fashion, thus leaving the patient susceptible to potentially fatal opportunistic infections. Recently, some agents (i.e., cyclosporine and FK506) have been found to diminish immune responses in a somewhat more specific fashion, but their long-term use may have secondary adverse effects on organs.
Bone marrow transplantation represents a special case in which the graft itself comprises immunocompetent tissue and the host is either immunodeficient or immunosuppressed. Thus, there is the possibility of the graft mounting an immune response against foreign host cells and tissues, leading to graft-versus-host disease (90,91)
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