Transplantation of some organs and tissues between genetically non-identical humans is a well-established clinical procedure. Such grafts are called allografts. Xenografts, from non-human species, such as pigs, may become more widely available with the development of cloned animals having tissues more closely compatible with humans. The major drawback to graft transplantation is possible immunological rejection of the transplant. Body cells vary antigenically from individual to individual, and
differences between tissues of the transplant donor and recipient lead to rejection of the graft. Transplantation rejection in this situation is predominantly a type IV cellular immunological reaction showing both specificity and memory. Killing of the graft cells occurs through a complex combination of mechanisms, including direct contact with sensitized T-cytotoxic lymphocytes and natural killer (NK) cells. The ability to overcome immunologic rejection by treatment with immunosuppressive agents allows the grafts to survive. Perspective 18.1 discusses a very special transplantation situation, the fetus as an allograft. ■ T-cytotoxic cells, p. 394 ■ NK cells, p. 411
There are many different tissue antigens, but those of the major histocompatibility complex (MHC) system are the ones most commonly involved in transplantation graft rejections. Although these MHC antigens are found on many human cells, they are abundant on leukocytes and so have been called human leukocyte antigens or HLAs. MHC tissue typing is done in an effort to ensure that no major tissue incompatibility exists between a prospective tissue donor and the recipient patient. In addition to carefully matching donor and recipient tissue antigens, it is necessary to use immunosuppressant drugs indefinitely to prevent graft rejection. These drugs are needed because many minor antigens exist and except with identical siblings it is impossible to find a donor compatible in all of these tissue antigens. ■ MHC molecules, p. 407
Radiation and various cytotoxic immunosuppressive drugs interfere with the rejection process, but at the same time they make the patient highly susceptible to opportunistic infections and also more likely to develop cancer. Cyclosporin A (produced by a fungus) and tacrolimus (produced from a species of Streptomyces) are safer and more effective immuno-suppressants. They interfere with cellular signaling and thereby inhibit clonal expansion of activated T lymphocytes. These drugs specifically suppress T-cell proliferation, and thus they have fewer side effects than other immunosuppressants that affect many cell types.
Combinations of agents are commonly used to prevent allograft rejection. For example, cyclosporin A and steroids may be given, along with a monoclonal antibody preparation called basiliximab. This preparation binds to interleukin-2 receptors and blocks IL-2 binding.
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