The immune system is a protection against foreign substances, oоr "nonsetf ". The strength of the immune response to transplants increases with the genetic disparity between donor and recipient, but violent immune responses can occur even when donor and recipient are the same species, as in human cadaver kidney transplantation.

Graft rejection is initiated by foreign histocompatibility antigens on cell surfaces or free within the graft. Mismatched ABO blood group antigens can elicit strong graft rejections in recipients with natural isoantibodies. Vertebrate species have a major histocompatibility complex (MHC) that is primarily responsible for allograft rejection. The human MHC, located on chromosome 6, is the human leukocyte antigen (HLA) complex; it governs the production of cell surface antigens of major and minor strengths. The HLA complex, which has been divided into class I and class II, can be identified on cell surfaces by monospecific typing antisera (HLA typing). The class I antigens, such as HLA-A and HLA-B, were originally defined through the generation of cytotoxic allogeneic T lymphocytes. Usually these antigens are unable to initiate prolifteration of allogeneic lymphocytes. The class II antigens, such as HLA-DR, can initiate allogeneic helper T lymphocyte proliferation.

When an allograft is revascularized in a patient, the donor histocompatibility antigens initiate an immune response in the recipient. Strong allograft-specific responses result from the direct presentation of donor antigens on the surfaces of "macrophage type" cells in the graft. Donor antigens also may be processed by recipient macrophages, monocytes, or dendritic cells, which activate helper T lymphocytes and B lymphocytes in the recipient's spleen and lymph nodes. The multiple steps in this activation process are incompletely understood, but the lymphokines interleukin-1 and interleukin-2 are almost certainly important intercellular activation messengers.

The T lymphocytes (thymus-dependent) primarily mediate cellular immune responses. T lymphocyte subclasses can be defined by antigenic markers (e. g., T4 and T8) that purport to identify functionally distinct subsets (T4 helper and T8 cytotoxic); however, such absolute functional distinctions are questionable. Currently T4 is defined by its ability to recognize class II

antigens, and T8 is defined by its ability to recognize class I antigens.

The B lymphocytes are named after the avian bursa of Fabricius, the human functional analog of which is probably bone marrow and gut lymphoid tissue. B lymphocytes produce antibodies against donor antigens. These antibodies are not required for graft rejection, which can occur without antibody; however, alloantibodies against donor antigens participate in some forms of rejection.

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