Transplant rejection

Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant. Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant. The first successful organ transplant, performed in 1954 by Joseph Murray, involved identical twins, and so no rejection was observed. Otherwise, the number of mismatched gene variants, namely alleles, encoding cell surface molecules called major histocompatibility complex (MHC), classes I and II, correlate with the rapidity and severity of transplant rejection. In humans MHC is also called human leukocyte antigen (HLA). Though cytotoxic-crossmatch assay can predict rejection mediated by cellular immunity, genetic-expression tests specific to the organ type to be transplanted, for instance AlloMap Molecular Expression Testing, have a high negative predictive value. Transplanting only ABO-compatible grafts (matching blood groups between donor and recipient) helps prevent rejection mediated by humoral immunity. Because very young children (generally under 12 months, but often as old as 24 months) do not have a well-developed immune system, it is possible for them to receive organs from otherwise incompatible donors. This is known as ABO-incompatible (ABOi) transplantation. Graft survival and patient mortality is approximately the same between ABOi and ABO-compatible (ABOc) recipients. While focus has been on infant heart transplants, the principles generally apply to other forms of solid organ transplantation. The most important factors are that the recipient not have produced isohemagglutinins, and that they have low levels of T cell-independent antigens. UNOS regulations allow for ABOi transplantation in children under two years of age if isohemagglutinin titers are 1:4 or below, and if there is no matching ABOc recipient. Studies have shown that the period under which a recipient may undergo ABOi transplantation may be prolonged by exposure to nonself A and B antigens. Furthermore, should the recipient (for example, type B-positive with a type AB-positive graft) require eventual retransplantation, the recipient may receive a new organ of either blood type. Limited success has been achieved in ABO-incompatible heart transplants in adults, though this requires that the adult recipients have low levels of anti-A or anti-B antibodies. Kidney transplantation is more successful, with similar long-term graft survival rates to ABOc transplants. Rejection is an adaptive immune response via cellular immunity (mediated by killer T cells inducing apoptosis of target cells) as well as humoral immunity (mediated by activated B cells secreting antibody molecules), though the action is joined by components of innate immune response (phagocytes and soluble immune proteins). Different types of transplanted tissues tend to favor different balances of rejection mechanisms. An animal's exposure to the antigens of a different member of the same or similar species is allostimulation, and the tissue is allogenic. Transplanted organs are often acquired from a cadaver (usually a host who had succumbed to trauma), whose tissues had already sustained ischemia or inflammation. Dendritic cells (DCs), which are the primary antigen-presenting cells (APCs), of the donor tissue migrate to the recipient's peripheral lymphoid tissue (lymphoid follicles and lymph nodes), and present the donor's self peptides to the recipient's lymphocytes (immune cells residing in lymphoid tissues). Lymphocytes include two classes that enact adaptive immunity, also called specific immunity. Lymphocytes of specific immunity T cells—including the subclasses helper T cells and killer T cells—and B cells.