"1.15 ORGAN TRANSPLANTATION AND REJECTION A graft is the transplantation of an organ or tissue to a different location, with the goal of replacing a missing or damaged organ or tissue. Grafts are typically relocated without their attachments to the circulatory system and must reestablish these, in addition to the other connections and interactions with their new surrounding tissues. There are different types of grafts depending on the source of the new tissue or organ. Tissues that are transplanted from one genetically distinct individual to another within the same species are called allografts. An interesting variant of the allograft is an isograft, in which tissue from one twin is transplanted to another. As long as the twins are monozygotic (therefore, essentially genetically identical), the transplanted tissue is virtually never rejected. If tissues are transplanted from one area on an individual to another area on the same individual (e.g., a skin graft on a burn patient), it is known as an autograft. If tissues from an animal are transplanted into a human, this is called a xenograft. TRANSPLANT REJECTION The different types of grafts described above have varying risks for rejection (table 1.21). Rejection occurs when the recipient’s immune system recognizes the donor tissue as foreign (non-self), triggering an immune response. The major histocompatibility complex markers MHC I and MHC II, more specifically identified as human leukocyte antigens (HLAs), play a role in transplant rejection. The HLAs expressed in tissue transplanted from a genetically different individual or species may be recognized as non-self molecules by the host’s dendritic cells. If this occurs, the dendritic cells will process and present the foreign HLAs to the host’s helper T cells and cytotoxic T cells, thereby activating them. Cytotoxic T cells then target and kill the grafted cells through the same mechanism they use to kill virus-infected cells; helper T cells may also release cytokines that activate macrophages to kill graft cells. Graft Procedure Complications: Autograft—From self to self—No rejection concerns. Isograft—from identical twin to twin—Little concern of rejection. Allograft—from relative or nonrelative to individual—Rejection possible. Xenograft—from animal to human—Rejection possible. With the three highly polymorphic MHC I genes in humans (HLA-A, HLA-B, and HLA-C) determining compatibility, each with many alleles segregating in a population, odds are extremely low that a randomly chosen donor will match a recipient’s six-allele genotype (the two alleles at each locus are expressed codominantly). This is why a parent or a sibling may be the best donor in many situations—a genetic match between the MHC genes is much more likely and the organ is much less likely to be rejected. Although matching all of the MHC genes can lower the risk for rejection, there are a number of additional gene products that also play a role in stimulating responses against grafted tissue. Because of this, no non-self grafted tissue is likely to completely avoid rejection. However, the more similar the MHC gene match, the more likely the graft is to be tolerated for a longer time. Most transplant recipients, even those with tissues well matched to their MHC genes, require treatment with immunosuppressant drugs for the rest of their lives. This can make them more vulnerable than the general population to complications from infectious diseases. It can also result in transplant-related malignancies because the body’s normal defenses against cancer cells are being suppressed. GRAFT-VERSUS-HOST DISEASE A form of rejection called graft-versus-host disease (GVHD) primarily occurs in recipients of bone marrow transplants and peripheral blood stem cells. GHVD presents a unique situation because the transplanted tissue is capable of producing immune cells; APC"