19.3 Organ transplantation and rejection

Learning objectives

• Explain why human leukocyte antigens (HLAs) are important in tissue transplantation
• Explain the types of grafts possible and their potential for interaction with the immune system
• Describe what occurs during graft-versus-host disease (GVHD)

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 moved 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 allograft s . 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 ( [link] ). 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.

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.