Transplantation Immunology
A major limitation to the success of transplantation is the immune response of the recipient against donor tissue. Transplant rejection occurs when the recipient’s immune system recognizes the graft as foreign and mounts an immune response that ultimately destroys the transplanted tissue.
The likelihood and severity of rejection can be reduced by assessing molecular similarity between donor and recipient, particularly histocompatibility antigens, and by the use of immunosuppressive drugs following transplantation.
Immunology of Allogeneic Transplantation
Allogeneic transplantation involves the transfer of tissue between genetically different individuals of the same species. Alloantigens expressed on donor tissue elicit both cell-mediated and humoral immune responses.
Recognition of whether transplanted cells are self or foreign is determined by polymorphic genes inherited from both parents, which are expressed co-dominantly.
Recognition of Alloantigens
Alloantigens are recognized by the recipient immune system through two main pathways:
1. Direct Presentation
- Recipient T cells recognize intact donor MHC molecules displayed on donor antigen-presenting cells (APCs) within the graft.
- Essentially, recipient T cells recognize the structure of an intact allogeneic MHC molecule as foreign.
2. Indirect Presentation
- Donor MHC molecules are processed by recipient APCs and presented as peptides on recipient MHC molecules.
- In this pathway, donor MHC is treated like any other foreign antigen.
Activation of Alloreactive T Cells and Rejection of Allografts
Donor APCs migrate from the graft to the recipient’s regional lymph nodes, where they are recognized by recipient T cells. Alloreactive T cells may be
activated by both direct and indirect pathways. Once activated, these T cells migrate into the graft and initiate graft rejection.