Although transplantation of tissues to replace diseased organs has emerged as an important medical therapy, adaptive immune responses to the grafted tissues are a major impediment. Rejection is caused by immune responses to alloantigens on the graft, which are proteins that vary from individual to individual within a species and are therefore perceived as foreign by the recipient. When tissues containing nucleated cells are transplanted, T-cell responses to the highly polymorphic MHC molecules almost always trigger a response against the grafted organ. Matching the MHC type of the donor and the recipient increases the success rate of grafts, but perfect matching is possible only when donor and recipient are related, and even in these cases, genetic differences at other loci can still trigger rejection, although less severely. Nevertheless, advances in immunosuppression and transplantation medicine now mean that the precise matching of tissues for transplantation is no longer the major factor in graft survival. In blood transfusion, the earliest and most common tissue transplant, MHC matching is not necessary for routine transfusions, because red blood cells and platelets express small amounts of MHC class I molecules and do not express MHC class II molecules; thus, they are not usually T-cell targets. However, antibodies made against platelet MHC class I molecules can be a problem when repeated transfusions of platelets are required. Blood must be matched for ABO and Rh blood group antigens to avoid the rapid destruction of mismatched red blood cells by antibodies in the recipient (see Appendix I, Sections A-5 and A-7), but because there are only four major ABO types and two Rh types, this is a relatively easy form of tissue matching.
In this part of the chapter we examine the immune response to tissue grafts and also ask why such responses do not reject the one foreign tissue graft that is tolerated routinely—the mammalian fetus.
15-29 Graft rejection is an immunological response mediated primarily by T cells.
The basic rules of tissue grafting were first elucidated by skin transplantation between inbred strains of mice. Skin can be grafted with 100% success between different sites on the same animal or person (an autograft), or between genetically identical animals or people (a syngeneic graft). However, when skin is grafted between unrelated or allogeneic individuals (an allograft), the graft initially survives but is then rejected about 10–13 days after grafting
Fig. 15.45 Skin graft rejection is the result of a T-cell-mediated a second‑set rejection, and the accelerated response is MHC‑anti-graft response. Grafts that are syngeneic are permanently specific; skin from a second donor of the same MHC type is rejected accepted (first panels), but grafts differing at the MHC are rejected equally fast, whereas skin from an MHC‑different donor is rejected about 10–13 days after grafting (first‑set rejection, second panels). in a first‑set pattern (not shown). Naive mice that are given T cells When a mouse is grafted for a second time with skin from the same from a sensitized donor behave as if they had already been grafted donor, it rejects the second graft faster (third panels). This is called (final panels).
(Fig. 15.45). This response is called an acute rejection, and it depends on a T-cell response, because skin grafted onto nude mice, which lack T cells, is not rejected. The ability to reject skin can be restored to nude mice by the adoptive transfer of normal T cells.