MCH restriction to antigen presentation is not done for
Correct Answer: Graft rejection
Description: Ref Robbins 9/e p231-233 Immune Recognition of Allografts Rejection of allografts is a response mainly to MHC molecules, which are so polymorphic that most individuals in an outbred population differ in at least some of the MHC molecules they express (except, of course, for identical twins). There are two main mechanisms by which the host immune system recognizes and responds to the MHC mol- ecules on the graft (Fig. 4-23): * Direct recognition. Host T cells directly recognize the allo- geneic (foreign) MHC molecules that are expressed on graft cells. Direct recognition of foreign MHC seems to violate the rule of MHC restriction, which states that in every individual, all of the T cells are educated to recog- nize foreign antigens displayed by only that individual's MHC molecules. It is postulated that allogeneic MHC molecules (with any bound peptides) structurally mimic self MHC and foreign peptide, and so direct recognition of the allogeneic MHC is essentially an immunologic cross-reaction. Because DCs in the graft express high levels of MHC as well as costimulatory molecules, they are believed to be the major culprits contributing to direct recognition. The most impoant consequence of direct recognition is the activation of host CD8+ T cells that recognize class I MHC (HLA-A, -B) molecules in the graft. These T cells differentiate into CTLs, which kill the cells in the graft. Host CD4+ helper T cells may be trig- gered into proliferation and cytokine production by rec- ognition of donor class II MHC (HLA-D Indirect recognition. In this pathway, host CD4+ T cells recognize donor MHC molecules after these molecules are picked up, processed, and presented by the host's own APCs. This sequence is similar to the physiologic processing and presentation of other foreign (e.g., microbial) antigens. The activated CD4+ T cells then recognize APCs displaying graft antigens and secrete cytokines that induce inflammation and damage the graft. The indirect pathway is also involved in the pro- duction of antibodies against graft alloantigens; if these antigens are proteins, they are picked up by host B cells, and peptides are presented to helper T cells, which then stimulate antibody responses.
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