A variety of effector mechanisms participate in allograft rejection (Figure 21-6). The most common are cell-mediated reactions involving delayed-type hypersensitivity and CTL-mediated cytotoxicity; less common mechanisms are antibody-plus-complement lysis and destruction by antibody-dependent cell-mediated cytotoxicity (ADCC). The hallmark of graft rejection involving cell-mediated reactions is an influx of T cells and macrophages into the graft. Histologically, the infiltration in many cases resembles that seen during a delayed-type hypersensitive response, in which cytokines produced by Tdth cells promote macrophage infiltration (see Figure 14-15). Recognition of foreign class I alloantigens on the graft by host CD8+ cells can lead to CTL-mediated killing (see Figure 14-4). In some cases, CD4+ T cells that function as class II MHC-restricted cytotoxic cells mediate graft rejection.
In each of these effector mechanisms, cytokines secreted by Th cells play a central role (see Figure 21-6). For example, IL-2, IFN-7, and TNF-p have each been shown to be important mediators of graft rejection. IL-2 promotes T-cell proliferation and generally is necessary for the generation of effector CTLs (see Figure 14-1). IFN-7 is central to the development of a DTH response, promoting the influx of macrophages into the graft and their subsequent activation into more destructive cells. TNF-p has been shown to have a direct cytotoxic effect on the cells of a graft. A number of cyto-kines promote graft rejection by inducing expression of class I or class II MHC molecules on graft cells. The interferons (a, p, and 7), TNF-a, and TNF-p all increase class I MHC expression, and IFN-7 increases class II MHC expression as well. During a rejection episode, the levels of these cytokines increase, inducing a variety of cell types within the graft to express class I or class II MHC molecules. In rat cardiac allo-grafts, for example, dendritic cells are initially the only cells that express class II MHC molecules. However, as an allograft reaction begins, localized production of IFN-7 in the graft induces vascular endothelial cells and myocytes to express class II MHC molecules as well, making these cells targets for CTL attack.
Effector mechanisms (purple blocks) involved in allograft rejection. The generation or activity of various effector cells depends directly or indirectly on cytokines (blue) secreted by activated Th cells. ADCC = antibody-dependent cell-mediated cytotoxicity.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.