Page 1122 - Veterinary Immunology, 10th Edition

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FIG. 34.5 Role of antibodies and cell-mediated immunity in
different allograft rejection syndromes.

Graft Destruction

Once activated, cytotoxic T cells bind and destroy vascular
endothelium and other accessible cells through caspase-mediated
apoptosis. As a result, hemorrhage, platelet aggregation,

thrombosis, and stoppage of blood flow occur. The grafted tissue
+
dies because of the failure of its blood supply. CD4 T cells that
enter the graft may release cytotoxic cytokines such as TNF-α. This
triggers apoptosis in endothelial cells. Invading cytotoxic T cells can
also cross the basement membrane and cause apoptosis of renal

tubular cells. Activated macrophages releasing proinflammatory
cytokines impair graft function and intensify T cell–mediated
rejection.

Prevention of Allograft Rejection

In preventing allograft rejection, the transplantation surgeon seeks
to induce the minimal level of immunosuppression to prevent
rejection while not making the recipient more susceptible than

necessary to infection. Dogs mount very strong allograft responses,
and kidney allografts are rejected in 6 to 14 days in untreated
animals. Unrelated dogs with renal allografts show about 50% 1-
year survival when treated with azathioprine, prednisolone, and

cyclosporine. Survival is considerably enhanced by a simultaneous

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