Acute Rejection

Overview
  • Acute Rejection is a particular pattern of host immune rejection of donor tissue.
Pathogenesis
  • Overview
    • Acute Rejection is the result of both Humoral and Cell-mediated Immune Responses of the host against donor tissues. Because the Adaptive Immune Response to donor tissues takes time to develop and mature, the pathological consequences of Acute Rejection do not become apparent for days or weeks following transplantation and can be slowed with Immunosuppressive Drugs. However, even in those receiving Immunosuppressive therapy, the pathogenesis of Acute Rejection is only slowed and pathology may manifest months to years laster.
  • Cell-mediated Acute Rejection
    • Host Cell-mediated immunity to donor tissue essentially follows a Type IV Hypersensitivity reaction to cells which possess foreign MHC antigens. The Type IV Hypersensitivity reaction progresses via both Delayed-type Hypersensitivity (DTH) and T-cell-mediated Cytotoxicity mechanisms. The DTH response occurs when host Antigen Presenting Cells phagocytose and display fragments of donor MHC molecules, resulting in the generation of host CD4+ T-cells which infiltrate the donor organ and elaborate inflammatory cytokines. T-cell-mediated Cytotoxicity is thought to occur via a complex mechanism in which host CD8+ T-cells mistake donor MHC I molecules displaying donor self-antigens for host MHC I molecules displaying microbial antigens. This causes host cytotoxic CD8+ T-cells to mistakenly attack donor cells displaying non-microbial self-peptides.
  • Humoral Acute Rejection
    • Humoral Acute Rejection involves the development and maturation of host B-cells which secrete antibodies that bind donor antigens, especially donor MHC molecules. Binding of antibody to donor antigens can then cause activation of complement or direct recruitment of host inflammatory cells into donor tissue via the Fc Region of anti-donor antibody. Perhaps the more serious insult is the activation of the coagulation cascade which results in thrombosis and occlusion of donor vasculature.
Morphology
  • Overview
    • Both Cell-mediated and Humoral processes of acute rejection occur following an organ transplantation and result in inflammation and injury to the donor tissue. However, the histological pattern of inflammation will vary given which immune process dominates pathogenesis of Acute Rejection.
  • Cell-mediated Acute Rejection Predominates:
    • The inflammatory infiltrate in the donor organ is largely made up of T-cells of both CD4+ and CD8+ specificity. Inflammation is accompanied by interstitial edema and Hemorrhage.
  • Humoral Acute Rejection Predominates
    • Primarily results in a vasculitis with a predominantly neutrophilic infiltrate and may include thrombosis of micro-vasculature.
Prevention
  • Pathogenesis of Acute Rejection is reduced by matching of MHC protein alleles between recipient and donor.
Treatment
  • Treatment with immunosuppressive drugs can attenuate and slow the pathogenesis of Acute Rejection. Frequent drugs used include cyclosporine, glucocorticoids, azathioprine, as well as neutralizing monoclonal antibodies to T-cell Receptor. However, administration of these drugs can lead to profound reductions in immunity to certain infectious microbes.