Organ Graft Rejection Overview

Organ Graft Rejection

• Organ graft rejection is a reflection of the immune system's function to identify and destroy foreign cells.
• Different types of tissue or organ grafts exist, including autografts, isografts, allografts, and xenografts.
• Autografts are grafts transplanted to a different part of the same organism (e.g., skin graft).
• Isografts are grafts transplanted between genetically identical individuals (e.g., twins).
• Allografts are grafts between genetically different individuals of the same species (e.g., a dog receiving a kidney from a genetically different dog).
• Xenografts are grafts between animals of different species (e.g., a baboon heart transplanted to a human).
• Allografts are the most frequent type of organ graft
• Differences in MHC and blood group antigens lead to a strong immune response and rejection.
• Rejection of a graft occurs due to differences in MHC molecules, blood group antigens, and other foreign molecules on the graft cells.
• Grafts between genetically identical individuals are never rejected.
• Grafts between genetically different individuals are always rejected.
• Rejection of a graft can be hyperacute, accelerated, acute, or chronic.
  • Hyperacute usually occurs immediately,
  • accelerated rejection happens within 7 days of grafting,
  • acute rejection happens after 7 days of grafting,
  • chronic rejection appears months after grafting.
• Most current organ grafts come from healthy donor animals.
• Renal allografting is now a routine procedure in cats and dogs.
• Bone marrow allografts are useful in some tumor therapies.
• The rejection process has two stages: a direct and indirect pathway.
  • The direct pathway involves host lymphocytes encountering antigens on the graft and triggering a response.
  • The indirect pathway involves cytotoxic T cells and antibodies from the host entering the graft and destroying cells.
• The main mechanism in allograft rejection involves the immune system recognizing foreign MHC and blood group antigens on the graft.
• Acute rejection causes injury to the graft parenchyma and blood vessels, with damage mediated by alloreactive T cells and antibodies.
• Chronic rejection involves arterial occlusion due to smooth muscle proliferation and resulting in graft failure due to ischemic damage.

Prevention of Allograft Rejection

• The main goal of prevention is to minimize immunosuppression to prevent rejection without increasing susceptibility to infections.
• General strategies for prevention include inhibiting T cell signaling pathways, using antimetabolites, and anti-inflammatory drugs.
• Examples of inhibitors of T cell signaling pathways include cyclosporine and FK506.
• Examples of antimetabolites include azathioprine and mycophenolate mofetil.
• Function-blocking and depleting anti-lymphocyte antibodies and costimulatory blockade are also used in prevention.

Graft-Versus-Host Disease (GVHD)

• GVHD occurs when grafted T cells in bone marrow inoculum react against the host's antigens (alloantigens).
• GVHD happens when the host's immune system is suppressed, allowing the graft to survive.
• GVHD can occur as a result of total-body irradiation or cyclophosphamide treatment.
• Acute GVHD causes cell death in the skin, liver, and gastrointestinal tract, often manifested as rash, jaundice, diarrhea, and gastrointestinal hemorrhage.
• Chronic GVHD involves fibrosis and atrophy of various organs without evidence of acute cell death.

This quiz explores the concept of organ graft rejection, highlighting the immune system's role in identifying foreign cells. It covers various types of grafts such as autografts, isografts, allografts, and xenografts, along with the reasons for graft rejection due to different MHC molecules and blood group antigens.