Transplantation and Alloimmunity Quiz

Transplantation and Alloimmunity

• Organ transplantation significantly extends lifespans, but a key challenge is the rejection of transplanted tissue.
• Tissue/cell transfer between individuals often triggers a rejection response due to recognition as foreign.
• This process is known as alloreaction against alloantigens.
• A key factor in rejection is the highly polymorphic nature of MHC
• Finding suitable donor tissue is also a major hurdle, often relying on recently deceased donors.

Immune Responses

• Blood transfusions are a form of transplantation but simpler, lacking MHC class I or II complexities.
• Blood groups (O, A, B, AB) are determined by glycosylation of proteins and lipids on red blood cells (RBCs).
• Natural IgM antibodies are directed against some blood group antigens.

Skin Grafts in Mice

• Skin transplant complexity increases, as matching MHC is more difficult.
• Skin graft experiments in mice illustrate allorejection involves memory T-cells.
• These memory T-cells are a primary driver of chronic rejection after transplant.

Allograft Rejection Types

• Two main types of rejection are:
  • Transplant rejection
  • Graft-versus-host reaction (GVHR)

Additional Key Terms

• Autograft: Tissue transferred within the same individual.
• Syngeneic/Isograft: Transplant between genetically identical/similar individuals (e.g., twins).
• Allograft/Allogeneic Transplant: Transplant between genetically different individuals.

Hyperacute Rejection

• Occurs when pre-existing antibodies against donor antigens exist.
• Rapid rejection due to antibody binding, complement activation, and tissue destruction.
• Usually in the context of pre-existing antibodies to blood group antigens.

Acute Rejection

• More common type of rejection.
• Involves T-cell responses to HLA antigens.
• Takes several days to develop as an allogeneic response.
• Prevented by massive doses of immunosuppressive drugs.

Chronic Rejection

• Takes years to develop.
• Characterized by reactions within the graft vasculature which result in thickening and lack of blood supply (ischemia).
• Antibodies (particularly to class I antigens) are significant in this type of rejection.
• Damage of tissue vasculature by alloreactive antibodies leads to reduced blood flow.

Minor Histocompatibility Antigens

• Even with identical MHC, other genetic differences (minor histocompatibility antigens) can cause rejection.

Immune Suppression

• Corticosteroids are potent immunosuppressive drugs, but come with toxic effects on other organs/tissues.
• Drugs like cyclosporin A and FK506 inhibit T cell activation.

Maternal Fetal Tolerance

• Fetus has paternal MHC but is not rejected by the mother's immune system.
• Placenta, a fetal-derived tissue, is crucial in the prevention of maternal immune response against the fetus.
• Placenta doesn't express certain MHC class molecules, nor is it targeted by NK cells.
• Placenta may utilize cytokines and alternative mechanisms to regulate the maternal immune response.

Transplantation of Hematopoietic Stem Cells

• Used to correct genetic defects.
• Involves destroying diseased hematopoietic system. An infusion of healthy donor bone marrow is administered.
• Stem cells in the graft reconstitute a healthy immune system in the recipient.