Organ Transplantation and Rejection Notes
Learning Objectives
- Explain the importance of Human Leukocyte Antigens (HLAs) in tissue transplantation.
- Describe the different types of grafts and their interaction with the immune system.
- Understand the mechanics of graft-versus-host disease (GVHD).
Definition of Grafts
- Graft: Transplantation of organ/tissue to replace missing or damaged parts.
- Grafts are moved without circulatory connections and must establish new ones.
Types of Grafts
Autograft: Tissue transplanted from one location to another in the same individual.
- Example: Skin graft from one area of a burn patient to another area.
Isograft: Tissue transplanted between genetically identical individuals (e.g. twins).
- Notes: Very low risk of rejection due to genetic similarity.
Allograft: Tissue transplanted between genetically distinct individuals of the same species.
- Examples: Any organ transplant between non-identical humans.
Xenograft: Tissue transplanted from an animal to a human.
- Notes: Higher risk of rejection because of species difference.
Transplant Rejection
- Definition: Occurs when the recipient’s immune system identifies the graft as foreign.
- Mechanism:
- HLAs (Human Leukocyte Antigens) are recognized as non-self by the recipient’s immune cells (specifically dendritic cells).
- Dendritic cells activate helper T-cells and cytotoxic T-cells.
- Cytotoxic T-cells: Attack and destroy grafted cells.
- Helper T-cells: Release cytokines to enhance immune response.
Risks of Rejection by Graft Type
| Graft Type | Procedure | Complications |
|---|---|---|
| Autograft | From self | No rejection concerns |
| Isograft | From identical twin | Little concern of rejection |
| Allograft | From relative/non-relative | Rejection possible |
| Xenograft | From animal | Rejection possible |
- MHC Genes:
- MHC I markers (HLA-A, HLA-B, HLA-C) have multiple alleles.
- Low chances of matching a random donor's six-allele genotype.
- Preferred Donor: Blood relatives are ideal due to higher likelihood of matching HLAs.
Immunosuppression
- Most transplant recipients require lifelong immunosuppressant therapy due to rejection risk.
- Risks: Increased susceptibility to infections and potential for transplant-related cancers due to suppressed immune defense.
Graft-versus-Host Disease (GVHD)
- Occurrence: Primarily in bone marrow transplants and peripheral blood stem cells.
- APCs from the donor tissue may target the recipient's own tissues as foreign.
- Acute GVHD: Develops within weeks; affects skin, GI tract, liver, and eyes. Can induce fatal cytokine storms.
- Chronic GVHD: May develop months later; mechanisms are less understood.
- Prevention: Matching HLAs closely and processing bone marrow to reduce donor T-cells.
Future of Transplantation
- Historical Context: First successful organ transplant in 1954; rapid advancements in techniques since then.
- Research Directions:
- Creating organs from an individual’s cells to minimize rejection risks.
- Genetic modification of donor animals (e.g., pigs) to make organs that elicit less immune response.
- Challenges include identifying and removing rejection-related genes and managing potential viral risks from the donor genome.