Summary of "Transplantation"
Summary of Scientific Concepts, Discoveries, and Phenomena in Transplantation
Definition of Transplantation
Transplantation is the transfer of living cells, tissues, or organs from one part of the body to another or from one individual to another. It is primarily used to replace damaged or failed organs that cannot be treated by medication alone.
Common Indications for Liver Transplantation
- Adults:
- Most common: Liver cirrhosis due to Hepatitis C virus infection
- Second most common: Alcoholic liver disease
- Children:
- Biliary atresia
Sources of Donated Organs
- Deceased donors
- Living donors
- Animal donors (xenografts)
History
- The first successful kidney transplant was performed in 1954 by Dr. Joseph Murray between monozygotic identical twins, which avoided immunological rejection.
- Dr. Murray was awarded the Nobel Prize in Medicine in 1990 for this work.
Immunological Challenges
- Transplant rejection occurs due to an immune response against the graft.
- Transplantation between identical twins avoids rejection due to identical immune systems.
- Transplantation between different individuals requires immunosuppressive therapy to prevent graft rejection.
Immunosuppressive Therapy
- Early immunosuppressants included azathioprine and corticosteroids.
- Cyclosporine, discovered later, blocks interleukin-2 and inhibits lymphocyte proliferation, improving transplant success.
- Other immunosuppressants include tacrolimus and mycophenolate mofetil.
- Immunosuppression increases the risk of infections (bacterial, viral, fungal) and malignancies such as skin cancers and post-transplant lymphoproliferative disease caused by Epstein-Barr virus.
Types of Grafts
- Autograft: Transplant within the same individual (e.g., skin grafts, hair transplantation). No immune rejection or need for immunosuppression.
- Isograft: Transplant between genetically identical individuals (e.g., identical twins). No immune rejection.
- Allograft: Transplant between different individuals of the same species. Immune rejection occurs; immunosuppression needed.
- Xenograft: Transplant between different species (e.g., pig heart valves to humans). Immune rejection occurs; immunosuppression needed.
Graft Placement Types
- Orthotopic graft: Placed in the normal anatomical site (e.g., liver transplant in liver position).
- Heterotopic graft: Placed in a different anatomical site (e.g., kidney transplanted in iliac fossa).
Renal Transplantation Specifics
- The left kidney is preferred due to a longer renal vein.
- The kidney is transplanted in the iliac fossa with three anastomoses:
- Renal vein to external iliac vein
- Renal artery to external iliac artery
- Ureter to urinary bladder
- Most common cause for adult renal transplantation: Chronic kidney disease secondary to diabetic nephropathy.
- In children: Glomerulonephritis.
Immunological Basis of Graft Rejection
- Graft rejection is an immune response, not merely an inflammatory response.
- T lymphocytes (especially CD8+ and CD4+ subsets) play a central role.
- Human Leukocyte Antigens (HLA) are the major cause of graft rejection.
- HLA antigens are encoded by the Major Histocompatibility Complex (MHC) genes on chromosome 6.
- HLA Class I antigens: A, B, C (recognized by CD8+ T cells).
- HLA Class II antigens: DP, DQ, DR (recognized by CD4+ T cells).
- Matching donor and recipient HLA antigens, especially HLA-B and HLA-DR, reduces rejection risk.
Mechanism of Graft Rejection
- CD8+ T cells recognize HLA Class I antigens and release cytotoxic molecules (perforins, granzymes) to kill graft cells.
- CD4+ T cells recognize HLA Class II antigens and release interferon-gamma, activating macrophages to destroy the graft.
- CD4+ T cells also stimulate B cells to produce antibodies against graft antigens.
Types of Allograft Rejection
- Hyperacute rejection
- Occurs within minutes to hours.
- Caused by preformed antibodies (Type II hypersensitivity).
- Common in kidney transplants, rare in liver (liver is resistant).
- Characterized by thrombosis and vascular damage.
- Acute rejection
- Occurs within weeks to 6 months.
- Mediated by T lymphocytes (Type IV hypersensitivity).
- Can be reversed with immunosuppressive therapy.
- Chronic rejection
- Occurs after 6 months.
- Major cause of graft failure.
- Characterized by vascular changes, fibrosis, and ischemia.
- Also a Type IV hypersensitivity reaction.
Graft-versus-Host Disease (GVHD)
- Occurs when immunocompetent graft cells attack an immunocompromised recipient.
- Common after bone marrow, liver, and small bowel transplants.
- Prevented by irradiated or leukocyte-depleted blood products.
- Also a complication of blood transfusions.
Immunosuppressive Agents
- Aim to maximize graft survival with minimal side effects.
- Common agents include:
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- Corticosteroids
- Antiproliferative agents
- Side effects include nephrotoxicity, hypertension, infections, and malignancies.
- Risk of infection is highest in the first 1–6 months post-transplant.
- Cytomegalovirus infection is common after 3–6 months and is managed with antiviral drugs (e.g., ganciclovir).
Organ Preservation
- Donor organs are flushed with University of Wisconsin (UW) solution or Euro-Collins solution.
- Stored at 0–4°C to reduce ischemic damage.
- Two ischemic times are important:
- Warm ischemic time: Time between blood supply interruption and organ cooling.
- Cold ischemic time: Time the organ is preserved on ice before transplantation.
- Kidneys have the longest cold ischemic time (up to 36 hours).
- Hearts have the shortest cold ischemic time (3–6 hours).
Outcomes
- Transplantation improves quality and duration of life.
- One-year survival rates are greater than 90% for kidney, liver, and heart transplants.
- Five-year survival rates exceed 80%.
- Lung and small bowel transplant outcomes are less favorable.
- Chronic rejection remains the leading cause of graft failure.
Key Points and Methodologies
- Types of grafts: Autograft, Isograft, Allograft, Xenograft.
- Immunosuppressive therapy: Use of agents to suppress immune response (cyclosporine, corticosteroids, etc.).
- HLA matching: Essential for reducing graft rejection; focus on HLA-A, B, DR.
- Types of rejection: Hyperacute (minutes to hours), Acute (weeks to months), Chronic (months to years).
- Graft placement: Orthotopic vs. heterotopic transplantation.
- Renal transplant technique: Left kidney preferred; three vascular and ureteral anastomoses in iliac fossa.
- Organ preservation: Use of UW solution; cold ischemic time critical.
- GVHD prevention: Use irradiated or leukocyte-depleted blood products.
- Infection risk management: Prophylaxis and monitoring for bacterial and viral infections post-transplant.
Researchers and Sources Featured
- Dr. Joseph Murray: Performed the first successful kidney transplant (1954); Nobel Prize in Medicine (1990).
- Schwartz and James (1959): Discovered 6-mercaptopurine with immunosuppressive properties.
- General references to immunosuppressive drugs and transplantation immunology concepts.
This summary captures the core scientific principles, clinical practices, immunological mechanisms, and historical milestones related to transplantation.
Category
Science and Nature
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