TRANSPLANTATION AND GRAFT REJECTION.pptx

Future research aims to improve long-term graft survival and reduce the need for lifelong immunosuppression.

1. TRANSPLANTATION AND GRAFT REJECTION Lecture 2

2. TRANSPLANT AND GRAFT REJECTION Transplantation refers to the process of transferring cells , tissues, or organs from one individual (donor) to another (recipient) to replace damaged or diseased structures. Transplants are performed: To improve or save the recipient's life , To alleviate symptoms, To restore normal bodily functions. 1/28/2025 2

3. TYPES OF GRAFTS There are four types of grafts: 1 . Autograft : An autograft is the transfer of individual’s own tissue or organ from one site to another site in the body. In other words, the recipient is also the donor. Common examples of autografts include skin transplants in burn patients and bypass surgery in patients suffering from coronary heart disease. 1/28/2025 3

4. Contd 2. Syngraft : A syngraft is a transfer of tissue between two genetically identical individuals, i.e., identical twins. The first successful human kidney transplant was a syngraft , carried out in 1954 between identical twins . 1/28/2025 4

5. Contd 3. Allograft: An allograft is the transfer of tissue or an organ between genetically different members of the same species , i.e., from one human to another . This is the predominant form of transplantation today, and allografts have dominated transplant research for many years. 1/28/2025 5

6. Contd 4. Xenograft : A xenograft is the transfer of tissues or organs between members of different species. It represents the most disparate of genetic relationships and is always rejected by an immunocompetent recipient . 1/28/2025 6

7. 1/28/2025 7 TYPES OF GRAFTS

8. Types of transplants 1. Organ Transplants : The transplantation of whole organs from a donor to a recipient. Common organ transplants include heart, liver, kidney, lung, and pancreas transplants. 2. Tissue Transplants : The transplantation of specific tissues , such as corneas, skin, bone, tendons, cartilage, and heart valves. Tissue transplants can help restore function, promote healing, or improve quality of life . 3. Cellular Transplants : The transplantation of specific cells or cell products, such as : hematopoietic stem cells (used in bone marrow transplantation) islet cells (used in pancreatic islet cell transplantation for diabetes), or specialized cells for regenerative medicine purposes. 1/28/2025 8

9. The types of organ transplant Heart transplant: Heart is the hardest working muscle , which pumps blood throughout the body. People with heart diseases such as coronary artery disease, cardiomyopathy or weakening of heart muscle may need a heart transplant. Kidney transplant : Kidney’s function is to remove wastes from the body , filter the blood, control the electrolyte balance, and regulate blood pressure. Kidney transplant becomes necessary due to inherited kidney disease such as polycystic kidney disease. Diabetes and high blood pressure are also common cause of the kidney failure which makes transplantation necessary. Liver transplant : The liver functions to break down harmful substances , detoxify the body, and production of bile for digestion. Any viral infection, genetic disorders or even alcoholism may result in liver failure which leads to the necessity of liver transplantation (the diseased liver is removed and replaced with a healthy one ).

10. The types of organ transplant, …. Lung transplant : A person can live a normal life, if the lung functions at least 30 percent. People with severe lung diseases such cystic fibrosis, COPD (chronic obstructive pulmonary disease) and emphysema in advanced stages may require lung transplant. Pancreas transplant: The pancreas is a gland located just behind the stomach. It produces juice or enzymes that help in the breakdown of food . It also releases the hormone, insulin that helps to control blood sugar levels. People who have pancreas-related problems such as pancreatitis or inflammation of the pancreas, genetic disorder, cystic fibrosis, and pancreatic cancer may require pancreas transplant. Intestine transplant : This kind of transplant is rare and is usually done in combination with liver, stomach, and pancreas. People who have short bowel syndrome (caused by lack of function of the small intestine) may need an intestine transplant.

11. Organ donation Organ donation is a process that involves the donation of organs to a living recipient (who is in need of a transplant). There are two types of organ donors such as: 1. Living donor : The living donor is the person decides to donate his or her organ to the person who in need of a transplant. Living donors commonly provide organs such as kidneys or portions of the liver or lung. Living donors have to undergo some medical testing as suggested by the doctors to be selected as the suitable donor. 2. Deceased donor (Cadaver): Deceased donors are those whose organs are harvested once they become brain-dead . For this type of transplant, the recipient has to wait till the suitable organ based on the recipient medical profile is available. Compatibility between the donor and recipient is assessed through medical, immunological, and genetic matching 1/28/2025 11

12. Transplantation process Donor Selection : Donors can be deceased or living individuals . Living donors commonly provide organs such as kidneys or portions of the liver or lung. Compatibility between the donor and recipient is assessed through medical, immunological, and genetic matching. After removing the organ from the body, it is stored in a chemical solution. Before transplantation, the donated organ would be stored under controlled conditions , depending upon the varying time length of the organ such as a heart for 4-6 hours, liver for 12-24 hours, kidneys for 48-72 hours, and lung for 4-6 hours. 1/28/2025 12

13. Donor Selection The minimum D\R matching for Renal Tx is: DR : B : A 1 : 1 : 1 Other HLA antigens(CW, DQ& DP) are not essential in Renal Tx Example: R Typing : A(1,2) B(7,8) BW-\6 DR(1,2)DR51 D1Typing: A(1,3) B(7,51) BW-\6 DR(1,-)DR51 D2Typing: A(3,26) B(71,-) BW-\6 DR(4,7)DR53 13

14. Cross Match(X-M) After selection of suitable Donor, X-M will be done to detect HLA-Abs in the recipient serum against donor HLA- Ags : Pt serum + D-cells Cell death ( Positive ). ( This means the Pt is previously sensitized) Pt serum + D-cells No death ( Negative ). ( This means the Pt is not sensitized ) Now Anti-HLA Panel Reactive Antibodies 14

15. Revising For renal Transplantation, the HLA types showing below are done for a recipient and four donors. Specify which of the donors is more suitable. Recipient Typing: A(1,50) B(7, - ) BW-\6 DR(1,2) Donor1 Typing: A(1,50) B(7,51) BW-\6 DR(1,-) Donor2 Typing: A(3,26) B(71,-) BW-\6 DR(4,7) Donor3 Typing: A(3,26) B(7,-) BW-\6 DR(1,8) Donor4 Typing: A(3,50) B(7,-) BW-\6 DR(1,-) 15

16. Evaluation and Pre-transplant Preparation : Recipients undergo comprehensive medical evaluations to determine their suitability for transplantation. This includes assessing their overall health, organ function, and psychological readiness. Pre-transplant preparation may involve medical treatments, immunosuppressive medications, and lifestyle modifications 1/28/2025 16

17. Transplant Surgery : The transplant surgery itself involves removing the diseased or damaged organ or tissue from the recipient and replacing it with the donated organ or tissue. The surgical procedure can vary depending on the specific transplant being performed. 1/28/2025 17

18. Post-transplant Care : Following the surgery, recipients require close monitoring and long-term medical management. Transplantation carries risks , including surgical complications, infection, organ dysfunction, and long-term complications associated with immunosuppressive medications . This includes the use of immunosuppressive medications to prevent organ rejection, regular medical check-ups, and lifestyle adjustments to support the transplanted organ's function 1/28/2025 18

19. Challenges and considerations Organ Shortage : The demand for organs exceeds the supply , resulting in long waiting lists for transplant candidates. Efforts to increase organ donation rates and explore alternative sources, such as living donors and regenerative medicine approaches, are ongoing 1/28/2025 19

20. Contd Immune Response and Rejection : The recipient's immune system may recognize the transplanted organ as foreign and mount an immune response, leading to organ rejection. Immunosuppressive medications are administered to suppress the immune response and prevent rejection, but they can have side effects and require careful management 1/28/2025 20

21. GRAFT REJECTION When a transplant is performed, the recipient's immune system recognizes the transplanted material as foreign and activates an immune response to eliminate it. Immunosuppressive medications are administered to suppress the immune response and prevent rejection, but they can have side effects and require careful management Graft rejection refers to the immune response mounted by the recipient's immune system against a transplanted organ, tissue, or cells. Graft rejection can occur in both solid organ transplants and tissue/cellular transplants 1/28/2025 21

22. TYPES OF GRAFT REJECTION Hyper acute Rejection : Hyperacute rejection occurs usually within the first few hours post-transplantation and is mediated by preformed antibodies against ABO or MHC antigens of the graft. Antibodies directed against other alloantigens , such as vascular endothelial antigens, play a role in this type of rejection . Rejection can be caused either by activation of the complement system , which results in the chemotactic attraction of granulocytes and the triggering of inflammatory circuits by Antibody-Dependent Cell-Mediated Cytoxicity 1/28/2025 22

23. Pathological features of hyperacute rejection Pathological features of hyperacute rejection are following: The hyperacute rejection episodes are irreversible and invariably results in graft loss. This is associated with the formation of massive intravascular platelet aggregates leading to thrombosis, ischemia, and necrosis. With proper cross-matching techniques, this type of rejection is almost 100% avoidable. The hyperacute graft rejection by antibodies to all human cellular antigens is the major limitation of xenogeneic transplantation (e.g., pig to human). 1/28/2025 23

24. 2. Acute Rejection : Up to 70% of graft recipients experience one or more acute rejection episodes. Acute rejection occurs mostly in the first few days or weeks after transplantation It is primarily a cell-mediated immune response, involving T lymphocytes, against the transplanted organ. When acute rejection takes place in the first few days after grafting , it may correspond to a secondary (second set) immune response. This indicates that the patient had been previously sensitized to the HLA antigens present in the organ donor (as a consequence of a previous transplant, pregnancy, or blood transfusions ). When graft rejection occurs first week after grafting , it usually corresponds to a first-set (primary) response. 1/28/2025 24

25. Acute rejection is predominantly mediated by T lymphocytes . CD4 helper T lymphocytes are believed to play the key role in acute rejection of the graft . This is because they release growth factors like IL-2 and IL-4 for the promotion of clonal expansion of CD8 lymphocytes and B cells 1/28/2025 25

26. Diagnosis of acute rejection The initial diagnosis of acute rejection is usually based on clinical suspicion : Functional deterioration of the grafted organ is the main basis for considering the diagnosis of acute rejection. Confirmation usually requires a biopsy of the grafted organ . Findings: Mononuclear cell infiltration in tissues of rejected graft tissue is characteristic finding. The measurement of cytokines (such as IL-2) in serum and in urine (in the case of renal transplants ) is another diagnostic approach. In most cases, acute rejection, if detected early, can be reversed by increasing the dose of immunosuppressive agents or by briefly administering additional immunosuppressants . 1/28/2025 26

27. 3. Chronic Rejection : This is characterized by progressive loss of function of the grafted organ. The functional deterioration associated with chronic rejection appears to be due to both immune and non-immune processes . Vascular endothelial injury is the most common feature. Granulocytes, monocytes, and platelets are found to increasingly adhere to injured vascular endothelium. The damaged endothelium is covered by a layer of platelets and fibrin , and eventually by proliferating fibroblasts and smooth muscle cells . The end result is a proliferative lesion in the vessels, which progresses toward fibrosis and occlusion . 1/28/2025 27

28. FACTORS CONTRIBUTING TO GRAFT REJECTION Human Leukocyte Antigens (HLA) Mismatch : HLA molecules on the surface of cells play a crucial role in immune recognition. Mismatches between the donor and recipient HLA antigens increase the risk of graft rejection . Immune System Activation : The recipient's immune system recognizes the transplanted tissue as foreign due to differences in HLA antigens and other proteins. This triggers an immune response, leading to graft rejection. Immunologic Memory : The recipient's immune system may have memory cells from previous exposures to antigens, such as through prior transplants, blood transfusions, or pregnancies. These memory cells can mount a more rapid and aggressive immune response against the transplanted tissue. 1/28/2025 28

29. GRAFT REJECTION PREVENTION AND TREATMENT 1. Immunosuppressive Medications : Recipients of solid organ transplants are typically prescribed immunosuppressive drugs to dampen the immune response and prevent graft rejection. These medications include corticosteroids, calcineurin inhibitors, antimetabolites, and biological agents targeting specific immune pathways. 1/28/2025 29

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31. CONTD 2. HLA Matching : Efforts are made to match the donor and recipient HLA antigens as closely as possible to reduce the risk of rejection . Close HLA matching improves transplant outcomes. 1/28/2025 31

32. CONTD 3. Monitoring and Surveillance : Regular monitoring of transplant recipients is essential to detect signs of rejection early. This involves frequent clinical assessments, laboratory tests, imaging studies, and biopsies of the transplanted organ when necessary. 1/28/2025 32

33. CONTD 4. Rejection Treatment : If graft rejection occurs, treatment strategies may include: increasing immunosuppressive medications, using targeted immunotherapies, or adjusting the immunosuppressive drug regimen. Severe rejection episodes may require hospitalization and intensive interventions. 1/28/2025 33