transplant rejection.pptx transplant rejection.pptx

transplant rejection.pptx

1. TRANSPLANT REJECTION Presented by:

2. What is Transplant rejection? Transplant rejection  is process in which the transplanted tissue (of donor) is rejected by the recipient's immune system and may result in fatal illness if not treated/removed early.

3. Based on genetic relationship between donor and recipient there are four types of Grafting methods: 1. Autografts are grafts in which the donor and recipient is the same individual. 2. Isografts are grafts between the donor and recipient of the same genotype. 3. Allografts are those in which the donor is of the same species but of a different genotype. 4. Xenografts are those in which the donor is of a different species from that of the recipient.

4. For any successful tissue transplant without immunological rejection, matched Major Histocompatibility Locus Antigens (HLA) between the donor and recipient are of paramount importance. The greater the genetic disparity between donor and recipient in HLA system, the stronger and more rapid will be the rejection reaction.

5. All types of grafts have been performed in human beings but xenografts have been found to be rejected invariably due to genetic disparity. Most commonly practiced grafting are: Skin grafting Kidney Bone marrow transplantation .

6. Exceptions in Rejections: Cornea transplants are rarely rejected because the cornea has no blood supply. Also, transplants from one identical twin to another are almost never rejected.

7. Graft versus Host Reaction In some cases esp. when the transplanted tissue is bone marrow, a peculiar illness arises besides rejection of the transplanted bone marrow called GRAFT Vs HOST REACTION. The intensity of GVH reaction depends upon the extent of genetic disparity between the donor and recipient.

8. The clinical features of Graft Vs Host reaction include: Fever, Weight Loss, Anaemia, Dermatitis, Diarrhoea, Intestinal Malabsorption, Pneumonia, Hepatosplenomegaly.

9. MECHANISMS OF GRAFT REJECTION Except for autografts and isografts, an immune response against allografts is inevitable/unavoidable. The development of immunosuppressive drugs has made the survival of allografts in recipients possible. Rejection of allografts involves both cell-mediated and humoral immunity.

10. 1. CELL-MEDIATED IMMUNE REACTIONS Mainly responsible for graft rejection and are mediated by T cells (mainly by cytotoxic T cells) . T cells attack the graft and destroy it.

11. 2. HUMORAL IMMUNE REACTIONS In addition to the cell-mediated immune reactions, humoral antibodies cause certain rejection reactions.

12. TYPES OF REJECTION REACTIONS Based on the underlying mechanism and time period, rejection reactions are classified into 3 types: 1- Hyperacute Rejection 2- Acute Rejection 3- Chronic Rejection

13. 1. HYPERACUTE REJECTION Hyperacute rejection appears within minutes to hours of placing the transplant and destroys it. It is mediated by Humoral system antibodies. This type of rejection is seen when a recipient is given the wrong type of blood. For example, when a person is given type A blood when he or she is type B.

14. 2. ACUTE REJECTION This usually becomes evident within a few days to a few months of transplantation. Acute graft rejection may be mediated by cellular or humoral mechanisms.

15. 3. CHRONIC REJECTION Chronic rejection may develop slowly over a period of months to a year or so. The underlying mechanisms of chronic rejection may be immunologic or ischaemic . Patients with chronic rejection of renal transplant show progressive deterioration in renal function as seen by rising serum creatinine levels.

16. How to overcome transplant rejection? Tissue typing is done to prevent transplant rejection Here both the organ donor and the person who is receiving the organ tissue typing is done to ensure that the organ or tissue is as similar as possible to the tissues of the recipient. The more similar the antigens are between the donor and recipient, the less likely that the organ will be rejected. No match is usually 100 percent identical. No two people, except identical twins, have identical tissue antigens.

17. Evaluation Laboratory Studies Prevention of a transplantation rejection response is the standard of care for transplant procedures, which involves assessing the compatibility between the recipient and the donor tissue. The following laboratory studies are performed for this evaluation:’ Blood group testing : Both the donor and recipient must have compatible blood types. Group O is the universal donor. Serum crossmatch : In this test, donor T and B cells are mixed with recipient serum. A transplant surgery cannot be performed if the serum crossmatch is positive, which occurs when anti-graft antibodies, if present, attack and destroy the donor cells. A "virtual crossmatch" is another method that can be performed that compares recipient anti-HLA antibodies against donor HLA antigens; detected anti-HLA antibodies meeting established adverse response thresholds is considered a positive test. Virtual crossmatching is sometimes preferred due to the ability to obtain results faster and with greater sensitivity than serum crossmatch testing. [9]   HLA typing : Histocompatibility is vital between donor and recipient, which is assessed with HLA typing. The most critical loci are HLA-A, HLA-B, and HLA-DR.

18. Evaluation Following transplantation procedures, patients with suspected acute rejection may be evaluated with laboratory studies to exclude differential diagnoses or assess organ function. However, these tests are not diagnostic of acute rejection, though they may be supportive. Diagnostic confirmation of acute graft rejection is typically obtained with tissue biopsy demonstrating histologic inflammatory changes ( eg , lymphocytic infiltration or cellular damage). [10][1][2]  If transplantation is unsuccessful, retransplantation surgery should be considered. Imaging Studies Imaging studies are utilized to monitor donor tissue following transplantation for pathologic changes suggestive of acute rejection, though not diagnostic. [11]  Various modalities may be preferred depending on the area being imagined. Ultrasound has become the most commonly used monitoring method after kidney transplantation, as renal blood perfusion can be optimally visualized with this modality. [12]  However, following lung transplantation, chest x-ray or computed tomography imaging are better studies to demonstrate perihilar and basilar consolidations, interstitial opacities, pleural effusions, and nodules findings associated with acute rejection. Imaging studies may also help differentiate acute transplantation from differential diagnoses associated with the donor organ ( eg , acute tubular necrosis, reimplantation response, infection). [11]

19. Treatment / Management Acute rejection occurs in all transplants except between identical twins. Acute rejection begins as early as 1 week after transplant, with the risk being highest in the first 3 months. After clinical suspicion or histologic confirmation of acute renal rejection, therapy should start within a 3-day course of intravenous methylprednisolone and periodic testing of serum creatinine levels. Subsequently, if the patient has similar rejection episodes postoperatively, the clinician should treat with intravenous corticosteroids. In a patient with a good response, cyclosporin-A should be discontinued after 9 months; however, a daily maintenance dose of immunosuppressive drugs should be continued. Common maintenance regimens include azathioprine 50 mg daily or prednisolone 5 mg daily Retransplantation should be considered on a clinical basis in patients with no definite improvement despite treatment. Primary cytomegalovirus (CMV) infection in the recipient due to transplantation of a CMV-positive kidney into a CMV-negative recipient can be treated with a combination of ganciclovir and CMV-specific immune globulin. Cases refractory to immunosuppressive therapy or intravenous antibodies can be treated with extracorporeal photoimmune therapy to inactivate graft-specific immunoglobulins

20. Treatment / Management Additionally, emerging monoclonal antibodies offer promising avenues for treating acute transplantation rejection. These antibodies target specific immune pathways implicated in rejection, enhancing graft tolerance and minimizing adverse effects. The following novel monoclonal antibodies are some of the acute transplantation rejection treatments that offer targeted immunomodulation, potentially improving graft survival and minimizing systemic immunosuppression-related adverse effects: Anti-CD3 antibodies: Targeting T-cell activation and proliferation, antibodies, eg , muromonab-CD3, can rapidly suppress rejection in various solid organ transplants. Anti-CD25 antibodies (IL-2 Receptor Antagonists): Agents ( eg , basiliximab and daclizumab) selectively inhibit IL-2 receptors on activated T cells, effectively suppressing immune responses without global immunosuppression. Anti-CD52 antibodies: Alemtuzumab targets CD52 on T and B cells, inducing profound lymphocyte depletion and suppressing rejection, especially in renal transplantation.

21. Treatment / Management Anti-CD20 antibodies: Rituximab depletes B cells, reducing alloantibody production and preventing antibody-mediated rejection. This antibody is commonly used in kidney and heart transplants. Anti-CD40 antibodies: Agents ( eg , CFZ533) block CD40-CD154 costimulation , inhibiting T-cell activation and B-cell differentiation and potentially reducing the risk of rejection. Anti-IL-6 receptor antibodies: Tocilizumab inhibits IL-6 signaling , attenuating inflammatory responses and graft damage. These antibodies show promise in preventing acute rejection in liver transplants. Anti-CCR5 antibodies: Maraviroc targets CCR5 on memory T cells, reducing infiltration into grafts and mitigating rejection, particularly in kidney transplantation. Anti-TNF-α antibodies: Infliximab and Etanercept neutralize TNF-α, dampening inflammatory cascades and mitigating graft damage, explored in various transplant settings.