Transplantation immunology

History
Introduction
Classification of grafts
The Immunology of Allogeneic Transplantation
Genetics of graft rejection
Types of rejection
Recognition of Alloantigens
Effector Mechanisms of Allograft Rejection
Prevention of graft rejection
Graft versus host reaction
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1. Transplantation immunology Rinkesh Joshi M.Sc Sem : 3 Bioscience ( Micro) 09924113838 Surat , Gujarat.

2. C ontents History Introduction Classification of grafts The Immunology of Allogeneic Transplantation Genetics of graft rejection Types of rejection Recognition of Alloantigens Effector Mechanisms of Allograft Rejection Prevention of graft rejection Graft versus host reaction

3. H istory 1944 : Medawar showed that skin allograft rejection is a host versus graft response. 1954 : The first successful identical twin transplant of a human kidney was performed by Joseph E. Murray in Boston 1967 : The first successful liver transplant was done by Dr. Thomas E. Starzl 1967 : The first heart transplantation by Christian Barnard 1968 : T he first successful bone marrow transplant was done by E. Donnall Thomas

4. Introduction Transplantation is a act of transferring cells , tissue, or organ from one site to another Graft : Implanted cell, tissue or organ Donor : Individual who provides the graft Recipient or host : Individual who receives the graft

5. Classification of grafts

6. Autograft Self tissue is transferred from one body site to another Antigen present in autograft is same as that present in body So immune system recognizes the autograft antigen as a self antigen No immune response is elicited A utograft survive through out the life Eg ., - Transferring healthy skin to burned area, - Use of healthy blood vessels to replace blocked coronary arteries, - Plastic surgery of skin.

7. Iso graft It is also called syngraft Tissue is transferred between genetically identical individuals of same species In isograft the histo compatibility antigens are identical hence the graft survives and not rejected . Eg in human isograft can be performed between two twins.

8. A llograft Tissue is transferred between two genetically different members of same species In allograft histocompatibility antigens are dissimilar hence immune response is elicited and graft is rejected Eg ., In humans graft is transferred from one individual to another

9. X enograft Tissue is transferred between two different species Eg ., Graft of human transferred to animal In xenografts histocompatibility complex antigens are so different that the graft is more vigorously rejected

10. The Immunology of Allogeneic Transplantation Alloantigens elicit both cell-mediated and humoral immune responses. Recognition of transplanted cells that are self or foreign is determined by polymorphic genes that are inherited from both parents and are expressed co-dominantly.

11. Genetics of graft rejection

12.   Allograft rejection display specificity and memory Rate of allograft rejection varies according to tissue involved Skin graft are rejected faster than other tissue organ kidney or heart If inbred mouse of strain A is grafted with skin from strain B , P rimary graft rejection occur called first set rejection When again strain A is grafted with skin from strain B , S econdary graft rejection occur called second set rejection

13. First- and Second-set Allograft Rejection

14. Recognition of Alloantigens Direct recognition of Alloantigens host T cells recognize intact allo -MHC molecules on the surface of the donor cell. host T cells see allo -MHC molecule + allo -peptide as being equivalent in shape to self-MHC + foreign peptide and hence recognize the donor tissue as foreign. This pathway is the dominant pathway.

15. Ind irect recognition of Alloantigens Donor MHC is processed and presented by recipient APC Basically, donor MHC molecule is handled like any other foreign antigen

16. Activation of Alloreactive T cells and Rejection of Allografts Donor APCs migrate to regional lymph nodes and are recognized by the recipient’s T cells Alloreactive T cells in the recipient may be activated and they migrate into the graft and cause graft rejection

17. Effector Mechanisms of Allograft Rejection Used by immune system to reject allograft It is based on histopathological features or time duration of rejection after transplantation There are three type of patterns Hyperacute Rejection Acute Rejection Chronic Rejection

18. Hyperacute Rejection Graft is rejected within minutes to hours because vascularization is rapidly destroyed. It occurs because the recipient has pre-existing antibodies in circulation against the graft. Which could be induced by prior blood transfusions , multiple pregnancies , prior transplantation , or xenografts . Antibodies bind with donor endothelial cell . The antigen-antibody complexes activate the complement system, causing massive thrombosis in the capillaries, which prevents the vascularization of the graft. The kidney is most susceptible to hyperacute rejection.

19. Preformed Ab , complement activation, Neutrophil margination , I nflammation , Thrombosis formation.

20. Acute Rejection Vascular and parenchymal injury mediated by T cells and antibodies that usually begin after the first week of transplantation if there is no immunosuppressant therapy Antibodies from after transplantation may also contribute to vascular injury.

21. Chronic rejection Occurs in most solid organ transplants Heart Kidney Lung Liver Characterized by fibrosis and vascular abnormalities with loss of graft function over a prolonged period

22. Arthrosclerosis Cell proliferation Occlusion

23. Prevention of graft rejection Blood grouping Cytotoxic antibody testing Tissue matching Immunosuppressive drugs ( azathioprine,cyclosporine,rapamycin , corticosteroids)

24. Graft versus host reaction In some instance the graft tissue elicits an immune response against host antigen and that immune response is called graft versus host reaction Graft versus host reaction brings damage to host cells and host When grafted tissue has mature T cells, they will attack host tissue leading to GVHR.

25. Mechanism of GVHR Graft lymphocytes aggregate in the host lymphoid organs Graft lymphocytes are stimulated by the host lymphocyte Stimulated lymphocytes of graft produce lymphokines Lymphokines activate host T- cell which produce polyclonal b-cell activation Activated b-cell react with the self antigens and cause damage to the host cell

26. Clinical symptoms of GVHR Skin rash Emaciation ( becoming thin) Retarded growth Diarrhoea Hepatomegaly Splenomegaly Increase in bilirubin production Bileducts are damaged anaemia

27. Thank You …. Very Much….