1. Transplantation Immunology

2. Introduction
Transplantation: The process of taking cells, tissues, or organs from one individual and placing them into a different individual or different site of the same individual
Graft: Transplanted cells, tissues, or organs
Donor: The individual who provides the graft
Recipient: The individual who Receives the Graft, also called the host

3. Allograft Rejection Displays Specificity and Memory.
Autograft
Isograft ( Syngenic Graft )
Allograft
Xenograft
The most formidable barrier is the Immune System
Allograft Rejection Displays Specificity and Memory.

5. Genetic Basis of Transplant Rejection
Inbred mouse strains - all genes are identical
Transplantation of skin between strains showed that
rejection or acceptance was dependent upon
the genetics of each strain
Skin from an inbred mouse grafted onto the same strain of mouse
ACCEPTED
Skin from an inbred mouse grafted onto a different strain of mouse
REJECTED

6. Immunological basis of graft rejection
Primary rejection of
strain skin
e.g. 10 days
Lyc
Transfer lymphocytes
from primed mouse
6 months
Naïve mouse
Secondary rejection of
strain skin
e.g. 3 days
Primary rejection of
strain skin
e.g. 10 days
Transplant rejection is due to an antigen specific immune response with immunological memory

9. Transplantation Antigens
Major Histocompatibility Complex (MHC) Molecules
ABO Blood Group Antigens and Tissue Specific Antigens

10. Mechanisms of Allograft Rejection
The Immune Responses in Allogeneic Transplantation:
T cell mediated rejection of allograft
Antibody mediated rejection of allograft

11. T cell mediated rejection of allograft
1) Recognition of alloantigens
2) Activation of T cells and rejection of allograft

12. Recognition of alloantigens

13. ① Direct recognition of alloantigens
Recognition of an intact MHC molecule displayed by donor APC in the graft
An allogeneic MHC molecule with a bound peptide can mimic the determinant formed by a self MHC molecule plus peptide

14. Fast and strong reaction in acute rejection

15. Direct recognition is a cross-reaction of a normal TCR ( which was selected to recognize self MHC molecules plus foreign peptides) with an allogeneic MHC molecule (plus peptide)
As many as 2% of an individual’s T cells are capable of directly recognizing and responding to a single foreign MHC molecule.

16. Direct Recognition of Allogeneic MHC Molecules by TCR
T cell from recipient
CD8+T
CD8+T
APC from donor
CD4+T

17. Direct Recognition of Allogeneic MHC Molecules by TCR
CTL
T cells from Recipient
CTL
Donor Tissue cells

18. ② Indirect Recognition of Alloantigens
Donor MHC molecules may be Processed and Presented by Recipient APCs that enter Grafts, and the Processed MHC Molecules are Recognized by T cells like Conventional Foreign Antigens

19. Indirect Recognition of Allogeneic MHC Molecules by TCR
Host T cell
CD8+T
Host APC
CD8+T
CD4+T
self APC uptakes Graft
processing
Presentation by self APC

21. Antibody Mediated Rejection of Allograft
Complement activated by antibody involved in transplantation rejection

23. Classification of Allograft Rejection
Hyper-Acute
Acute
Chronic

24. Hyper-Acute Rejection
Within Minutes to 1-2 days after host blood vessels are anastomosed to graft vessels
Characterized by thrombotic occlusion of the graft vasculature
Mediated by preexisting antibodies in the host circulation that bind to donor endothelial antigens
Results in Complement Activation, Endothelial Damage, Inflammation and thrombosis
Immune suppression is not effective

26. Acute tubulointerstitial rejection: Mononuclear interstitial infiltrate.

27. Chronic Rejection
Develops Months or years after Transplantation
Characterized by fibrosis and vascular abnormalities with Loss of Graft Function
The mechanisms of chronic rejection include both humoral and cell-mediated responses

28. Chronic Vascular Rejection - Concentric Fibrous Intimal Thickening and Lymphocytic Infiltration

29. Prevention and Treatment of Allograft Rejection
① Reducing the Immunogenicity of Allografts（Tissue Typing)
② Immuno-suppression

30. ① Reducing the Immunogenicity of Allografts
Donors and Recipients are Typed for ABO and MHC Antigens
Blood Group Antigen Matching, Cross Match
MHC Matching
HLA-A, B and HLA-DR is important for Predicting outcome.

31. ② Immunosuppression
Immunosuppressive drugs that inhibit or kill T cells Cyclosporine(CsA), FK506
Anti-inflammatory agents are also routinely used
Corticosteroids to block the synthesis and secretion of cytokines

33. Xenotransplantation lack of organs for Transplantation
Hyper acute Rejection
Lack of Inhibitory Mechanisms of Complement
Transgenic Pigs

34. GVHD