1. Transplantation of Tissues and Organs
Chapter 15
Transplantation of Tissues and Organs
Immune response
against grafted cells, tissues, or organs

2. Lymphocyte activation
Signal 1-3
Lymphocyte activation
Innate
immunity
Effector
response

4. The transplant patient is already inflamed before transplantation
Donation program
Safety
Living healthy donors
Donated organ may also be inflamed
Ischemia
局部缺血

5. Donor

6. Major histocompatibility complex (MHC)
Identity of transplantation antigens
Major histocompatibility complex (MHC)
MHC Ag
Class I
Class II
Autograft
Isograft
Allograft
Xenograft

7. Identity of transplantation antigens Erythrocyte Ag : ABO, Rh, etc.
Blood transfusion
Erythrocyte Ag : ABO, Rh, etc.
15.3
A RHD-
The most widespread kind of transplantation in clinical medicine

8. Type of immune response in rejection of solid organs
Hyperacute rejection (within 24h)
Acute rejection (first few weeks)
Chronic rejection (months - years)

9. Hyperacute rejection Pre-existing Ab e.g. Anti-MHC, A/B/O ABO/MHCI Ag
C’, blood clotting
Immediate graft death

10. Source of pre-existing antibody
Repeated blood transfusions
Repeated pregnancies
Previous graft
Sensitization
Panel reactive antibody (PRA)
A representative HLA panel of individuals from the population
The higher the PRA value , the more difficult to find a suitable transplant donor
15.5

11. The prevention of hyperacute rejection
Blood typing
Cross-matching test
移植前
Serum D Ab

12. Cell-mediated immunity (CMI)
Acute rejection
(first few weeks)
Cell-mediated immunity (CMI)
Th1 response
Macrophages (Type IV hypersensitivity)
CTLs
Cross reactivity
MHC polymorphism
Allogeneic T cells
The frequency of T cells specific for
any non-self MHC molecules is relatively high

13. Affinity Cross reactivity High frequency of allogeneic T cells
Self
Cross reactivity
High affinity to non-self MHC Ag

14. Acute rejection
Anti-CD3
Donor DC
15.9

15. In vitro mixed lymphocyte reaction (MLR)
15.10
T: recipient
APC: donor

16. The prevention of acute rejection Tissue typing of HLA-I/II
Blood typing
Tissue typing of HLA-I/II
Serological typing
DNA analysis
Immunosuppressive agents

17. 15.14

18. Immunosuppressive agents
Steroids
15.17

19. 15.18

20. Killing of proliferating cells
Immunosuppressive agents
Cytotoxic drugs
Killing of proliferating cells
Pro-drug
15.25
Side effect:
liver, kidney, etc

21. Inhibition of T-cell activation
Immunosuppressive agents
Cyclosporin A (CsA)
Tacrolimus (FK506)
Inhibition of T-cell activation
15.19
Anti-T antibody

22. mTOR: mammalian target of rapamycin Activated by associated proteins
Reduce T-cell proliferation
G1 phase arrest
Promote apoptosis
Increase Treg number
Kinase
Activated by associated proteins

23. Increase the risk of cancer and infection
Immunosuppressive agents
Increase the risk of cancer and infection

24. Chronic rejection (months - years) FcR Antibody against HLA-I:
Infiltration of CD40 B
cells and CD40L TH cells

25. Chronic rejection (months - years) Antibody against HLA-I:
Infiltration of CD40 B
cells and CD40L TH cells
Fig

26. Major type of Ag presentation in transplantation rejection
Chronic rejection
Dead
cells
Acute rejection
15.12

27. Minor histocompatibility Ag
HLA matching
Minor histocompatibility Ag
Male Ag
15.40

28. Transplantation that not requiring tissue typing of HLA-I/II
No immunosuppressive therapy
15.29
Liver

29. Bone marrow transplantation
Genetic diseases
of blood cells
Cancer therapy
Intravenous infusion
Chemotherapy
Repopulation
Reconstitution of the patient’s immune system
and also their red cells and platelets

30. Genetic diseases of blood cells
15.32

31. 15.34

32. 移植相容性
Genetics of MHC 遺傳

33. 移植
相容性
Transplantation

34. HLA-haploidentical
family members

35. T cells : thymus MHC restriction
Positive selection

36. MHCa
MHCaxb
Hematopoiesis
MHCb
APC
MHCa
MHCaxb
MHCb

37. Thymic non-lymphoid stroma: MHC restriction Bone marrow-derived APC
Bone marrow chimera
Blood type
Thymic non-lymphoid stroma: MHC restriction
Bone marrow-derived APC
The more HLA allotypes they share, the better it works

38. Colonization of HSC in the bone of recipient
Engraftment:
Colonization of HSC in the bone of recipient
Myeloablative therapy
Enrichment
Niche
Fig. 1.13

39. Stringent T-cell depletion
15.35
Stringent T-cell depletion

40. Activation of allogeneic T cells
膽紅素
15.36
Tissue inflammation
Cytokine storm
Acute GVHD:
First few months
Activation of allogeneic T cells

41. Graft-versus-leukemia effect
Graft-versus-tumor effect

42. graft-specific tolerance
Hematopoietic cell transplantation
can induce tolerance to
solid organ transplants
Induction of
graft-specific tolerance
15.44

43. A non-immunogenic tissue barrier An immune privileged site
Fetus
Natural allograft
A non-immunogenic tissue barrier
An immune privileged site