1. Responses to alloantigens and transplant rejection
CH15
Responses to alloantigens
and transplant rejection
Immune response
against grafted cells tissues, or organs
Ch16 Immune modulators

2. The immune system Chapter 15 Transplantation of tissues and organs
Third edition
Peter Parham (2009)
Chapter 15
Transplantation of tissues and organs

3. Bone marrow transplantation
Identity of transplantation antigens
Type and prevention of immune response
in rejection of solid organs
Bone marrow transplantation

4. Donor

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

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

7. Hyperacute rejection Pre-existing Ab (e.g. Anti-MHC, A/B/O) Immediate
Repeated blood transfusions
Repeated pregnancies
Previous graft
Immediate
graft death
C’, blood clotting

8. Hyperacute rejection

9. 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

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

11. Acute rejection
Anti-CD3
Donor DC

12. In vitro mixed lymphocyte reaction (MLR)
T: recipient
APC: donor
Target: donor

13. Minor histocompatibility Ag
HLA matching
Minor histocompatibility Ag
Polymorphic Ag (proteins that differ in amino acid sequence between individuals)

14. Two ways of allo-Ag recognition
Donor
Donor
Recipient

15. Chronic rejection
(months - years)
FcR
Infiltration
Fibrosis Atrophy

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

17. T cells : thymus MHC restriction
Positive selection

18. MHCa
MHCaxb
Hematopoiesis
MHCb
APC
MHCa
MHCaxb
MHCb

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

20. HLA-haploidentical
family members

21. Myeloablative therapy
Enrichment
Engraftment:
Colonization of HSC in
the bone of recipient
Niche
Myeloablative therapy

22. Graft-versus-host disease (GVHD)
Recipient DC
Stringent T-cell depletion

23. Activation of allogeneic T cells
膽紅素
Tissue inflammation
Acute GVHD:
First few months
Cytokine storm
Graft-versus-leukemia effect
Graft-versus-tumor effect
Activation of allogeneic T cells