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CH15
Responses to alloantigens
and transplant rejection
Immune response
against grafted cells tissues, or organs
Ch16 Immune modulators
The immune system
Third edition
Peter Parham (2009)
Chapter 15
Transplantation of tissues and organs
Identity of transplantation antigens
Type and prevention of immune response
in rejection of solid organs
Bone marrow transplantation
Donor
Identity of transplantation antigens
Major histocompatibility complex (MHC)
MHC Ag
Class I
Class II
Autograft
Isograft
Allograft
Xenograft
Type and prevention of immune response
in rejection of solid organs
Hyperacute rejection (within 24h)
Acute rejection (first few weeks)
Chronic rejection (months - years)
Hyperacute rejection
Pre-existing Ab
(e.g. Anti-MHC, A/B/O)
Repeated blood transfusions
Repeated pregnancies
Previous graft
Immediate
graft death
C’, blood clotting
Hyperacute rejection
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
High frequency of allogeneic T cells
Affinity
Self
Cross reactivity
High affinity to non-self MHC Ag
Acute rejection
Donor DC
Anti-CD3
In vitro mixed lymphocyte reaction (MLR)
T: recipient
APC: donor
Target: donor
HLA matching
Minor histocompatibility Ag
Polymorphic Ag (proteins that differ in amino acid sequence between individuals)
Two ways of
allo-Ag recognition
Donor
Donor
Recipient
Chronic rejection
(months - years)
FcR
Infiltration
Fibrosis
Atrophy
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
T cells : thymus
MHC restriction
Positive selection
17
MHCaxb
MHCa
Hematopoiesis
MHCb
APC
MHCaxb
MHCa
MHCb
18
Bone marrow chimera
Blood type
Thymic non-lymphoid stroma
Bone marrow-derived APC
The more HLA allotypes they share, the better it works
HLA-haploidentical
family members
Enrichment
Engraftment:
Colonization of HSC in
the bone of recipient
Niche
Myeloablative therapy
Graft-versus-host disease (GVHD)
Recipient DC
Stringent T-cell depletion
膽紅素
Tissue inflammation
Cytokine storm
Graft-versus-leukemia effect
Graft-versus-tumor effect
Acute GVHD:
First few months
Activation of allogeneic T cells