Responses to alloantigens and transplant rejection Immune response against grafted cells tissues, or...
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- Responses to alloantigens and transplant rejection Immune
response against grafted cells tissues, or organs CH15 Ch16 Immune
modulators
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- Chapter 15 Transplantation of tissues and organs The immune
system Third edition Peter Parham (2009)
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- Identity of transplantation antigens Type and prevention of
immune response in rejection of solid organs Bone marrow
transplantation
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- Donor
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- Autograft Isograft Allograft Xenograft MHC Ag Class I Class II
Major histocompatibility complex (MHC) Identity of transplantation
antigens
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- Hyperacute rejection (within 24h) Acute rejection (first few
weeks) Chronic rejection (months - years) Type and prevention of
immune response in rejection of solid organs
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- Hyperacute rejection C, blood clotting Pre-existing Ab (e.g.
Anti-MHC, A/B/O) Repeated blood transfusions Repeated pregnancies
Previous graft Immediate graft death
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- Hyperacute rejection
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- Cell-mediated immunity (CMI) Acute rejection Th1 response
Macrophages (Type IV hypersensitivity) CTLs Allogeneic T cells The
frequency of T cells specific for any non-self MHC molecules is
relatively high Cross reactivity (first few weeks) MHC
polymorphism
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- Cross reactivity Self High affinity to non-self MHC Ag Affinity
High frequency of allogeneic T cells
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- Donor DC Acute rejection Anti-CD3
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- In vitro mixed lymphocyte reaction (MLR) APC: donorT: recipient
Target: donor
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- Minor histocompatibility Ag HLA matching Polymorphic Ag
(proteins that differ in amino acid sequence between
individuals)
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- Donor Recipient Donor Two ways of allo-Ag recognition
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- Chronic rejection (months - years) FcR Infiltration Fibrosis
Atrophy
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- Cancer therapy Genetic diseases of blood cells Chemotherapy
Repopulation Reconstitution of the patients immune system and also
their red cells and platelets Intravenous infusion Bone marrow
transplantation
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- T cells : thymus MHC restriction Positive selection 17
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- Hematopoiesis MHC a MHC b MHC axb APC 18
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- Bone marrow-derived APC Thymic non-lymphoid stroma Bone marrow
chimera Blood type The more HLA allotypes they share, the better it
works
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- HLA-haploidentical family members
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- Engraftment: Colonization of HSC in the bone of recipient
Myeloablative therapy Niche Enrichment
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- Graft-versus-host disease (GVHD) Recipient DC Stringent T-cell
depletion
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- Tissue inflammation Cytokine storm Activation of allogeneic T
cells Acute GVHD: First few months Graft-versus-leukemia effect
Graft-versus-tumor effect