responses to alloantigens and transplant rejection immune response against grafted cells tissues, or...
TRANSCRIPT
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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