By cumulave acute rejecon episodes

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Unformatted text preview: allogra; mount an alloresponse against the recipient’s cells –  Clinically, this response translates into skin/GI/liver disease –  Generally due to mismatches in class I and/or class II MHC molecules –  Can also be triggered by minor histocompa#bility an#gens •  Most common in bone marrow transplanta#on, rare in solid organ transplanta#on •  Presence of donor’s alloreac#ve T cells against recipient’s cells can be detected by the mixed lymphocyte reac#on (MLR) •  Treated with immunosuppression •  A degree of GVHD is beneficial in BMT for leukemia •  Some donor’s T cells can recognize mHA or tumour- specific an#gens and kill leukemic cells, preven#ng leukemia relapse •  •  •  State in which the allogra; is not recognized as foreign Some#mes occurs spontaneously through unclear mechanisms Natural Model = pregnancy –  Immune privileged site •  ? Lack of recogni#on •  ? HLA- G –  Inducer of an immunosuppressive response •  ?Nutrient deple#on (IDO) •  ?Immunodevia#on: TGF- β, IL-10 •  ?Treg •  •  Intensive search for therapies to induce it Examples: –  –  –  –  –  Thymectomy Donor cell injec#on Stem cell transplanta#on Bone marrow transplanta#on Blockade of ac#va#on of alloreac#ve T cells •  Dele#on of alloreac#ve clones •  Immunodevia#on: Th1 à༎ Th2 •  Regulatory T cells: –  CD4+CD25+ Treg: •  •  •  •  Naturally occurring or induced Foxp3+ Deple#on of Treg accelerate rejec#on Likely inhibit capacity of APC to ac#vate T cells –  CD8+ CD28- Treg: •  anergic phenotype •  not cytotoxic against donor cells •  CD94hi –  Increasing Treg numbers decrease GVHD •  Accommoda#on = a state of decreased alloreac#vity with #me a;er transplant. Unknown mechanism, likely mul#factorial •  Pigs as poten#al organ donors to increase organ supply •  Xenogra;s are rejected hyperacutely due to the presence of IgM an#- α- gal in humans (α- gal is expressed in the pig endothelial cells) •  Compounded with poor func#on of complement regulatory proteins (DAF, CD59, MCP) •  Gene#cally modified pigs have been generated (α- gal KO, DAF transgenic) •  Not clinically available •  Use of stem cell technology to regenerate damage #ssue: –  Mesenchymal stem cells have low immunogenicity –  Control of...
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