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Pathway : Graft-versus-host disease

Identifier  05332 Description  Graft-versus-host disease GVHD is a lethal complication of allogeneic hematopoietic stem cell transplantation HSCT where immunocompetent donor T cells attack the genetically disparate host cells GVHD pathophysiology can be summerized in a three-step process Step 1 involves the development of an inflammatory milieu resulting from damage in the host tissues induced by the preparative chemotherapy or radiotherapy regimen Damaged tissues secrete inflammatory cytokines, including interleukin 1 IL-1, and tumor necrosis factor TNF-alpha During step 2, antigen-presenting cells APCs trigger the activation of donor-derived T cells, which induce further T-cell expansion, induce cytotoxic T lymphocytes CTL and natural killer NK cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1 Also, nitric oxide NO is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3 During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B

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