KEGG   PATHWAY: pps05332
Entry
pps05332                    Pathway                                

Name
Graft-versus-host disease - Pan paniscus (bonobo)
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.
Class
Human Diseases; Immune disease
Pathway map
pps05332  Graft-versus-host disease
pps05332

Organism
Pan paniscus (bonobo) [GN:pps]
Gene
100967827  IL6; interleukin 6 [KO:K05405]
100994286  IL1A; interleukin 1 alpha [KO:K04383]
100993613  IL1B; interleukin 1 beta [KO:K04519]
100977674  TNF; tumor necrosis factor [KO:K03156]
100986750  HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752]
100987433  HLA class II histocompatibility antigen, DRB1-10 beta chain-like [KO:K06752]
100987081  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
100967723  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
100972641  HLA class II histocompatibility antigen, DQ beta 2 chain [KO:K06752]
100967376  RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752]
100979649  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
100968989  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
100968410  MHC-DMB; HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
100995577  HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
100995226  Papa-DPB1; HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
100970847  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
100973583  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
100972994  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
100993847  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
100993508  HLA class II histocompatibility antigen, DQ alpha 1 chain [KO:K06752]
100975083  uncharacterized LOC100975083 [KO:K10785]
100985012  uncharacterized LOC100985012 [KO:K10785]
100988366  uncharacterized LOC100988366 [KO:K10785]
100982662  uncharacterized LOC100982662 [KO:K10785]
100983000  uncharacterized LOC100983000 [KO:K10785]
100995080  uncharacterized LOC100995080 [KO:K10785]
100988045  uncharacterized LOC100988045 [KO:K10785]
100967832  CD80; CD80 molecule [KO:K05412]
100981251  CD86; CD86 molecule [KO:K05413]
100992093  CD28; CD28 molecule [KO:K06470]
100984780  IL2; interleukin 2 [KO:K05429]
100978457  MHC-F; patr class I histocompatibility antigen, CH28 alpha chain [KO:K06751]
100978112  Papa-A; patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
100979338  HLA-H; putative HLA class I histocompatibility antigen, alpha chain H [KO:K06751]
100978774  MHC-G; patr class I histocompatibility antigen, alpha chain G [KO:K06751]
100993452  HLA class I histocompatibility antigen, A-3 alpha chain-like [KO:K06751]
100977055  patr class I histocompatibility antigen, alpha chain E [KO:K06751]
100982294  Papa-C; class I histocompatibility antigen, Gogo-C*0202 alpha chain [KO:K06751]
100982859  PAPA-B; class I histocompatibility antigen, Gogo-B*0101 alpha chain [KO:K06751]
100970360  FASLG; Fas ligand [KO:K04389]
100988526  FAS; Fas cell surface death receptor [KO:K04390]
100979698  PRF1; perforin 1 [KO:K07818]
100987153  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
100991779  IFNG; interferon gamma [KO:K04687]
100986982  killer cell immunoglobulin-like receptor 2DL5A [KO:K24232]
100987319  KIR2DL1; killer cell immunoglobulin-like receptor 2DL3 [KO:K07980]
100994016  KIR3DL3; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 3 [KO:K07980]
103784706  KIR3DL2; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 2 [KO:K07980]
100992623  putative killer cell immunoglobulin-like receptor-like protein KIR3DX1 [KO:K07980]
100990924  KLRC1; killer cell lectin like receptor C1 [KO:K06541]
100992162  KLRD1; killer cell lectin like receptor D1 [KO:K06516]
Compound
C00338  Lipopolysaccharide
C00533  Nitric oxide
Reference
  Authors
Ferrara JL, Reddy P.
  Title
Pathophysiology of graft-versus-host disease.
  Journal
Semin Hematol 43:3-10 (2006)
DOI:10.1053/j.seminhematol.2005.09.001
Reference
  Authors
Reddy P.
  Title
Pathophysiology of acute graft-versus-host disease.
  Journal
Hematol Oncol 21:149-61 (2003)
DOI:10.1002/hon.716
Reference
  Authors
Sun Y, Tawara I, Toubai T, Reddy P.
  Title
Pathophysiology of acute graft-versus-host disease: recent advances.
  Journal
Transl Res 150:197-214 (2007)
DOI:10.1016/j.trsl.2007.06.003
Reference
  Authors
Jaksch M, Mattsson J.
  Title
The pathophysiology of acute graft-versus-host disease.
  Journal
Scand J Immunol 61:398-409 (2005)
DOI:10.1111/j.1365-3083.2005.01595.x
Reference
  Authors
Vogelsang GB, Lee L, Bensen-Kennedy DM.
  Title
Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant.
  Journal
Annu Rev Med 54:29-52 (2003)
DOI:10.1146/annurev.med.54.101601.152339
Reference
  Authors
Reddy P, Ferrara JL.
  Title
Immunobiology of acute graft-versus-host disease.
  Journal
Blood Rev 17:187-94 (2003)
DOI:10.1016/S0268-960X(03)00009-2
Reference
  Authors
Blazar BR, Murphy WJ.
  Title
Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
  Journal
Philos Trans R Soc Lond B Biol Sci 360:1747-67 (2005)
DOI:10.1098/rstb.2005.1701
Reference
  Authors
Couriel D, Caldera H, Champlin R, Komanduri K.
  Title
Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management.
  Journal
Cancer 101:1936-46 (2004)
DOI:10.1002/cncr.20613
Reference
  Authors
Jacobsohn DA, Vogelsang GB.
  Title
Acute graft versus host disease.
  Journal
Orphanet J Rare Dis 2:35 (2007)
DOI:10.1186/1750-1172-2-35
Related
pathway
pps04060  Cytokine-cytokine receptor interaction
pps04210  Apoptosis
pps04514  Cell adhesion molecules
pps04612  Antigen processing and presentation
pps04620  Toll-like receptor signaling pathway
pps04650  Natural killer cell mediated cytotoxicity
pps04660  T cell receptor signaling pathway
KO pathway
ko05332   

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