KEGG   PATHWAY: ecb05332
Entry
ecb05332                    Pathway                                
Name
Graft-versus-host disease - Equus caballus (horse)
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
ecb05332  Graft-versus-host disease
ecb05332

Organism
Equus caballus (horse) [GN:ecb]
Gene
100034196  IL6; interleukin-6 precursor [KO:K05405]
100064969  IL1A; interleukin-1 alpha precursor [KO:K04383]
100034237  IL1B; interleukin-1 beta [KO:K04519]
100052414  IL1B; interleukin-1 beta [KO:K04519]
111768185  interleukin-1 beta-like [KO:K04519]
100033834  TNF; tumor necrosis factor [KO:K03156]
100061035  HLA class II histocompatibility antigen, DM alpha chain-like precursor [KO:K06752]
100060770  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
100052249  DQA; MHC class II DQ-alpha precursor [KO:K06752]
100052310  DRB; MHC class II DR-beta chain precursor [KO:K06752]
100052364  DRB; MHC class II DR-beta chain precursor [KO:K06752]
100051944  DRA; MHC class II DR alpha chain precursor [KO:K06752]
100052184  DQB; MHC class II DQ-beta chain precursor [KO:K06752]
100061127  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
100060996  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
100052006  DRB; MHC class II DR-beta chain precursor [KO:K06752]
100052125  DQA; MHC class II DQ-alpha chain precursor [KO:K06752]
100060531  HLA class II histocompatibility antigen, DQ beta 2 chain isoform X1 [KO:K06752]
100052063  DQA; MHC class II DQ-alpha chain [KO:K06752]
100060320  DQB; MHC class II DQ-beta chain precursor [KO:K06752]
111767457  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
100060697  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
111772100  uncharacterized protein LOC111772100 [KO:K10784]
106783094  uncharacterized protein LOC106783094 [KO:K10785]
100071012  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
100060767  CD86; T-lymphocyte activation antigen CD86 isoform X5 [KO:K05413]
100067829  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
100034204  IL2; interleukin-2 precursor [KO:K05429]
100034212  MHCB3; MHC class I heavy chain precursor [KO:K06751]
100056062  MHC class I antigen 9.2 precursor [KO:K06751]
100034210  EQMHCB2; MHC class I heavy chain precursor [KO:K06751]
100054114  HLA class I histocompatibility antigen, alpha chain G isoform X1 [KO:K06751]
100051657  7-51 putative nonclassical MHC class I antigen precursor [KO:K06751]
100057920  HLA class I histocompatibility antigen, Cw-12 alpha chain isoform X2 [KO:K06751]
100050550  EQMCE1; MHC class I antigen 3.7 precursor [KO:K06751]
100056182  HLA class I histocompatibility antigen, B-40 alpha chain isoform X1 [KO:K06751]
100056391  MHCX1; MHC class I antigen 3.5 precursor [KO:K06751]
100034211  EQMHCC1; MHC class I heavy chain precursor [KO:K06751]
100049798  class I histocompatibility antigen, Gogo-OKO alpha chain isoform X12 [KO:K06751]
100050473  class I histocompatibility antigen, Gogo-B*0103 alpha chain isoform X1 [KO:K06751]
100050706  saoe class I histocompatibility antigen, A alpha chain isoform X1 [KO:K06751]
100053918  HLA class I histocompatibility antigen, B-46 alpha chain isoform X2 [KO:K06751]
100054397  saoe class I histocompatibility antigen, A alpha chain [KO:K06751]
100054448  HLA class I histocompatibility antigen, alpha chain G isoform X3 [KO:K06751]
100056309  HLA class I histocompatibility antigen, B-15 alpha chain-like [KO:K06751]
100056099  HLA class I histocompatibility antigen, alpha chain G isoform X1 [KO:K06751]
100056231  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
100059994  HLA class I histocompatibility antigen, B-15 alpha chain isoform X1 [KO:K06751]
100060096  H-2 class I histocompatibility antigen, Q9 alpha chain-like [KO:K06751]
100052326  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
100071639  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
100072744  PRF1; perforin-1 [KO:K07818]
100033978  GZMB; granzyme B precursor [KO:K01353] [EC:3.4.21.79]
100049805  granzyme B [KO:K01353] [EC:3.4.21.79]
100050711  granzyme H isoform X1 [KO:K01353] [EC:3.4.21.79]
100052229  granzyme B-like isoform X1 [KO:K01353] [EC:3.4.21.79]
100052901  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
100052689  granzyme B [KO:K01353] [EC:3.4.21.79]
100053327  granzyme B-like [KO:K01353] [EC:3.4.21.79]
100052951  granzyme B [KO:K01353] [EC:3.4.21.79]
100055651  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
111768988  granzyme B-like isoform X1 [KO:K01353] [EC:3.4.21.79]
111767413  granzyme B-like isoform X1 [KO:K01353] [EC:3.4.21.79]
111768996  granzyme B(G,H)-like isoform X1 [KO:K01353] [EC:3.4.21.79]
100053001  granzyme H-like [KO:K01353] [EC:3.4.21.79]
100052638  granzyme B isoform X1 [KO:K01353] [EC:3.4.21.79]
111771745  granzyme B-like [KO:K01353] [EC:3.4.21.79]
111768663  granzyme-like protein 2 [KO:K01353] [EC:3.4.21.79]
100034181  IFNG; interferon gamma precursor [KO:K04687]
100034224  KIR3DL; killer cell immunoglobulin-like receptor with three domains and long cytoplasmic tail precursor [KO:K07980]
100062846  NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
100062823  NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
100062618  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
100062789  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
106780861  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
106783293  NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
100062688  NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
100062540  KLRD1; natural killer cells antigen CD94 [KO:K06516]
Compound
C00338  Lipopolysaccharide
C00533  Nitric oxide
Reference
PMID:16412784
  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
PMID:14735553
  Authors
Reddy P.
  Title
Pathophysiology of acute graft-versus-host disease.
  Journal
Hematol Oncol 21:149-61 (2003)
DOI:10.1002/hon.716
Reference
PMID:17900507
  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
PMID:15882431
  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
PMID:12359826
  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
PMID:14556773
  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
PMID:16147539
  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
PMID:15372473
  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
PMID:17784964
  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
ecb04060  Cytokine-cytokine receptor interaction
ecb04210  Apoptosis
ecb04514  Cell adhesion molecules
ecb04612  Antigen processing and presentation
ecb04620  Toll-like receptor signaling pathway
ecb04650  Natural killer cell mediated cytotoxicity
ecb04660  T cell receptor signaling pathway
KO pathway
ko05332   
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