KEGG   PATHWAY: mna05332
Entry
mna05332                    Pathway                                

Name
Graft-versus-host disease - Miniopterus natalensis
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
mna05332  Graft-versus-host disease
mna05332

Organism
Miniopterus natalensis [GN:mna]
Gene
107540295  IL6; interleukin-6 [KO:K05405]
107528654  IL1A; interleukin-1 alpha [KO:K04383]
107528631  IL1B; interleukin-1 beta [KO:K04519]
107538974  TNF; tumor necrosis factor [KO:K03156]
107545174  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
107536419  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
107544122  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
107542667  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
107542672  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
107542674  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
107545091  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
107545092  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
107531685  uncharacterized protein LOC107531685 [KO:K10784]
107527336  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
107527343  CD86; T-lymphocyte activation antigen CD86 [KO:K05413]
107524832  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
107529760  IL2; interleukin-2 [KO:K05429]
107538488  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
107538961  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
107525813  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
107546126  LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-6-like [KO:K06751]
107546127  class I histocompatibility antigen, Gogo-C*0101/C*0102 alpha chain-like [KO:K06751]
107528441  H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X1 [KO:K06751]
107543787  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
107543257  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
107526074  PRF1; perforin-1 [KO:K07818]
107544835  granzyme B-like [KO:K01353] [EC:3.4.21.79]
107544836  granzyme H-like [KO:K01353] [EC:3.4.21.79]
107527227  IFNG; interferon gamma [KO:K04687]
107543999  LOW QUALITY PROTEIN: NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
107544001  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
107543998  natural killer cells antigen CD94-like [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
mna04060  Cytokine-cytokine receptor interaction
mna04210  Apoptosis
mna04514  Cell adhesion molecules
mna04612  Antigen processing and presentation
mna04620  Toll-like receptor signaling pathway
mna04650  Natural killer cell mediated cytotoxicity
mna04660  T cell receptor signaling pathway
KO pathway
ko05332   
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