KEGG   PATHWAY: ocu05332
Entry
ocu05332                    Pathway                                

Name
Graft-versus-host disease - Oryctolagus cuniculus (rabbit)
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
ocu05332  Graft-versus-host disease
ocu05332

Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100008733  IL6; interleukin 6 [KO:K05405]
100009250  IL1A; interleukin 1 alpha [KO:K04383]
100008990  IL1B; interleukin 1 beta [KO:K04519]
100009088  TNF; tumor necrosis factor [KO:K03156]
100328929  RLA-DR-ALPHA; major histocompatibility complex, class II, DR alpha [KO:K06752]
100348904  RLA-DRB1; HLA class II histocompatibility antigen, DRB1-8 beta chain [KO:K06752]
100349408  HLA class II histocompatibility antigen, DRB1-1 beta chain [KO:K06752]
100349667  HLA class II histocompatibility antigen, DRB1-1 beta chain [KO:K06752]
100350656  RLA-DRB1; HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752]
100350168  Orcu-DRB; HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752]
100343144  Orcu-DQA; SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
100351163  RLA-DQB; HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
100351416  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
100341358  RLA class II histocompatibility antigen, DP beta chain [KO:K06752]
100352927  RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
100352672  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
100355948  RLA-DMB; histocompatibility antigen DM heterodimer light chain-like [KO:K06752]
100352415  RLA-DMA; histocompatibility antigen DM heterodimer heavy chain-like [KO:K06752]
108175645  uncharacterized LOC108175645 [KO:K10785]
100009377  CD80; CD80 molecule [KO:K05412]
100008999  CD86; CD86 molecule [KO:K05413]
100008998  CD28; CD28 molecule [KO:K06470]
100302458  IL2; interleukin 2 [KO:K05429]
100354611  BOLA class I histocompatibility antigen, alpha chain BL3-7 [KO:K06751]
100338822  RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100349085  RLA-A2; RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100339821  RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100348995  RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100355380  HLA class I histocompatibility antigen, A-36 alpha chain [KO:K06751]
100349247  HLA class I histocompatibility antigen, B-7 alpha chain [KO:K06751]
100349757  RLA class I histocompatibility antigen, alpha chain 11/11 [KO:K06751]
100328967  RLA-A1; MHC RLA region class I 19-1 [KO:K06751]
100356371  RLA-A3; MHC class I antigen-like [KO:K06751]
100344073  FASLG; Fas ligand [KO:K04389]
100008609  FAS; Fas cell surface death receptor [KO:K04390]
100342396  PRF1; perforin 1 [KO:K07818]
100101600  granzyme H [KO:K01353] [EC:3.4.21.79]
103351183  duodenase-1 [KO:K01353] [EC:3.4.21.79]
100008602  IFNG; interferon gamma [KO:K04687]
100337728  NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
103348990  natural killer cells antigen CD94 [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
ocu04060  Cytokine-cytokine receptor interaction
ocu04210  Apoptosis
ocu04514  Cell adhesion molecules
ocu04612  Antigen processing and presentation
ocu04620  Toll-like receptor signaling pathway
ocu04650  Natural killer cell mediated cytotoxicity
ocu04660  T cell receptor signaling pathway
KO pathway
ko05332   
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