KEGG   PATHWAY: hsa05332Help
Entry
hsa05332                    Pathway                                

Name
Graft-versus-host disease - Homo sapiens (human)
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 diseases
BRITE hierarchy
Pathway map
Graft-versus-host disease
hsa05332

All organismsOrtholog table
Disease
H00084  
Graft-versus-host disease
Organism
Homo sapiens (human) [GN:hsa]
Gene
3569  
IL6; interleukin 6 [KO:K05405]
3552  
IL1A; interleukin 1 alpha [KO:K04383]
3553  
IL1B; interleukin 1 beta [KO:K04519]
7124  
TNF; tumor necrosis factor [KO:K03156]
3108  
HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  
HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  
HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  
HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  
HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  
HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  
HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  
HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  
HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3122  
HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  
HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  
HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  
HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  
HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
HLA-DRB1; HLA class II histocompatibility antigen, DRB1-7 beta chain [KO:K06752]
941  
CD80; CD80 molecule [KO:K05412]
942  
CD86; CD86 molecule [KO:K05413]
940  
CD28; CD28 molecule [KO:K06470]
3558  
IL2; interleukin 2 [KO:K05429]
3105  
HLA-A; major histocompatibility complex, class I, A [KO:K06751]
3106  
HLA-B; major histocompatibility complex, class I, B [KO:K06751]
3107  
HLA-C; major histocompatibility complex, class I, C [KO:K06751]
3134  
HLA-F; major histocompatibility complex, class I, F [KO:K06751]
3135  
HLA-G; major histocompatibility complex, class I, G [KO:K06751]
3133  
HLA-E; major histocompatibility complex, class I, E [KO:K06751]
356  
FASLG; Fas ligand [KO:K04389]
355  
FAS; Fas cell surface death receptor [KO:K04390]
5551  
PRF1; perforin 1 [KO:K07818]
3002  
GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
3458  
IFNG; interferon, gamma [KO:K04687]
3824  
KLRD1; killer cell lectin like receptor D1 [KO:K06516]
3802  
KIR2DL1; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 1 [KO:K07981]
3803  
KIR2DL2; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 2 [KO:K07981]
3804  
KIR2DL3; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3 [KO:K07981]
3811  
KIR3DL1; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1 [KO:K07980]
3812  
KIR3DL2; killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 2 [KO:K07980]
3821  
KLRC1; killer cell lectin like receptor C1 [KO:K06541]
57292  
KIR2DL5A; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 5A [KO:K07981]
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)
Reference
  Authors
Reddy P.
  Title
Pathophysiology of acute graft-versus-host disease.
  Journal
Hematol Oncol 21:149-61 (2003)
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)
Reference
  Authors
Jaksch M, Mattsson J.
  Title
The pathophysiology of acute graft-versus-host disease.
  Journal
Scand J Immunol 61:398-409 (2005)
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)
Reference
  Authors
Reddy P, Ferrara JL.
  Title
Immunobiology of acute graft-versus-host disease.
  Journal
Blood Rev 17:187-94 (2003)
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)
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)
Reference
  Authors
Jacobsohn DA, Vogelsang GB.
  Title
Acute graft versus host disease.
  Journal
Orphanet J Rare Dis 2:35 (2007)
KO pathway
 

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