Allograft rejection (Homo sapiens)
From WikiPathways
Description
This pathway illustrates molecular interactions involved in the fundamental adaptive immune response for allograft destruction. This pathway was adapted in large part from KEGG. In the initial step of this diagram, antigen presenting cells (APC's), either those from the donor (direct pathway) or from the recipient (indirect pathway) activate naive t cells leading to both CD8+ and CD4+ T cell maturation. CD8+ stimulated T cells lead to apoptosis of the allograft donor cells whereas CD4+ T cells differentiate into TH1, TH2, T17, and Treg cells. Activated TH1 produces TNFA and NO and damages donor graft cells by cytotoxicity. TH2 cell activates B cells. Activated B cells lead to plasma cell formation followed by IgG antibodies and the complement cascade pathway in acute antibody-mediated rejection (AMR) and chronic AMR with C3 being the therapeutic target. Exogenous treatment with YCF inhibits C3, thus preventing AMR. Eculizumab binds to C5 which prevent C5a production and the membrane attack complex. C3a and C35 act as potent chemotactic factors, promoting the infiltration of pro-inflammatory cells. Belatacept inhibits CD80/86 binding to CD28. Corticosteroids inhibit pro-inflammatory cytokines. Corticosteroids contribute to immune suppression such as CTLA4 which inhibits T-cell activation.
Quality Tags
Ontology Terms
Bibliography
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- Heeger PS, Dinavahi R; ''Transplant immunology for non-immunologist.''; Mt Sinai J Med, 2012 PubMed Europe PMC Scholia
- Satterwhite T, Chua MS, Hsieh SC, Chang S, Scandling J, Salvatierra O, Sarwal MM; ''Increased expression of cytotoxic effector molecules: different interpretations for steroid-based and steroid-free immunosuppression.''; Pediatr Transplant, 2003 PubMed Europe PMC Scholia
- Stegall MD, Chedid MF, Cornell LD; ''The role of complement in antibody-mediated rejection in kidney transplantation.''; Nat Rev Nephrol, 2012 PubMed Europe PMC Scholia
- Dragun D, Philippe A, Catar R; ''Role of non-HLA antibodies in organ transplantation.''; Curr Opin Organ Transplant, 2012 PubMed Europe PMC Scholia
- Sigdel TK, Li L, Tran TQ, Khatri P, Naesens M, Sansanwal P, Dai H, Hsieh SC, Sarwal MM; ''Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury.''; J Am Soc Nephrol, 2012 PubMed Europe PMC Scholia
- Zarkhin V, Kambham N, Li L, Kwok S, Hsieh SC, Salvatierra O, Sarwal MM; ''Characterization of intra-graft B cells during renal allograft rejection.''; Kidney Int, 2008 PubMed Europe PMC Scholia
- Nankivell BJ, Alexander SI; ''Rejection of the kidney allograft.''; N Engl J Med, 2010 PubMed Europe PMC Scholia
- Roedder S, Kimura N, Okamura H, Hsieh SC, Gong Y, Sarwal MM; ''Significance and suppression of redundant IL17 responses in acute allograft rejection by bioinformatics based drug repositioning of fenofibrate.''; PLoS One, 2013 PubMed Europe PMC Scholia
- Naesens M, Lerut E, Sarwal M, Van Damme B, Vanrenterghem Y, Kuypers DR; ''Balancing efficacy and toxicity of kidney transplant immunosuppression.''; Transplant Proc, 2009 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ABCB1 | GeneProduct | ENSG00000085563 (Ensembl) | |
AGTR1 | GeneProduct | ENSG00000144891 (Ensembl) | |
BHMT2 | GeneProduct | ENSG00000132840 (Ensembl) | |
BOLA class I histocompatibility antigen | GeneProduct | 652614 (Entrez Gene) | Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
Basiliximab | Metabolite | 152923-56-3 (CAS) | |
Belatacept | Metabolite | 706808-37-9 (CAS) | |
C1QA | GeneProduct | 712 (Entrez Gene) | update: C1QA HUMAN |
C1QB | GeneProduct | 713 (Entrez Gene) | |
C1QC | GeneProduct | 714 (Entrez Gene) | update C1QC HUMAN |
C2 | GeneProduct | 717 (Entrez Gene) | |
C3 | GeneProduct | ENSG00000125730 (Ensembl) | |
C4A | GeneProduct | 720 (Entrez Gene) | |
C4B | GeneProduct | 721 (Entrez Gene) | |
C5 | GeneProduct | ENSG00000106804 (Ensembl) | |
C6 | GeneProduct | 729 (Entrez Gene) | |
C7 | GeneProduct | 730 (Entrez Gene) | |
C8A | GeneProduct | 731 (Entrez Gene) | |
C8B | GeneProduct | 732 (Entrez Gene) | |
C9 | GeneProduct | 735 (Entrez Gene) | |
CASP3 | GeneProduct | ENSG00000164305 (Ensembl) | |
CASP7 | GeneProduct | ENSG00000165806 (Ensembl) | |
CASP8 | GeneProduct | ENSG00000064012 (Ensembl) | |
CASP9 | GeneProduct | ENSG00000132906 (Ensembl) | |
CCL19 | GeneProduct | ENSG00000172724 (Ensembl) | |
CCL21 | GeneProduct | ENSG00000137077 (Ensembl) | |
CD28 | GeneProduct | 940 (Entrez Gene) | Original kegg element: gene;36;hsa:940 |
CD40 | GeneProduct | 958 (Entrez Gene) | Original kegg element: gene;37;hsa:958 |
CD40LG | GeneProduct | 959 (Entrez Gene) | Original kegg element: gene;38;hsa:959 |
CD55 | GeneProduct | 1604 (Entrez Gene) | |
CD80 | GeneProduct | 941 (Entrez Gene) | Original kegg element: gene;35;hsa:941 hsa:942 |
CD86 | GeneProduct | 942 (Entrez Gene) | Original kegg element: gene;35;hsa:941 hsa:942 |
COL5 | GeneProduct | ENSG00000130635 (Ensembl) | |
CSNK2A2 | GeneProduct | ENSG00000070770 (Ensembl) | |
CTLA4 | GeneProduct | ENSG00000163599 (Ensembl) | |
CXCL11 | GeneProduct | ENSG00000169248 (Ensembl) | |
CXCL12 | GeneProduct | ENSG00000107562 (Ensembl) | |
CXCL13 | GeneProduct | ENSG00000156234 (Ensembl) | |
CXCL9 | GeneProduct | ENSG00000138755 (Ensembl) | |
CXCR5 | GeneProduct | ENSG00000160683 (Ensembl) | |
Cell adhesion molecules (CAMs) | GeneProduct | path:hsa04514 (KEGG Genes) | Original kegg element: map;7;path:hsa04514 |
Ciclosporin | Metabolite | 59865-13-3 (CAS) | |
Daclizumab | Metabolite | 152923-56-3 (CAS) | |
ECULIZUMAB | Metabolite | 219685-50-4 (CAS) | |
FAS | GeneProduct | 355 (Entrez Gene) | Original kegg element: gene;17;hsa:355 |
FASLG | GeneProduct | 356 (Entrez Gene) | Original kegg element: gene;18;hsa:356 |
FOXP3 | GeneProduct | ENSG00000049768 (Ensembl) | |
Fenofibrate | Metabolite | 49562-28-9 (CAS) | |
GABPA | GeneProduct | ENSG00000154727 (Ensembl) | |
GDNF | GeneProduct | ENSG00000168621 (Ensembl) | |
GNLY | GeneProduct | ENSG00000115523 (Ensembl) | |
GZMB | GeneProduct | 3002 (Entrez Gene) | Original kegg element: gene;21;hsa:3002 |
GZMB | GeneProduct | ENSG00000100453 (Ensembl) | |
HARS | GeneProduct | ENSG00000170445 (Ensembl) | |
HLA-A | GeneProduct | 3105 (Entrez Gene) | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
HLA-B | GeneProduct | 3106 (Entrez Gene) | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
HLA-C | GeneProduct | 3107 (Entrez Gene) | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
HLA-DMA | GeneProduct | 3108 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DMB | GeneProduct | 3109 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DOA | GeneProduct | 3111 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DOB | GeneProduct | 3112 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DPA1 | GeneProduct | 3113 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DPB1 | GeneProduct | 3115 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DQA1 | GeneProduct | 3117 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DQA2 | GeneProduct | 3118 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DQB1 | GeneProduct | 3119 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DRA | GeneProduct | 3122 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DRB1 | GeneProduct | 3123 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DRB3 | GeneProduct | 3125 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DRB4 | GeneProduct | 3126 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-DRB5 | GeneProduct | 3127 (Entrez Gene) | Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 |
HLA-E | GeneProduct | 3133 (Entrez Gene) | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
HLA-F | GeneProduct | 3134 (Entrez Gene) | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
HLA-G | GeneProduct | 3135 (Entrez Gene) | Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 |
IFNG | GeneProduct | 3458 (Entrez Gene) | Original kegg element: gene;34;hsa:3458 |
IFNG | GeneProduct | ENSG00000111537 (Ensembl) | |
IL10 | GeneProduct | 3586 (Entrez Gene) | Original kegg element: gene;31;hsa:3586 |
IL10 | GeneProduct | ENSG00000136634 (Ensembl) | |
IL12A | GeneProduct | 3592 (Entrez Gene) | Original kegg element: gene;41;hsa:3592 hsa:3593 |
IL12B | GeneProduct | 3593 (Entrez Gene) | Original kegg element: gene;41;hsa:3592 hsa:3593 |
IL13 | GeneProduct | ENSG00000169194 (Ensembl) | |
IL17A | GeneProduct | ENSG00000112115 (Ensembl) | |
IL1A | GeneProduct | ENSG00000115008 (Ensembl) | |
IL1B | GeneProduct | ENSG00000125538 (Ensembl) | |
IL21 | GeneProduct | ENSG00000138684 (Ensembl) | |
IL22 | GeneProduct | ENSG00000127318 (Ensembl) | |
IL2 | GeneProduct | ENSG00000109471 (Ensembl) | |
IL2RA | GeneProduct | ENSG00000134460 (Ensembl) | |
IL4 | GeneProduct | 3565 (Entrez Gene) | Original kegg element: gene;26;hsa:3565 |
IL4 | GeneProduct | ENSG00000113520 (Ensembl) | |
IL5 | GeneProduct | 3567 (Entrez Gene) | Original kegg element: gene;27;hsa:3567 |
IL5 | GeneProduct | ENSG00000113525 (Ensembl) | |
IL8 | GeneProduct | ENSG00000169429 (Ensembl) | |
LRRK2 | GeneProduct | ENSG00000188906 (Ensembl) | |
MICA | GeneProduct | 100507436 (Entrez Gene) | |
Methylprednisolone | Metabolite | 83-43-2 (CAS) | |
Nitric oxide | Metabolite | C00533 (KEGG Compound) | |
PDGFRA | GeneProduct | ENSG00000134853 (Ensembl) | |
PECR | GeneProduct | ENSG00000115425 (Ensembl) | |
PRF1 | GeneProduct | 5551 (Entrez Gene) | Original kegg element: gene;22;hsa:5551 |
PRF1 | GeneProduct | ENSG00000180644 (Ensembl) | |
PRKCZ | GeneProduct | ENSG00000067606 (Ensembl) | |
Prednisone | Metabolite | 53-03-2 (CAS) | |
STAT1 | GeneProduct | ENSG00000115415 (Ensembl) | |
Sirolimus | Metabolite | 53123-88-9 (CAS) | |
TGFB1 | GeneProduct | ENSG00000105329 (Ensembl) | |
TNF | GeneProduct | 7124 (Entrez Gene) | Original kegg element: gene;39;hsa:7124 |
TRAV | GeneProduct | 6955 (Entrez Gene) | Previously: ko:K10784 ; T cell receptor alpha chain V region |
TRBV | GeneProduct | 6957 (Entrez Gene) | previously: ko:K10785 ; T-cell receptor beta chain V region |
TUBA1B | GeneProduct | ENSG00000123416 (Ensembl) | |
Tacrolimus | Metabolite | 104987-11-3 (CAS) | |
VEGFA | GeneProduct | ENSG00000112715 (Ensembl) | |
VIM | GeneProduct | ENSG00000026025 (Ensembl) | |
immunoglobulin
heavy chain | GeneProduct | XP_011544500 (NCBI Protein) | Previously: ko:K06856 |
Annotated Interactions
No annotated interactions