Allograft rejection

This pathway illustrates molecular interactions involved in the fundamental adaptive immune response for allograft destruction. This pathway was adapted in large part from [http://www.genome.jp/kegg/pathway/hsa/hsa05330.html 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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2328 CPTAC Assay Portal]

本路径图描绘了参与同种异体移植物破坏的基本适应性免疫反应的分子相互作用。该路径图大部分改编自[http://www.genome.jp/kegg/pathway/hsa/hsa05330.html KEGG]。在图示的初始步骤中，抗原呈递细胞（APC's），无论是来自供体（直接途径）还是受体（间接途径），激活了原始T细胞，导致CD8+和CD4+ T细胞的成熟。CD8+激活的T细胞导致同种异体移植物供体细胞的凋亡，而CD4+ T细胞分化为TH1、TH2、T17和Treg细胞。激活的TH1细胞产生TNFA和NO，通过细胞毒性损害供体移植物细胞。TH2细胞激活B细胞。激活的B细胞导致浆细胞形成，随后在急性抗体介导的排斥反应（AMR）和慢性AMR中，通过补体级联途径产生IgG抗体，其中C3是治疗靶点。外源性应用YCF抑制C3，从而预防AMR。依库单抗与C5结合，防止C5a的产生和膜攻击复合物的形成。C3a和C35作为强效的趋化因子，促进促炎细胞的浸润。贝拉塔cept抑制CD80/86与CD28的结合。皮质类固醇抑制促炎细胞因子。皮质类固醇有助于免疫抑制，如CTLA4，它抑制T细胞的激活。本路径上的蛋白质可通过[https://assays.cancer.gov/available_assays?wp_id=WP2328 CPTAC检测门户]进行针对性的检测。