title: Innate alloimmunity: history and current knowledge.
abstract: The history of innate alloimmunity begins in 1994 with the publication of clinical data from the Munich superoxide dismutase trial, which suggests that renal allograft reperfusion injury initiates acute allograft rejection and contributes to the development of chronic rejection. This clinical observation led to construction of an Injury Hypothesis. By 2007, growing evidence in favor of this hypothesis was seen. In particular, there was increasing experimental evidence in support of the notion that an oxidative allograft injury leads to generation of damage-associated molecules, such as heat shock protein 72, high mobility group box 1, and a hyaluronan fragment, all of which act as endogenous ligands of Toll-like receptors. These molecules are recognized by intragraft donor-derived and recipient-derived, Toll-like receptor 4- and Toll-like receptor 2-bearing dendritic cells that mature and subsequently initiate cytokine-driven development of the recipient's adaptive alloimmune response. Initial evidence suggests that injury-induced, Toll-like receptor-triggered signaling pathways involved in establishing innate alloimmunity utilize adaptor proteins and transcription factors that play a crucial role in the host's defense against pathogens.
authors.affiliation: Başkent University, Ankara, Turkey. walterland@aol.com
authors.forename: Walter
authors.initials: W
authors.lastname: Land
mesh_terms: D000486:Allergy and Immunology / Q000266:history; D002908:Chronic Disease; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007113:Immunity, Innate; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D018448:Models, Immunological; D015427:Reperfusion Injury / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D051193:Toll-Like Receptors