title: Injury-induced allograft rejection: A rendezvous with evolution.
abstract: Modern immunology, in many ways, is based on three major paradigms: the clonal selection theory, the pattern recognition theory, and the danger/injury theory. The last theory holds that any cell stress and tissue injury, including allograft injury, via induction of damage-associated molecular patterns, induces immunity, including alloimmunity, leading to allograft rejection. On the other hand, the concept precludes that non-self per se induces immunity as proposed by the two former theories. Recently, the danger/injury model has gained considerable acceptance by immunologists, in particular as promoted by new insights into the function of the mammalian gut microbiota, representing a huge assemblage of non-self. Harboring microbiota by hosts is characterized by the fact that harmless noninjurious commensal microbes are protected by innate immunity-based tolerance, whereas intestinal injury-causing pathogenic microbes are immunologically attacked. Plausibility and validity of the danger/injury concept is stringently supported by observations of similar phenomena across the tree of life: the ability of the immune system to discriminate between harmful life-threatening non-self to induce immunity and harmless beneficial non-self to induce tolerance has apparently emerged during evolution. Immune defense responses to injuring/injured non-self (e.g., as reflected by plant resistance to biotic and abiotic stresses on one hand, and allograft rejection on the other hand) as well as immunity-controlled protection of beneficial non-self (e.g., as reflected by microbiota and the fetus of placental mammals) are processes in the interest of evolution and, thus, evolved under pressure across the phylogenetic tree.
authors.forename: Walter G
authors.initials: WG
authors.lastname: Land
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology; D005075:Biological Evolution; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D008322:Mammals; D010802:Phylogeny; D010944:Plants; D015398:Signal Transduction / Q000276:immunology; D014184:Transplantation, Homologous