Phylogenetic aspects of the complement system

During evolution two general systems of immunity have emerged: innate or, n atural immunity and adaptive (acquired), or specific immunity. The innate s ystem is phylogenetically older and is found in some form in all multicellu lar organisms, whereas the adaptive system appeared about 450 million years ago and is found in all vertebrates except jawless fish. The complement sy stem in higher vertebrates plays an important role as an effector of both t he innate and the acquired immune response, and also participates in variou s immunoregulatory processes. In lower vertebrates complement is activated by the alternative and lectin pathways and is primarily involved in the ops onization of foreign material. The Agnatha (the most primitive vertebrate s pecies) possess the alternative and lectin pathways while cartilaginous fis h are the first species in which the classical pathway appears following th e emergence of immunoglobulins. The rest of the poikilothermic species, ran ging from teleosts to reptilians, appear to contain a well-developed comple ment system resembling that of the homeothermic vertebrates. It seems that most of the complement components have appeared after the duplication of pr imordial genes encoding C3/C4/C5, fB/C2, Cls/Clr/MASP-1/MASP-2, and C6/C7/C 8/C9 molecules, in a process that led to the formation of distinct activati on pathways. However, unlike homeotherms, several species of poikilotherms (e.g. trout) have recently been shown to possess multiple forms of compleme nt components (C3, factor B) that are structurally and functionally more di verse than those of higher vertebrates. We hypothesize that this remarkable diversity has allowed these animals to expand their innate capacity for im mune recognition and response. Recent studies have also indicated the possi ble presence of complement receptors in protochordates and lower vertebrate s. In conclusion, there is considerable evidence suggesting that the comple ment system is present in the entire lineage of deuterostomes, and regulato ry complement components have been identified in all species beyond the pro tochordates, indicating that the mechanisms of complement activation and re gulation have developed in parallel. (C) 2001 Elsevier Science Ltd. All rig hts reserved.