Origins and evolutionary relationships between the innate and adaptive arms of immune systems

Long before vertebrates first appeared, protists, plants andanimals had evolved diverse, effective systems of innate immunity.Ancestors of the vertebrates utilized components of the complementsystem, protease-inhibitors, metal-binding proteins, carbohydrate-bindingproteins and other plasma-born molecules as humoral agents ofdefense. In these same animals, immunocytes endowed with a repertoireof defensive behaviors expressed Toll-like receptors. They madeNADPH oxidase, superoxide dismutase and other respiratory burstenzymes to produce toxic oxygen radicals, and nitric oxide synthaseto produce nitric oxide. Antimicrobial peptides and lytic enzymeswere in their armory. Immune responses were orchestrated bycytokines. Furthermore, genes within the immunoglobulin superfamilywere expressed to meet a variety of needs possibly includingdefense. However, recombination activating genes played no role.With the acquisition of one or more transposases and the resultingcapacity to generate diverse receptors from immunoglobulin genefragments, the adaptive (lymphoid) arm of the immune systemwas born. This may have coincided with the elaboration of theneural crest. Naturally, the role of the adaptive arm was initiallysubservient to the defensive functions of the pre-existing innatearm. The strong selective advantages that stemmed from having"sharp-shooters" (cells making antigen-specific receptors) onthe defense team ensured their retention. Refined through evolution,adaptive immunity, even in mammals, remains dependent upon cellsof the innate series (e.g., dendritic cells) for signals drivingtheir functional maturation. This paper calls for some freshthinking leading to a clearer vision of the origins and co-evolutionof the two arms of modern immune systems, and suggests a possibleneural origin for the adaptive immune system.