ImmunpEvolution extinct fishes that arose during the devonian period.The other majoreventsuch as the movement from water to land cartilaginous fishes(chondricthyes)and the bony fishes that could have affected the evolution of the immune system.The stral toer ure the lungfish,order Dipnoi.The cotylosaurs were the stem lymphoid precurs After all the thymus in thisregionis reptiles that arose from the labyrinthodont amphibians or essential for gencrating the master regulators of the the microsaur amphibians during the Carboniferous includes the helper,cytotoxic and the thecodo fthe immune responses as and mammals.respectively.We surmise that immune Is that are Further Reading to attempt a synthesis and to make informed deductions the domin Cooper EL(1976)Comparative.Englewood Clffs.NJ: the numerous cells.molecules.tissues and organs of the Co the Co movement to development o oper EL and Nisbet-Bro wn E (eds)(1993)Developmental Inmmunol e body plan when the amphibians emerged.All of the equipment for nvertebrate efecting immune responses was present in the sea,but the Janeway C and Natori S(eds)(1994)Per pectives in th caused a vertebrate immune recogni th e evolution of positive selection edistibutioninvolhcdthcstcsforhacmalopoicesBOa marrow as we know it in terrestrial vertebrates did notexist vay CA Jr (19 ）The imn 11-16 d (th releva ology 32:13- which was then responsible for seeding the with imm de th LCand Davidson EH(1992)Theechinoidimmun precur This nocompetent cells als as a Today 13:356 362 successful model.From then on there was probably no 8 ENCYCLOPEDIA OF LIFE SCIENCES/001 Nature Publishing Group/www.els.netextinct fishes that arose during the Devonian period. The cartilaginous fishes (chondricthyes) and the bony fishes (osteichthyes) arose from different placoderm lines during the Devonian period (Figure 5). The crossopterygians were ancestral to the amphibians; the nearest living relative is the lungfish, order Dipnoi. The cotylosaurs were the stem￾reptiles that arose from the labyrinthodont amphibians or the microsaur amphibians during the Carboniferous period. From the stem-reptiles there emerged two forms, the thecodonts and the therapsids, which gave rise to birds and mammals, respectively. We surmise that immune response patterns developed phylogenetically, based on the data gained from living or extant animals that are relatives of extinct species. Certainly the fossil record can tell us nothing about a functioning immune system. Thus, it is essential to examine present-day living forms in order to attempt a synthesis and to make informed deductions concerning origins. We may now ask what the dominant themes were that coincided with the advent of vertebrates. Without listing the numerous cells, molecules, tissues and organs of the immune system, there were probably two major events: movement from water to land and development of the vertebrate body plan. First, there was the movement from an aquatic environment inhabited by fishes to the land when the amphibians emerged. All of the equipment for effecting immune responses was present in the sea, but the development of the so-called terrestrial body plan caused a tremendous change in the location and distribution of relevant cells, tissues and organs. Probably the greatest redistribution involved the sites for haematopoiesis. Bone marrow as we know it in terrestrial vertebrates did not exist in the sea. Instead, blood cell formation occurred in other sites that were retained but distributed differently. In this regard, amphibians, especially the anurans, were crucial in having developed long bones that housed bone marrow, which was then responsible for seeding the body with precursors of immunocompetent cells and their descen￾dants. This body plan of haematopoietic sites housed in long bones was retained in reptiles, birds and mammals as a successful model. From then on there was probably no other major event such as the movement from water to land that could have affected the evolution of the immune system. The focus of the thymus became more pronounced, perhaps a relic from our protochordate ancestors in whom, in the pharyngeal region, there is strong evidence of lymphoid precursors. After all, the thymus in this region is essential for generating the master regulators of the immune response. This includes the helper, cytotoxic and suppressor cells so crucial in all of the immune responses as we know them best in mammals. Further Reading Beck G, Cooper EL, Habicht GS and Marchalonis JJ (eds) (1994) Primordial Immunity, Foundations for the Vertebrate Immune System. New York: New York Academy of Sciences. Burnet FM (1968) Evolution of the immune process in vertebrates. Nature 218: 426–430. Cooper EL (1976) Comparative Immunology. Englewood Cliffs, NJ: Prentice-Hall. Cooper EL (1992) Overview of immunoevolution. Bolletino di Zoologia 59: 119–128. Cooper EL and Nisbet-Brown E (eds) (1993) Developmental Immunol￾ogy. New York: Oxford University Press. Cooper EL, Rinkevich B, Uhlenbruck G and Valembois P (1992) Invertebrate immunity: another viewpoint. Scandinavian Journal of Immunology 35: 247–266. Hoffman JA, Janeway C and Natori S (eds) (1994) Perspectives in Immunity: The Insect Host Defense. Austin, TX: RG Landes. Humphreys T and Reinherz EL (1994) Invertebrate immune recogni￾tion, natural immunity and the evolution of positive selection. Immunology Today 15: 316–320. Janeway CA Jr (1992) The immune system evolved to discriminate infectious non-self from non-infectious self. Immunology Today 13: 11–16. Marchalonis JJ and Schluter SF (1990) On the relevance of invertebrate recognition and defense mechanisms to the emergence of the immune response of vertebrates. Scandinavian Journal of Immunology 32: 13– 20. Smith LC and Davidson EH (1992) The echinoid immune system and the phylogenetic occurrence of immune mechanisms in deuterostomes. Immunology Today 13: 356–362. Stewart J (1992) Immunoglobulins did not arise in evolution to fight infection. Immunology Today 13: 396–399. Immune Response: Evolution 8 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net