Immunologic Phylogeny

There are two now classic reasons for the widespread and continuing interest in the phylogeny of immune reactivities and structure. First is the fundamental concern of biologists with the evolution of defense mechanisms. We are eager to discover origins, mechanisms, and adaptive specializations of immunocompetence because the very existence of individuals and entire species is involved in a most essential way. Second is the strong biomedical interest in adaptive immune mechanisms to increase understanding of health and disease in man. If man and placental mammals represent the quintessence of immunoresponsiveness with complex interdependent pathways, the less elaborate but fully functional systems of immunity in "lower" animals proffer insights applicable to immediate concerns in medicine. Recent approaches to organ transplantation, immunotherapy of cancer and repair of immunodeficiency diseases, to name just a few areas, have depended greatly on phylogenetic perspectives.

In a larger sense, intelligent wildlife conservation, utilization of food resources, and adequate environmental protection all hinge on knowing how diverse species survive or otherwise succumb to insults, injuries, and disease. The phylogenetic immunologist also seeks detailed information on the structure of the immunoglobulins which relates directly to the evolutionary history of living animals. Perhaps genetic mechanisms responsible for the evolution of these proteins may be revealed as spin-off information. The vast number of immunoglobulin specificities and effector structures, coupled with the remarkable phylogenetic conservation of certain polypeptide regions, makes these molecules especially useful to protein chemists as well as immunologists. Although many still talk glibly about higher and lower animals as if a hierarchy of superior versus relatively inferior functions were being classified, the immunologic phylogeneticist already knows better.

The lower animals, including invertebrates of course, have a much longer history of coping successfully with a myriad of potentially infectious and pathogenic agents in every conceivable habitat. Several major new insights are emerging from studies presented at this conference on Immunologic Phylogeny. Different levels of recognition and reaction to foreign agents are now discernible in phylogenetic progression all the way from coelenterates to mammals. The immune systems of advanced vertebrates may represent highly specialized versions of more general systems of receptors and mediators. Recent findings summarized in this monograph indicate that immunologic specificity and memory may both be viewed as adaptively evolving characteristics. Cell-mediated immunity associated with so-called T-cell functions is evident in advanced invertebrates and surely precedes in phylogeny the B-cell immunoglobulin production first detectable in primitive fishes.

Integrated cellular and humoral antibody immunity as shown by helper T-lymphocyte and B-lymphocyte cooperation is demonstrable in advanced bony fishes. At this level, two distinct molecular classes of immunoglobulins are also first discernible. Much still remains to be discovered about the structure and functions of vertebrate antibodies. At the level of primitive fishes (i.e., cyclostomes or agnathans), even the essential polypeptide composition of the apparently singular immunoglobulin remains in doubt. Indeed, the homology of non-mammalian immunoglobulins to those of mammals cannot be made until covalent structures are revealed. Complex immunoregulation now being extensively studied in certain birds and mammals appears to depend upon selective synthesis of multiple molecular classes and subclasses of immunoglobulins. Parallel specialization of T-cell functions may also be characteristic of these advanced vertebrates.

However, earlier manifestations of immunoreactivity (e.g., mitogen and allogeneic responsiveness, transplantation immunity, tumor immunity) seem to have been retained during progressive evolution and diversification of immunocyte functions. Although the generalization that invertebrates lack specific immunologic capability must now be rejected, assumption of a continuous phylogenetic progression in immune mechanisms extending from primitive invertebrates to advanced vertebrates is surely debatable. Many information gaps remain at all levels of phylogeny! The immunologic phylogenist or phylogenetic immunologist in 1975 retains two unusual joys as a biological scientist. First is the realization that many orders, classes, and even whole phyla of animals have yet to be studied in any detail by anyone. In other words, it is not too late to become a "founding father" - to put forward and test quite new hypotheses.

Second is the realization that with so few workers studying the immunocompetence of any unusual species or group, one can truly enjoy his research with little worry of someone else publishing first on the same topic.