Dixon F.J., Kunkel Henry G. Advances in immunology, Volume 34 (1983)

Academic Press, 1983. — 323 p. — ISBN-10: 0120224348, ISBN-13: 978-0120224340.The selection of subjects presented in this volume reflects the broad scope of immunologic interest. Most of the progress in our field depends upon elucidation of the genetic basis underlying the immune system’s structure and function, and three important genetic areas are
represented. They include presentation of a new group of T cell alloantigens with many similarities to the immunoglobulin isotype markers for B cells, discussion of the recently recognized heterogeneity of Class I MHC antigens, and a review of the structure and function of
human Ir genes. Additional areas of expanding interest are indicated by three reviews that derive in part from neighboring fields of science but deal with matters of considerable immunologic importance. These are a discussion of interferon, particularly as it relates to and influences immunologic events, a review of the acute phase response to injury which has many paraIlels to and interfaces with the immune response, and, finally, a description of the lectin receptor markers of immunocytes and the imaginative lectin technology that has contributed significantly to the identification of the various functionally heterogeneous lymphocyte populations. A new group of T cell alloantigens encoded by a cluster of tightly linked genes on murine chromosome 12 is described in the first article by Dr. F. L. Owen. Drawing heavily on his and his associates’ work, he defines the gene cluster, designated IgT-C because of its proximity to the immunoglobulin genes, and its four recognized structural genes Tpre, Tthy, Tend, Tsu. The products of these genes appear on T cells at characteristic points during their maturational pathway in the order just listed. Although these antigens are distinct from the Lyt series of
markers, their presence is related to T cell regulatory function. Cells bearing three (thy, end, and su) of these markers appear to have distinct suppressing and/or delaying effects on immunologic responses in uitro, and the pre-marker appears to be associated with a nonregulatory, perhaps precursor cell. The maturational pathway defined by these markers is presented in detail with its functional and anatomical correlates and its relationship to other T cell markers. The apparent
,function of these gene products is discussed with special emphasis on the possibility that they represent constant regions of T cell antigen receptors distributed differentially on various T cell subsets in the same way that immunoglobulin isotypes serve as differentiation markers
for B cells. In the second article, Drs. Hansen, Ozato, and Sachs present recent research that is revealing a newly appreciated serologic, molecular, genetic, and functional heterogeneity of Class I H-2 antigens. The focus of this review is on the H-2D region associated genes and their
products, a subject to which the authors have been major contributors. Exactly how many genes exist in each region is not yet certain; however, it is clear that the past dogma citing only one gene product for each H-2K or H-2D region is incorrect, at least for some haplotypes.
The emerging picture is one of Class I genes as multigene families in which certain members undergo continuous evolutionary expansion and contraction. Finally, the contribution of the concept of Class I multigene families to our understanding of the evolution of these genes and to the roles played by recombination, duplication, and gene conversion in the process is presented and clearly related to appropriate experimental data. A timely view of the structure and possible function of human Ir genes appears in Article 3 by Drs. Gonwa, Peterlin, and Stobo. Thegenetic basis and chemical characterization of human Ia molecules, HLA-DR, and related HLA-DC and HLA-SB are described and compared to those of their less complex murine counterparts. The possible mechanisms by which Ir gene products might regulate immunologic responsiveness are reviewed along with examples of such apparent regulation. Particularly pertinent is the authors’ work on the immune response of humans to collagen indicating the HLA-DR4 relationship, the genetic characteristics, and the cellular events involved. Current knowledge about the several varieties of interferons such as their cells of origin, modes of induction, control of synthesis, and numerous actions, particularly those related to the immune system, is presented by Drs. Friedman and Vogel in the fourth article. Although most of this information on the actions of interferon comes from studies employing naturally derived and therefore limited amounts of interferon, it provides an essential background for intelligent exploitation of the large amounts of interferon now being made available by recombinant DNA technology. Apparently, all the interferons, a, p, and y , can either modulate immunologic mechanisms directly and/or retard
the growth of pathogens-the targets of immune responses. Gamma interferon, the product of stimulated T cells, is quite properly considered an immunoregulatory lymphokine which can enhance macrophage function, suppress responding B cells, and inhibit T suppressor activity. Another striking immunologic effect of interferon is its stimulation of natural killer (NK) cells presumably via the accelerated differentiation of pre-NK cells to fully cytolytic forms. One of the least well understood yet most challenging aspects of interferon is its apparent antitumor activity. This complex area is thoroughly discussed, and the several mechanisms of antitumor action, immunologic and nonimmunologic, elicited by interferon are analyzed and evaluated.
The acute phase response is the name given to a characteristic increase in concentrations of numerous serum proteins following a wide variety of infections, inflammations, or other tissue injuries and constitutes a significant component of the overall systemic reaction to injury.
Although this paraimmunologic event has been well recognized since the identification of C-reactive protein, one of its major constituents, some 50 years ago, its precise role in host defense is poorly understood. However, the fact that many components of the acute phase
response have enjoyed evolutionary conservation throughout the vertebrate kingdom would suggest that they subserve a beneficial function. In the fifth article, Drs. Pepys and Baltz review this subject covering the factors initiating and controlling the response, the chemistry of
its more prominent components, their biologic properties and functions, and, finally, their role in the diagnosis and monitoring of human disease. From initiation of the acute phase response via injury-induced activation of macrophages and interleukin-1 formation, which then stimulates synthesis of most of the acute phase reactants by hepatocytes, to the interaction of these reactants with microbial or endogenous molecules that may result in complement activation and modulation of inflammation, the parallelism between the acute phase and immune responses is evident. The former is a relatively nonspecific, extremely rapid defense in contrast to the latter specific but delayed reaction. With recognition of the great functional heterogeneity and extensive cooperative interactions that mark cells of the immune system comes the need for means to identify and isolate the separate and distinct cellular entities. Two major tools to achieve this end have been developed: antibodies reactive with lymphocyte surface antigens and lectins reactive with surface saccharides. In the final article, Dr. Sharon discusses lectin receptors as lymphocyte surface markers and draws on his extensive experience in detailing the use of lectins in the recognition and purification of lymphocyte subpopulations. Cell surface lectin
receptors are carbohydrates that reside in the oligosaccharide sequences of membrane glycoproteins or glycolipids as secondary gene products, just as ABO blood group determinants do. Lectins, which are largely of plant origin, are oligomeric proteins with several sugarbinding
sites per molecule, and these sites interact with their target noncovalently primarily via hydrophobic and hydrogen bonds. Al though the functions of lectin receptors on lymphocyte and other cell surfaces are not known, a large number of such markers have been identified and correlated with cell surface antigens as well as with maturational and functional characteristics of cells. Techniques capable of recognizing lectin receptors on cells in situ and of separating
and purifying specific cellular populations have been developed by using a variety of lectins. The use of this technology in diverse experimental situations as well as its potential clinical application in the preparation of non-graft-versus-host reactive bone marrow transplants are also presented.