Contemporary topics in immunobiology – serie

The problem that virtually all cells have in discriminating between "self" and "non-self" molecules and cells has been considered at great length in immuno­ biology. However, cells that clearly are incapable of carrying out mammalian­ type immune functions can exhibit exquisite specificity in their capacity to discriminate among syngeneic, allogeneic, and xenogeneic cells. In this volume of Contemporary Topics in Immunobiology we have chosen to consider the general problem of self/non-self discrimination as it is manifest in recognition reactions of plants and invertebrates and in the evolutionary development of the immune response of vertebrates. A broad, many-faceted approach is taken toward fundamental issues in immunobiology in order to develop innovative concepts of receptor function as well as to delineate traditional views. The capacity of plants to discriminate between self and non-self is addressed in Chapter 1 by R. B. Knox and Adrienne E. Clarke. These authors provide examples of cell-cell recognition in plants that parallel those occurring in in­ vertebrates and vertebrates. In general, tolerance (acceptance) of grafts is re­ stricted to plants within closely related genera. Recognition is mediated by callus cells, which proliferate at wound surfaces in higher plants, and there is a correlation between cell and tissue type and antigenic markers detectable with the use of mammalian antibodies. Certain flowering plants exhibit precise discrimination in fertilization, when pollen must be from the same species, but fertilization occurs only if the pollen is genetically non-self.

This second volume of Contemporary Topics in Immunobiology considers many aspects of thymus dependency in order to exemplify the role of the thy­ mus in different species and different immunological responses. It is not in­ tended to be a compendium of the responses which have been shown to be thymus dependent but rather to illustrate for the reader the criteria he should apply in thinking about the significance of the thymus in immune responses. We are grateful to the editors and publishers of the Annals of the New York Academy of Science, the Australian Journal of Experimental Biology and Medical Science, Clinical and Experimental Immunology, Immunology, the Journal of Experimental Medicine, the Journal of Immunology, Laboratory Investigation, Nature, and the Proceedings of the Royal Society of Medicine and to Springer-Verlag, Berlin, for permission to reproduce illustrations. Specific references are given in the text. We would also like to thank the contributors for their time and energy and willingness to submit to the editorial red pencils. The exercise of these censori­ ous instruments meant that the manuscripts had to be reorganized and retyped. Mrs. J. Pettis, Mrs. A. Inglefield, and Miss M. Butt all helped, and we are most grateful to them. A.J.S.D. R.L.e.

This fourth volume of Contemporary Topics In Immunobiology treats in­ vertebrate immunity. Specifically, the results represent several approaches to humoral and cellular immunity. It is evident that invertebrates do have function­ ing immune systems. For example, cellular immunity is characterized by both specificity and memory, but it is still problematical whether vertebrate immune capacity evolved directly from invertebrates. Most of the manuscripts were formally presented at the International Symposium on Invertebrate Pathology, University of Minnesota, August 1972, held in connection with the 25th anniversary celebration of the American Insti­ tute of Biological Sciences. I wish to express my appreciation to the contributors and to beg their indulgence in what may have been overzealous editing. This was done, though, in the interest of clarity and to seek uniformity. Because of earlier problems, time limitations did not permit consultations between submission of manuscripts and final editing. For assistance, I extend a special note of gratitude to Mrs. Lois Gehringer who unselfishly retyped many of the manuscripts. The preparation of this volume was aided partially by NSF Grant GB17767, two grants from The California Institute for Cancer Research, and a grant from The Brown-Hazen Corporation. E.L.C. Contents Introduction: General Comments and a Note on Taxonomy ....................... .

It has long been suspected, and recently confirmed, that there is an etiologic relationship between several viruses and naturally occurring neoplasias. Virus precursors in the form of nucleic acids or antigens have consistently been associated with certain neoplasias. However, the role of these virus-specified precursors in etiology remains obscure. Recent studies of virus-associated neo­ plasias have led to advances in molecular techniques, which have yielded increas­ ingly sensitive assays for detection of virus-specific nucleic acids, and which have enabled the disruption of virus particles without concomitant loss in antigenicity of the components. These procedures have, in turn, resulted in molecular probes that allow more definitive evaluation of the host response to its virus and to the tumor cell with which the virus or its precursors are associated. Evaluations of the immune response and status of the host have provided important informa­ tion about carcinogenesis and the tools for seroepidemiological studies of a variety of cancers. These seroepidemiological studies have demonstrated that several human cancers, e. g. , Burkitt's lymphoma and nasopharyngeal carcinoma, are probably virus-induced, and that antibodies that are diagnostic and prog­ nostic for these diseases are detectable. The conclusion that feline leukemia is a disease transmitted horizontally by a virus resulted primarily from immunologi­ cal experiments.

And even I can remember A day when historians left blanks in their writings, I mean for things they didn't know. -Ezra Pound, Canto XIII * The prefaces to the previous volumes of this series have all expressed in various ways the actual motivation behind these collective efforts. There was agreement in most instances that we are facing some kind of publication explosion, and that the present type of compact and personalized reviews may be of help, from both a conceptual and a purely informational standpoint. The aims of the series were, and still are, to focus attention on the rapidly changing fields within the realm of immunology, and to present in each chapter the summation of results generated by an investigator or group of Investigators, either as an analysis of their own work or as a correlation of such work with the general field in question. The present volume does not differ in its construction from its predecessors, although it does concentrate on a single target, the T lymphocyte and its biology. The selection of subjects as well as contributors has been the sole responsi­ bility of this editor; however, the actual format and length of the individual contributions was left to the discretion and inspiration of the different authors. Even the styles, ranging from the concise statement to the meticulously detailed review, attest to the freedom of format.

Because of several valid (and some invalid) reasons, the research field of tumor immunology has been declining in popularity. The Simplistic dogmas, articles of faith, and theories of the late 1960s and early 1970s on the immuno­ logical mechanisms of the host-tumor interrelationships have frequently been refuted by some of the new developments in cancer biology, cancer biochem­ istry, and immunology. Furthermore, some of the conventional assays used to monitor "tumor-host immune relations" did not always reflect the host's true clinical situation or his prognosis. Several approaches to immunological interven­ tion were less successful than expected. In addition, the concept of "immune surveillance," which was basic to many researchers in the field of cancer im­ munology, seemed to fall apart. Much of the criticism was based on results from solid, well-performed, and well-controlled experiments, but there was also un­ just criticism based on ill-conceived and badly performed studies, and on misin­ terpretations of experimental data. There are many misconceptions about the tumor-host relationship. It is very often assumed that tumor immunity, as expressed systemically, is truly reflected at the tumor site. Several studies reported in this volume and elsewhere indicate that such is not always the case. Certain immune effectors may be selectively prevented from reaching the tumor site or the close vicinity of the tumor cells because of mechanical or chemical barriers, whereas others may be selectively attracted to the site by chemotaxis or other mechanisms.

Although the field of contemporary immunobiology continues to diversify and encompass an increasing array of biomedical disciplines and topics, there are frequently several themes that will receive special emphasis and prominence at any given time. It is our hope that this series will reflect these themes and pro­ vide an appropriate venue for exposure of such topics at a useful time. Although this particular volume is not designated as one of the special topics volumes in this series, the selected topics have in essence come together to con­ sider aspects of two major areas of considerable research interest in immuno­ biology today. These concern new approaches and insights into an understanding of the tumor-host relationship, and aspects of cellular interactions and networks as approached by various different lines of investigation. The province of tumor immunology remains one of the most challenging areas to immunologists, as it of necessity involves not only developing an under­ standing of the neoplastic process itself and how the immune system responds, but of eventually using this information in a diagnostic or therapeutic manner.

The phenomena involved in infections of man and domestic animals with metazoan or protozoan parasites present formidable practical problems as well as a theoretical challenge to immunologists, molecular biologists, and evolu­ tionary biologists. With respect to the public health and economic problems, malaria, for example, remains a major health problem with approximately 200 million people being infected yearly and, on the basis of World Health Organiza­ tion estimates, more than 1 million children die each year of malaria infections (Chapter 4). This volume addresses state-of-the-art immunologic approaches to the development of vaccines for parasitic diseases (Chapter 9) and analyses of studies bearing on the antigenic characterization of protozoan and metazoan parasites (Chapters 4, 5, and 7), on investigations of the role of precise mecha­ nisms underlying natural resistance or non permissiveness of the host to parasitic infections (Chapters 1, 2, and 12), on induced mechanisms including the genera­ tion of parasite-specific T-cell lines and clones (Chapter 6), and on the generation of monoclonal antibodies (Chapters 4 and 5) to parasite antigens of distinct de­ velopmental stages. Great progress has been made in characterizing parasite antigens capable of inducing a protective response in the vaccinated host; further progress in this area strongly depends on biochemistry and molecular biology with the long-term goal of synthesizing such antigens chemically or producing them by means of recombinant DNA technology (Chapter 4).

Immune Complexes and Human Cancer, the fifteenth volume of Contem­ porary Topics in Immunobiology, is a compilation of information derived from recent studies on the role of circulating immune complexes (CIC) in the patho­ genic manifestations of a variety of human cancers. Technical improvements in the detection of CIC in body fluids have resulted in data that indicate that CIC do occur in different types of cancer. In addition, tumor-associated antigens and antibodies have been detected in immune complexes of cancer patients' sera. Until recently the exact role and clinical relevance of immune complexes have been the subject of debate, partially because of the problems encountered in measuring immune complexes. But these problems are being confronted as more accurate measurement protocols are developed. Technical refinements, along with strict protocols, have provided evidence of heterogeneity in CIC, a factor that makes accurate detection of immune complexes in cancer patients difficult. Recent insights indicate that the measurement of immune complexes in cancer patients may be clinically useful not only as a tumor marker, but also in regard to the deranged immune response of tumor-bearing hosts and other disorders such as nephrotic syndrome, immune anemias, and clotting dysfunction.