Any professional concerned with immunology will be interested in this book dedicated to the memory of Milan Hasek, former director of the Prague Institute of Experimental Biology and Genetics. Prof. Hasek was a congenial scientist and most amiable person - a personal friend of almost all leading immunologists around the world. He was displaced from his post of director in 1970, yet had a lasting impact upon his students and the group known as the Prague School of Immunogenetics. The topics covered in the contributions range from tolerance, immune network, and immunogenetics to the immunology of bacterial and viral infections. They are written by 27 of Prof. Hasek's former co-workers who emigrated to western countries around or after 1968 and became well-known and distinguished scientists in the field. The papers include their personal reflections of the Prague Institute, their impressions upon arriving abroad and their interesting experimental work since then. The book also provides a complete bibliography of their publications after leaving Czechoslovakia.

The fourth workshop on Mechanisms in B-Ce11 Neoplasia was held in Bethesda. Maryland. at the National Institutes of Health on March 24. 25 and 26. 1986. The meeting was attended by approximately 150 participants and 58 presentations were given. The purpose of these workshops and the yearly publications has been to provide a means for exchanging the rapidly developing information in this field and to bring maJor problems into focus. Edited trans- cripts of the 1983 and 1985 workshops were published by Editiones Roche Bas1e, Switzerland. Papers brought to the 1984 workshop were published in Current Topics in Microbiology and Immunology, Vol. 113. Numerous retrovira1 recombinant viral constructs are now in general use in a variety of test systems, both in vivo and in vitro. These are proving to have interesting bio10gica1-prQperties. ------- Kecent1y developed systems for inducing B cell tumors are described: 1) The development of spontaneous ~-ce11 tumors in transgenic mice carrying deregulated mlGBP genes and the Ig heavy chain promoter; 2) a method for inducing *p1asmacytomas in BAL~/c mice with short latent periods of ca 70 days by infecting pristane treated mice with retroviruses carrying various types of deregulated mlGBP genes; 3) induction of pre-B cell tumors with erbB containing recombinant retroviruses; 4) induction of B-ce11 and other tumors by infection of neonates with recombinant retroviruses. Several retrovira1 constructs containing mlGBP sequences do not induce B-ce11 tumors in pristane conditioned mice *.

During the past few decades we have witnessed an era of remarkable growth in the field of molecular biology. In 1950 very little was known of the chemical constitution of biological systems, the manner in which information was transmitted from one organism to another, or the extent to which the chemical basis of life is unified. The picture today is dramatically different. We have an almost bewildering variety of information detailing many different aspects oflife at the molecular level. These great advances have brought with them some breath-taking insights into the molecular mechanisms used by nature for replicating, distributing and modifying biological information. We have learned a great deal about the chemical and physical nature of the macro molecular nucleic acids and proteins, and the manner in which carbohydrates, lipids and smaller molecules work together to provide the molecular setting of living systems. It might be said that these few decades have replaced a near vacuum of informa tion with a very large surplus. It is in the context of this flood of information that this series of monographs on molecular biology has been organized. The idea is to bring together in one place, between the covers of one book, a concise assessment of the state of the subject in a well-defined field. This will enable the reader to get a sense of historical perspective what is known about the field today - and a description of the frontiers of research where our knowledge is increasing steadily."

F. B. Michel Asthmology is the neologism I suggested for ideas which were acceptable at the begin the title of a book published in 1981 on ning of the 20th century, and in particular bronchial asthma [4,5]. to Pasteur's concept of "one cause, one ill ness", many syndromes like high blood Among a certain number of scientific pressure or asthma are the result of the publications on this subject, it is one of the overlapping of hereditary factors and ac few suggestions that I have the weakness to quired factors. This is one reason why asth feel somewhat proud of. In fact, this word has had the career I hoped it would and, ma is not really an illness in the real sense judging by the frequency with which it is of the word but, a clinical and functional respiratory syndrome [1]. used in both written and spoken language, it did answer a need. I had no intention of The innate, the "terrain", transmitted by suggesting one more neologism but it heredity, can possibly concern two factors: seemed to me that the word asthmology The bronchial hyperreactivity factor (BHR), had an element of novelty and, above all, is often present in early childhood and its produced the necessary awareness of the reality is a result of the studies of large need to bring together, within a kind of groups of homo- and heterozygotic twins.

When I entered the field of allergy in the early 1970s, the standard textbook was a few hundred pages, and the specialty was so compact that texts were often authored entirely by a single individual and were never larger than one volume. Compare this with Allergy Frontiers: Epigenetics, Allergens, and Risk Factors, the present s- volume text with well over 150 contributors from throughout the world. This book captures the explosive growth of our specialty since the single-author textbooks referred to above. The unprecedented format of this work lies in its meticulous attention to detail yet comprehensive scope. For example, great detail is seen in manuscripts dealing with topics such as "Exosomes, naturally occurring minimal antigen presenting units" and "Neuropeptide S receptor 1 (NPSR1), an asthma susceptibility gene." The scope is exemplified by the unique approach to disease entities normally dealt with in a single chapter in most texts. For example, anaphylaxis, a topic usually confined to one chapter in most textbooks, is given five chapters in Allergy Frontiers. This approach allows the text to employ multiple contributors for a single topic, giving the reader the advantage of being introduced to more than one vi- point regarding a single disease.

If tumor viruses did not exist in nature they might have been created by scientists interested in basic mechanisms of develop- ment, differentiation, and tumorigenesis. In contemporary euka- ryotic cell biology tumor viruses playa similar role to that which bacteriophages once had for the molecular biology of prokary- otes. Tumor viruses provide extremely useful probes for the above cellular processes since their life cycle is genetically pro- grammed and can be followed at DNA, RNA, and protein levels. The experimental systems reviewed in this volume utilize a wide variety of viruses. A comprehensive introduction to this field has recently been published in the volumes of Molecular Biology o/Tumor Viruses: DNA Tumor Viruses, 2nd edition, edited by J. Tooze; and Molecular Biology o/Thmor Viruses: RNA Tumor Viruses, 2nd edition, edited by R. Weiss, N. Teich, H. Varmus, and J. Coffm, by Cold Spring Harbor Laboratories in 1980 and 1982. Polyoma and SV40 viruses (see the chapter by A. Levine) and adenoviruses (see the chapter by W. Doerfler) are double- stranded DNA-containing viruses. Polyoma and SV40 are struc- turally related viruses which contain a genome of approximately 5 kilo basepairs, while the DNA of adenovirus is about 7 times more complex. These DNA tumor viruses are understood at a genetic and molecular level which is comparable to our know- ledge of A and T4 bacteriophages. Retroviruses, the subject of the remaining four chapters, con- tain a single-stranded RNA genome of 5-8 kilobases.

Due to the topology and structure of the lymph nodes, their role in the pathogenesis and development of diseases is a very special one. Each organ and even each organ-related region of the body has its own group of lymph nodes, specific topological reactions, such as in circumscribed inflammation or in the metastatic spread of malignant tumors. On the other hand, all the lymph nodes of an organism join in a uniform function effected by highly differentiated structures. Volume 84 of Current Topics in Pathology presents our current knowledge about the structure and reaction patterns of this "sec ondary" lymphoid organ. Despite our original intention to publish all the contributions in one book, it became necessary to divide them: Part 1 focuses on the involved nodal compartments, cell types, and functions, while Part 2 describes their reactions in inflammatory, neo plastic, and immune-deficient diseases. Even with the cooperation of more than 30 authors, the coverage cannot be exhaustive. The scope of both parts is limited to those reactions that can be described by direct and indirect morphological methods, including modern tech niques such as immune electron microscopy."

The rapid and continuous upsurge of interesting data in the subject of tumor immunology necessitates the publication of an annual series to furnish the updated materials to the students, researchers, and clinicians in this rapidly advancing field. Concepts and methodologies are ever changing. Also, current research in tumor immunology promises to offer breakthroughs in the future. Important is the need to communicate to the right people the exact role of immunodiagnostic methods and immunological intervention in cancer preven tion and treatment. The role of immunotherapy in combination with conven tional modalities of treatment needs to be understood in its proper perspective. Oncogene, interferon, lymphokines, monoclonal antibodies, natural killer cells, platelet-mediated cytotoxicity of antibody-coated target cells, suppressor cells, platelet-derived factors, plasma-blocking factors, control of suppressor cell func tion, abrogation of plasma-blocking factors, and so forth, are some of the areas that are continually advancing. Progress in these areas will have implication in cancer therapy. Further, it is already understood that if immunocompetence of the host can be maintained at a reasonably good level, there exists the potential to increase the therapeutic indexes of conventional modalities of treatment. This series will attempt to present updated information in all these areas based on con tributed and solicited articles."

Contents: Introduction and Overview Lymphopoietic Growth Factors: Pathophysiology of T-Cell Mediated Shock Induced by Bacterial Superantigens - Natural Killer Cells and Interleukin-2-Activated Killer Cells - TumourImmunogenicity Induced by Exogenous Interleukins - Cytokine Gene Therapy of Cancer - Analysis of T-Cell Receptor Variability in Tumour Infiltrating Lymphocytes - Clinical Studies with Interleukin-2: An Overview - Clinical Trials with Local Administration of Lymphopoietic Growth Factors - Clinical Trials with Interlaukin-2. The Rome Experience. Haematopoietic Growth Factors: Lymphohaematopoietic Growth Factor Use in Lung Cancer Patients - Clinical Trials with Haematopoietic Growth Factors and Peripheral Blood Stem Cells

"Le secret d'ennuyer est celui de tout dire. " Voltaire (Discours sur l'homme) Atopic dermatitis (AD) is frequently seen by dermatologists and pediatricians, by allergologists, and by many practitioners. The amount of data on AD is vast as it has been recognized for a very long time, has a worldwide distribution, and has a chapter or section devoted to it in every textbook or review of skin diseases. Difficulty arises in evaluating certain aspects of this complex disease, for many studies have been concerned with only some of its facets and with small numbers of patients. In addition a monograph on AD should also try to encompass the important theoretical aspects of this fascinating disease. There fore, the problem in presenting a monograph on AD lies more in the critical se lection than in the gathering of information, much of which is conflicting. This applies both to basic data and to details. Furthermore, the many divergent opinions in almost every field make it extremely difficult to draw unanimous conclusions. Consequently, the author has no option but to quote antagonistic views, try to make a compromise between these, and express his own opinion based on clinical experience and fundamental literary work.

When comparing the number of contributions for the proceedings of the third symposium on The Influence of Antibiotics on the Host-Parasite Relationship with those of its two predecessors, one becomes aware of the progress that has been made in this field. It is obvious that the design of experiments has substantially refined and therefore the clinical relevance of the results has gained in significance. The editors of this volume would like to thank all the colleagues who contributed to this book. It is hoped that interest in this field will develop further and that it will finally yield results which one day may be the basis for an improvement of antibiotic therapy. Bochum WOLFGANG OPFERKUCH Contents Opening Remarks P. G. Quie .... Interactions Between Antibiotics, Phagocytes, and Bacteria W. L. Hand, N. L. King-Thompson, T. H. Steinberg, and D. L. Hand. With 2 Figures and 5 Tables . . . . . . .. 4 Influence of Antibiotics on the Cell Surface of Escherichia coli H. Leying, S. Suerbaum, H.-P. Kroll, J. Gmeiner, and W. Opferkuch. With 2 Figures and 3 Tables . . . . . 17 Pseudomonas aeruginosa: Alterations Induced by Low Concentrations of 4-Quinolones M. T. Labro, A. Bryskier, C. Babin-Chevaye, and J. Hakim.

Important progress in the elucidation of the mechanisms influencing bacterial pathogenicity has recently been made through the introduction of modem genetic techniques. Molecular cloning allows the isolation of genes for pheno- types that epidemiological surveys have suggested play an important role in pathogenesis. The structural analysis of determinants for pathogenic traits can lead to the identifica- tion not only of the primary sequence but also of the possi- ble secondary and tertiary structures for important viru- lence factors such as toxins and adhesins. From these data, the prediction of antigenic domains suitable for the devel- opment of new vaccines appears to be feasible. The regula- tion of virulence determinants by endogenous and exoge- nous factors can be more clearly understood through the functional analysis of the cloned virulence genes. This volume surveys representative virulence properties of gram-positive and gram-negative bacteria to which the genetic approach has been successfully applied. The exam- ples described here include important bacterial toxins (e.g., diphtheria toxin, cholera toxin, toxic shock syndrome toxin, hemolysins), adhesion structures from E. coli and Neisseria gonorrhoeae, and factors supporting iron uptake, serum resistance, and invasiveness in a variety of bacteria. Both the present state and the possible futural develop- ments of these systems are described.

The all new Concepts in Viral Pathogenesis III contains the widely praised format of presenting up-to-date information in pithy, easily read "mini-review" style and complements previous editions with contributions by leading international authorities on structure-function relationships, gene regulation, cell biology of viral infections, transgenic mice, expression of viral genes, retroviruses, and evolving concepts in viral diseases. Taken together, Volume I, II and III of Concepts in Viral Pathogenesis contain 145 unique chapters each representing the latest thinking in important areas of virology by the foremost investigators in the field. Clinicians, laboratory scientists, students, and others seeking authoritative overviews of current knowledge on the mechanism of viral diseases will welcome this valuable resource.

The humoral response of the immune system to a foreign antigen usually requires the recognition of two antigenic determinants. The one, called the carrier, is recognized by T-Iymphocytes, the other, called the hapten, by B-Iympho cytes. As a consequence, T - and B-Iymphocytes proliferate, B-Iymphocytes produce hapten-specific antibodies, and the system develops memory to the antigens. It was long thought that antigens would form a bridge to mediate the cooperation of T - and B-Iymphocytes. However, it now appears that antigens are broken down to fragments which then act as carrier determinants for T -lymphocytes. The cells which originally process antigen are called an tigen-presenting cells. They have phagocytic properties. They can take up and degrade antigens, in the case of pro teins to peptides. The peptides of protein antigens reappear on the surface of the antigen-presenting cells, where they must become associated with membrane proteins encoded by genes of the major histocompatibility complex (MHC) in order to be recognized by T-Iymphocytes. To activate helper T-Iym phocytes which cooperate in antibody responses, MHC class II molecules have to be expressed on the surface of the antigen-presenting cells. Once T -lymphocytes have be come activated, they are ready to cooperate with B cells."

For more than ten years cell fusion techniques have been applied in studies on various lymphocyte functions. Ig expression was first studied in hybrids obtained by fusing myeloma cells with fibroblasts (1) or lymphomas (2), both of which do not produce Ig, and with Ig producing myelomas (3) or human blood lymphocytes (4). Kohler and Milstein (5) fused a myeloma with spleen cells from immunized mice. Up to 10% of the hybrids obtained secreted antibodies specific for the immunizing antigen. This suggested that plasma cells preferenti ally fused with the myeloma cells, a finding which was of enormous practical value. It was found that both Band T lymphocytes could be fused with the T cell tumor BW5147, which is however not permissive for Ig synthesis (6). A very large number of T cell hybridomas were generated by fusing BW5147 with cell populations containing in vivo or in vitro activated cells (7). The hybrids showed no specific T cell functions and binding assays for T cell receptors were not available. In particular, no hybrids were obtained which expreS1ed specific cytolytic activity that could be tested in short-term Cr release assays (8). However, the frustrations expressed about these failures, published in January, 1978 (9), were relieved by Taniguchi and Miller's publication a few months later of T cell hybridomas producing antigen-specific suppressor factors (10). Unfortunately, their hybrids rapidly lost factor production."

The cells of the immune system generate a large variety of binding sites which differ in their binding specificities and can therefore react specifically with a large variety of ligands. These binding sites are part of receptor molecules, enabling the system to react to the universe of antigens. The classical antigen receptor is the antibody molecule, and accord ingly the first session of this colloquium deals with a classical sub ject, namely antibody structure. Dramatic recent advances in this field make it possible to interrelate primary and three-dimensional struc ture both to each other and to function, i.e. the binding of antigen and possible reactions occurring in the antibody molecule upon antigen binding. The latter point is of particular interest since it may be relevant not only for effector functions of antibodies such as the binding of complement, but also for the triggering of a lymphocyte through its antibody receptor for antigen."

This volume of Current Topics in Microbiology and Immunology is concerned with a class of molecules that are the most potent polyclonal stimulators of T lymphocytes of several species. These molecules have been named "superantigens" because they use a mechanism of T cell stimulation closely mimicking MHC-restricted recognition of specific antigen: they act on variable parts of T cell antigen receptors and are presented by MHC class II molecules. Prototypes of these molecules are the pyrogenic exotoxins produced by S. aureus and S. pyogenes, of which the staphylococcal enterotoxins and the toxic shock syndrome toxin are the best known. Superantigens also occur endogen ously in mice, most notably the enigmatic Mis determinants, that have withstood characterization for nearly 20 years. Only very recently was it found that Mis is probably encoded by endogenous retroviruses. The list of candidates that are implicated as being superantigens is growing. In many cases, however, the proof that a given molecule indeed falls into this category is still missing.

Many RNA viruses have been known for decades to be genetically and biologically quite variable. Some well-known examples are influenza viruses, foot and mouth disease viruses, and Newcastle disease virus. During the past decade, it has become clear that most, it not all. , RNA viruses (riboviruses and retroviruses) are much more mutable than was recognized previously, and that this great mutability generates extremely complex populations consisting of indeterminate mixtures of related variants (Le. , "mutant swarms" or "quasispecies" populations). This is also true of DNA viruses (such as hepatitis DNA genomes via RNA transcripts B virus) which replicate their that are reverse-transcribed back to DNA. This hypermutability of RNA replicons provides great biological adaptability for RNA virus genomes. It also allows (but does not necessitate) RNA viruses, so that they can extremely rapid evolution of evolve over a million times more quickly than their eukaryotic DNA-based hosts. The genetics of RNA replicons is so unusual (and often counterintuitive) that it has many important biological conse quences which are neither readily apparent nor widely under stood. Failure to understand the distinctive aspects of RNA genetics frequently generates confusion and controversy and can adversely impact vaccine and antiviral drug programs and other applications of medical virology. The 14 chapters in this volume describe advances in a number of significant areas of RNA virus genetics and evolution.

This book has been written from two points of view: firstly, from the viewpoint of those who are involved in the diagnosis and treatment of lymphoid malignancies, who must meet the challenge of integrating the new biological insights into their knowledge of these diseases; and secondly, from the viewpoint of those who are involved in basic biological approaches to malignancy and immunology, who wish to know more about the function of the lymphoid tissues and their malignant diseases. Neoplasia of lymphocytes is a focus for considering many of the most important biological advances impinging on cancer in the past two or three decades, because malignant lymphoproliferative diseases offer unequalled opportunities for studying many aspects of cancer. We probably know more about lymphocytes than other normal cells because of the ease with which they can be obtained. For the same reason we probably know more about malignant lymphocytes. One or other aspect of most of the momentous advances in biology of the past two or three decades has implications for lymphoid malignancies: hybridoma technology and the use of monoclonal antibodies, gene technology, the understanding of oncogenes and growth factors in the control of growth and differentiation, insights into causation of cancer by potent tumour promoters such as the phorbol esters and by viruses, and knowledge of the control of growth function of lymphocytes themselves. Conversely, many of the advances in understanding lym phocytic leukaemias and lymphomas have implications for other cancers."

The first few months of any pregnancy are of supreme importance to the success of that pregnancy. This statement is so obvious as to be almost a platitude, yet it must be said that no aspect of pregnancy has been more neglected in the human than the first three months. Little is known of the morphological changes that occur at that time and our knowledge of the mechanisms that control this vital stage of pregnancy is almost non-existent. The explanation for this neglect of what is an obvious area for study is the difficulty of obtaining normal material. It is rare to have material to study from a healthy first trimester pregnancy and the study by Hertig and Rock!l) of early conception found by chance in hysterectomy speci mens must be unique. The information that we do have about early pregnancy is mostly gained from animal studies or single miscarriages in humans. Chromosomal defects are common but are not an explanation for the majority of recurrent miscarriages. Obstetricians have hypothesised many causes for this condition and have deve loped numerous metQods for treating it, but the studies have been poorly con trolled so that our understanding of the cause(s) has not advanced. Treatment of women with a history of recurrent miscarriage by paternal leuco cyte infusion (immunotherapy) may be yet another form of treatment that is hailed as a new advance only to be rejected when subject to rigorous testing.

The Second International Symposium on "The Influence of Antibiotics on the Host Parasite Relationship" was held in Munich, F. R. G. , from March 28 to 30,1985. The topics of the meeting dealt with the aspects of changes in bacterial metabolism and structure which occur under the influence of antibiotics, and with the effects of such changes on the antibacterial host resistance. The influence on pathogenicity factors, changes in the outer membrane of bacteria, as well as the influence on the individual components of the defence system were analysed in detail. In addition, these studies showed that antibiotics proved to be an excellent tool for the examination of bacterial physiology, so that, 50 years after the introduction of antibiotics, additional important knowledge can be gained about the effect of these substances on bacteria. Considering the observations reported, it appears justifiable to postulate that new antibiotics should be routinely tested with respect to their possible effects on antiinfectious resistance. Of course, a consensus will have to be found on which to base methods and criteria employEUROd. The symposium documented an increasing interest of microbiologists and clini cians for this field of research. It would not have been possible to organize it without the substantial support of the Paul Ehrlich Society as well as of Squibb-Von Heyden Pharma, Inc. Particular help concerning the organization has been given by Werner Kremer of Squibb-Von Heyden Pharma.

The skin allograft has been used as the test tool since the beginning of investiga tions of the fate of skin transplanted between two individuals of ordinary genetic diversity. This monograph is designed to furnish the transplantation work er with a review of the significant papers in which skin allografts and xeno grafts, applied to experimental animals and man, have played a role in acquiring a body of knowledge concerning the behavior and fate of these transplants and the reaction of the body to their presence. Skin, an essential organ for survival, a barrier between the "milieu inte rieur" of Claude Bernard and the "milieu exterieur," will remain the most frequently used transplant in transplantation research. Because it is highly antigenic, the final solution of the problem of acceptance of allografts of various tissues and organs will probably depend upon the achievement of a permanent survival of skin allografts. My personal interest in transplantation, which originated during my surgi cal training, was rekindled when I met Peter Medawar (today Sir Peter) in England during World War II. I had joined, in 1940, an American Volunteer Surgical Unit (The American Hospital in Britain), organized and headed by Dr."

This volume is not intended as review of the large literature on tumor antigenicity and efforts at tumor immunotherapy. Its pur pose, rather, is to present discursively an outline of the likely approaches to immunological intervention in neoplastic diseases which present themselves today, in light ofthe probable antigenic properties of cancer cells. References are cited only selectively, in illustration of some of the major considerations to which allusion is made and of some of the supportive evidence. No attempt is made at inclusiveness in the citation of concepts and fmdings. If undue emphasis appears to be given to some aspects of the litera ture and only sparse documentation to others, the grounds do not lie necessarily with a critical estimation of the extent or quality of reported work, but rather with the bias of the writer who consi ders stress on some facets of the field more appropriate than on others for elaboration of his arguments. The references brought in support of a given point are often intentionally varied, including both reports of original work and reviews, very recent observa tions and contributions that gave initial impetus to investigations, in an attempt to exemplify the pertinent literature; and reference is made both to data presented and to concepts advanced."