Sepsis and infection are the major enemies of the intensive care patient in whom immunological defenses are severely impaired. This major problem is thefocus of attention in this book, based on the presentation of the First International Congress on the Immune Consequences of Trauma, Shock, and Sepsis, which is one of the first attempts to exchange ideas on the state-of-the-art in this area of immunology. Both basic and clinical research, including new centres of attention, are described. The growing role of immunology in medicine opens new avenues to the under- standing of trauma and sepsis and will allow the design of novel therapeutic approaches.

Oral immunization has a fascinating and frequently successful history, yet it has been largely overshadowed by other immunization methods. Various vaccines that lead to the induction of antibodies in respiratory, gastrointestinal, and genitourinary tracts are currently under development, and others are in use for the immunization of animals as well as humans. This volume gives oral immunization the attention it deserves in light of recent methodological and technical advances in antigen delivery systems.

The papers in this book were presented at the 6th Workshop on Mechanisms in B-Cell Neoplasia, held in Bethesda, March 23-25, 1988. On alternate years this meeting is sponsored by the . ;. Basel Institute of Immunology in Basel, Switzerland and by the National Cancer Institute in Bethesda, and is attended by 100 to 150 parti cipants. This 6th workshop, like the preceding five, was characterized by intense and enthusiastic discussion which reflects, we think, the exciting growth and development of this field. It is quite clear, however, that despite many general advances an understanding of the precise underlying mechanisms in B-cell tumor development is not yet defined. Probably, there is no single mechanism for all the various forms of B-cell neo plastic development. Many different forms of B-cell neoplasms are known, and these are distinguished by several characteristics: 1) the stage of development attained by the tumor stem cells; 2) mode of growth (slow or fast); 3) association with natural or inductive etiologic agents and 4) specific and consistent mutational mechanisms such as retroviral insertion, chromosomal rearrangement. Those charac teristic forms which arise naturally in relatively high frequency or those tumors with hallmark properties which can be induced consistently are the models most frequently studied, e. g. , endemic Burkitt's lymphoma, follicular lymphoma, acute and chronic lymphocytic leukemia and mUltiple myeloma in man; bursal lymphoma in chickens; Abelson virus induced pre B cell lymphomas and plasmacytomas in mice and immunocytomas in rats. Each model system, has special problems and advantages.

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."

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

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.

This volume focuses on the evidence for or against molecular mimicry as a cause of autoimmunity. Contributions from recognized experts present their original findings, and the final chapter reviews the overall perspective of molecular mimicry, how to use its principles in clinical investigation and list the conceptual traits by which autoimmune disaese can occur.

This volume contains the contributions to the workshop "The Semiotics of Cellular Communication in The Immune System" which took place at "11 Ciocco" in the hills north of Lucca, Italy, September ~-12, 1986. The workshop was the first meeting of what we hope will be a broad consideration of communication among lymphocytes, and focused on the new interdisciplinary branch of biological sciences, immunosemiotics. It is in the realm of the possible, if not the probable, that in the future a number of scientists larger than the thirty present at 11 Ciocco will find immunosemiotics to fill a need in scientific thinking and a gap between biology and the humanities. This might lead to growth and flourishing of the branch, and in this case the first conference and this first book could be blessed by the impalpable qual ity of becoming "historical", if in an admittedly 1 imited sense. Just in case this should happen the organizers/editors think it wise to set the record straight at this particular time, about the sequen~e of events and circumstances that crystallized the archeology of the "11 Liocco" gathering. They feel a sort of obligation to this endeavor: it has happened all too often that innocent historians have been left in utter confusion by the careless founders of new religions, schisms, revolutions, et cetera, who simply forget to jot down the facts before the whirlwind of time engulfs them in its fog.

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."

The findings of immunogenetic linkages, autoantibodies including autoislet cell and autoinsulin antibodies-and viruses in diabetes has attracted increasing interest among immunologists, virologists, geneticists and clinicians. To gather together the recent avalanche ef new and exciting information emerging in this area, Current Topics in Microbiology and Immunology has put together two volumes on this subject. The first volume, CTMI 156, (see page VI for contents) provided data on the animal models and experimental approaches currently employed to evaluate both the autoimmune and virologic factors contributing to the causation and patho genesis of diabetes. The second is this current volume. It is edited by Drs. BAEKKESKOV and HANSEN and focuses on current knowledge in human diabetes. This volume on human diabetes contains ten chapters from leading researchers. The book is arranged in two components. The first part critically analyzes the genes in man that playa role in susceptibility to insulin dependent diabetes mellitus (IDDM). The second segment analyzes the role(s) that various environ mental factors play in IDDM and provides data on the autoantigens, aberrant immune responses, and the role of cytokines and free radicals in the pathogenesis of diabetes. La Jolla, California MICHAEL B. A. OLDSTONE, M.D. This collection of studies was conceived as part of a two-volume review of the immunology of diabetes. The contents of Volume 156, which forms part 1, are listed below."

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 prevention and control of infectious diseases represents, even today, an important public health problem for responsible national and international authorities. Newly emerging p.athogens such as human immunodeficiency virus (HIV), legionella, and bovine spongiform encephalopathy (BSE) have captured current public awareness. Despite significant success against smallpox, polio myelitis, mumps, and measles, the vast majority of infectious diseases are yet to be satisfactorily controlled. Limited efficacy of some vaccines, e. g., against influenza viruses, or their nonavailability have hampered an effective control of many infections. A meaningful reduction of the health risks posed by microbial pathogens is of crucial importance. Increased efforts need to be exerted in areas of active and passive immunization as well as in stimulation of enhanced nonspecific resistance .. Progress in the field of infectious diseases can be accelerated when a generation of new improved vaccines are developed. These vaccines should be capable of activat ing the cellular and the humoral immune responses as well as inducing persistent immunological memory. Development of novel regimens for enhancing natural resistance against infections is also progressively gaining in importance. The urgency increases as chemotherapy against viral and other infections further continues to be plagued by a carousel of a limited number of licensed drugs, problems of side effects, and development of drug resistance. It is becoming expedient that future strategies embrace a policy directed towards triggering mechanisms capable of inducing specific and nonspecific host defences."

A host of environmental factors regulate the embryonic development of neurons. In adults, the survival of neurons, the regeneration of damaged axons, and plastic changes in axonal arborization are also controlled by a complex array of environmental cues. An important category of regulatory influences involves target-derived hormone-like peptides act ing on neuronal cell surface receptors. Nerve growth factor (NGF) was the first such factor to be characterized (LEVI MONTALCINI and HAMBURGER 1953) and has served as the model against which all similar factors are compared. A number of factors with properties similar to NGF have been described with activities toward differing populations of neurons. Many of these factors have been characterized only poorly at the biochemical level. However, several factors have been charac terized to the extent that molecular clones are available and complete amino acid sequences are known. These include: three structurally related factors, NGF itself (SCOTT et al. 1983), brain-derived neurotrophic factor (BDNF) (LEIBROCK et al. 1989), and neurotrophin-3 (NT-3) (MAISONPIERRE et al. 1990; HOHN et al. 1990); ciliary neurotrophic factor (CNTF) (LIN et al. 1989) and a second set of structural homologs; acidic and basic fibroblast growth factors (aFGF, bFGF) (ABRAHAM et al. 1986; JAYE et al. 1986). Investigators have cloned the receptors for NGF (JOHNSON et al. 1986; RADEKE et al. 1987) and FGF (LEE et al. 1989)."

CURRENT TOPICS IN MEDICAL MYCOLOGY, VOLUME 4, like the pre- ceding three volumes in the series, is intended to summarize current research advances inmedical mycology. Topics ex- plored in this volume include skin kinetics of azole anti- fungal drugs; killer system interactions; fusarium-caused hyalohyphamycosis; molecular technique for epidemiologic ty- ping of Candida species; and the need for a mycoses-repor- ting system.

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 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 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."

African and South American trypanosomiases are notable features of clinical and veterinary practice in their respective endemic areas and, as such, are of considerable economic importance. Scientifically, however, their importance ex tends beyond their clinical significance, as the trypano somes are intriguing and easily manipulated models for the study of the control of gene expression, membrane chemistry, proliferation and differentiation. It is clear from the scientific press that the rate of advance has "hotted" up in these areas of trypanosome research over the past 5 years and so a single-topic volume within the scope of the present series seemed timely. As ever, the final admix ture of review topics was a compromise between what was appropriate and what was available - fortunately with the former in vast excess. I should like to highlight two omissions, made for en tirely different reasons. The first is a detailed treatment of the molecular biology of the variant surface glycopro teins of the African trypanosomes (in particular Trypano soma brucei and T. equiperdum). This topic has been the subject of several reviews, for example, BORST and CROSS (1982)1 and TURNER (1982)2, and so was excluded from the present volume. The second omission is a review of the first-class work on genetic recombination from the group of Dr. Leo Jenni at the Schweizerisches Tropeninsti tut, Basel. This group has used isoenzyme markers to show that T."

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."

The diversity of antigen-binding structures of antibody molecules is so vast that every conceivable antigen can be bound by an antibody molecule within the immune system. This is true even for the antigen binding sites of antibodies called idiotypes, which are bound by complementary bind ing sites of other antibodies called anti-idiotypes. Thus, anti-idiotypes are structural homologues of antigens. These idiotypic-anti-idiotypic interactions constitute a network within the immune system. Since one lymphocyte produces only one type of antibody molecule, this network is in fact a network of cells. We expect that the network is functional: the appearance of antigen will disturb the equilibrium of the network at the point where it competes with the anti idiotypic lymphocyte for binding to the idiotypic lympho cyte. It has been known for quite some time that anti idiotypic antibody can be used to prime the immune system for memory to an antigen that it has never seen. This phe nomenon is now being explored for possible use in immuni zation against viruses, bacteria, parasites and tumors as well as for the modulation of autoimmunity. The ability of anti-idiotypes to mimic, both antigenically and function ally, the corresponding biologically active molecules seen by an idiotypic antibody was first demonstrated for the hormone insulin and is now being observed in many other systems. The papers assembled in this volume. bring the reader to the cutting edge of the potential practical applica tions of the network theory of the immune system."

From the preface: "The importance of the lymphatic system has been known for a long time. It was therefore surprising to learn that the status of dermal lymphatics, under both normal and pathological conditions of man, had been largely neglected to date, particularly with respect to their ultrastructure. Moreover, the existing information is incomplete, relating only to narrow segments of the skin, and it is controversial. This monograph represents an effort to overcome some of the existing deficiencies in the area of the structure (with emphasis on ultrastructure) of lymphatic capillaries. It is an account of our experience in the evaluation of dermal lymphatics in normal, edematous, and some other pathological conditions in man and in experimental animals. It is hoped that this information will prove useful for other investigators as a basis for evaluation of the structural and functional status of dermal lymphatics under a wide variety of pathological conditions."

The third component of complement, C3, is one of the most versatile proteins and an important participant in immune surveillance and immune response pathways. Its multifunctio nality is based on its ability to interact specifically with multiple serum complement proteins, cell surface receptors, and mem brant;-associated regulatory proteins. One of its most intriguing strategies of interaction with cell surfaces is the covalent binding of activated C3 through the internal thioester. The field has expanded over the past 10 years and a wealth of information has accumulated. C3 from various species and many of the human C3 binding proteins have been cloned and expressed. Numerous cellular responses mediated by the diffe rent fragments of C3 have been described. The findings that C3 interacts in a ligand-receptor-like fashion with proteins of nonself origin such as the gC of herpes simplex virus, a 70-kDa protein from Candida albicans, proteins from Epstein-Barr virus, etc. has opened a new field of investigation. The papers assembled in this volume summarize the wealth of data on the various aspects of the C3 interactions; together they bring to the reader new information on the chemistry, molecular gene tics, biology, and pathophysiology of C3 and C3-binding proteins. Emphasis is given to structural features as they relate to functions. Spring 1989 JOHN D. LAMBRIS, HANS J. MULLER-EBERHARD Table of Contents J. E. VOLANAKIS: Participation of C3 and Its Ligands in Complement Activation . . . . . . . . . . . 1 S. R. BARNUM, G. FEY, and B. F. TACK: Biosynthesis and Genetics of C3 . . . . . . . . . . . . .