In 1966, the first Germinal Centre Conference was held in Bern, Switzerland, as a result of an initiative from C. C. Longdon of Oak Ridge, Tennessee and H. Cottier of Bern. Fifteen years later, in June of 1981, the 7th conference in this series was held in Groningen, the Netherlands. At this "International Conference on Lymphatic Tissues and Germinal Centers in Immune Reactions," instead of focusing on germinal centres only, the intricate relationships between various constituents of the lympho-myeloid complex consti tuted the theme of the meeting. As Yoffee stated in 1966, "Perhaps we should consider not only the germinal centre itself but the surrounding tissue as well. " Over the years, these conferences have brought together a small but dedicated group of scientists, sharing (1) a fundamental interest in the physiology of the lymphoid system proper, and (2) the recognition that, only in the in vivo situation can the final answers be obtained, however ingeniously in vitro experiments may mimic reality. In 1966, the conference lasted three days and included 57 contributions "which were discussed at length. " The present conference accomodated 62 free papers and 64 poster presentations as well as some 24 additional abstracts selected from more than 200 submissions. Prominent among the selection criteria was the adage "in vivo veritas. " This volume represents the presentations from the 1981 Germinal Centre Conference."

During the past several decades, a significant international research effort has been directed towards understanding the composition and regulation of the preocular tear film. This effort has been motivated by the recognition that the tear film plays a critical role in maintaining corneal and conjunctival integrity, protecting against microbial challenge and preserving visual acuity. In addition, research has been stimulated by the knowledge that alteration or deficiency of the tear film, which occurs in numerous individuals throughout the world, may lead to desiccation of the ocular surface, ulceration and perforation of the cornea, an increased incidence of infectious disease, and potentionally pronounced visual disability and blindness.

The area of the Lake of Galilee, which is the site of the Fifth Confer ence on Lymphatic Tissues and Germinal Centers, has been a germinal center of dramatic events in human history. Thus, some two million years ago, it seems to have harbored an important phase of human evolu tion, when the descendants of the African Australopithecus migrated north wards, attempting to become Homo sapiens. Two thousand years ago, this very place was a germinal center for a new religion which determined some of the most important components of the history of western civilization. This may have been the first significant contribution of the people of the Lake of Galilee area to the world of ideas and values. More recently, some 70 years ago, this very place was a germinal center for a great ex periment aimed at the translation into actual reality of ethical and social values, by the establishment of the first kibbutz in Israel on this shore. We, therefore, hoped that by selecting this place for the Fifth Germinal Centers Meeting we could expect the inspiration of the site to generate new concepts and views."

Cells of the immune system are activated by a variety of stimuli that are derived from other cells, ingested material or from invading microorganisms. This issue of CTMI focuses on the mechanisms of phosphoinositide-mediated protein recruitment to intracellular membranes.

Salmonella infections of man and animals continue to be a distressing health problem worldwide. Far from disappearing, the incidence of typhoid fever in developing countries may be far higher than we had imagined. Salmonella food poisoning has increased to one of the major causes of gastroenteritis in the developed world, in itself also an indication that animal salmonellosis is still a major cause for concern. The situation requires a concerted multidisciplinary research effort in order to generate the new information and technology needed to assist in the control of these diseases. This concept was the driving force behind the NATO Advanced Research Workshop on "Biology of Salmonella" held at Portorosa, Messina, Italy, May 11-15, 1992. With additional support from the University of Messina, Medeva Group Research (UK) and the Swiss Serum and Vaccine Research Institute, the meeting brought together epidemiologists, microbiologists, molecular biologists, immunologists and clinicians. All the participants were actively working on different but related aspects of Salmonella and salmonellosis, with most of the leading laboratories worldwide being represented. The workshop provided an excellent opportunity for interdisciplinary consultation; it is not often that the topic of Salmonella and salmonellosis is covered to such breadth and depth in one extended meeting. Keynote addresses by invited speakers were interspersed with offered papers, many by younger members of the scientific community, and this volume presents the collated manuscripts of the lectures and extended summaries of the offered papers.

Development of new-generation vaccines is now more challenging than ever, as identifying, purifying and evaluating vaccine antigens is a complex undertaking. Most importantly, once the relevant antigens have been identified, key focus then shifts to the development of suitable delivery systems and formulations to achieve maximum in vivo potency with minimum potential side effects. These novel formulations-many of which will be nanoparticulates-can deliver the antigens to the desired site, to the relevant antigen presenting cells, and prevent systemic exposure of the immune potentiators. The proposed book will outline all the critical steps that need to be considered for successful development of various types of nanoparticulate delivery systems for vaccine antigens. These contributions from leading experts in the area of vaccine formulation and delivery systems will tie in what is the most current status, including clinical evaluations with these novel vaccine technologies.

A very early step in microbial colonization and pathogenesis is that involving recog nition of the host by the microbe. In the final analysis such recognition is due to interaction between specific molecules on the two sides, without which host and microbe would ignore each other. It is therefore exciting to learn the rules that govern host-microbe interaction at to a large extent determines whether or not we are infected by the molecular level, which influenza virus, leishmanias, staphylococci and other pathogens. This book is a compendium of the addresses delivered at a symposium on molecular interaction at Porvoo, Finland in August 1991. Realizing that there are no a priori differ ences in receptor recognition in viruses, eukaryotic parasites and bacteria, we freely inter mingled these microbes at the symposium, and in this book. We found the interdisciplinary discussions and comparisons both educative and stimulating. Thus the book is divided into parts that focus on host cell receptors, on microbial recognition molecules and molecules that mediate microbial interaction with a host cell receptor and, briefly, on the molecular events that follow. Although many microbes and many cellular receptors are missing from the book -owing to the limited duration and size of the symposium -the articles presented here constitute an impressive body of examples of how initial host-microbe interaction can come about. We believe that as such the book is a useful and interesting overview of the mechanisms and principles involved in these interactions.

The German land of Hesse (Bundesland Hessen) is well known for its excellent wines (Rheinhessen), for its financial centre and for its airport (FrankfurtlMain). It is, unjustifiably, far less well known for its importance to thennoregulation. Within the small area of Bad Nauheim, Giessen and Marburg (in alphabetical order) a greater concentration of students of thenno regulation has been trained or worked or is working than probably in any other single area of Europe, if not the world. It is thus most appropriate to hold the Ninth International Symposium on the Pharmacology of Thennoregulation in Giessen, from August 7 to 12, 1994. The community of students of thennoregulation was extremely grateful that Professor Kurt Bruck and the lustus-Liebig-University of Giessen had extended this invitation. The same community was even more saddened that Kurt Bruck died on April 27, 1992 and thus could not participate in this event that had been planned to honour his achievements. As a small token of friendship and affection, the many friends of Kurt Bruck from all over the world who will participate in this event dedicate this symposium to the memory of Kurt Bruck. Another staunch friend, researcher of temperature regulation and supporter of this series of symposia died in October 1993: Professor Wilhelm Siegmund Feldberg. We feel fortunate to be able to start this volume with two brief infonnal and personal accounts of professors Bruck and Feldberg."

This volume will address an important emergent area within the field of immunomics: the discovery of antigens and adjuvants within the context of reverse vaccinology. Conventional approaches to vaccine design and development requires pathogens to be cultivated in the laboratory and the immunogenic molecules within them to be identifiable. Conventional vaccinology is no longer universally successful, particularly for recalcitrant pathogens. By using genomic information we can study vaccine development in silico: 'reverse vaccinology', can identify candidate subunits vaccines by identifying antigenic proteins and by using equally rational approaches to identify novel immune response-enhancing adjuvants.

This book explores the many mechanisms by which the most prevalent Spirochetal pathogens persist in a healthy immune-competent host. Among them are the direct and indirect suppression of host immune signals, phase and antigenic variation, escaping recognition by host complement proteins, and seclusion into immune privileged sites. We also explore antibiotic therapy for control of infection, a baffling topic that lends itself to exalted interpretation.

This second edition of this book expands further on the first edition, which explored the relationship between the human immune system and the skeletal structure. In the past, scientists involved in immune and bone-cell investigations have rarely interacted in a significant way, as these disciplines have developed independently and, for the most part, remain separate. This book brings together ideas of international scientists from both fields in pursuit of new collaborations. This may facilitate greater understanding of the relationship between these fields.

Immunosenescence is a unique, multi-disciplinary approach to the understanding of immune aging. It addresses the topic from the biological, as well as the psychological, social and behavioral perspectives. It is, thus, a valuable and timely addition to the literature in this area. Contributors include experts in the field, reviewing the state of the art in research.

During the two years since the publication of the first edition of this book, the global spread of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has continued. HIV was estimated by the World Health Organization (WHO) in 1993 to have at least 13 million individuals worldwide, with 1 million infected infected in the United States. HIV/AIDS in the United States has become the leading cause of death among men 25 to 44 years of age and the fifth leading cause of death among women of the same age group. Prevention of HIV infection remains a global challenge. Testing for HIV is the cornerstone for surveillance and prevention programs and for the provision of appropriate medical care for those who are infected. Such testing is equally essential to the search for effective antivirus drugs and vaccines. This second edition of AIDS Testing incorporates the most current thinking on test methodology and interpretation, some of which has changed considerably over the past two years. This edition also has been expanded to include a section consisting of six chapters on test applica tions and a section consisting of four chapters on management issues. This edition, like the first, describes in clear terms all the complex ele ments of testing, including applications, scientific principles, quality assurance, safety, and medical, ethical, and legal considerations.

The induction of immune responses against tumor cells by vaccination is rapidly evolving as a therapeutic modality with new potentials for the treatment of cancer. It is based on the fact that our immune system can identify tumor cells and, once activated, is capable of developing specific immunity against the neoplastic cells. Numerous observations and intense research clearly document the major contribution of the immune system to the prevention of cancer. And there are many re ports of patients suffering from malignant melanoma or other tumors who mount a spontaneous immune response against their tumor cells that results in tumor regression. Based on the recent advances in our understanding of the compo nents of our immune system, their interactions and the regulation of immune responses, we are now able to design vaccination strategies that induce or enhance cell-mediated immunity against tumors. A ma jor advancement came with the identification and characterization of relevant tumor antigens, which are suitable target structures for anti-tu mor immune response. First clinical trials using such vaccine strategies have yielded encouraging results in patients. However, in spite of many reported cases of successful therapy of cancer by vaccination many patients still do not experience relief after such treatments. These initial clinical trials and the accompanying investigations have revealed a number of important results that indicate the direction of future re search and development in the field.

Immunopharmacology: A New Discipline of Immense Potential Among the looming triumphs of the biologic revolution is the rapidly developing understanding of the mechanisms of bodily defense. In the short span of 35 years, knowledge of immunologic machinery has progressed from crudest description to major understanding in cellular and molecular terms. Antibodies, immunoglobulins, and the complement system have been almost completely defined in detailed molecular terms. Organs, like thymus, spleen and lymph nodes-so long enigmatic black boxes-are beginning to be understood not only in cellular terms but in molecular, physiologic, and endocrinologic terms. With this surging new information about the immune system comes the possi bility of developing a pharmacology which can modulate and control immunologic functions. Immunopharmacology most broadly conceived must address (1) control of development and function of the cellular components of the immunologic appara tus; (2) facilitation and suppression of function of the immunologically competent cells of the several subclasses, like T helpers, suppressors, and effectors, and B effectors and suppressors; (3) manipulation and repair of the major biologic amplifi cation systems, e. g., the complement system and kinin-kallikrein system, and (4) utilization, modulation, and inhibition of the galaxy of molecules generated by T lymphocytes, the lymphokines. This new pharmacology must deal with the funda mental effector mechanisms of immunity, namely inflammation, phagocytosis, vascular reactivity, and blood coagulation. Furthermore, immunopharmacology must address and manipulate cell-cell communication and interaction, so vital to control of the immunological apparatus."

Recent advances in the field of recombinant antibodies have permitted the manipulation of genes encoding specific antibodies, thus allowing their ectopic expression in a wide variety of non-lymphoid cells. This volume describes how the ectopic expression of antibodies, as secreted or as intracellularly retargeted molecules, can be exploited to block biological functions or to confer new phenotypic traits (e.g. resistance to a virus). This is the first book describing this emerging technology, which is receiving increasing attention for application in many different fields and biological systems - from human gene therapy to plant biotechnology.

Considerable scientific and political interest has been expressed, parallelling public concern about the effects of chemicals on the immune system and the implications of those effects for health. Coupled with speculation about the magnitude and extent of the problem is discussion of needs for predictive testing and regulatory control measures. The first international seminar on the immunological system as a target for toxic damage was held in Luxembourg in 1984. It was organized by the International Programme on Chemical Safety (United Nations Environment Programme-International Labour Office World Health Organization) and the Commission of the European Communities with the support of the US Environmental Protection Agency and the National Institute of Environmental Health Sciences (USA) and the participation of the International Society of Immunopharmacology. In view of the perceived importance of imrnunotoxicity, it was considered necessary to organize a follow-up meeting. Thus, an international workshop on the immunotoxicity of metals and immuno toxicology was held in Hanover, Federal Republic of Germany, on 6-10 November 1989.

The topic of biological response modifiers has attracted the attention of many biomedical investigators, including immunologists, oncologists, pharmacologists, microbiologists, and biochemists, as well as clinical practitioners of medicine. This has occurred mainly because of the realization that the complex system of cellular and humoral interactions culminating in a productive immune response is under exquisite regulatory control for normal immune responses and that loss of control may markedly influence the capability of a host to respond in a productive manner to the numerous immunologic "insults" encountered in the environment. Furthermore, biological response modification is considered by many to be a natural offshoot of the relatively new application of "immunotherapy" to cancer. It is widely recognized that "immunotherapy" was practiced at the end of the last century and the beginning of this century when it was recognized that microbial infections were caused by distinct species of bacteria and that passive administration of serum con taining antibody to these microbes or their products could, in many cases, favorably influence the outcome of an infectious process."

The 9th International Conference on Lymphatic Tissues and Germinal Centres in Immune Reactions was held in Oslo, 9-14 August, 1987. These conferen ces, by the regular devotees just referred to as the germinal centre con ferences or GCC, have been held regularly at roughly three-year intervals since 1966. The credo of these conferences is "in vivo veritas", signifying that investigating components, like molecules and cells, only gives partial truth. The components must ultimately be explored in their natural con text, to see how they interact with other parts and are integrated to a whole. To the biologist it is obvious that the world must be investigated at many different levels of organization. At each level the patterns observed represent just some of many possible ways of putting together the elements of the lower levels. These patterns are not predetermined, but the results of evolution, i.e. of a history in which stochastic processes play a major role. The organic world can therefore not be torn apart and then reconstructed from basic principles alone. This realization is often expressed as the whole being more than the sum of its parts.

The International Symposium on the Immunoglobulin A System was organized in observance of the twenty-fifth anni versary of the School of Dentistry of the University of Ala bama in Birmingham. Immunoglobulin A was chosen as the sub ject of the Symposium because of its broad scope in relation to all biologic sciences, as well as for its particular rele vance to prevention of the most common human disease--dental caries. More than 500 scientists, from 13 countries, met in Birmingham, Alabama to review critically past and current research on IgA and to outline goals for integrating future investigations of the many facets of the IgA system. It is our pleasure to express sincere appreciation to the following, whose efforts made the Symposium possible: to Dr. Sidney B. Finn, Chairman, and all members of the Twenty fifth Anniversary Planning Committee for their advice and assistance; to Dr. Charles A. McCallum, Dean of the School of Dentistry, for his enthusiastic approval and support; to Dr. Frederick W. Kraus, Symposium Chairman, for the countless hours of meticulous planning that ensured the smooth execution of the Symposium; to Ms. Tonnia C. Maddox whose unstinting dedication was indispensable to the organizational success of the meeting; to those who assisted with the transcription of manuscripts and discussions: Ms. Shirley Snow, Ms. Jan Allen, Ms. Janice Buchanan, Ms. Joy Fisher, Ms. Pam Honeycutt, Ms. Mary Huckabee, Ms. Charlotte Hughes, Mr. Stephen Miles, Ms."

The OHOLO conferences have been convened annually as from the spring of 1956; they have covered very wide areas from different and overlapping disciplines, as can be seen from the following list: 1956 Bacterial Genetics (not published) 1957 Tissue Cultures in Virological Research (not published) 1958 Inborn and Acquired Resistance to Infection in Animals (not published) 1959 Experimental Approach to Mental Diseases (not published) 1960 Cryptobiotic Stages in Biological Systems* 1961 Virus - Cell Relationships** 1962 Biological Synthesis and Function of Nucleic Acids** 1963 Cellular Control Mechanism of Macromolecular Synthesis** 1964 Molecular Aspects of Immunology** 1965 Cell Surfaces** 1966 Chemistry and Biology of Psychotropic Agents (not published) 1967 Structure and Mode of Action of Enzymes** 1968 Growth and Differentiation of Cells in vitro** 1969 Behaviour of Animal Cells in Culture** 1970 Microbial Toxins** 1971 Interaction of Chemical Agents with Cholinergic Mechanisms** The participants at these meetings from the different scien tific institutions of Israel and from many countries, are engaged in fields of study which represent widely divergent approaches to biology. Thus, a characteristic feature of the OHOLO meetings has been their multi-disciplinary nature. These small international conferences are distinguished by the relaxed atmosphere in which they are held, with ample time for informal as weIl as formal discussions. *Published by Elsevier Publishing Co. , Amsterdam (1960). **Published by the Israel Institute for Biological Research, Ness Ziona.

The First International Workshop on Mechanisms in Cell-Mediated Cytoxicity was held at Carry-Ie-Rouet, France, September 14-16, 1981. The Workshop brought together for the first time leading investiga tors in each of the principal areas of cell-mediated cytotoxicity, as well as experts in the area of complement-mediated cytoxicity. Formal research presentations were held to a minimum, the emphasis being on open discussion of current knowledge about mechanisms of cytoxicity in each of the systems under consideration. The major objectives of the Workshop were 1) to compare and integrate what is known about the mechanism(s) of cytoxicity in each system; 2) to determine whether, on the basis of information in hand, it seems likely that the mechanisms of cytotoxicity in the various systems are the same or are unique; and 3) to stimulate thinking about new approaches to elucidating the fundamental mechanisms by which certain cells are able to kill other cells."

Apoptosis is a fascinating concept for the basic scientist. This is not only because of the multifaceted variety of proposed and discovered mechanisms, but because apoptosis represents a fundamental pathway for cell renewal. The study of apoptosis has resulted in an array of discoveries on signal transduc tion and downstream effects that have facilitated and advanced many fields in biology, including research on cancer and other diseases. Thus, the apoptotic process can be viewed as the largest effort of the scientific community to understand how cells work and tissues assemble or remodel. The most direct consequence of this accumulated knowledge is a greater understanding of disease and pathological mechanisms. The end result of these efforts will be significant contributions to health and the adoption of new, never anticipated, therapeutic approaches. This book represents the summation of considerable effort from a significant group of contributors from all over the world as well as from its editors. In this fashion, many viewpoints have been collected and SUbjected to thorough academic discussion. The concepts contained in this medically important volume will stimulate and renew the ideas of scientists and indeed, will generate additional work to advance biological knowledge even further. The emphasis of this volume cements what has been established, adds what has not been explored fully, and creates a fertile ground for further hypotheses that will lead to a more complete understanding of the apoptotic process."

Seventeen years after its initial description, nuclear factor-KB (NF-KB) endures as one of the most studied transcription factors. NF-KB has attracted widespread interest based on the variety of stimuli that activate it, the diverse genes and bio logical responses that it controls, the striking evolutionary conservation of struc ture and function among species, and its involvement in a variety of human diseases. The biochemical basis by which several stimuli converge to activate NF-KB has been largely elucidated during recent years. While first discovered as a key regulatory factor of the immune system, NF-KB is now recognized as an important player in the functioning of many organs and cell types. The ongoing examination of NF-KB signaling has revealed its ever expanding role in immune and inflammatory responses, but also in cancer and development. For this reason, numerous efforts are underway to develop safe inhibitors of NF-KB to be used in the treatment of both chronic and acute disease situations. The present book is the first to review and synthesize our knowledge of this interesting transcription factor. As such, the choice of subjects to review was daunting. To set the stage, an introductory chapter on activators and target genes, as well as the role they play in several responses, has been included."