Technological advances, together with a better understanding of the molecular biology of infectious microorganisms, are creating exciting possibilities for a new generation of replicating vaccines. Historically, live vaccines have been either directly derived from a natural source or attenuated by empirical approaches using serial passages and host cell adaptation. Currently, we are witnessing a quantum leap in our technological capabilities to specifically modify the genetic make-up of viruses and bacteria, making it possible to generate improved live vaccines and to develop completely new types of replicating vaccines, such as vectored vaccines, single-round infectious vaccines and replicon vaccines. This book highlights some of the most exciting recent developments towards a new generation of replicating vaccines.

In this volume, a wide-ranging series of reviews reveal how systems biology -- a holistic and inter-disciplinary approach requiring the combined talents of biologists, mathematicians, and computer scientists -- is changing the face of infectious disease research. Leading experts discuss how the use of high-throughput and computational approaches are generating exciting -- and often unexpected -- new insights into the microbial-host interactions of a variety of bacterial and viral pathogens, including Salmonella, Yersinia, Mycobacterium, influenza virus, human and simian immunodeficiency virus, and hepatitis C virus. Additional chapters focus on systems approaches to innate immunity, intra- and inter- cellular signaling, biomarker discovery, and the evaluation and rational development of improved vaccines. Systems biology has both been hailed as a paradigm shift that will revolutionize biological science and criticized as overly expensive and complex. While the truth no doubt lies somewhere in between, the approach is yielding increasingly detailed and comprehensive views of biological systems and processes, including those that dictate the host response to infection and disease outcome. Systems Biology of Infectious Disease is highly informative reading for investigators already engaged in systems biology research as well as for those scientists and clinicians who may be seeking an introduction to the field.

This volume summarizes the state-of-the-art in the fast growing research area of modeling the influence of information-driven human behavior on the spread and control of infectious diseases. In particular, it features the two main and inter-related "core" topics: behavioral changes in response to global threats, for example, pandemic influenza, and the pseudo-rational opposition to vaccines. In order to make realistic predictions, modelers need to go beyond classical mathematical epidemiology to take these dynamic effects into account. With contributions from experts in this field, the book fills a void in the literature. It goes beyond classical texts, yet preserves the rationale of many of them by sticking to the underlying biology without compromising on scientific rigor. Epidemiologists, theoretical biologists, biophysicists, applied mathematicians, and PhD students will benefit from this book. However, it is also written for Public Health professionals interested in understanding models, and to advanced undergraduate students, since it only requires a working knowledge of mathematical epidemiology.

Impressive progress has been made in the general field of immunology which has made possible new understanding and pragmatic approaches to the patient with allergic disease. Indeed, one working in the field of immunology senses a major revolution of immunobiologic thinking, much of which has relevance to the clinical practice of allergy. To the practicing allergist, pediatrician, or internist who must deal with allergic patients, the surging new information may seem confusing and bewildering. As part of our comprehensive series on modern immunobiology which aims to digest this progress, we believe it is appropriate to devote an entire volume to the fundamental principles, new knowledge, and clinical lore on which the modern practice of allergy must be based. In the present volume we strive to bring together relevant contributions from leaders in the field of immunobiology with those whose work stands at the forefront of clinical practice. The advancing understanding has in numerous instances reached the point of clinical application, and we have tried to encompass in this volume the entire scope of modern allergy.

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 volume comprises the written contributions of participants in a symposium held in Dallas, Texas, June 3-5, 1980, entitled "HAMSTER IMMUNE RESPONSIVENESS AND EXPERIMENTAL MODELS OF INFECTIOUS AND ONCO LOGIC DISEASES." This meeting followed its predecessor, "Hamster Immune Responses: Experimental Models Linking Immunogenetics, Oncogene sis and Viral Immunity" by three years. This more recent meeting was more pointed in its focus and the contributions appeared to be more tightly associated. These meetings are part of an extend d effort by experimentalists using the Syrian hamster as an animal model system to bring together workers in potentially related areas for the exchange of ideas and information. The success of the symposia derives partly from the scientific excellence of the contributing scientists, and partly from the financial support of the National Institutes of Health through the Fogarty International Center. The administration of the University of Texas Health Science Center at Dallas, under President Charles C. Sprague, also donated time, facilities, and financial sup port. Preparation of the manuscripts in this volume, as camera-ready copy for the publisher, was the diligent and dedicated effort of Ms. Sara Howard. Copy editing was expertly performed by Ms. Sandra Schulte and proof-reading was the responsibility of Dr. Patricia Fultz and Ms. Alix Gerboth. However, final responsibility for any errors and omis sions in the published volume is taken by the five local editors: J. Wayne Streilein David A. Hart Joan Stein-Streilein William R. Duncan R. E."

This publication, "Viruses, Immunity and Immunodeficiency," is based on the first symposium in a series of International Biomedical Symposia sponsored by the College of Medicine of the University of South Florida in Tampa, Florida. There is an explosive interest concerning the effects of viruses on the immune response, especially the immunosuppressive effects of viral infection. This has come about because of the recognition that the Acquired Immunodeficiency Syndrome, which has taken biomedical scientists and the public in general by surprise, is just one of the many examples that viruses can influence the immune response system and, under appropriate circumstances, alter immunity in such a way that an infected individual becomes hi lly susceptible to a variety of other organisms to which normal individuals would be resistant. This symposium series, sponsored by the University of South Florida College of Medicine, brings to the biomedical con(r)unity topics of current interest. We thank the members of the faculty of various departments of the College of Medicine and the administration of the College for their support and encouragement in having these symposiaat this medical school. This volume, based or. this symposium onviruses and immunity is a good exam ple of the interdisciplinary nature of modern irrJ 1I1nobiology and modern biomedical science in general. Many investigators with many different back grounds and training experiences, including microbiologists, immunologists, biochemists, oncologists, and physicians, are interested in how and why viruses influence the immune response system."

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."

Increasing interest in the immunology of mucosal surfaces is obvious from the number of publications in scientific journals and from the frequency of national and international symposia devoted to this subject. Particularly encouraging are the large numbers of young investigators who have chosen to work in this area of theoretical immunology with profound practical implications. The two volumes represented here are the result of an International Congress Of Mucosal Immunology held at the Niagara Falls Convention Center and the Niagara Falls Hilton on June 29 - July 3, 1986. This satellite meeting of the International Congress of Immunology placed emphasis on all aspects of the Mucosal Immune System. This included the regulation of differentiation of mucosal lymphocytes, mucosa-associated lymphoreticular tissue and lymphocyte homing, the immunology of mucosa associated tissues and glands, effector functions in mucosal immunity, and the effects of environmental antigens on the immune response, all of which are included in Volume I. The second volume has emphasized studies of the immune response and effector functions, IgA biosynthesis and transport, IgA proteases and effector functions, developmental aspects and immunodeficiency, the immunopathology of IgA and mucosal immunoprophylaxis. A total of 218 papers are included in these two volumes and a comparison to past meetings held at four to five year intervals indicates the explosive growth of mucosal immunology."

By 1940, immunological mechanisms had been proved to have fundamental influ ences on a great number and variety of skin reactions, and skin diseases had brought to light a great number of fundamental immunological mechanisms that were basic to a wide range of different diseases, dermatological and nondermato logical. The preeminence of dermatological research in the advancement of immu nological knowledge should not astonish anyone. For the skin is not only the most easily accessible tissue for producing and studying immunological reactions, it is also the great organ of protection that meets the first onslaughts of inimical environmental forces and agents-potential enemies, both living and dead. And protection is in essence what immunology is all about. To get an idea of the long-established role that testing the skin and the study of its many reactions has played in advancing general immunology, one need recall only smallpox vaccination; tuberculin testing; testing with fungal extracts; skin testing in hay fever, asthma, and serum sickness; skin tests with toxins and toxoids; the patch test; the passive transfer of skin-adhering antibodies (reagins); skin sensitization by simple chemicals; and similar dermatological procedures that have exerted their influence on medical and scientific disciplines far beyond dermatology.

Lyme Borreliosis is a worldwide infectious disease causing a multisystem illness with considerable morbidity, particularly in North America and Europe. The causative agent is the spirochaete Borrelia burgdorferi, which is usually transmitted by the ixodid tick from animal reservoirs. This book is formed by contributions from the Second European Symposium on Lyme Borreliosis, held at St George's Hospital Medical School, London in 1993, which reviewed the current state of knowledge of the condition with regard to clinical manifestations, diagnosis, treatment, ecology, epidemiology, biology and immunopathogenesis. In this book, important data is reviewed concerning the clinical manifestations of Lyme Borreliosis. It seems that strain variation of the spirochaete is the main cause of regional differences seen in the clinical presentation of patients. One striking example of this, is the relatively high incidence of Lyme arthritis in the USA and apparent rarity of this manifestion in some areas of Europe. These important studies open the way for exciting new research that focuses on the immunological and molecular mechanisms that result in disease. A full insight into the ecology of Borrelia burgdorferi is essential to a balanced understanding of the disease and a number of excellent reviews on this subject are included. Significant advances with regard to the biology of Borrelia burgdorjeri and the immunopathogenic mechanisms that result in disease have been made, enabling the role of the Band T lymphocytes in disease to be established and the development of sophisticated phenotyping methods, improved diagnostic tests and effective vaccines.

This is the proceedings of the International Conference on AIDS Associated Syndromes held at Irvine on December 7-8, 1984. The purpose of this conference was to bring together investigators who are actively engaged in AIDS research to present their most recent data with regard to etiological agent(s) of AIDS, immunological characteristics of some of the patients in early stages of AIDS and various therapeutical modalities that are available for the treatment of AIDS, early AIDS (persistent generalized lymphadnopathy) or for those who demonstrate asymptomatic acquired immunodeficiency. In the area of etiological agents, the discussions are presented dealing with the questions of whether HTLV III/LAV alone or with other co-factor(s) like EBV or CMV are responsible for AIDS. What is the relationship of these viruses to Kaposi's sarcoma, since Kaposi's sarcoma in AIDS cannot be simply explained on the basis of the underlying immune deficiency? Data are presented for HTLV III/LAV interactions with the T4 molecule on the surface of helper T cells. A paper is presented with epidemiologicai evidence for AIDS being an African disease which perhaps was brought to the United States and then to Haiti."

Investigation of the morphology and function of lym- phatic tissue evolved rapidly during the past few years. Many new aspects and dimensions have proved to be of gre- at significance for the understanding of processes which are triggered by immunological means. The cellular coor- dination that operates in immune response emphasizes aga- in the importance of immuno-ecologic relations in the lymphatic tissue. It has become obvious that both the morphologic and the molecular properties of lymphatic cells are essential for their functional expression. Furthermore, the emerging body of evidence clearly shows that nonlymphatic cells (e.g. reticular cells and neu- rons) and substances that exert neurohumoral and hormo- nal activities should be regarded as normal constituents of the microenvironment of lymphatic tissue. The immune phenomena are, therefore, direct derivates of processes that occur in this microenvironment. Such a view of the microenvironment of immunity calls for immunoendocrino- logic, immunoneurologic and immunopharmacologic projects, it stimulates the creative imagination, and encourages research workers to enter into unexplored areas of the immunosciences. This book illustrates the joint efforts made by scientists from various parts of the world and armed with different ideas and views, to solve some of the mysteries of lymphatic tissue microenvironment. The Fourth Conference took place in the lovely set- ting of Dubrovnik and in the shade of olive trees under which philosophers used to meditate in ancient times.

Since 1966, at ro~ghly three-yearly intervals, an internation- al group of immunologists has met somewhere in Europe to discuss the latest developments in our understanding of the mechanisms governing the functioning of the immune system in vivo. These meetings have become known as the International C,mferences on Lymphatic Tissues and Germinal Centers in Immune Reactions, or for the regular devotees, simply as the Germinal Cent'~r Conferences (GCC). This volume represents the proceedings of the 8th GCC, which was held in Babraham, near Cambridge, UK, between the 14th and 17th August, 1984. When one considers how cellular immunology has become increas- ingly dominated by in vitro methodology over the past twenty years, it may seem remarkable that these conferences*hav~ survived at all, let alone prospered. However, I for one do not find this surprising, since I suspect that the exquisitely :omplex architect- ure and microenvironments of the lymphoid system will never be fully understood through in vitro studies. If "tae proper study of mankind is ~an", then surely ultimately the proper study of all the interacting elements which comprise the immune system has to be in vivo. This belief is shared by a substantial number of immunol- ogists, as the contents of this volume will attest. Although the GCC were originally devoted to unravelling the mysteries of the germinal center response (and these are still not fully resolved), over the years the scope of the meetings has inevitably broadened.

This volume gathers the leading research on antibody-drug conjugates and immunotoxins. Following a rigorous overview, the volume delves into focused sections on all aspects of ADCs and ITs from clinical development through to targeted therapeutic applications and the latest technologies.

The convening of the 3rd International Workshop on Monoclonal Antibodies and Breast Cancer had the character of a self-search exercise. After almost a decade of research in the basic and applied aspects of the use of serological means to diagnose and possibly treat breast cancer several milestones have been reached. Among them a clear understanding of immunopathological use and limitations of monoclonal antibodies against breast epithelium, the complete development and clinical use of immunoassays for circulating breast epithelial antigens, the striking advances in the diagnostic use of monoclonal antibodies to estrogen and progesterone receptor proteins and the first communications on proposed immunotherapeutic use of different conjugates of anti-breast antibodies. New areas of investigation have developed in our field, some which are reaching a full blossom while others are still facing obstacles and at times a re-definition of their goals and objectives. These meetings have acted in a way as a clearing house and have permitted their attendees to derive predictions that have helped shape future research and fine-tune objectives. But above all, the re-evaluation of past research at these Workshops and the renewed excitement brought to them by new information has helped generate a momentum and enthusiasm that assures for the future large scientific gains.

The realization of essential cellular'interactions in the immune response convokes a better understandin~ of the fixed and free cellular components of lymphatic tissue. Ger~inal centers of lymphatic tissue have long been considered to have a funda~ental role in the immune reaction, and have been suspected of being topographic regions where so~e of these essential cellular inter- actions may occur. The physiological significance of these topo- graphic regions in lynphatic tissue is only now becoming clarified from recent studies of antigen localization, but the histo2enic relation of the cellular compartments still needs to be resolved. This book represents the Proceedings of the Second International Conference on Lymphatic Tissue Germinal Centers, held at the University of Padova, Padova, Italy, June 26-28, 1968. The aim of the ~eeting was to bring together current infor~ation on the physiological significance of germinal centers in ly~rhatic tissue and their possible role in the immune response. The range of interests extended from phylogenesis and ~orphology to studies of antigen and viral localization, cytokinetics and cytodifferen- tiation, immunochemistry, and im~unosuppression. The interactions of central lymphoid organs, such as the thymus and bursa, are studies having an essential role in these Proceedings. Also, several studies deal with lymphatic tissue germinal centers in delayed hypersensitiv- ity and neoplastic disease. The effects of immunosuppressive drugs, antilymphocyte serum, radiation and hormones on lymphatic tissue and germinal centers are also areas covered in these Proceedings.

This volume serves as a follow-up to our previous book, MonoclonalAntibodies Hybridomas: A New Dimension in Biological Analyses. We continue the theme of monoclonal antibodies and their applications, attempting to cover some of the areas not covered in the previous volume. We again include an appendix de scribing methods useful to those who ar-e beginning to apply these techniques in their own laboratories. This volume will be followed by another concentrating on the combination of monoclonal antibody techniques with molecular genetic techniques to study structure/function relationships at the level of both the gene and gene product. Roger H. Kennett Kathleen B. Bechtol Philadelphia, Pennsylvania Thomas J. McKearn Princeton, New Jersey IX Acknowledgments Roger Kennett acknowledges the patience and support of his wife, Carol, and his family, friends, and colleagues during the work on this volume, and again thanks, above all, the Lord, Jesus Christ. Kathleen Bechtol wishes to thank colleagues and friends for their support and understanding during the months of preparation of this volume. Tom McKearn acknowledges and thanks his wife, Pat, and his family for their support and encouragement. Xl Contents PART I INTRODUCTION 1 Introduction: Reflections on Nine Years of Monoclonal Antibodies from Hybridomas 3 ROGER H. KENNETT, KATHLEEN B. BECHTOL, AND THOMAS J. McKEARN 1. Biotechnology'S "Coming of Age." . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 II. Monoclonal Antibodies-An Overview of Applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 III. Commercialization of Monoclonal Antibody Technology.. . . .. ... . .... .... .. . ... . . 10 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 . . . . . . . . . . . . . . . . . . . . ."

The knowledge of Th17 cells and other cell populations which secrete IL-17A, and/or IL-22 has expanded tremendously since the publication of the first edition "Th17 Cells: Role in Inflammation and Autoimmune Disease" in 2008. The present volume has been completely revised with the addition of new chapters on the IL-17 receptor family and signaling, and an in-depth review of IL-22 and innate lymphoid cells. The differentiation of na ve T cells into regulatory T cells and Th17 cells as well as the plasticity of Th17 cells is discussed. The role of IL-22 in cutaneous inflammation including psoriasis has been reviewed. In addition, the volume contains critical updates on autoimmunity, organ transplantation, tumor immunology and genetic mouse models for mechanistic studies. Lastly, the latest clinical progress in neutralizing antibodies to IL-17A, IL-17RA not only confirms the therapeutic promise foreseen in 2008, but also improves our knowledge of the pathogenesis of autoimmune diseases. In summary, this is a timely update and important review of the clinical and experimental aspects of IL-17, IL-22 and their producing cells.

Vaccination, chiefly responsible for the eradication of smallpox and the control of poliomyelitis and German measles in man and of foot-and mouth, Marek's and Newcastle disease in domestic animals, remains the best answer to infectious diseases. Early vaccines were live wild type organ isms but these have been largely replaced by attenuated or killed organisms or by purified components (subunits) thereof. More recently, developments in recombinant DNA techniques, the advent of monoclonal antibodies and progress in our understanding of the immunological structure of proteins, have laid the foundations for a new generation of vaccines. For instance, subuni t vaccines have been produced through gene cloning and a number of peptides mimicking small regions of proteins on the outer coat of viruses and capable of eliciting virus neutralizing antibodies, have been synthes ized. Such vaccines are defined at the molecular level, can elicit immune responses controlling specific infectious organisms and are, thus, potent ially free of the problems inherent in conventional ones. However, because subunit and peptide vaccines are only weakly or non-immunogenic, they re quire the presence of immunological adjuvants. These are a diverse array of agents that promote specific humoural and/or cell-mediated immunity responses to antigens. This book contains the proceedings of the 1st NATO Advanced Studies Institute "Immunological Adjuvants and Vaccines" held in Cape Sounion Beach, Greece during 24 June-5 July, 1988.

The immune response is largely dependent on molecular inter actions involving proteins. The recognition of antigen molecules, whether they are proteins or non-proteins, whether they are self or non-self, takes place at the molecular-cellular interface through membrane receptor molecules that are proteins. The initial step of recognition activates a complex series of cellular events requiring some mechanism of cell-cell interactions and communi cations, eventually leading to antibody production. This biolo gical cascade is controlled at several positions along its con secutive pathways by protein molecules, either in the free form or as receptors on membranes of cells committed to this activity. Clearly, then, the proper understanding of the response by cells of the immune system will depend, to a great measure, on the definition of the molecular events involving protein interactions. Obviously, cells work via molecules and molecules work via cells and, at this level of functional resolution, molecular immunology and cellular immunology will merge and will depend heavily on protein chemistry."

Course covers topics in infectious diseases in children and is intended for Pediatric Infectious disease trainees, trainers, and all those who manage children with infections.

The ontogeny of lymphoid cells seems the most appropriate place to start. The early events in T and B cell ontogeny are still confusing. There seems to be no agreement on the data and on the semantics of the question of progenitor vs. stem cells. Nevertheless, we are beginning to understand more about progenitor cells which are committed to particular cell lines, and about stem cells in the sense of having almost unlimited capability of giving rise to undifferentiated progeny. An important future development will be to determine the nature of the substances that attract stem cells and which are produced by specialized thymus epithelium, and perhaps by the bursa. The way stem cells recognize these signals is an important question to answer. Not predictable from mammalian models has been the observation that there is a lack of cells called into the bursa even before the signal for entry of stem cells has been shut off. A likely model suggested that after a certain point in development there were no longer any cells capable of migrating into the bursa and becoming B cells. A fascinating possibility is the suggestion that a cell comes into the bursa, is not committed, then can still wander into the thymus. This cell does not appear to have B cell characteris tics; that is, immunoglobulin is not expressed on its surface."

In Immunotherapy for Infectious Disease, Jeffrey M. Jacobson, MD, and a panel of leading researchers review the state-of-the-art for treating various infections-particularly HIV-by manipulating the immune system's response rather than by chemical drugs. The contributors synthesize the principles of immune defense on the molecular level (monoclonal antibodies, vaccines, methods of antigen presentation, and cytokines and cytokine antagonists), as well as on the cellular and clinical levels levels as a protection against infection. The review of the current state of anti-HIV immunotherapy covers HIV-specific passive and active immunization strategies, gene therapy, and host cell-targeted approaches for treating HIV infection and restoring immune function.