An AIDS vaccine is still elusive and HIV treatment continues to develop multidrug resistance at alarming rates. Because of the similarities between HIV and immune deficiency infections in a variety of animals, it is only natural that scientists use these animals as models to study pathogenesis, treatment, vaccine development and many other aspects of HIV. Part of the series Infectious Agents and Pathogenesis, this volume reviews the immune deficiency virus in a variety of hosts. Pathogenesis, vaccine and drug development, epidemiology, and the natural history of the monkey, mouse, cat, cow, horse, and other animal viruses are detailed and compared to HIV. Also included are chapters on the history and future of animal models, as well as a chapter on ethical and safety considerations in using animal models for AIDS studies.

Presenting the basic concepts and clinical implications of respiratory infection, with special emphasis on the role of the immune system, the field's leading researchers contribute detailed chapters on most of the major pathogenic and opportunistic bacteria, fungi, and viruses. Their work will stimulate new research by microbiologists and immunologists, teach clinicians the interaction between microorganisms and the host, and provide health professionals with information necessary to evaluate public health procedures.

It is now just 40 years since coxsackieviruses were first isolated by Dalldorf and Sickles in the "eponymous" town of Coxsackie, New York. Yet the overall contribution of coxsackieviruses to clinically evident dis ease of humans is still largely an open problem. Following their discov ery, coxsackieviruses were under intense clinical and laboratory scrutiny for a long time. Because of their relationship to polioviruses, the under standing of their structure, biochemistry, biology, and epidemiology ad vanced rapidly as a result of the formidable efforts that eventually led to the defeat of poliomyelitis. The ability of these viruses to infect mice permitted dissection of their pathogenicity in an experimental host and elucidation of conditions that influence its expression. Coxsackieviruses have been progressively associated with an increasing array of widely diverse human diseases. However, only some of the suggested causal correlations have been substantiated with satisfactory certainty. For others, conclusive evidence has so far resisted investigation. Most impor tant, among the latter are chronic maladies, such as dilated car diomyopathy and juvenile diabetes, that demand consideration. In recent times, there has been a partial eclipse of the subject of coxsackieviruses in the medical literature. In addition to the difficulties encountered in pinpointing their pathogenic potential, possible reasons include the general decline of interest in enteroviruses, which ensued after the conquest of poliomyelitis, and the continuous appearance in the limelight of new, more esoteric, and therefore more "appealing" viruses."

Experts in microbiology and autoimmunity examine the association between microorganisms and the development of specific categories of autoimmune diseases. The opening chapters explore the bacterial induction of diseases considered autoimmune in nature. Subsequent chapters describe the role of viruses in the induction of these diseases and of diseases with an autoimmune component. Specific topics include: the role of streptococcal infection in rheumatic fever and the role of Klebsiella in the development of ankylosing spondylitis.

Biomedical scientists widely acknowledge that individuals' immune respon siveness is important in resistance to infections by microorganisms, including fungi. Because of the devastating acquired immunodeficiency syndrome (AIDS) epidemic, caused by the human immunodeficiency retrovirus, it is now accepted that suppressed immune responses, especially cellular immu nity, are important contributors to increased individual susceptibility to opportunistic infections-including infections caused by fungi which were at one time thought to be very lowly or nonpathogenic. Within the last few years, there has been an almost explosive increase in interest and studies concerning the nature and mechanisms of the immune response to fungal infections. Many immunologists who are not well versed in mycology have begun to study the nature and mechanisms of antifungal immunity using a wide variety of newer as well as more conventional immunologic technologies, both in vivo and in vitro. Up to the 1980s, however, there was little interest among basic immunologists concerning fungal immunity. This situation has changed dramatically in the past half decade, mainly because of AIDS.

Chlamydia pneumoniae is a bacteria that is most commonly known for causing colds and pneumonia. However, researchers have recently found a link between C. pneumoniae and atherosclerosis, a clogging of the arteries that causes heart attack and stroke. In addition, ongoing research is showing that certain strains may play a role in asthma, multiple sclerosis, Alzheimer's disease, and arthritis. This volume, part of the Infectious Agents and Pathogenesis series, is a complete portrait of C. pneumoniae and what is currently known about it.

Busy clinicians and health practitioners recognize the importance of speedy detection of pathogens to impede the further spread of infection, and to ensure their patients' rapid and complete recovery. This reader-friendly reference is a unique collection of the newest and most effective diagnostic techniques currently in use in clinical and research laboratories. Instructive commentary regarding the application of these often complex methods is provided. This essential text aids readers in selecting the most efficient method, finding the necessary resources, and avoiding the most common pitfalls in implementation.

Although virology and immunology are now considered separate disciplines, history shows that these areas ofinvestigation always overlapped and one cannot really exist without the other. This trend has become particularly significant and fruitful in the past few years in the area of herpesvirus research. The genomes of the most important herpesviruses have been sequenced, a significant portion of their genes have been identified, and many secrets of regulation of gene expr- sion have been unraveled. Now this progress sets the stage for a true revolution in herpesvirus research: analysis of interactions between the host and the virus. Because herpesviruses can induce, suppress, and fool the immune system, the most productive herpesvirologists are also expert immunologists, and the current results ofthis interdisciplinary effort are truly remarkable. Because herpesviruses cause many important human diseases, the devel- ment of vaccines against these agents is a very significant goal. This effort is also very challenging because of the complexity of herpesviruses and the lack of sufficient information about immune responses. The remarkable ability of herpesviruses to escape immune responses is - other feature that brings immunology and virology together. Herpesviruses - code many proteins that interact with and down-regulate some key elements of the immune system. Thisproperty of herpesviruses represents amajor challenge in developing strategies against these viruses. On the positive side, these viral proteins also provide novel tools for analyzing specific immune reactions and molecular mechanisms.

Opportunistic, intracellular bacterial infections are in the forefront of research today because of the challenges they present to the immunocompromised patient. In this volume, the pathogenesis and immune reaction of these intracellular infections is featured, as are the most typical problems related to antimicrobial chemotherapy, and current approaches to their solution. Notable chapters set the pace for research on the pathogenic and immune reactions to such infections as * Mycobacterium tuberculosis * Legionella pneumophila * Chlamydia trachomatis and * Brucella.

Endotoxins are constituents of all gram negative bacteria, as well as many other microorganisms. Since their original discovery and study at the beginning and middle parts of this century, many investigations have been performed concerning their immunochemistry and physicochemistry, as well as their pharmacologic activities and physiologic effects on the host. It became widely recognized during the beginning of this century that the pyrogenicity of many microbial infections may be associated with endotoxins. Furthermore, some 80 years ago, attempts were begun to "treat" a variety of illnesses including neoplasia, with such "pyrogens," Le., bacterial endo toxins. Inconclusive results were observed including some detrimental ones as well as, in some cases, beneficial ones. It became widely accepted that during infections with many gram negative organisms the fever occurring in patients, as well as many of the untoward pathophysiological effects of the infections, seemed to be due to the endotoxin the bacteria contained or released. In this regard, septic shock has been studied in detail by many clinicians, physiologists and pharmacologists and attempts have been made to relate the devastating effects of infection on metabolic and physiologic alterations caused by endotoxins. Recently, however, many beneficial effects of endotoxin have also been studied."

The discovery of the human T cell leukemia virus type I in the late 1970s heralded a new era in retrovirology. For the first time, it was demonstrated that a retrovirus could play a role in the development of a human disease, in this case adult T cell leukemia (ATL). Several years later, the acquired immunodeficiency syndrome (AIDS) epidemic began, and it was dem- strated that a retrovirus, originally designated the human T cell lymp- tropic virus type 3, was the causal agent of this syndrome. This virus, later named the human immunodeficiency virus type 1 (HIV-1), has since been extensively studied in terms of its pathogenesis as well as its ability to elicit immune responses. In that time, a tremendous amount of information has been obtained about the virus. Although recent drug regimens have been useful in significantly lowering viral loads and perhaps maintaining an asymptomatic state among individuals infected with HIV-1, an established "cure" for AIDS eludes us. In addition, the effective drug therapies are very expensive, and are not available to infected people in the third world, where greater than 90% of new infections occur. Furthermore, the development of viral resistance against the drug therapies is an additional concern. Despite extensive study, no effective vaccine has been developed. One of the problems in developing an effective vaccine against HIV-1 is the ability of the virus, particularly in the immunogenic envelop glycoprotein, to undergo amino acid hypervariability.

Introduction and Perspectives This volume is based on the proceedings of the 7th annual symposium on the topic Neuroimmune Circuits, Infectious Diseases and Drugs of Abuse, Bethesda, Maryland, Oc- ber 7-9, 1999. This symposium, as in the past, focused on newer knowledge concerning the relationship between the immune and nervous systems with regards to the effects of drugs of abuse and infections, including AIDS, caused by the immunodeficiency virus. Presentations discussed the brain-immune axis from the viewpoint of drugs of abuse rather than from the subject of the brain or immunity alone. The major aim of this series of conferences has been to clarify the consequences of immunomodulation induced by drugs of abuse in regards to susceptibility and pathogenesis of infectious diseases, both in man and in various animal model systems. The recreational use of drugs of abuse such as morphine, cocaine, and marijuana by large numbers of individuals in this country and around the world has continued to arouse serious concerns about the consequences of use of such drugs, especially on the normal physiological responses of an individual, including immune responses. Much of the recent data accumulated by investigators show that drugs of abuse, especially opioids and cannabinoids, markedly alter immune responses in human populations as well as in experimental animals, both in vivo and in vitro.

As a group, rickettsiae, and related bacteria, contain a number of human pathogens that have recently named as causes of 'emerging diseases'. This unique volume offers a thorough and current review of information on the pathogenesis and immune response elicited by memebers of the genera Rickettsia, Ehrlichia, Coxiella, Orlentia, and Bartonella, in contributions authored by the expert clinicians and researchers who work with these organisms.

The discovery and concept that Helicobacter pylori is associated with gastric disease including gastric cancer which is one of the most common and frequently lethal forms of malignancy, heralded a new and rapidly expanding field recognizing the emergence of many new pathogens and disease syndromes in clinical medicine, as well as basic infectious disease research. There is now an extensive and widely known literature of how H. pylori is involved in a wide variety of disease syn dromes. As summarized in the introductory chapter of this volume, many major advances have been made in diagnosis, both serologic and endoscopic in time of the involvement of this organism in patients with upper GI ailments as well as its presence in those who are not clinically ill. The Introduction describes the rapid development of understanding the role of this organism in disease. The basic bacteriology of H. pylori is then described in the second chapter. Diagnostic tests for detecting H. pylori infection is then highlighted, as well as the role of such infection in gastric cancer. Current knowledge concerning risk factors and peptic ulcer pathology associated with H. pylori is then described. Newer information concerning therapy of H. pylori infection and colonization is described in a subsequent chapter as well as one concerning the effects of anti biotics on H. pylori infection. The extensive literature on natural substances with anti-H.

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."

An extraordinary development of the knowledge, concepts and biomedical applications has occurred during the past two decades in the biological sciences, including the Reticuloendothelial Sys- tem (RES). For example, it is now widely recognized that distinct classes of cells are involved in the recognition of "exogenous" invaders of the body such as microorganisms and other foreign an- tigens, as well as of "endogenous" parasites represented by trans- formed neoplastic cells and altered "self" antigens. Prominent among cell populations involved in such recognition of antigens and subsequent immune responses are those constituting the RES. In recent years, there has been much discussion and indeed contro- versy as to what constitutes such a system and even whether the term "RES" is appropriate. Some investigators feel that the phago- cytes are the most important cells of the RES as they playa major role in the defense mechanism of the host. Mononuclear phagocytes include tissue macrophages ~s well as circulating monocytes and their precursors. Although phagocytosis is a major functional ac- tivity, it is only one of their several functions. The important role of phagocytes and other mononuclear cells in antibody forma- tion, cell-mediated immunity, specific and non-specific resistance to microorganisms and tumor cells, as well as homeostatic adjust- ments in general has become the focus of attention for many inves- tigators.

This volume is based on the Proceedings of the International Conference on "Microbial Infections: Role of Biological Response Modifiers" held in Tampa, FL, May 29-31, 1991. The major purpose of this conference was to bring together in one forum prominent investigators from around the world studying a variety of microbial pathogens, including bacteria, viruses, and fungi, and the effects of biological response modifiers (BRM) on the immune response to these microorganisms. BRM have been widely utilized in the area of antitumor resistance and include not only experimental tumor cell vaccines, but also biologically active substances such as cytokines, i. e., interferons, tumor necrosis factor, and interleukins, as well as products from bacteria which influence host resistance mechanisms. It is the belief of the organizers of this Conference that it was very timely to discuss in detail BRMs as they impact on microbial infections per se. It is now widely accepted that immunocompromised individuals, including those exposed to immunosuppressive substances such as antimetabolites used for chemothera py of malignancies, or infectious agents, such as the human immunodeficiency virus and other viruses which depress the immune response and, in turn, affect a host so as to become highly susceptible to opportunistic microorganisms, benefit from BRM stimulation of their immune system. A wide variety of immunomodulators are now being studied in terms of treating infectious diseases, as well as malignancy and autoimmune diseases."

Assembling the latest research by an international group of contributors, this volume covers the epidemiology, pathogenesis, clinical features, and control measures of this elusive microorganism. It will provide a deeper understanding of the pathogen to physicians and surgeons caring for patients infected, or at risk of becoming infected, with Pseudomonas Aeruginosa.

This volume represents the proceedings of the 2nd annual symposium on the Brain Immune Axis and Substance Abuse held at the Breakers Hotel in Palm Beach, FL in June 1994. The history of productive studies concerning the relationship between the nervous and the immune systems is relatively recent. Studies on the effects of drugs of abuse on the immune system and on infections among individuals who abuse drugs are also of recent vintage. Only in the last decade have investigators begun to describe the role of drugs of abuse and their endogenous counterparts on the brain-immune axis. Thus, the involvement of the neuroendocrine system in the interactions of drugs of abuse and the immune system has only recently been appreciated. In addition, it has been recognized that direct neural inputs impact immune function. Given the complexity of these interactions, characterization of biologically significant phenomena and elucidation of their mechanisms of action often requires a multidisciplinary approach. This meeting, on which the chapters in this book are based, brought together scientists from an array of biomedical disciplines whose work is focused on the effects of drugs of abuse on the neuro-endocrine immune axis. The meeting was unique in focusing on the brain-immune axis from the viewpoint of drugs of abuse rather than either immunity itself or the brain itself. Presentations addressed the direct effects of drugs of abuse on various components of the immune system, as well as those mediated indirectly by the central nervous system and the neuroendocrine system.

Tuberculosis once again occupies a special position in the areas of infec tious diseases and microbiology. This disease has been important to mankind since even before biblical times. Tuberculosis has been a major cause of morbidity and mortality in humans, especially in highly ur banized Europe, until a few decades ago. Indeed, this disease became a center of many novels, plays, and operas, since it appeared to be quite popular to have the heroine dying of "consumption. " Most importantly, tuberculosis also became the focus of attention for many investigations during the 19th and even the 20th centuries. Major advances were made in the areas of isolation and identification of M. tuberculosis and related microorganisms. The discovery, by Robert Koch, that tuberculosis was caused by an infectious agent revolutionized our thinking about dis eases. Koch's postulates were developed with tuberculosis in mind and became a focal point for many advances in microbiology and medicine. Studies with mycobacteria as a central focus have also led to revolu tionary new concepts about immunology in general. Koch himself showed that those exposed to M. tuberculosis develop a skin hypersen sitivity or allergy to the microorganism's antigens, an observation which was the starting point for many important developments. Indeed, imme diate-type hypersensitivity and atopic or IgE-mediated allergy were de fined in relation to the delayed-type cutaneous hypersensitivity evi denced with the tubercle bacillus."

It is now widely acknowledged that at the beginning of this century Claude von Pirquet first pointed out that a viral disease, i. e., measles, resulted in an anergy or depression of preexisting immune response, namely, delayed continuous hypersensitivity to PPD derived from Mycobacterium tuberculosis. Thereafter ob servations that viral infections may result in immunosuppression have been recorded by many clinicians and infectious disease investigators for six or seven decades. Nevertheless, despite sporadic reports that infectious diseases caused by viruses may result in either transient or prolonged immunodepression, investigation of this phenomenon languished until the mid-1960s, when it was pointed out that a number of experimental retroviral infections of mice with tumor viruses may result in marked immunosuppression. However, it was not until the recognition of the new epidemic of acquired immunodeficiency syn drome (AIDS) caused by the human immunodeficiency virus and related vi ruses that acquired immunodeficiencies associated with virus infection became general knowledge among biomedical investigators as well as the lay public. A number of reviews published during the past decade or so pointed out that numerous viruses may affect humoral and cellular immune responses. Furthermore, expanding knowledge about the nature and mechanisms of both humoral and cellular immunity and pathogenesis of viral infections has pro vided clinical and experimental models for investigating in depth how and why viruses of man and animals profoundly affect immune responses."

This comprehensive treatise on the reticuloendothelial system is a project jointly shared by individual members of the Reticuloendothelial (RE) Society and bio medical scientists in general who are interested in the intricate system of cells and molecular moieties derived from these cells which constitute the RES. It may now be more fashionable in some quarters to consider these cells as part of what is called the mononuclear phagocytic system or the lymphoreticular system. Nevertheless, because of historical developments and current interest in the subject by investigators from many diverse areas, it seems advantageous to present in one comprehensive treatise current information and knowledge con cerning basic aspects of the RES, such as morphology, biochemistry, phylogeny and ontogeny, physiology, and pharmacology as well as clinical areas including immunopathology, cancer, infectious diseases, allergy, and hypersensitivity. It is anticipated that by presenting information concerning these apparently heterogeneous topics under the unifying umbrella of the RES attention will be focused on the similarities as well as interactions among the cell types constitut ing the RES from the viewpoint of various disciplines. The treatise editors and their editorial board, consisting predominantly of the editors of individual vol umes, are extremely grateful for the enthusiastic cooperation and enormous task undertaken by members of the biomedical community in general and especially by members of the American as well as European and Japanese Reticuloendothe lial Societies."

It is almost axiomatic that an explosive increase in knowledge and interest concerning host immune defense mechanisms and the immune response system in general is occurring. Many new developments are evident at the interphase between the areas of immunology, infectious diseases, and host defenses to microorganisms. It is now widely rec ognized that a functioning host immune defense system consists of a variety of lymphoid cells. These include effector and affector cells consisting of both Band T cells and their progeny. Mononuclear phago cytes which are widely distributed throughout the body are also intimately involved in these processes. These cells are involved not only in the clearance of particulate matter including bacteria, viruses and fungi, but also presumably in host defense against neo plasia. Among the many triumphs of the biological revolution over the past decade or so is the rapidly developing understanding of how these cells and their products, including antibody, lymphokines, monokines, etc., function and interact. It is now recognized that although the immune defense system is involved in defense against infectious agents, it is also now be coming quite clear that many infectious agents, including bacteria, viruses and fungi, as well as their products, can interact with the immune response system. For example, it has been long recognized that many of the "adjuvants" which enhance the immune responses in nonspecific ways are derived from microorganisms. Microbial products have marked effects on the immume response system."

This volume is based on the program of the International Conference on Drugs of Abuse, Immunity and Immunodeficiency held in Clearwater Beach, Florida. It was sponsored by the University of South Florida College of Medicine with the support of the National Institute on Drug Abuse. During the past few decades, drugs of abuse, including marijuana, cocaine, opiates and alcohol, have been studied by biomedical scientists in terms of the systemic effects of the drugs as well as alterations in neurophysiology and the psychology. More recently, the scope of such investigations has been broadened to include alterations within the immune system, and the influence of altered immunity on physiological and psychological consequences of drug abuse. In this regard, participants in the Clearwater Beach conference provided new information concern ing both basic and clinical aspects of drugs of abuse and immunity, especially immunodeficiency. Advances have been made in recent years in understanding the nature and mechanisms regulating the immune response and the mechanisms by which drugs may influence immune responses. In particular, the emergence of psychoneuroimmunology as a new discipline has heightened interest in immune responses influenced by psychoactive drugs. This has resulted in interdisciplinary investigations involving clinical and basic scientists including microbiologists, immu nologists, physiologists, psychiatrists, oncologists and others. The recreational use of the above mentioned drugs by large numbers of individuals has aroused serious concern about the consequences of this activity.