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.

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.

The purpose of this book is to bring together, in a single volume, the most up-to-date information concerning microbes with potential as bioterrorist weapons. The primary audience includes microbiologists, including bacteriologists, virologists and mycologists, in academia, government laboratories and research institutes at the forefront of studies concerning microbes which have potential as bioterrorist weapons, public health physicians and researchers and scientists who must be trained to deal with bioterrorist attacks as well as laboratory investigators who must identify and characterize these microorganisms from the environment and from possibly infected patients.

Legionella pneumophila is an emerging human pathogen that resides in natural environments as a parasite of freshwater. There have been new developments in this field including the publication of three whole genome sequences, the discovery of a developmental cycle and novel cyst-like highly infectious form, and the bacteria have been used as a probe for macrophage cellular function to unravel fundamental new knowledge in the area of cellular biology. Legionella has also become a model system for the study of innate as well as adaptive immunity. Information on Legionella continues to increase in the U.S. and abroad. Columbia University has started the first Legionella Genome Project with a multi-million dollar grant from the NIH. In addition, The European Working Group for Legionella infections was formed in 1986. Members are scientists with an interest in improving knowledge and information on the clinical and environmental aspects of legionnaires' disease through developments in diagnosis, management and treatment of the disease. The volume brings together all of the lastest research on this pathogen, the interest in which is rapidly growing.

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.

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®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 book contains 32 chapters based on the corresponding papers delivered at the International Symposium on Antimicrobial Agents and Immunity, held in Siena, Italy on May 2-4, 1985 as a Satellite Symposium of the Third International Conference on Immunopharmacology, held in Florence, Italy on May 6-10, 1985. As editors we express our profound appreciation and gratitude to the authors who have contributed so richly to this volume, and we think that it may not be too much to hope that a new cadre of investigators and students will share this gratitude for these records of experience and insight into antibiotic and host-parasite interactions. We owe a very special gratitude to Mrs. Christine Abarca for her outstanding editorial assistance in the preparation of this book. Andor Szentivanyi, M.D. University Distinguished Professor Departments of Pharmacology and Internal Medicine University of South Florida College of Medicine Tampa, Florida Herman Friedman, Ph.D. Professor and Chairman Department of Medical Microbiology and Immunology University of South Florida College of Medicine Tampa, Florida Gunther Gillissen, M.D., Ph.D. Professor and Chairman Department of Medical Microbiology Faculty of Medicine RWTH, Aachen, F.R.G.

This volume represents the Proceedings of the Symposium on AIDS, Drugs of Abuse and the Neuroimmune Axis. This meeting was held in San Diego, California, November 11-13, 1995. As in the previous symposia in this series, productive studies were reviewed concerning the relationship between the nervous and the immune systems in regards to the relationship between drugs of abuse and infections, especially infections by the immunode ficiency virus that causes AIDS. In recent years, various investigators have begun to describe the role of illicit drugs and their endogenous counterparts on the brain-immune axis. It is widely recognized that the neuroendocrine system is intimately involved in the effects and manifestations of the interactions of drugs of abuse and the immune system. The meeting on which the chapters in this book are based brought together many biological scientists from an array of various scientific disciplines whose work is focused on the effects of drugs of abuse on the neuroendocrine-immune axis and its relationships to immunodeficiency caused by the AIDS virus. As in the past, the symposium was unique in focusing on the . brain-immune axis from the viewpoint of drugs of abuse rather than from the viewpoint of immunity or the brain itself.

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.

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.

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.

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.

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.

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.

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.

The use of recreational drugs of abuse by large numbers of individuals in this country and abroad has aroused serious concerns about the consequences of this activity. For example, it is recognized that marijuana is currently widely used as a recreational drug in the United States as well as other countries. Similarly, abuse of cocaine, especially crack cocaine, is considered to be an epidemic. “The war on drugs” by the US Government was directly aimed at the illicit use of cocaine, marijuana, and opiates as well as other drugs of abuse. Furthermore, alcohol is also considered a major problem of abuse in this country as well as in many other countries. It is estimated there are at least 10 million alcoholics in the United States alone. A signi?cant portion of those hospitalized with infectious diseases are alcoholics. Similarly, there have been many reports of association between marijuana use and increased susceptibility to infection as well as a re- tion between use of opiates and infections. The relationship between drug abuse and increased incidence of various infections has stimulated increased investi- tion of whether and how such drugs affect immune function, especially imp- tant for resistance against infectious agents. During the last decades, a wide variety of studies have shown that drugs of abuse, including marijuana, cocaine, or opiates, as well as alcohol, alter both neurophysiological as well as pathological responses of individuals.

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.

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.

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.

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.

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.

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.

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.

Staphylococcus aureus is now acknowledged as being the most important bacterial pathogen of humans. It usually produces localized disease but can be rapidly invasive, spreading through the tissues, invading bone, and seeding the bloodstream to produce a fulminant picture of septic shock, disseminated intravascular coagulation, and rapid death. Moreover, most strains of staph infections are becoming resistant to most antibiotics, thus posing a significant problem for hospitals and health care facilities. This book, a volume in the Infectious Agents and Pathogenesis series, presents chapters by the major researchers in the field.

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.

During the past few decades, drugs of abuse, including marijuana, cocaine, opiates, and alcohol have been studied in detail by biomedical scientists in terms of their effects on the neurophysiology and psychological responses of individuals. Research over the last few years has provided increased knowledge about possible mechanisms by which such drugs increase the likelihood of infections in humans and experimental animals. In Drugs of Abuse, Immunity, and Infections prominent investigators review important new information concerning the effects of recreational drugs on susceptibility to infection by microorganisms.
The volume examines the effects of drugs such as cocaine, morphine, marijuana, and opiates on immunity in humans and animals. It covers the molecular and cellular mechanisms of drug-induced immunosuppression and describes the overall enhanced susceptibility to infection in recreational drug users. It discusses the alteration of susceptibility to the retrovirus that causes the acquired immunodeficiency syndrome (AIDS) and the consensus that drugs of abuse may serve as a possible cofactor in the progression of AIDS. Drugs of Abuse, Immunity, and Infections also includes important information concerning public health aspects of drugs of abuse and infection.

Opportunistic, intracellular bacterial infections are at the forefront of research because of the challenges they present to immunocompromised patients. 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. Individual chapters set the pace for research on pathogenic and immune reactions to such infections as, mycobacterium tuberculosis, legionella pneumophila, chlamydia trachomatis and brucella.

DNA tumor viruses have long been useful experimental models of carcinogenesis and have elucidated several important mechanisms of cell transformation. Re search in recent years has shown that human tumors have a multifactorial nature and that some DNA tumor viruses may playa key role in their etiology. The aim of this book is to assess our knowledge of DNA tumor viruses by reviewing animal models, mechanisms of transformation, association with human tumors, and possi bilities of prevention and control by vaccination. Animal models of tumor virology have contributed significantly to our under standing of the epidemiology and pathogenesis of virus-induced tumors. Bovine papillomaviruses induce papillomas in the intestine of cattle. The papillomas undergo a transition to carcinomas in cows feeding on bracken fern, which pro duces a toxin with radiomimetic and immunosuppressive functions. This example of cooperation between a virus and chemical carcinogens parallels the cooperative role of human papillomaviruses (HPVs) and herpes simplex virus type 2 (HSV-2) with environmental carcinogens in the pathogenesis of cervical cancer. Likewise, hepatocarcinomas appearing in woodchucks chronically infected by woodchuck hepatitis virus (WIN) provide strong support for the relationship between hepatitis B virus (HBV) infection and human hepatocellular carcinoma. Also, the fact that WIN DNA integrates closely to cellular oncogenes suggests a possible molecular mechanism for the tumorigenesis induced by HBV.

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.

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.

Introduction and Perspectives This volume represents the Proceedings of the Fifth Annual Symposium on Drugs of Abuse, Immunomodulation, and AIDS. The meeting was held in Nashville, Tennessee, June 12-14, 1997. In this symposium, as in the past, newer knowledge was reviewed concerning the relationship between the immune and the nervous systems with regard to the effects of drugs of abuse. This symposium focused on the relationship between the immune system and the nervous system with regard to the effects of drugs of abuse and infections such as the immunodeficiency virus that causes AIDS. As in the past symposia, presentations fo cused on the brain-immune axis from the viewpoint of drugs of abuse rather than from the subject of the brain or immunity alone. The aim of this series of conferences has been to clarify the consequences ofimmunomodulation induced by drugs of abuse on susceptibility and pathogenesis of infectious diseases, both in man and in various animal model systems. Recreational use of drugs of abuse, such as morphine, cocaine, and marijuana, as well as alcohol, by large numbers of individuals in this country and around the world has aroused serious concerns about the consequences of use of such drugs, especially on the normal physiological responses of an individual, including immune mechanisms. It is now widely known that many drugs of abuse, including marijuana, are used by millions ofindi viduals in this country and by even more abroad.

There has been a tremendous increase in interest in the neuropathogenicity of viruses during the past decade as we have come to recognize that the human immunodeficiency virus, which causes the acquired immunodeficiency syndrome (AIDS), can infect glial cells and cause neurological disease. Yet this increase has not been limited to AIDS but has extended to viruses that infect either or both the central and peripheral nervous systems. The changes examined here include both neurological and psychological diseases or syndromes. Moreover, the chapters in this volume review the interaction of the host immune system with the viruses examined and how such interactions may increase or decrease the neuropatho genicity of the viruses. Questions regarding viral neuropathogenesis include: (I) What is the mode of transmission of virus to the nervous system? (2) What types of cells are infected, and do they contain receptors for the virus? (3) What is the extent of damage that results from viral infection? (4) What are the immunologic mecha nisms by which damage is mediated or limited? Many of these questions remain unanswered, but this volume delves into efforts to provide some answers.

As we approach the end of this millennium, enteric diseases remain impor tant public health problems. In many parts of the world, sanitary measures have advanced little over the last century, although some of the governments in those areas are striving to improve facilities for sanitation and to educate their people in proper handling of food, water, sewage, and other modes of transmission of pathogenic microbes. Even in highly developed countries, outbreaks of diarrheal diseases occur today. Globally, the annual morbidity from enteric infections is estimated at several billion and deaths at several million per year. In this volume, descriptions of some of these diseases, of immunity that results from them, of clinical studies that promote under standing of individual and community immunity, of molecular factors of pathogenesis, and/or of advances in vaccine development have been pro vided by leading researchers. At present, the application of molecular methods is enhancing the identification of protective antigens of many microorganisms. In addition, new methods for design and delivery of vac cines are being devised. Perhaps then more effective tools for reducing at least some of these diseases will be available within the next decade. Lois J. Paradise Herman Friedman Mauro Bendinelli vii Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv LOIS J. PARADISE 1. Indigenous Microorganisms as a Host Defense 1 KENNETH H. WILSON 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Composition of Intestinal Biota. . . . . . . . . . . . . . . . . . . . . . . . 2 3. Molecular Approaches to Determine Composition of the Biota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4. Role of the Host in Determining the Composition of the Biota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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.

The subject matter of this volume was the basis for a confer ence held in Philadelphia in June, 1981, and is an important one in the contemporary area of how the host interacts with micro organisms. In conception, it grew out of a graduate course entitled, "The Infectious Process," which has been taught in the Department of Microbiology and Immunology at Temple University School of Medicine during the past twelve years. This course has explored the broad areas of mechanisms of microbial pathogenesis and host resistance by in-depth consideration of selected models of experimental infection and immunity, as well as the clinical literature. It is noteworthy that there is no adequate text for this material, as the subject matter naturally crosses a wide spectrum of traditional disciplinary lines, encompassing topics as diverse as the mechanisms of action of bacterial toxins, the role of complement and antibody in phagocytosis, and the importance of cross-reacting bacterial polysaccharide antigens in vaccine development. A major portion of the course has always considered "cellular immunity" as it applies to host defenses to intracellular pathogens. It is in this area that the necessity for amalgamation of information from different disciplines is most evident, for one must be intimately concerned with the interactions between the microbe and the phagocyte, both before and after specific immune recognition.