Herman Friedman

Burt M. Sharp

John J. Madden

Toby Eisenstein

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 Brain Immune Axis and Substance Abuse

Mauro Bendinelli

Steven Specter

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.

Neuropathogenic Viruses and Immunity

Giuseppe Barbanti-Brodano

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.

Oncogenic Mechanisms

DNA Tumor Viruses

Yoshimasa Yamamoto

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.

Infection and Disease

Chlamydia pneumoniae

Burt Anderson

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.

Rickettsial Infection and Immunity

Herman Chmel

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.

Pulmonary Infections and Immunity

Andor Szentivanyi

This unique volume contains reviews by some of the most prominent immunologists in the world. The authors present vital facts for each of their areas of expertise and provide individual perspectives on how their own contributions were developed and how these contributions influenced general immunological thinking and development. This impressive collection of personal reviews by these internationally renowned immunologists makes The Immunologic Revolution an important and lasting contribution to the entire biomedical community.

Facts and Witnesses

The Immunologic Revolution

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.

A General Update

Coxsackieviruses

Toby K. Eisenstein

Paul Actor

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.

Proceedings of a conference held in Philadelphia, Pennsylvania, June 10-12, 1981

Host Defenses to Intracellular Pathogens

Allen Honeyman

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.

Staphylococcus aureus Infection and Disease

Paul Hoffman

The volume brings together all of the latest research on this pathogen, the interest in which is rapidly growing. Legionella pneumophila is an emerging human pathogen that resides in natural environments as a parasite of freshwater. There have been major new developments in this field, including the publication of three whole genome sequences and the discovery of a developmental cycle and novel cyst-like highly infectious form.

Legionella Pneumophila: Pathogenesis and Immunity

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.

Virus-Induced Immunosuppression

Eugénie Bergogne-Bérézin

There is currently increasing interest concerning the biology and disease caused by Acinetobacter species. Such interest, however, developed relatively slowly because of the necessity to clarify the confusing taxonomy of these organisms. Much work was needed to identify various species as members of this genus, to recognize their epidemiologic profile, their pathogenic role and their increasing importance as multi-antibiotic resistant organisms. In recent years improvement of genetic approaches, recognition of plasmids, integrons and chromosomal sources of resistance mechanisms aroused interest on the role of Acinetobacters in disease by many microbiologists and clinicians, especially internists and infectious disease specialists. In this regard, physicians are frequently confronted with extremely difficult therapeutic approaches for treatment and prevention of severe nosocomial infections due to multi antibiotic resistant Acinetobacter. Moreover, recent observations of community acquired infections have been reported, especially in patients with various risk factors such as immuno-deficiencies. Also, it is now becoming evident that Acinetobacter infections occur frequently in violent situations such as earthquake or war zones. The mechanisms of Acinetobacter virulence are becoming increasingly clear, providing new insights into their pathogenic role in community acquired infections. It is apparent the time is appropriate for detailed review of the increasing knowledge concerning important new information, both clinical and therapeutic, especially information concerning virulence, resistance mechanisms and typing of Acinetobacter spp. Many new findings are accumulating in almost an exponential manner since publication of previous books on this subject in 1991 and 1996.

Biology and Pathogenesis

Acinetobacter

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.

Viruses, Immunity, and Immunodeficiency

Kenneth E. Ugen

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.

Immunological and Therapeutic Control

Human Retroviral Infections

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.

In vivo Models of HIV Disease and Control

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.

Microorganisms and Bioterrorism

Thomas W. Klein

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.

Herman Friedman

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