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