The First International Workshop on Mechanisms in Cell-Mediated Cytoxicity was held at Carry-Ie-Rouet, France, September 14-16, 1981. The Workshop brought together for the first time leading investiga tors in each of the principal areas of cell-mediated cytotoxicity, as well as experts in the area of complement-mediated cytoxicity. Formal research presentations were held to a minimum, the emphasis being on open discussion of current knowledge about mechanisms of cytoxicity in each of the systems under consideration. The major objectives of the Workshop were 1) to compare and integrate what is known about the mechanism(s) of cytoxicity in each system; 2) to determine whether, on the basis of information in hand, it seems likely that the mechanisms of cytotoxicity in the various systems are the same or are unique; and 3) to stimulate thinking about new approaches to elucidating the fundamental mechanisms by which certain cells are able to kill other cells."

The existence of a unique kind of immune cell the killer lymphocyt- which destroys other cells in a highly specific manner, has fascinated immunologists for almost half a century. How do these cells, whose precursors have lived in communal harmony with their host, decide that some of their cohabitants must die? And how do they kill them? The definition of killer lymphocytes came from discovery of their roles in a wide range of in vivo phenomena such as transplant rejection, virus infection and its related immunopathologies, and anti-tumor responses. Yet for the most part almost everything we know about these cells has come from studying them in vitro. They have yielded their secrets slowly and reluctantly. To understand fully how they work, geneticists and immunologists had to unravel the major histocompatibility systems of vertebrates, a long and torturous road that provided some of the darkest hours of immunology. The search for antigen-sensing receptors on both T cells and NK cells was scarcely less frustrating. And the holy grail of ce- mediated cytotoxicity defining the mechanism by which killer cells take down their adversaries sorely tested the ingenuity, patience and mutual good will of laboratories around the world. These questions have now largely been answered. But do we really understand these cells? We can tame them to a large degree in transplant rejection. It may yet turn out that we can harness their immunotherapeutic potential in treating viral and malignant disease."

We have known about the existence of killer lymphocytes since 1960, when they were discovered in connection with transplant rejection in vivo. Since then we have uncovered at least five subsets of lymphocytes that can kill other cells in vitro, establishing the study of cell-mediated cytotoxicity (CMC) as a major field of immunological inquiry. Berke and Clark summarize the extensive literature based on the study of CMC in vitro. Several important questions about killer cells have now been answered, for example, how they go about destroying other cells. Research ultimately revealed at least three lytic mechanisms available to killer lymphocytes. But do killer cells actually use these mechanisms in vivo? The possible involvement of CMC in transplant rejection, control of intracellular parasites, cancer, autoimmunity, and immune homeostatic regulation is analyzed in detail, yielding some surprising findings, and outlining important questions that remain unanswered.

This extensively documented, comprehensive survey of cell-mediated cytotoxicity traces the history of killer lymphocytes from 1960 to the present, providing a definitive resource for specialists and non-specialists alike.

Our immune system is the only thing standing between us and a sea of microbial predators that could send us to an early and ugly death. Equipped with genetic, chemical and cellular weapons, it evicts unwelcome microrganisms that find the human body a delightful place to live, carefully admitting only the few microbes that our bodies need to help us digest food and process vitamins. When the system works successfully, the vast majority of disease-causing microbes - bacteria, viruses, molds and a few parasites - are kept at bay. But the immune system isn't perfect. The same system that could save us in the event of a bioterrorist attack, prevents us from accepting potentially life-saving organ transplants. It overreacts at times, turning too much force against foreign invaders, causing serious - occasionally lethal - collateral damage to our tissues and organs. Worse yet, our immune systems may decide we ourselves are foreign and begin snipping away at otherwise healthy tissues, resulting in autoimmune disease. And the system itself is the target of one of the most deadly viruses humans have ever known: HIV, the agent of AIDS. In In Defense of Self, William Clark invites you on a whirlwind tour of your immune system. Along the way, he introduces some of most important medical advances and challenges of the past hundred years, from the development of vaccines and the treatment of allergies, autoimmunity and cancer, to prolonging organ transplants and combating AIDS. William Clark not only explains how a vital part of our bodies works to "serve and protect," he also provides background for the exciting research themes of today that will produce the medical breakthroughs of tomorrow.

This scarce antiquarian book is a selection from Kessinger Publishing's Legacy Reprint Series. Due to its age, it may contain imperfections such as marks, notations, marginalia and flawed pages. Because we believe this work is culturally important, we have made it available as part of our commitment to protecting, preserving, and promoting the world's literature. Kessinger Publishing is the place to find hundreds of thousands of rare and hard-to-find books with something of interest for everyone!

This scarce antiquarian book is a selection from Kessinger Publishing's Legacy Reprint Series. Due to its age, it may contain imperfections such as marks, notations, marginalia and flawed pages. Because we believe this work is culturally important, we have made it available as part of our commitment to protecting, preserving, and promoting the world's literature. Kessinger Publishing is the place to find hundreds of thousands of rare and hard-to-find books with something of interest for everyone!

Death, for bacteria, is not inevitable. Protect a bacterium from predators, and provide it with adequate food and space to grow, and it would continue living--and reproducing asexually--forever. But a paramecium (a slightly more advanced single-cell organism), under the same ideal conditions, would stop dividing after about 200 generations--and die. Death, for paramecia and their offspring, is inevitable. Unless they have sex. If at any point during that 200 or so generations, two of the progeny of our paramecium have sex, their clock will be reset to zero. They and their progeny are granted another 200 generations. Those who fail to have sex eventually die. Immortality for bacteria is automatic; for all other living beings--including humans--immortality depends on having sex. But why is this so? Why must death be inevitable? And what is the connection between death and sexual reproduction?
In Sex and the Origins of Death, William R. Clark looks at life and death at the level of the cell, as he addresses such profound questions as why we age, why death exists, and why death and sex go hand in hand. Clark reveals that there are in fact two kinds of cell death--accidental death, caused by extreme cold or heat, starvation, or physical destruction, and "programmed cell death," initiated by codes embedded in our DNA. (Bacteria have no such codes.) We learn that every cell in our body has a self-destruct program embedded into it and that cell suicide is in fact a fairly commonplace event. We also discover that virtually every aspect of a cell's life is regulated by its DNA, including its own death, that the span of life is genetically determined (identical twins on average die 36 months apart, randomly selected siblings 106 months apart), that human tissue in culture will divide some 50 times and then die (an important exception being tumor cells, which divide indefinitely). But why do our cells have such programs? Why must we die? To shed light on this question, Clark reaches far back in evolutionary history, to the moment when "inevitable death" (death from aging) first appeared. For cells during the first billion years, death, when it occurred, was accidental; there was nothing programmed into them that said they must die. But fierce competition gradually led to multicellular animals--size being an advantage against predators--and with this change came cell specialization and, most important, germ cells in which reproductive DNA was segregated. When sexual reproduction evolved, it became the dominant form of reproduction on the planet, in part because mixing DNA from two individuals corrects errors that have crept into the code. But this improved DNA made DNA in the other (somatic) cells not only superfluous, but dangerous, because somatic DNA might harbor mutations. Nature's solution to this danger, Clark concludes, was programmed death--the somatic cells must die. Unfortunately, we are the somatic cells. Death is necessary to exploit to the fullest the advantages of sexual reproduction.
In Sex and the Origins of Death, William Clark ranges far and wide over fascinating terrain. Whether describing a 62-year-old man having a major heart attack (and how his myocardial cells rupture and die), or discussing curious life-forms that defy any definition of life (including bacterial spores, which can regenerate after decades of inactivity, and viruses, which are nothing more than DNA or RNA wrapped in protein), this brilliant, profound volume illuminates the miraculous workings of life at its most elemental level and finds in these tiny spaces the answers to some of our largest questions.

We live in a sea of seething microbial predators, an infinity of invisible and invasive microorganisms capable of setting set up shop inside us and sending us to an early grave. The only thing keeping them out? The immune system.
William Clark's In Defense of Self offers a refreshingly accessible tour of the immune system, putting in layman's terms essential information that has been for too long the exclusive province of trained specialists. Clark explains how the immune system works by using powerful genetic, chemical, and cellular weapons to protect us from the vast majority of disease-causing microbes-bacteria, viruses, molds, and parasites. Only those microbes our bodies need to help us digest food and process vitamins are admitted. But this same system can endanger us by rejecting potentially life-saving organ transplants, or by overreacting and turning too much force against foreign invaders, causing serious--occasionally lethal--collateral damage to our tissues and organs. Worse yet, our immune systems may react as if we ourselves are foreign and begin snipping away at otherwise healthy tissues, resulting in autoimmune disease. In Defense of Self covers everything from how antibodies work and the strategies the body uses to distinguish self from not self to the nature of immunological memory, the latest approaches to vaccination, and how the immune system will react should we ever be subjected to a bioterrorist attack. Clark also offers important insights on the vital role that the immune system plays in cancer, AIDS, autoimmunity, rheumatoid arthritis, allergies and asthma, and other diseases.
Of special interest to all those suffering from diseases related to theimmune system, as well as their families, In Defense of Self lucidly explains a system none of us could live without.

Books such as Richard Dawkins's The Selfish Gene have aroused fierce controversy by arguing for the powerful influence of genes on human behavior. But are we entirely at the mercy of our chromosomes? In Are We Hardwired?, scientists William R. Clark and Michael Grunstein say the answer is both yes--and no.
The power and fascination of Are We Hardwired? lie in their explanation of that deceptively simple answer. Using eye-opening examples of genetically identical twins who, though raised in different families, have had remarkably parallel lives, the authors show that indeed roughly half of human behavior can be accounted for by DNA. But the picture is quite complicated. Clark and Grunstein take us on a tour of modern genetics and behavioral science, revealing that few elements of behavior depend upon a single gene; complexes of genes, often across chromosomes, drive most of our heredity-based actions. To illustrate this point, they examine the genetic basis, and quirks, of individual behavioral traits--including aggression, sexuality, mental function, eating disorders, alcoholism, and drug abuse. They show that genes and environment are not opposing forces; heredity shapes how we interpret our surroundings, which in turn changes the very structure of our brain. Clearly we are not simply puppets of either influence. Perhaps most interesting, the book suggests that the source of our ability to choose, to act unexpectedly, may lie in the chaos principle: the most minute differences during activation of a single neuron may lead to utterly unpredictable actions.
This masterful account of the nature-nurture controversy--at once provocative and informative--answers some of our oldest questions in unexpected new ways

Why do we age? Is aging inevitable? Will advances in medical knowledge allow us to extend the human lifespan beyond its present limits? Because growing old has long been the one irreducible reality of human existence, these intriguing questions arise more often in the context of science fiction than science fact. But recent discoveries in the fields of cell biology and molecular genetics are seriously challenging the assumption that human lifespans are beyond our control. With such discoveries in mind, noted cell biologist William R. Clark clearly and skillfully describes how senescence begins at the level of individual cells and how cellular replication may be bound up with aging of the entire organism. He explores the evolutionary origin and function of aging, the cellular connections between aging and cancer, the parallels between cellular senescence and Alzheimer's disease, and the insights gained through studying human genetic disorders--such as Werner's syndrome--that mimic the symptoms of aging. Clark also explains how reduction in caloric intake may actually help increase lifespan, and how the destructive effects of oxidative elements in the body may be limited by the consumption of antioxidants found in fruits and vegetables. In a final chapter, Clark considers the social and economic aspects of living longer, the implications of gene therapy on senescence, and what we might learn about aging from experiments in cloning. This is a highly readable, provocative account of some of the most far-reaching and controversial questions we are likely to ask in the next century.

Human beings have on the order of 100,000 different genes encoding the molecules needed to build and operate the human body; defects in any one of them can lead to disastrous consequences. There are an estimated 4,000 genetic diseases, which can be every bit as devastating as the diseases caused by bacteria or viruses, and in one way they are much worse: we pass them on to our children, generation after generation after generation. The New Healers is the story of the devastation these diseases cause, and the scientific researchers and doctors who struggle to combat them. Science and medicine have provided us with clues to the treatment of a few genetic diseases, although by their very nature they have never been considered curable. But, as William R. Clark shows, that is about to change through one of the most profound revolutions in modern medicine: gene therapy, a branch of the new field of molecular medicine. Clark takes us to the laboratories which have been able to isolate human genes, to make billions of copies of them, and to reintroduce healthy genes into unfortunate individuals who have inherited damaged or functionless genes. He also shows us how this same technology, turned around on itself, can also be used to deliberately introduce "bad" genes to attack and destroy unwanted cells, such as cancer cells or those infected with the AIDS virus. Molecular medicine will be a major part of our lives in the new millennium. The New Healers outlines the powerful and compelling logic behind molecular medicine: that everything we know about molecular biology tells us that it can work, and that it will work. Clark introduces us to the scientists working now to map out the entire human genome, easily the medical equivalent of going to the moon, taking human beings to a completely new level of understanding of our biological selves. Clark also helps us to begin thinking about how we will manage that understanding, and how we will use the information we gain. The New Healers is a clear and compelling introduction to this important new frontier of human medicine, outlining for readers all the basic elements of molecular biology necessary to understand molecular medicine, and illustrating the fascinating stories of those doctors and patients already a part of this exciting future -- a future as full of promise as anything we have witnessed in this past century of remarkable progress.

William Clark's At War Within takes us on a fascinating tour through the immune system, examining the history of its discovery, the ways in which it protects us, and how it may bring its full force to bear at the wrong time or in the wrong place.

Scientists have only gradually come to realize that this elegant defence system not only has the potential to help, as in the case of smallpox, but also the potential to do profound harm in health problems ranging from allergies to AIDS, and from organ transplants to cancer. Dr Clark discusses the myriad of medical problems involving the immune system, and systematically explains each one, making the complexities of this delicately balanced mechanism comprehensible to the lay reader.

In the seventeenth century, smallpox reigned as the world's worst killer. Luck, more than anything else, decided who would live and who would die. That is, until Lady Mary Wortley Montagu, an English aristocrat, moved to Constantinople and noticed the Turkish practice of "ingrafting" or inoculation, which, she wrote, made "the small- pox...entirely harmless." Convinced by what she witnessed, she allowed her six-year-old son to be ingrafted, and the treatment was a complete success--the young Montagu enjoyed lifelong immunity from smallpox. Lady Montagu's discovery would, however, remain a quiet one; it would be almost 150 years before inoculation (in the more modern form of vaccination) would become widely accepted while the medical community struggled to understand the way our bodies defend themselves against disease.
William Clark's At War Within takes us on a fascinating tour through the immune system, examining the history of its discovery, the ways in which it protects us, and how it may bring its full force to bear at the wrong time or in the wrong place. Scientists have only gradually come to realize that this elegant defense system not only has the potential to help, as in the case of smallpox, but also the potential to do profound harm in health problems ranging from allergies to AIDS, and from organ transplants to cancer. Dr. Clark discusses the myriad of medical problems involving the immune system, and he systematically explains each one. For example, in both tuberculosis and AIDS, the underlying pathogens take up residence within the immune system itself, something Clark compares to having a prowler take up residence in your house, crawling around through the walls and ceilings while waiting to do you in. He discusses organ transplants, showing how the immune system can work far too well, and touching on the heated ethical debate over the use of both primate and human organs. He explores the mind's powerful ability to influence the performance of the immune system; and the speculation that women, because they have developed more powerful immune systems in connection with childbearing, are more prone than men to contract certain diseases such as lupus. In a fascinating chapter on AIDS, arguably the most deadly epidemic seen on Earth since the smallpox, Clark explains how the disease originated and the ways in which it operates. And, in each section, we learn about the most recent medical breakthroughs.
At first glance, it may appear that our immune system faces daunting odds; it must learn to successfully fend off, not thousands, but millions of different types of microbes. Fortunately, according to Clark, it would be almost impossible to imagine a more elegant strategy for our protection than the one chosen by our immune system, and his At War Within provides a thorough and engaging explanation of this most complex and delicately balanced mechanism.