These past few years have witnessed a revolution in our understanding of microglia, especially since their roles in the healthy central nervous system (CNS) have started to unravel. These cells were shown to actively maintain health, in concert with neurons and other types of CNS cells, providing further insight into their involvement with diseases. Edited by two pioneers in the field, Marie-Eve Tremblay and Amanda Sierra, Microglia in health and disease aims to share with the broader scientific community some of the recent discoveries in microglia research, from a broad perspective, with a collection of 19 chapters from 52 specialists working in 11 countries across 5 continents.

To set microglia on the stage, the book begins by explaining briefly who they are, what they do in the healthy and diseased CNS, and how they can be studied. The first section describes in more details their physiological roles in the maturation, function, and plasticity of the CNS, across development, adolescence, adulthood, neuropathic pain, addiction, and aging. The second section focuses on their implication in pathological conditions impairing the quality of life: neurodevelopmental and neuropsychiatric disorders, AIDS, and multiple sclerosis; and in leading causes of death: ischemia and stroke, neurodegenerative diseases, as well as trauma and injury."

Immunotherapy is now recognized as an essential component of treatment for a wide variety of cancers. It is an interdisciplinary field that is critically dependent upon an improved understanding of a vast network of cross-regulatory cellular populations and a diversity of molecular effectors; it is a leading example of translational medicine with a favorable concept-to-clinical-trial timeframe of just a few years. There are many established immunotherapies already in existence, but there are exciting new cancer immunotherapies just on the horizon, which are likely to be more potent, less toxic and more cost effective than many therapies currently in use. Experimental and Applied Immunotherapy is a state-of-the-art text offering a roadmap leading to the creation of these future cancer-fighting immunotherapies. It includes essays by leading researchers that cover a wide variety of topics including T cell and non-T cell therapy, monoclonal antibody therapy, dendritic cell-based cancer vaccines, mesenchymal stromal cells, negative regulators in cancer immunology and immunotherapy, non-cellular aspects of cancer immunotherapy, the combining of cancer vaccines with conventional therapies, the combining of oncolytic viruses with cancer immunotherapy, transplantation, and more. The field of immunotherapy holds great promise that will soon come to fruition if creative investigators can bridge seemingly disparate disciplines, such as T cell therapy, gene therapy, and transplantation therapy. This text is a vital tool in the building of that bridge.

Antibodies are indispensable tools for research, diagnosis, and therapy. Recombinant approaches allow the modification and improvement of nearly all antibody properties, such as affinity, valency, specificity, stability, serum half-life, effector functions, and immunogenicity. "Antibody Engineering" provides a comprehensive toolbox covering the well-established basics but also many exciting new techniques. The protocols reflect the latest "hands on" knowledge of key laboratories in this still fast-moving field. Newcomers will benefit from the proven step-by-step protocols, which include helpful practical advice; experienced antibody engineers will appreciate the new ideas and approaches. The book is an invaluable resource for all those engaged in antibody research and development.

This volume features contributions from participants of the ESRF symposium on Immunotherapy in 2020-Visions and Trends for Targeting Inflammatory Diseases held in Potsdam near Berlin, Germany, in October 2006. The symposium presentations covered the main mechanisms of immunoregulation.

From the 39th annual conference of the International Society on Oxygen Transport to Tissue (ISOTT), held in Washington, DC, USA in July 2011, this volume covers aspects of oxygen transport from air to the cells, organs and organisms; instrumentation and methods to sense oxygen and clinical evidence. Oxygen Transport to Tissue XXXIV includes contributions from scientists (physicists, biologists and chemists), engineers, clinicians and mathematicians.

The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as 'ER stress'. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.

This new volume in the series Emerging Infectious Diseases of the 21st Century is a novel book on the role of microbes in the pathogenesis of common and disabling non-infectious diseases. New insights have emerged over the past several years suggesting that our commensal microflora of the gut is extremely important in regulating physiological and immune functions of the body. Covered are the perturbations of the normal composition of our endogenous microbiota, influenced by diet and genetic predispositions, as well as the mechanisms to produce common disorders such as obesity, diabetes, irritable bowel syndrome, colon cancer and atherosclerotic vascular diseases. Also explored is the evidence suggesting that predisposition to increasingly common afflictions such as asthma and multiple sclerosis is influenced, in combination with our genetic composition, by early life exposure to environmental microbes and the time of onset of common viral infections. Chapters provide the most recent information on these disorders with regards to epidemiology, current concepts on pathogenesis and mechanisms of their biology, recent research and data on the role of microbes, analysis of their validity and conclusive remarks and areas for future research. The Role of Microbes in Common Non-Infectious Diseases is an excellent resource for both physicians and investigators from a broad range of disciplines that will help to stimulate new concepts of disease pathogenesis and lead to the unraveling of their mechanisms of diseases and to novel treatments.

Erika Jensen-Jarolim and Manuel L. Penichet 1. 1 Background Infectious diseases, being the major burden in the history of mankind worldwide th until the beginning of the 20 century, were important triggers in the understanding of immunological mechanisms. In contrast to infectious diseases, reports of all- gies and cancers were less common, but increased tremendously within the last century. Based on the US mortality data of the National Center for Health Statistics, Centers for Disease Control and Prevention 2009, a recent report from the American Cancer Society indicated that the number of cancer deaths increased approximately from 100,000 to 550,000 per year between 1930 and 2006, paralleling the increase of the total population during this period. Leading causes of death from cancer are lung and bronchus cancer, in men prostate cancer, and in women breast c- cer [1, 2]. Normalization to population size shows that the cancer death rate for most malignancies has been generally stable, although the mortality rate of certain malignancies, such as lung and bronchus cancer, has increased over the last 50 years [1-3]. In allergy, the situation is less clear, because for the time period around the turn of th the 19 century, only imprecise information is available. However, within the last 30 years the incidences of allergies has doubled not only in industrial countries, but in developing countries as well [4].

The term humanized mouse in this text refers to a mouse in which human tissues and cells have been transplanted and show the same biological function as they do in the human body. That is, the physiological properties and functions of tra- planted human tissues and cells can be analyzed in the mouse instead of using a living human body. It should therefore be possible to study the pathophysiology and treatment of human diseases in mice with good reproducibility. Thus, the hum- ized mouse can be used as a potent tool in both basic and clinical research in the future. The development of appropriate immunodeficient mice has been indispensable in the creation of the humanized mouse, which has been achieved through many years of efforts by several laboratories. The first stage on the road to the humanized mouse was the report on nude mice by Isaacson and Cattanach in 1962. Thereafter, nude mice were studied in detail by Falanagan and, in 1968, Pantelouris found that these mice have no thymus gland, which suggested that the mice lack transplan- tion immunity against xenografts such as human hematopoietic stem cells. At the Nude Mouse Workshops (organized by Regard, Povlsen, Nomura and colleagues) that were held nine times between 1972 and 1997, the possibility of creating a humanized mouse using nude mice was extensively examined. The results, however, showed that certain human cancers can be engrafted in nude mice, but unfortunately engraftment of normal human tissue was almost impossible.

Controversy still exists regarding how early disease-modifying agents (DMA) should be commenced and whether all patients with relapsing-remitting MS should in fact be treated. To answer these questions, it is also important to know the natural history of the disease. MS affects nearly 400,000 people in the United States. With their novel, multifaceted approach to basic science, the authors of this book offer help to clinicians and hope to patients.

The growing knowledge on tumor-immune response interactions and on the tumor microenvironment did not translate so far into better control of cancer by anti-tumor vaccination. The percentage of patients who benefited from vaccination strategies is still too small to justify their general use. It is the aim of this book to present an alternative to the conventional approach of developing injected tumor vaccines to activate anti-tumor immunity, which will fight cancer. It is argued that in situ tumor ablation (destruction) that involves tumor antigen release; cross presentation and the release of danger associated molecular patterns (DAMPs) can make the tumor its own cellular vaccine. Tumor ablation methods using chemicals, radiation, photodynamic therapy, cryoablation, high-temperature, radiofrequency, high intensity focused ultrasound, and electric-based ablation have been developed for focal tumors. In this book experts will deal with two main topics: I. What are the principles of the various ablation modalities, and II. How each method affects the tumor cells and their microenvironment, and how these effects are responsible for the induction of specific anti-tumor immunity. The aims of this book are thus: 1. Familiarize the readers with various methods of in situ tumor ablation. 2. Review the literature and stimulate comparisons on the efficacy of different ablation methods for the treatment of tumors of different histotypes. 3. Review the literature on the effects of various ablation methods on systemic and local anti tumor immunity and on other manifestations of the interactions of tumors with their microenvironment. 4. Stimulate comparative studies on the immunostimulatory effects of different ablation modalities.

Malaria is still a major global health problem, killing more than 1 million people every year. Almost all of these deaths are caused by Plasmodium falciparum, one of the four species of malaria parasites infecting humans. This high burden of mortality falls heavily on Sub-Saharan Africa, where over 90% of these deaths are thought to occur, and 5% of children die before the age of 5 years. The death toll from malaria is still growing, with malaria-specific mortality in young African children estimated to have doubled during the last twenty years. This increase has been associated with drug resistance of the parasite, spread of insecticide resistant mosquitoes, poverty, social and political upheaval, and lack of effective vaccines. This collection of reviews addresses many of these important issues of malarial immunity and immunopathology. They are of interest not only to malariologists, but hopefully also to the broader immunological community. Strong interactions with, and feedback from immunologists working in other infectious diseases and in basic immunology will help us to move the field of malaria immunology and therapeutic intervention forward more quickly.

The purpose of this review is to examine the potential role of molecular mimicry in the pathogenesis of human T-lymphotropic virus type 1 ((HTLV- 1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)). Comp- hensive reviews on the pathogenic mechanisms of HTLV-1-associated human diseases are available throughout the medical literature (Bangham 2000,, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Osame 2002). Approximately 25 years ago the ?rst human retrovirus, HTLV-1, was isolated (Poeisz et al. 1980). Subsequently, infection with HTLV-1 was shown to cause adult T-cell leukemia (ATL) and HAM/TSP (Gessain et al. 1985; McFarlin and Blattner 1991; Osame et al. 1986; Poeisz et al. 1980; Yoshida et al. 1987). HTLV-1 may infect up to 30% of people in endemic areas and 10-20 million people worldwide (Barmak et al. 2003; Edlich et al. 2000). However, only 1%-5% develop either ATL or HAM/TSP, the remainder being clinically asymptomatic carriers of HTLV-1 (Bangham 2000, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Osame 2002). Why infection with HTLV-1 causes ATL or HAM/TSP in some people while the vast majority of individuals are asymptomatic is largely - known. Some possible factors that may differentiate the asymptomatic from the diseased state include viral strain, human histocompatibility leukocyte antigen (HLA), viral load, and the immune response (Bangham 2000, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Nagai et al. 1998; Niewiesk et al. 1994; Osame 2002).

Helminth infections are common, cause considerable pathology, and alter a host's immune profile. This can have important consequences not only on the host's ability to control a helminth infection, but also on their ability to control unrelated infections. In endemic areas, understanding how helminth infection influences the outcome of common infectious diseases and changes the efficacy of childhood vaccination programs is an important public health question. This book reviews how host immunity to helminths alters our ability to respond to the major pathogens that exist in helminth endemic regions. Current understanding of how helminths alter important but relatively neglected contributors to the host's anti-helminth immune responses are addressed, namely host antibody responses and how maternal infection may alter a child's immune development. These are discussed in relation to the control of helminth infection and unrelated infections. Also covered are how helminth infections alter the host's ability to control TB, HIV and malarial infections along with neglected bacterial infections, such as cholera, and how endemic helminth infections are likely to alter our ability to respond to life-saving vaccination strategies.

This volume reviews the unique and common features of rhabdoviruses, which have a very wide host range and are associated with human diseases and also infect domestic livestock and agricultural plants, causing enormous economic loss.

This book brings together the world's leading authorities on tumor immunology. This book describes the basic immunology principles that form the foundation of understanding how the immune system recognizes and rejects tumor cells. The role of the innate and adaptive immune responses is discussed and the implications of these responses for the design of clinical strategies to combat cancer are illustrated.

A comprehensive review of all known immune mechanisms for medically important fungal pathogens from the organ perspectives of the human body. This authoritative guide is organized by organ system, as one particular fungus can have several different effects.

This book provides a lucid summary of behavioral, neural and endocrine regulation of immune responses and of the effects of immune system activity on neural and endocrine functions and behavior. The underlying premise is that the brain and immune system represent a single, integrated system of defense. The discussion includes such topics and stress induced modulation of innate resistance and adaptive immunity in influenza viral infections.

During the past twenty years Listeria monocytogenes has emerged as one of the most intensely studied bacterial pathogens. New windows are constantly being opened into the complexity of host cell biology and the interplay of the signals connecting the various cells and organs involved in the host response. This volume includes research from studies at the molecular level on the pathogenesis of Listeria monocytogenes and the response of the host to its infections.

Insights into the regulation of immune cell lineage differentiation and specification as well as into the control of lineage integrity, stability and plasticity are of fundamental importance to understanding innate and adaptive immune responses. In this volume, leading experts provide an up-to-date and comprehensive overview of recent advances in the transcriptional control mechanisms and transcription factor networks that regulate these processes in a variety of different immune cell lineages. The chapters cover the regulation of T versus B cell lineage choice, discuss early B cell development and pre-B cell leukemia prevention, address transcriptional control mechanisms during the differentiation, in regulatory T cells and iNKT cells, detail genomic switches in helper cell fate choice and plasticity and highlight the role of the BTB-zinc finger family of transcription factors in T cells. Moreover, the chapters discuss transcriptional networks in DCs, NK cells and in innate lymphoid cells. Together, the reviews illustrate key transcriptional control mechanisms that regulate the development and function of immune cells and demonstrate the impressive advances made over the last decade.

This book will assemble the views of many of the world's experts in the field of viruses and diabetes. It will look critically at some unanswered questions, in the field. Among these, How do viruses destroy or modify the pancreatic islet? Which viruses are involved? What is the role of virus-induced cytokines> Could vaccines prevent virus-induced diabetes? Until recent technological advances, progress in the understanding of the relationship between viruses and diabetes has been hampered. New technologies are helping shed new light on these mysteries. This will be the first comprehensive volume on this topic.

Phagocytosis has been at the forefront of cell biology for more than a century. Initially, phagocytosis, which comes from Greek words meaning "devouring cells," was discovered in the late 19th century by Ilya Metchnikoff, who was awarded, together with Paul Ehrlich, the Nobel Prize in Physiology and Medicine in 1908 "in recognition of their work on immunity." At that time Metchnikoff had already identified a function for phagocytes not only in host defense but also as scavengers of degenerating host cells during metamorphosis of tadpoles, thus providing one of the first descriptions of apoptotic cell clearance by macrophages (Kaufmann 2008). Since then, much has been learned about phagocytosis, and the previous several decades have witnessed outstanding progress in understanding the functions and the molecular mechanisms of phagocytosis. Two main types of targets are cleared by phagocytosis: microbial pathogens and dying cells. Rapid recognition and clearance of dying cells by phagocytes plays a pivotal role in development, maintenance of tissue homeostasis, control of immune responses, and resolution of inflammation. Clearance of dying cells can be divided into several stages, including sensing, r- ognition, binding and signaling, internalization, and immunological responses. In this book, our contributors address these different stages of dead cell cle- ance and examine how impaired clearance of dying cells may lead to human d- eases. We have attempted to provide sufficient cross-referencing and indexing to enable the reader to easily locate the ideas elaborated in the different chapters.

Muscle disease represents an important health threat to the general population. There is essentially no cure. Gene therapy holds great promise to correct the genetic defects and eventually achieve full recovery in these diseases. Significant progresses have been made in the field of muscle gene therapy over the last few years. The development of novel gene delivery vectors has substantially enhanced specificity and efficiency of muscle gene delivery. The new knowledge on the immune response to viral vectors has added new insight in overcoming the immune obstacles. Most importantly, the field has finally moved from small experimental animal models to human patients. This book will bring together the leaders in the field of muscle gene transfer to provide an updated overview on the progress of muscle gene therapy. It will also highlight important clinical applications of muscle gene therapy.

Avoiding infection has always been expensive. Some human populations escaped tropical infections by migrating into cold climates but then had to procure fuel, warm clothing, durable housing, and crops from a short growing season. Waterborne infections were averted by owning your own well or supporting a community reservoir. Everyone got vaccines in rich countries, while people in others got them later if at all. Antimicrobial agents seemed at first to be an exception. They did not need to be delivered through a cold chain and to everyone, as vaccines did. They had to be given only to infected patients and often then as relatively cheap injectables or pills off a shelf for only a few days to get astonishing cures. Antimicrobials not only were better than most other innovations but also reached more of the world's people sooner. The problem appeared later. After each new antimicrobial became widely used, genes expressing resistance to it began to emerge and spread through bacterial populations. Patients infected with bacteria expressing such resistance genes then failed treatment and remained infected or died. Growing resistance to antimicrobial agents began to take away more and more of the cures that the agents had brought.

Vaccinology, the concept of a science ranging from the study of immunology to the development and distribution of vaccines, was a word invented by Jonas Salk. This book covers the history of the methodological progress in vaccine development and to the social and ethical issues raised by vaccination. Chapters include "Jenner and the Vaccination against Smallpox," "Viral Vaccines," and "Ethical and Social Aspects of vaccines." Contributing authors include pioneers in the field, such as Samuel L. Katz and Hilary Koprowski. This history of vaccines is relatively short and many of its protagonists are still alive. This book was written by some of the chief actors in the drama whose subject matter is the conquest of epidemic disease.