This book provides readers an extensive overview of recent progress in basic and clinical research on cancer immunotherapy. Thanks to rapid advances in molecular biology and immunology, it has become increasingly evident that cancer growth is influenced by host immune responses. With the success of a number of clinical trials, immunotherapy has become a promising treatment modality of cancer. This book covers five major topics, including monoclonal antibodies, biological response modifiers, cancer vaccines, adoptive cellular therapy and oncolytic viruses. It also examines the combination of different immune strategies as well as the combination of immunotherapy with other treatments to increase anti-tumor effects. Through the comprehensive discussion of the topic, the book sheds valuable new light on the treatment of tumors.

The latest in a series of books from the International Hypoxia Symposia, this volume spans reviews on key topics in hypoxia, and abstracts from poster and oral presentations. The biannual International Hypoxia Symposia are dedicated to hosting the best basic scientific and clinical minds to focus on the integrative and translational biology of hypoxia. Long before 'translational medicine' was a catchphrase, the founders of the International Hypoxia Symposia brought together basic scientists, clinicians and physiologists to live, eat, ski, innovate and collaborate in the Canadian Rockies. This collection of reviews and abstracts is divided into six sections, each covering new and important work relevant to a broad range of researchers interested in how humans adjust to hypoxia, whether on the top of Mt. Everest or in the pulmonary or cardiology clinic at low altitude. The sections include: Epigenetic Variations in Hypoxia High Altitude Adaptation Hypoxia and Sleep Hypoxia and the Brain Molecular Oxygen Sensing Physiological Responses to Hypoxia

This volume provides current methods and protocols for gene and protein delivery based on both lentivirus-generated and spontaneously released nanovesicles. Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools guides readers through methods on macromolecule delivery and chapters describe the LV-based protocols of gene engineering. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools aims to ensure successful results in the further study of this vital field.

This book provides basic, simple, and logical explanations for choices to be made to run the best Elispot possible. It allows the newcomer to truly understand the best options for specific protocol steps, reagents and materials, and provides even the experienced Elispot user with insight into best practices. The techniques presented here are supported by the author's twenty-plus years of first-hand experience working with this assay, as well as the shared experiences of numerous colleagues and collaborators. The enzyme-linked immunospot (Elispot) assay is a widely used technique to monitor cells on the single cell level for the release of analytes like cytokines, chemokines or immunoglobulins (antibodies), in response to particular stimuli. The most important feature of Elispot is its outstanding sensitivity, allowing the detection of specific cells in very low frequencies. The advantages of Elispot have resulted in it being widely adapted for use in research and translational applications in numerous fields including cancer, infectious diseases, autoimmunity, and transplantation.

The third edition of this volume is aimed at providing both beginners and more experienced researchers a choice of methods to isolate and analyze dendritic cells(DC). An introductory review provides an overview of recent advances in the characterization of DC subsets in mouse and human. While additional chapters provide methods to culture human and mouse dendritic cells, protocols for the isolation of dendritic cells, the isolation of dendritic cell progenitors from mouse, and the purification of dendritic cells from human blood. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Dendritic Cell Protocols, Third Edition aims to ensure successful results in the further study of this vital field.

This book provides a comprehensive overview of the cascade of events activated in the body following the implant of biomaterials and devices. It is one of the first books to shed light on the role of the host immune response on therapeutic efficacy, and reviews the state-of-the-art for both basic science and medical applications. The text examines advantages and disadvantages of the use of synthetic versus natural biomaterials. Particular emphasis is placed on the role of biomimicry in the development of smart strategies able to modulate infiltrating immune cells, thus reducing side effects (such as acute and chronic inflammation, fibrosis and/or implant rejection) and improving the therapeutic outcome (healing, tissue restoration). Current cutting-edge approaches in tissue engineering, regenerative medicine, and nanomedicine offer the latest insights into the role immunomodulation in improving tolerance during tissue transplant in the treatment of orthopaedic, pancreatic, and hepatic diseases. "Immune Response to Implanted Materials and Devices" is intended for an audience of graduate students and professional researchers in both academia and industry interested in the development of smart strategies, which are able to exploit the self-healing properties of the body and achieve functional tissue restoration.

Target pattern recognition in innate immunity is responsible for the immediate, usually protective, responses shown against invading microorganisms, and it is the principal feature of self and non-self recognition by virtue of the recognition of structures on the microbial pathogens, which are not found on host cells. This is an area that has been very actively researched, over approximately the past 12 years, and therefore this volume provides a timely comprehensive, and up to date, summary of the types and range of cell surface, intracellular, and secreted, host proteins involved in the recognition of microbial products, and of the protective mechanisms triggered as a result of the recognition events.

The Toll-like receptors, first described in Drosophila and now well-characterised on human cells, provide an excellent demonstration of the wide range of different microbial products recognised by this family of receptors and of the signalling pathways which are triggered thus leading to induction of inflammatory cytokines and the activation of genes producing antimicrobial products. In addition, several cell surface proteins involved in target pattern recognition have been described on the surfaces of macrophages (macrophage mannose receptor and macrophage scavenger receptors), and on dendritic cells (DEC205), and to be involved with the uptake and clearance of whole microorganisms and polyanioic ligands. Pattern recognition is also utilised by intracellular receptors, with NOD-like receptors in the cytosol recognizing microbial molecules and activating the production of inflammatory cytokines or pathways that induce the production of inflammatory molecules. Secreted proteins, such as the pentraxins, which includes the acute phase reacting, C-reactive protein (CRP) and serum amyloid protein (SAP), and the collectins (mannan binding lectin, lung surfactant protein A and D) and ficolins can also readily recruit killing and clearance systems. Indeed, the serum complement system, which is one of the major defence systems in the bloodstream, is efficiently activated by CR P on its binding to the phosphocholine groups of microbial phospholipids and the subsequent interaction of the bound CR P with C1q to give classical pathway activation, or MBL, or ficolin, binding to arrays of mannose or N-acetyl-glucosamine residues, respectively, on the surfaces of microorganisms to give lectin pathway activation. Also, in addition to the activation and clearance events associated with complement activation by some of the secreted pattern recognition receptors, it is accepted that all these pattern recognition receptors can generally accelerate the uptake and clearance of microbes via phagocytic cells.

In view of the growing interest in the cross-talk between innate and adaptive immunity, a thorough understanding of the initial recognition and triggering events, mediated via innate immune receptors, as addressed in this volume, is clearly very useful in helping to also fully understand the mechanisms of activation and control of the adaptive immune system and to allow a full assessment of the relative roles played by innate immunity and adaptive immunity against a particular infection in higher organisms."

This volume reviews the current state of research on the IgM antibody and its multiple receptors and binding proteins. Interactions of the IgM ligands with these molecules are important for protection against infections as a first line of defense, as well as for regulation of immune responses to pathogens and self-antigens. The book includes up-to-date information on: (i) the phylogeny of three IgM-binding receptors [polymeric Ig receptor (pIgR), Fc receptor for both IgA and IgM (Fc /R), and Fc receptor for IgM only (FcR)]; (ii) the lymphocyte-restricted distribution and unique ligand-binding activity of FcR; (iii) the definition and potential function of Fc receptor-like molecule A (FCRLA) as a resident endoplasmic reticulum protein that binds IgM, but also IgG and IgA; (iv) IgM antibody-mediated enhancement of humoral immune responses, highlighting the importance of complement and its receptors, (v) the numerous important roles of IgM natural antibodies in regulation of inflammation. It is an invaluable resource for researchers and clinicians alike.

To celebrate the 40th anniversary of the discovery of Natural Killer (NK) cells, this volume focuses on the recent advances in our understanding of NK cell development and differentiation and their acquisition of functional properties, as well as the latest models for NK-cell analysis in mice and applications in clinical medicine. NK cells have travelled a circuitous path from their initial description as 'spontaneous killers' (for some simply an experimental artifact) to being a bona fide subset of innate lymphoid cells with a complementary mode of action in immune defense and an important mediator of immune reactivity in health and disease. Together, these reviews provide a timely and concise picture of the evolution of NK cells as essential agents in immunity and as potent weapons against disease. This book offers an appealing and insightful resource for scientists and clinicians.

This book explores the major cytokines, such as IL-1 and IFN- , with respect to the regulation of their gene expression and protein production in specific immune cell types. It discusses both healthy physiological settings and in pathological situations in which the expression of some cytokines could be dysregulated, resulting in either immunodeficiency or exacerbated inflammatory sequelae in animal models as well as in human patients. Cytokines are important regulators of immune responses that require the highly coordinated participation and communication of multiple cell types. The expression of cytokines by various producer cell types is therefore carefully regulated in response to environmental cues at multiple levels: transcription, translation and posttranslational modification. Presenting cutting-edge advances in our understanding of the regulation of cytokine expression, this book is a valuable resource for anyone involved or interested in immune regulation.

Currently, malaria kills more than 300,000 people per year, making it a top priority of world leaders and international organizations, who are working towards implementing and coordinating efforts to eradicate this disease. An effective malaria vaccine is recognized as the key element that will decide between success and failure in this fight. At present, despite intensive research efforts, such a vaccine is not yet available for use. However, there are a number of advanced candidate vaccines with high chances of success in the short term. Malaria: Immune Response to Infection and Vaccination provides a comprehensive view on the immune response to malaria and to the different vaccines under development. The book offers the following: - Contributions by top research leaders in the field, - Comparisons of the immune responses to both malaria infection and malaria vaccines, which are traditionally treated separately, - Coverage of the immune responses to the different stages of malaria, which are frequently treated as separate fields of research.

In spite of their relatively low prevalence, systemic vasculitides have been the object of intensive basic and clinical investigations over the last few years. As a consequence, important advancements have been achieved: from updated diagnostic and classification criteria and a more rational nomenclature to the recognition of an expanding spectrum of clinical manifestations and potentially devastating complications; from the recognition of the viral etiology of conditions such as HCV-related cryoglobulinemic vasculitis and HBV-associated polyarteritis nodosa to newly named variable vessel vasculitis exemplified by Behcet's disease; from single-organ vasculitis such as central nervous system vasculitis to the more recently emerging features of the IgG4-related, immune-mediated diseases that are showing remarkable clinical heterogeneity. In addition, intriguing pathogenetic hypotheses are being reported for certain chronic, relapsing vasculitides that are improving our understanding of their biology and basic pathophysiology. New avenues are being explored that will hopefully allow a deeper comprehension of the relationships between certain virus-driven vasculitides and lymphoproliferation, and possibly lead to the identification of novel biomarkers that may be used to single out patients at an increased risk of relapse. This explosion of knowledge is obviously resulting in state-of-the-art, personalized treatments of systemic vasculitides. This book is a collection of reviews on the major vasculitides, written by scientists and clinicians with a multi-year experience in this field. We hope it will provide the reader with a stimulating container of new advances in scientific knowledge and more rational therapeutic approaches to this fascinating chapter of pathology.

Aimed at both beginners and experienced researchers unfamiliar with the technique, this book provides a concise and easy-to-understand guide to using immunohistochemistry. It identifies the proper place and purpose of each component of immunohistochemistry, emphasizes the components that are of critical importance, and explains the logistics of experimental approaches. Understanding the principles of immunohistochemistry allows for the identification and localization of protein targets and is of crucial use in the following experiments: * producing transgenic animals * studying the effects of drug treatments * electrophysiological studies * animal surgery * isolating and differentiating stem cells * super-resolution microscopy Immunohistochemistry for the Non-Expert is aimed at a wide audience, including molecular biologists, pharmacologists, immunologists, chemists, cell biologists, physiologists, and researchers involved with animal anatomy studies.

Second comprehensive volume focuses on anti-inflammatory nutraceuticals and their role in prevention and therapy of various chronic diseases. Food and drug administration (FDA) approved drugs such as steroids, non-steroidal anti-inflammatory drugs (NSAIDS), statins and metformin have been shown to modulate inflammatory pathways, but their long-term intake has been associated with numerous side effects. Thus dietary agents which can modulate inflammatory pathways in humans, are likely to exhibit enormous potential. Leading experts describe the latest results of anti-inflammatory nutraceuticals and their role in prevention and therapy of various chronic diseases.

This volume provides readers with methods and protocols for understanding the development of recombinant viruses and their use as vaccines platforms. Recombinant Virus Vaccines: Methods and Protocols details the use of recombinant vaccines that are employed to either produce immunogens in vitro or elicit antibody production in vivo. The chapters in this book are divided into four parts: Part I explores double-stranded DNA viruses; Part II discusses negative sense single-stranded RNA viruses; Part III talks about positive sense single-stranded RNA viruses; and Part IV describes bacteriophages. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and cutting-edge, Recombinant Virus Vaccines: Methods and Protocols is a valuable resource for scientists and clinicians who are interested in learning about and adopting methods for use in basic and biomedical research directed toward generating and developing recombinant viral vaccines.

The concept of immunotherapy was in infancy when the first edition was written; since then, major advances have been made, not only with several prominent clinical trials, but also with the approval of cell-based therapy by the FDA for the treatment of cancer in 2010. These events resulted in a gradually narrowing gap between early scientific knowledge and the late development of immune-based therapies. Consequently, the significance and magnitude of these advances warranted a revision of this contribution; this revised edition will provide a deeper understanding of the recent advances and discoveries related to the function of the immune response and their applications in the development of novel therapies to treat human diseases. Some of the key discoveries during the past five years include: the identification of the new subsets of helper T cells; new cytokines and their networks; and novel signal transduction mechanisms. For example, the identification of TH17 subset of helper T cells, in addition to TH1 and TH2 cells, not only advanced our understanding of the function of the basic immune response, but also raised our awareness of the possible etiology and pathogenesis of diseases such as allergy, asthma, rheumatoid arthritis, and other auto-immune/immune system based diseases. The newly identified powerful cytokine networks, that regulate both innate and acquired immune responses, emerged as a result of the finding of new cell types such as innate lymphoid cells and iNKT. Identification of the novel cytokines and their networks has advanced our knowledge of the mechanisms involved in the maintenance of tissue homeostasis, including inflammation and tissue repair during stress and injury. The development of HIV vaccines has also seen dramatic changes over the last few years. There has been a shift from a sole focus on T cell vaccines to a holistic approach that pertains to the induction of both humoral and cellular elements. This entails the induction of antibodies - both binding and neutralizing - to prevent infection. The cellular vaccination produces a safety net of CD8+ T-cell responses to suppress the replication of the virus in the infected patients, and both of the effector arms are aided by helper T cells. From the perspective of clinical applications, significant advances have also been made in: oral immunotherapy for allergic disease, the possible treatment of HIV infection, the development of new monoclonal antibodies and their fragments to treat human diseases, and immune cell based therapies for cancer.

This volume brings together recent developments in quasispecies theory extended to variable environments and practical applications in elucidating viral dynamics and treatment designs. In particular, the existence of an error threshold in rugged fitness landscapes has opened the way to a new antiviral strategy termed lethal mutagenesis, which is now under intensive theoretical, experimental and clinical investigation. As such the book explains how an understanding of quasispecies dynamics within infected organisms has increased our knowledge of viral disease events. From a clinical perspective, population dynamics highlights important problems for viral disease control, such as the selection of drug-resistant mutants that often accompanies treatment failures, and suggests means of increasing the effectiveness of antiviral treatments. The book is intended for students and scientists interested in basic and applied aspects of biophysics, chemistry, biology, evolution and medical virology.

This book offers an overview of our current understanding of host defense peptides and their potential for clinical applications as well as some of the obstacles to this. The chapters, written by leading experts in the field, detail the number and diversity of host defense peptides, and discuss the therapeutic potential not only of antibacterial, but also of antifungal, antiviral, plant antimicrobial and anticancer host defense peptides. The authors provide new insights into their mechanisms of action and their immunomodulatory properties, and review recent advances in the design of novel therapeutic molecules. Lastly, their potential to prevent preterm births and Staphylococcus aureus infections is highlighted. The book is of interest to researchers, industry and clinicians alike.

Cancer care is undergoing a radical transformation as novel technologies are directed toward new treatments and personalized medicine. The most dramatic advances in the treatment of cancer have come from therapeutics that augment the immune response to tumors. The immune checkpoint inhibitors are the best-known and most highly advanced examples of Immune Therapeutics targeting tumor cells and include approved antibody drugs directed at the cell surface proteins CTLA4 and PD-1. These are now considered foundational treatments for several solid tumor indications, and that list of indications is growing quickly. More broadly, antibodies have become workhorse molecules across the entire immunotherapy landscape. Antibodies to novel targets modulate the activity of diverse immune cell regulatory proteins. Engineered antibodies can induce tumor cell death or expose tumor cells to poisonous toxins (ADCC and ADC, respectively). Bi-specific antibodies can engage multiple tumor targets simultaneously, or can redirect lymphocytes to attack tumor cells. The antigen-binding domains within antibodies can be spliced onto cell stimulatory domains and transduced into T cells or NK cells, creating remarkable tumor-specific cellular therapeutics (CAR-T, CAR-NK). Beyond antibody-based therapies there are highly diverse and differentiated technology tool kits being applied to immunotherapy. Small molecule drugs are being developed to attack the tumor microenvironment, novel tumor vaccine approaches are showing great promise, patient lymphocytes are being isolated, expanded and reintroduced to patients, gene-editing techniques are becoming widely deployed, and a vast number of new tumor targets, and mutated tumor proteins (neoantigens), are being discovered. The past decade has seen unprecedented success in the treatment of diverse cancers. The authors of this volume have been asked to not only review progress to date, but importantly, to look ahead, and anticipate the evolution of cancer treatment across diverse Immune Therapeutic approaches. Our hypothesis is that the advances we are seeing across the immunotherapy landscape will further evolve and synergize, leading us finally to outright cures for many cancers.

This book describes modern biophysical techniques that enable us to understand and examine dynamic processes of infection at the molecular level. Cutting-edge research articles, laboratory protocols, case studies and up-to-date reviews cover topics such as single-molecule observation of DNA replication repair pathways in E. coli; evolution of drug resistance in bacteria; restriction enzymes as barriers to horizontal gene transfer in Staphylococcus aureus; infectious and bacterial pathogen biofilms; killing infectious pathogens through DNA damage; bacterial surfaces in host-pathogen interactions; bacterial gene regulation by riboswitches; transcription regulation in enterobacterial pathogens; the bacterial flagellar motor; initial surface colonization by bacteria; Salmonella Typhi host restrictions; as well as monitoring proton motive force in bacteria; microbial pathogens using digital holography; mathematical modelling of microbial pathogen motility; neutron reflectivity in studying bacterial membranes; force spectroscopy in studying infection and 4D multi-photon imaging to investigate immune responses. The focus is on the development and application of complex techniques and protocols at the interface of life sciences and physics, which increase the physiological relevance of biophysical investigations.

This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton's Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.

This text provides a practical guide providing step-by-step protocol to design and develop vaccines. Chapters detail protocols for developing novel vaccines against infectious bacteria, viruses, fungi, and parasites for humans and animals. Volume 1: Vaccines for Human Diseases has an introductory section on how vaccines impacted diseases, the immunological mechanism of vaccines, future challenges for vaccinologists, and current trends in vaccinology. The design of human vaccines for viral, bacterial, fungal, parasitic and prion diseases as well as vaccines for drug abuse, allergy, and tumor vaccines are also described in this volume. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Vaccine Design: Methods and Protocols, Volume 1: Vaccines for Human Diseases aims to ensure successful results in the further study of this vital field.

This second edition volume expands on the first edition with new developments on Toll-Like Receptors (TLRs) controlling events such as cross-priming of associated pattern recognition receptors, post-transcriptional regulation, interaction with other cellular and biologic systems, and cancer progression. This book is divided into five sections: Part I outlines methods for TLR detection, interaction, and intracellular trafficking; Part II describes methods and assays to investigate how TLRs cross-prime other pattern recognition receptors, including intracellular DNA receptors and inflammasome formation; Part III highlights RNA regulation, detailing how TLRs can induce RNA transcripts and molecules such as lncRNAs and microRNAs; Part IV explores TLR detection and activation in systems such as epithelial barrier function, metabolism and the circadian clock, as well as cellular systems including T and B lymphocytes; and Part V describes models to delineate the role of TLRs in diseases such as dermatitis, arthritis, and gastric cancer. Written in the highly successful Methods in Molecular Biology series format, each chapter contains a summary, a list of required materials, step-by-step, readily reproducible laboratory protocols, useful notes to investigate TLRs in cell culture, systems and disease, and tips on troubleshooting and avoiding known pitfalls. Practical and cutting-edge, Toll-Like Receptors: Methods and Protocols, Second Edition is a valuable resource to any immunologist, molecular or medical biologist working in a laboratory setting. It will add skill to both students and the more advanced molecular biologist who wishes to learn a new technique or move to a different area within their current repertoire of practical knowledge.

This book provides a comprehensive review of the major barriers to HIV cure and vaccine. It covers the fundamental virology and immunology leading to HIV transmission, protection from infection and long term HIV persistence on antiretroviral therapy. In addition, strategies being tested to eliminate persistent HIV and the rational design of vaccines to induce protective immunity are covered. This book also discusses the challenges related to the design of clinical trials for testing the safety and efficacy of these innovative approaches. This book will provide a systematic overview and also discuss controversial issues for researchers in virology and immunology, as well as practicing physicians, and scientists in the pharmaceutical industry.