Immunology, Phenotype First: How Mutations Have Established New Principles and Pathways in Immunology


Book Description

This monograph deals with the impact of classical genetics in immunology, prov- ing examples of how large immunological questions were solved, and new fields opened to analysis through the study of phenotypes, either spontaneous or induced. As broad as biology has become, there are those who do not fully understand what the genetic approach is, and how it differs fundamentally from most of the methods available to natural scientists. They may hold the opinion that genetics has run its course since Mendel read his paper on peas in 1865. “Why bother with classical genetics,” they may ask. “Won’t all genes be knocked out soon anyway?” Or they are intimidated by genetics, with its heavy reliance on model organisms that seem so alien. “What has C. elegans to do with me?” the questioning might go. “It doesn’t even have lymphocytes. ” Such skeptics may be unaware that the mouse is fast becoming as tractable a model organism as the fly, and that humans may not be too far behind. So I would like to introduce the topic with a few words about the power of genetics, and why it has contributed so much to immunology, and to bi- ogy in general. Genetics, as the word is used here, is not merely the science of heredity, but much more than that. It is the science of exceptions: the science that takes note of heritable variation and seeks to explain it at the most fundamental level.




Immunology, Phenotype First: How Mutations Have Established New Principles and Pathways in Immunology


Book Description

This monograph deals with the impact of classical genetics in immunology, prov- ing examples of how large immunological questions were solved, and new fields opened to analysis through the study of phenotypes, either spontaneous or induced. As broad as biology has become, there are those who do not fully understand what the genetic approach is, and how it differs fundamentally from most of the methods available to natural scientists. They may hold the opinion that genetics has run its course since Mendel read his paper on peas in 1865. “Why bother with classical genetics,” they may ask. “Won’t all genes be knocked out soon anyway?” Or they are intimidated by genetics, with its heavy reliance on model organisms that seem so alien. “What has C. elegans to do with me?” the questioning might go. “It doesn’t even have lymphocytes. ” Such skeptics may be unaware that the mouse is fast becoming as tractable a model organism as the fly, and that humans may not be too far behind. So I would like to introduce the topic with a few words about the power of genetics, and why it has contributed so much to immunology, and to bi- ogy in general. Genetics, as the word is used here, is not merely the science of heredity, but much more than that. It is the science of exceptions: the science that takes note of heritable variation and seeks to explain it at the most fundamental level.




Immunological Synapse


Book Description

The proper physiological functioning of most eukaryotic cells requires their assembly into multi-cellular tissues that form organized organ systems. Cells of the immune system develop in bone marrow and lymphoid organs, but as the cells mature they leave these organs and circulate as single cells. Antigen receptors (TCRs) of T cells search for membrane MHC proteins that are bound to peptides derived from infectious pathogens or cellular transformations. The detection of such speci?c peptide–MHC antigens initiates T cell activation, adhesion, and immune-effectors functions. Studies of normal and transformed T cell lines and of T cells from transgenic mice led to comprehensive understanding of the mole- lar basis of antigen-receptor recognition and signaling. In spite of these remarkable genetic and biochemical advances, other key physiological mechanisms that par- cipate in sensing and decoding the immune context to induce the appropriate cellular immune responses remain unresolved. TCR recognition is tightly regulated to trigger sensitive but balanced T cell responses that result in the effective elimination of the pathogens while minimizing collateral damage to the host. The sensitivity of TCR recognition has to be properly tempered to prevent unintended activation by self-peptide–MHC complexes that cause autoimmune diseases. It is likely that once the TCR is engaged by a peptide– MHC and TCR signaling begins, additional regulatory mechanisms, involving other receptors, would increase the ?delity of the response.




Cancer Immunology and Immunotherapy


Book Description

The interplay between tumors and their immunologic microenvironment is complex, difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. The present review discusses tumor-immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment.




Visualizing Immunity


Book Description

Researchers have used a variety of techniques over the past century to gain fun- mental insights in the field of immunology and, as technology has advanced, so too has the ability of researchers to delve deeper into the biological mechanics of immunity. The immune system is exceedingly complex and must patrol the entire body to protect us from foreign invaders. This requires the immune system to be highly mobile and adaptable - able to respond to diverse microbial challenges while maintaining the ability to distinguish self from a foreign invader. This latter feature is of great importance because the immune system is equipped with toxic mediators, and a failure in self/non-self discrimination can result in serious diseases. Fortunately, in most cases, the immune system operates within the framework of its elegant design and protects us from diverse microbial challenges without initiating disease. Because the immune system is not confined to a single tissue, a comprehensive understanding of immunity requires that research be conducted at the molecular, cellular, and systems level. Immune cells often find customized solutions to h- dling microbial insults that depend on the tissue(s) in which the pathogen is found.




Principles and Practice of Pediatric Infectious Diseases E-Book


Book Description

Principles and Practice of Pediatric Infectious Disease provides the comprehensive and actionable coverage you need to understand, diagnose, and manage the ever-changing, high-risk clinical problems caused by pediatric infectious diseases. With new chapters, expanded and updated coverage, and increased worldwide perspectives, this authoritative medical reference offers the latest need-to-know information in an easily-accessible, high-yield format for quick answers and fast, effective intervention! Spend less time searching thanks to a consistent, easily-accessible format featuring revised high-yield information boxes, highlighted key points, and an abundance of detailed illustrations and at-a-glance tables. Be prepared for the unexpected! A veritable "who's who" of global authorities provides practical knowledge to effectively diagnose and manage almost any infectious disease you may encounter. Quickly look up the answers you need by clinical presentation, pathogen, or type of host. Get expanded coverage for all types of infectious diseases including new chapters on infection related to pets and exotic animals, and tickborne infections. Apply the latest recommendations and treatments for emerging and re-emerging diseases including the H1N1 virus.




Autophagy in Infection and Immunity


Book Description

Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy’s ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy’s roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis; it acts both as an effector and a regulator of Toll-like receptor and other innate immunity receptor signaling; and it may help ward off chronic inflammatory disease in humans. With such a multitude of innate and adaptive immunity functions, the study of autophagy in immunity is one of the most rapidly growing fields of contemporary immunological research. This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity.




Biochemistry and Molecular Biology Compendium


Book Description

This book is an accessible resource offering practical information not found in more database-oriented resources. The first chapter lists acronyms with definitions, and a glossary of terms and subjects used in biochemistry, molecular biology, biotechnology, proteomics, genomics, and systems biology. There follows chapters on chemicals employed in biochemistry and molecular biology, complete with properties and structure drawings. Researchers will find this book to be a valuable tool that will save them time, as well as provide essential links to the roots of their science. Key selling features: Contains an extensive list of commonly used acronyms with definitions Offers a highly readable glossary for systems and techniques Provides comprehensive information for the validation of biotechnology assays and manufacturing processes Includes a list of Log P values, water solubility, and molecular weight for selected chemicals Gives a detailed listing of protease inhibitors and cocktails, as well as a list of buffers




Measles


Book Description

Measles virus, one of the most contagious of all human viruses, has been largely contained by the development and use of a vaccine that was introduced 50 years ago. These two volumes were timed to honor the introduction of the vaccine and to record the enormous advancements made in understanding the molecular and cell biology, pathogenesis, and control of this infectious disease. Where vaccine has been effectively delivered, endemic measles virus transmission has been eliminated. However, difficulties in vaccine delivery, lack of health care support and objection to vaccination in some communities continue to result in nearly 40 million cases and over 300,000 deaths per year from measles.




TT Viruses


Book Description

Eleven years ago the circular DNA of a novel single-stranded virus has been cloned and partially characterized by Nishizawa and Okamoto and their colleagues. According to the initials of the patient from whom the isolate originated, the virus was named TT virus. This name has been subsequently changed by the International Committee on Taxonomy of Viruses (ICTV) into Torque teno virus, permitting the further use of the abbreviation TTV. Although initially suspected to play a role in non A –E hepatitis, subsequent studies failed to support this notion. Within a remarkably short period of time it became clear that TT viruses are widely spread globally, infect a large proportion of all human populations studied thus far and represent an extremely heterogeneous group of viruses, now labelled as Anelloviruses. TT virus-like infections have also been noted in various animal species. The classification of this virus group turns out to be difficult, their DNA contains between 2200 and 3800 nucleotides, related so-called TT-mini-viruses and a substantial proportion of intragenomic recombinants further complicate attempts to combine these viruses into a unifying phylogenetic concept.