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Although, Phagocytosis was first described nearly 120 year ago, we are just recently beginning to understand the molecules that phagocytic cells use to bring about this complex cell function. Molecular Mechanisms of Phagocytosis was prepared as a series of up-to-date essays (chapters) that describe the present knowledge on the various steps of the phagocytic process from initial cell contact, through internalization of the foreign particle, to the final phagosome formation where the phagocytosed particle is destroyed.
Phagocytosis is the engulfment of particulate matter by cells. It is a fundamental (and probably “primitive”) cell biological process which is important in single celled organisms such as amoeba; multicellular animals including coelenterates; and in higher animals. In humans and other mammals, specialised immune cells (phagocytes) utilise phagocytosis in their crucial role of engulfing and destroying infecting microbes. Yet, surprisingly, the biophysics and biochemistry underlying the process has only become clear recently with the advent of genetic manipulation and advances in single cell imaging. In this volume, the aim is to bring together recent fundamental advances that give a clear picture of the underlying mechanism involved in phagocytosis. Not only is this an important topic in its own right, but a full understanding of the process will have a potential impact on human medicine, since as antibiotics become less effective in fight infection, researchers are looking at alternative approaches, including enhancing the “natural” immunity brought about by immune phagocytes. The aim is to provide a comprehensive volume on the topic, with separate chapters on identified recent advances, each written by the major contributors in each area. In addition, the volume will attempt to give a wider overview than is often the case in single author reviews, with an emphasis here on the cell biological understanding of phagocytosis using biophysical approaches alongside the biochemical and imaging approaches.
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.
The production of Interleukin (IL)-10, a major immunoregulatory cytokine, by phagocytes during clearance of apoptotic cells is critical to ensuring cellular homeostasis and suppression of autoimmunity. Little is known about the regulatory mechanisms involved in this fundamental process. In this study, we showed that IL-10 production stimulated by apoptotic cells is regulated primarily at the level of transcription in a manner dependent on the p38 mitogen-activated protein kinase, partially on the scavenger receptor CD36, and requires cell-cell contact but not actual phagocytosis. Using a reporter assay, we mapped the Apoptotic Cell Response Element (ACRE) in the human IL-10 promoter, and provide biochemical and physiological evidence in part I of this thesis that the ACRE mediates transcriptional activation by interacting with pre-B-cell leukemia transcription factor-1b in response to apoptotic cells.
Pathogenic bacteria for human and animals have developed sophisticated weapons, termed virulence factors, to ensure their replication and persistence into their hosts. The authors in this volume show a synthesis on how the various host cellular Rho GTPases activities are manipulated by bacteria to fulfil their virulence.
Amphioxus Immunity: Tracing the Origin of Human Immunity covers a remarkable range of information about Amphioxus and its evolutionary context. This compilation of what is currently known about Amphioxus, with a sharp focus on its immune system, includes 13 topics, such as: Amphioxus as a model for understanding the evolution of vertebrates basic knowledge of immunology immune organs and cells of amphioxus a genomic and transcriptomic view of the Amphioxus immunity pattern recognition system in Amphioxus transcription factors in Amphioxus the complement system of Amphioxus the oxidative burst system in Amphioxus immune effectors in Amphioxus lipid signaling of immune response in Amphioxus apoptosis in amphioxus; primitive adaptive immune system of Amphioxus and future research directions This valuable reference book is loaded with information that will be useful for anyone who wishes to learn more about the origin of vertebrates and adaptive immunity. Provides new evidence on the origin of the adaptive immune system, the evolution of innate immunity, and evolution-stage specific immune defense mechanisms Not only presents the cells and molecules involved in the adaptive immune response in Amphioxus, but also characterizes the origination and evolution of the gene families and pathways involved in innate immunity Includes much pioneering work, from the molecular, genomic, and cellular to the individual level
This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.