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The Mononuclear Phagocyte System (MPS) of vertebrates is composed of monocytes, macrophages and dendritic cells. Together, they form part of the first line of immune defense against a variety of pathogens (bacteria, fungi, parasites and viruses), and thus play an important role in maintaining organism homeostasis. The mode of transmission, type of replication and mechanism of disease-causing differ significantly for each pathogen, eliciting a unique immune response in the host. Within this context, the MPS acts as both the sentinel and tailor of the immune system. As sentinels, MPS cells are found in blood and within tissues throughout the body to patrol against pathogenic insult. The strategy to detect 'microbial non-self' relies on MPS to recognize conserved microbial products known as 'pathogen-associated molecular pattern' (PAMPs). PAMPs recognition represents a checkpoint in the response to pathogens and relies on conserved 'pattern recognition receptors' (PRRs). Upon PRR engagement, MPS mount a cell-autonomous attack that includes the internalization and compartmentalization of intracellular pathogens into toxic compartments that promote destruction. In parallel, MPS cells launch an inflammatory response composed of a cellular arm and soluble factors to control extracellular pathogens. In cases when innate immunity fails to eliminate the invading microbe, MPS serves as a tailor to generate adaptive immunity for pathogen eradication and generation of "memory" cells, thus ensuring enhanced protection against re-infection. Indeed, MPS cell functions comprise the capture, process, migration and delivery of antigenic information to lymphoid organs, where type-1 immunity is tailored against intracellular microbes and type-2 immunity against extracellular pathogens. However, this potent adaptive immunity is also a double-edge sword that can cause aberrant inflammatory disorders, like autoimmunity or chronic inflammation. For this reason, MPS also tailors tolerance immunity against unwanted inflammation. Successful clearance of the microbe results in its destruction and proper collection of debris, resolution of inflammation and tissue healing for which MPS is essential. Reciprocally, as part of the evolutionary process taking place in all organisms, microbes evolved strategies to circumvent the actions bestowed by MPS cells. Multiple pathogens modulate the differentiation, maturation and activation programs of the MPS, as an efficient strategy to avoid a dedicated immune response. Among the most common evasion strategies are the subversion of phagocytosis, inhibition of PRR-mediated immunity, resistance to intracellular killing by reactive oxygen and nitrogen species, restriction of phagosome maturation, modulation of cellular metabolism and nutrient acquisition, regulation of cell death and autophagy, and modulation of pro-inflammatory responses and hijacking of tolerance mechanisms, among others. The tenet of this eBook is that a better understanding of MPS in infection will yield insights for development of therapeutics to enhance antimicrobial processes or dampen detrimental inflammation for the host's benefit. We believe that contributions to this topic will serve as a platform for discussion and debate about relevant issues and themes in this field. Our aim is to bring expert junior and senior scientists to address recent progress, highlight critical knowledge gaps, foment scientific exchange, and establish conceptual frameworks for future MPS investigation in the context of infectious disease.
The mononuclear phagocyte system (MPS) comprises dendritic cells (DCs), monocytes and macrophages (MØs) that together play crucial roles in tissue immunity and homeostasis, but also contribute to a broad spectrum of pathologies. They are thus attractive therapeutic targets for immune therapy. However, the distinction between DCs, monocytes and MØ subpopulations has been a matter of controversy and the current nomenclature has been a confounding factor. DCs are remarkably heterogeneous and consist of multiple subsets traditionally defined by their expression of various surface markers. While markers are important to define various populations of the MPS, they do not specifically define the intrinsic nature of a cell population and do not always segregate a bona fide cell type of relative homogeneity. Markers are redundant, or simply define distinct activation states within one subset rather than independent subpopulations. One example are the steady-state CD11b+ DCs which are often not distinguished from monocytes, monocyte-derived cells, and macrophages due to their overlapping phenotype. Lastly, monocyte fate during inflammation results in cells bearing the phenotypic and functional features of both DCs and MØs significantly adding to the confusion. In fact, depending on the context of the study and the focus of the laboratory, a monocyte-derived cell will be either be called "monocyte-derived DCs" or "macrophages". Because the names we give to cells are often associated with a functional connotation, this is much more than simple semantics. The "name" we give to a population fundamentally changes the perception of its biology and can impact on research design and interpretation. Recent evidence in the ontogeny and transcriptional regulation of DCs and MØs, combined with the identification of DC- and MØ-specific markers has dramatically changed our understanding of their interrelationship in the steady state and inflammation. In steady state, DCs are constantly replaced by circulating blood precursors that arise from committed progenitors in the bone marrow. Similarly, some MØ populations are also constantly replaced by circulating blood monocytes. However, others tissue MØs are derived from embryonic precursors, are seeded before birth and maintain themselves in adults by self-renewal. In inflammation, such differentiation pathways are fundamentally changed and unique monocyte-derived inflammatory cells are generated. Current DC, monocyte and MØ nomenclature does not take into account these new developments and as a consequence is quite confusing. We believe that the field is in need of a fresh view on this topic as well as an upfront debate on DC and MØ nomenclature. Our aim is to bring expert junior and senior scientists to revisit this topic in light of these recent developments. This Research Topic will cover all aspects of DC, monocyte and MØ biology including development, transcriptional regulation, functional specializations, in lymphoid and non-lymphoid tissues, and in both human and mouse models. Given the central position of DCs, monocytes and MØs in tissue homeostasis, immunity and disease, this topic should be of interest to a large spectrum of the biomedical community.
The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Antibody Fc is the first single text to synthesize the literature on the mechanisms underlying the dramatic variability of antibodies to influence the immune response. The book demonstrates the importance of the Fc domain, including protective mechanisms, effector cell types, genetic data, and variability in Fc domain function. This volume is a critical single-source reference for researchers in vaccine discovery, immunologists, microbiologists, oncologists and protein engineers as well as graduate students in immunology and vaccinology. Antibodies represent the correlate of protection for numerous vaccines and are the most rapidly growing class of drugs, with applications ranging from cancer and infectious disease to autoimmunity. Researchers have long understood the variable domain of antibodies, which are responsible for antigen recognition, and can provide protection by blocking the function of their target antigen. However, recent developments in our understanding of the protection mediated by antibodies have highlighted the critical nature of the antibody constant, or Fc domain, in the biological activity of antibodies. The Fc domain allows antibodies to link the adaptive and innate immune systems, providing specificity to a wide range of innate effector cells. In addition, they provide a feedback loop to regulate the character of the immune response via interactions with B cells and antigen-presenting cells. - Clarifies the different mechanisms of IgG activity at the level of the different model systems used, including human genetic, mouse, and in vitro - Covers the role of antibodies in cancer, infectious disease, and autoimmunity and in the setting of monoclonal antibody therapy as well as naturally raised antibodies - Color illustrations enhance explanations of the immune system
Myelomonocytes are the multipotent cells in the stage of blood cell differentiation, which mainly comprise blood monocytes, tissue macrophages and subset of dendritic cells. Actually, their position and ability of judgement of the health of tissue or organ environment are the key initiators of tissue-specific immune response in a local and global fashion. Interestingly, the morpho-functional aspects of this group of cells vary to a wide range with their positional diversity. Their ability to communicate or represent the tissue microenvironment to the peripheral immune system and efficiency to engage the system to effector activation hold the key for a successful immune endeavour. The present volume shows some glimpses of such an extensive area of current immunology research.
The Evolution of the Immune System: Conservation and Diversification is the first book of its kind that prompts a new perspective when describing and considering the evolution of the immune system. Its unique approach summarizes, updates, and provides new insights on the different immune receptors, soluble factors, and immune cell effectors. - Helps the reader gain a modern idea of the evolution of the immune systems in pluricellular organisms - Provides a complete overview of the most studied and hot topics in comparative and evolutionary immunology - Reflects the organisation of the immune system (cell-based, humoral [innate], humoral [adaptive]) without introducing further and misleading levels of organization - Brings concepts and ideas on the evolution of the immune system to a wide readership
Autoimmune diseases are characterized by the occurrence of antibodies reacting with self-constituents of the body. The fully updated third edition of Autoantibodies is an in-depth review of the main autoantibodies identified up to now, with particular emphasis on those that display a diagnostic or prognostic clinical value. The new edition covers recent scientific advances, diagnostic techniques, and therapeutic technologies. Each chapter is focused on a single family of autoantibodies. This important reference contains historical notes, definitions, origins and sources of antigens recognized genetic associations, mediated pathogenic mechanisms, methods of detection, as well as clinical utility (disease prevalence and association, diagnostic value, sensitivity and specificity, prognostic value). This is an ideal reference for anyone involved in the field of autoimmune diseases. - Presents all known, important autoantibodies in a single source, focusing on the antibodies needed for autoimmune disorder diagnosis - Includes clinical applications for each autoantibody along with general information - Organized by disease and disorder type, by autoantibody family, and completely cross-referenced