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An understanding of the immune system is central to the understanding of how the body interacts with its surroundings, and how it both protects itself and responds to infectious disease. But what processes underpin the body's response to infection? How does our immune system remember its previous encounters? And what happens when the tight regulation of the immune system fails? Immunity: The Immune Response in Infectious and Inflammatory Disease presents an engaging insight into one of the most intricate yet conceptually challenging biological systems. With a unique emphasis on the immune response to infection, it presents the immune system as a dynamic interface with the outside world. Building up a complete picture of the subject, the book leads the student through both innate and adaptive immunity, how infection is detected, and how the cells of the immune system interact to generate a response, before examining the immune response to bacterial, viral, and fungal and parasitic infections. Finally, the book explores the relationship between the regulation of the immune response and immunological diseases - how the immune system is controlled, and the implications for our health when this control is lost - and immune memory and the development of vaccines. Immunity combines articulate prose with striking full colour illustrations, while the unique Primers in Biology modular structure integrates text, illustrations, definitions, and literature references for each topic into one double-page spread, bringing to the student's fingertips all the tools that they need to master that topic. The immune system is one of the most challenging yet rewarding biological systems to comprehend; Immunity: The Immune Response in Infectious and Inflammatory Disease is the ideal resource for any student wishing to develop a sound grasp of this fascinating subject. Anthony L. DeFranco graduated from Harvard University in biochemistry and molecular biology in 1975. He did his Ph.D. on bacterial chemotaxis with Daniel E. Koshland, Jr. at the University of California at Berkeley before turning to his present principal research interest, the activation of B lymphocytes, as a postdoctoral worker in the laboratory of William E. Paul at NIH in 1979. He is currently Chairman of the Department of Microbiology and Immunology at the University of California San Francisco Medical School, where his research interests are the mechanisms of signaling by the B cell antigen receptor and Toll-like receptors, and B cell autoimmunity. Richard M. Locksley graduated from Harvard University in Biochemistry in 1970 and in Medicine from the University of Rochester in 1976. He was at the Moffitt Hospital in San Francisco for four years as a Medical Resident, trained in infectious diseases at the University of Washington for three years, and then returned to the University of California in San Francisco where he served as Chief of the Division of Infectious Diseases from 1986–2004. He is currently the Sandler Distinguished Professor of Medicine and Microbiology and Immunity, Director of the Sandler Asthma Basic Research Center, and an HHMI Invertigator at UCSF. The principal focus of his research is on cellular immune responses in infectious and inflammatory disease. Miranda Robertson studied psychology at Birkbeck College London and at the University of Chicago in the 1960s without graduating from either, and then spent the greater part of a quarter-century on the editorial staff of Nature, ultimately as its Biology Editor. Since then, she has worked on behalf of Garland Publishing, Inc. and Current Biology, Ltd. with the authors of several outstanding textbooks. She is now the Managing Director of New Science Press, Ltd. Reviews and Commentary “The modular packaging of material into easily digestible bite-size nuggets makes this an excellent book that is both informative and fun to read. … this is a highly readable publication that admirably serves a dual role of both a textbook and reference.” — James D. Gorham, The Quarterly Review of Biology Contents 1. Overview of the Immune Response 1-0 Overview: The Protective Mechanisms of Immunity 1-1 Cells of the Immune System: Differentiation in the Bone Marrow 1-2 Cells of the Immune System: Functional Characteristics 1-3 Macrophage and Dendritic Cell Subsets 1-4 Clonal Selection of Antigen-Specific Lymphocytes 1-5 Major Histocompatibility Molecules and the Detection of Infection 1-6 The Lymphoid System and Lymphocyte Circulation 1-7 Architecture of Secondary Lymphoid Tissues 1-8 The Course of an Immune Response 2. Signaling and Adhesive Molecules of the Immune System 2-0 Overview: Immune Cell Surface and Signaling Molecules 2-1 The Immunoglobulin Superfamily: Structural Features 2-2 Signaling by Immunoglobulin Superfamily Receptors 2-3 Adhesion Molecules of the Immunoglobulin Superfamily 2-4 Integrins in Immune Function 2-5 C-Type Lectins and Carbohydrate Recognition 2-6 Cytokines and Cytokine Receptors 2-7 Cytokine Receptors that Signal via the Jak–STAT Pathway 2-8 Shared Subunits in Subfamilies of Type I Cytokine Receptors 2-9 The TNF Superfamily of Cell Regulators 2-10 NF-kB and Inflammatory Cytokine Action 2-11 Molecular Control of Apoptosis 2-12 Regulation of Apoptosis by Bcl-2 Family Members 2-13 Chemokines and Chemokine Receptors 2-14 Chemokines, Integrins and Selectins and Immune-Cell Homing 3. Innate Immunity 3-0 Overview: Evolution and Function of Innate Immunity 3-1 Barriers to Infection at the Epithelium 3-2 Innate Recognition by Soluble Collectins and Ficolins 3-3 Overview of the Complement System 3-4 Activation of the Complement Cascade 3-5 Complement Effector Actions and Receptors 3-6 Regulation of Complement and Evasion by Microbes 3-7 Recognition of Microbes by Phagocytes 3-8 Mechanisms of Phagocytosis 3-9 Destructive Mechanisms of Phagocytes 3-10 The Toll-Like Receptor Family of Innate Immune Receptors 3-11 Toll-Like Receptor Signaling to Cytokine Production 3-12 Intracellular Sensors of Bacterial Peptidoglycan Components 3-13 Inflammation: Initiation of an Inflammatory Response 3-14 Inflammation: Recruitment of Immune Cells 3-15 Inflammation: Regulation and Systemic Effects 3-16 Innate Defense Against Viruses: Interferon 3-17 Inhibition of Virus Replication by Interferon 3-18 Innate Defense Against Viruses: Induction of Apoptosis 3-19 Intracellular Defenses Targeting Viral Nucleic Acid 4. Adaptive Immunity and the Detection of Infection by T Lymphocytes 4-0 Overview: The Role of T Cells in the Adaptive Immune Response 4-1 Dendritic Cells in the Induction of Adaptive Immunity 4-2 The Structure and Function of MHC Molecules 4-3 The MHC and Polymorphism of MHC Molecules 4-4 Non-Classical MHC Class I Molecules 4-5 Peptide Binding by MHC Molecules 4-6 Antigen Presentation by Classical MHC Class I Molecules 4-7 Antigen Presentation by MHC Class II Molecules 4-8 Regulation of Antigen Presentation 4-9 Specialized Features of Antigen Presentation by Dendritic Cells 5. Activation and Effector Actions of T Cells 5-0 Overview: T Cell-Mediated Immune Responses 5-1 Antigen Recognition by T Cells: Structure of the Receptor 5-2 Antigen Recognition by T Cells: TCR Specificity and Coreceptors 5-3 Signaling from the T Cell Receptor 5-4 Regulation of TCR Signaling 5-5 T Cell Signaling to the Nucleus and the Role of CD28 5-6 Activation of Naïve T Cells in Secondary Lymphoid Tissue 5-7 Clonal Expansion of Naïve T Cells in Secondary Lymphoid Tissue 5-8 Costimulatory Signals in T Cell Proliferation and Survival 5-9 Effector T Cell Differentiation 5-10 The Polarization of TH1 and TH2 Cells 5-11 The Functions of TH1 Cells 5-12 The Functions of TH2 Cells 5-13 The Functions of TFH Cells, TH17 Cells and Induced TREG Cells 5-14 Effector Functions of CD8 T Cells 5-15 T Cell Homeostasis and the Termination of Immune Responses 5-16 T Cell Memory 6. B Cells and Humoral Immunity 6-0 B Cells and the Importance of Antibodies for Immune Defense 6-1 Structure of Antibodies 6-2 Structural Properties of Antibodies 6-3 Effector Functions of Antibodies 6-4 Monoclonal Antibodies 6-5 Antibody-Based Methods: Radioimmunoassay and Hemagglutination 6-6 Antibody-Based Methods: ELISA, Immunoblotting and FACS 6-7 Antigen Receptors of B Lymphocytes 6-8 B Cell Antigen Receptor Signaling and B Cell Coreceptors 6-9 Early and T Cell-Independent Responses by B Cells 6-10 Initiation of T Cell-Dependent Antibody Responses 6-11 Hypermutation and Isotype Switching in the Germinal Center 6-12 Selection and Differentiation of B Cells in the Germinal Center 7. Development of Lymphocytes and Selection of the Receptor Repertoire 7-0 Overview of Lymphocyte Development 7-1 Antigen Receptor Gene Structure and V(D)J Recombination 7-2 V(D)J Recombination: Mechanism of Recombination 7-3 V(D)J Recombination: Control of which Segments Recombine 7-4 Phylogenetic Diversity in Antigen Receptor Genes 7-5 B Cell Development in the Bone Marrow 7-6 Maturation of B Cells in the Periphery 7-7 Organization of the Thymus and Early T Cell Development 7-8 Positive Selection of T Cells in the Thymus 7-9 Proposed Mechanisms of Positive Selection 7-10 Negative Selection 7-11 Diseases Related to Lymphocyte Development 8. Specialized Lymphocytes in Early Responses and Homeostasis 8-0 Overview: Specialized Lymphocyte Populations 8-1 Natural Killer Cells and their Role in Immunity 8-2 Natural Killer Cell Signaling Pathways 8-3 NKT Cells 8-4 γδ T Cells 8-5 Intraepithelial Lymphocytes and Other Specialized T Cells 8-6 B1 Cells 8-7 Marginal Zone B Cells 9. The Immune Response to Bacterial Infection 9-0 Overview: Bacterial Pathogens and Host Defenses 9-1 Epithelial Barriers and Defenses against Infection 9-2 Evasion of Epithelial Defenses by Pathogenic Bacteria 9-3 Sepsis Syndrome: Bacterial Endotoxin 9-4 Sepsis Syndrome: Bacterial Superantigens 9-5 The Immune Response to Streptococcus pneumoniae 9-6 Listeria monocytogenes 9-7 Mycobacterium tuberculosis 10. The Immune Response to Viral Infection 10-0 Overview: Viral Infectious Strategies 10-1 Overview: Innate Strategies Against Viruses 10-2 Overview: Adaptive Immune Strategies Against Viruses 10-3 Subversion of Immune Mechanisms by Viruses 10-4 Origin and Structure of Human Immunodeficiency Virus 10-5 Tropism of Human Immunodeficiency Virus 10-6 AIDS Progression and Immune Control of HIV 10-7 Influenza Virus: Antigenic Shift and Drift 10-8 Influenza Virus: Innate and Adaptive Immunity 10-9 Lymphocytic Choriomeningitis Virus (LCMV) 11. The Immune Response to Fungal and Parasitic Infection 11-0 Overview: The Scope of Fungal and Parasitic Infections 11-1 Candida albicans 11-2 Pneumocystis 11-3 Leishmania major 11-4 Nippostrongylus brasiliensis 11-5 Schistosomiasis 12. Tolerance and Autoimmunity 12-0 Overview: Tolerance and Autoimmunity 12-1 Central Tolerance 12-2 Peripheral Tolerance Mechanisms 12-3 Regulatory T Cells 12-4 Autoimmune Diseases: General Principles 12-5 Organ-Specific Autoimmunity: Antibody-Mediated Diseases 12-6 Organ-Specific Autoimmunity: Cell-Mediated Diseases 12-7 Organ-Specific Autoimmunity: Animal Models 12-8 Systemic Autoimmunity: Lupus 12-9 Systemic Autoimmunity: Rheumatoid Arthritis 13. Allergy and Hypersensitivity 13-0 Overview: Causes and Nature of Hypersensitivity Reactions 13-1 Mast Cells and Allergic Reactions 13-2 Allergic Diseases 13-3 Asthma 13-4 IgG-Mediated Immune Pathology 13-5 Delayed-Type Hypersensitivity Reactions 13-6 Inflammatory Bowel Disease 14. Transplantation Immunology, Tumor Immunity and Vaccination 14-0 Overview: Boosting and Suppressing Immune Responses 14-1 Immunodeficiencies 14-2 Features of Successful Vaccines 14-3 Engineering Vaccines for Safety and Efficacy 14-4 Vaccines for Chronic Infections and Cancer 14-5 Tumor Immunity 14-6 Transplants and Transplantation Antigens 14-7 Transplant Recognition and Rejection 14-8 Immunosuppression of Transplant Recipients Glossary References Index
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