BOOK
Cellular and Molecular Immunology E-Book
Abul K. Abbas | Andrew H. H. Lichtman | Shiv Pillai
(2017)
Additional Information
Book Details
Abstract
The top required and recommended immunology text worldwide, Cellular and Molecular Immunology by Drs. Abul K. Abbas, Andrew H. H. Lichtman, and Shiv Pillai, is a clear, well-written, and superbly illustrated introduction to the field. The 9th Edition retains a practical, clinical focus while updating and revising all content to ensure clarity and comprehension, bringing readers fully up to date with new and emerging information in this challenging area.
- Highlights the implications of immunologic science for the management of human disease, emphasizing clinical relevance throughout.
- Provides a highly visual, full-color description of the key immunologic and molecular processes with a fully updated, comprehensive, and consistent art program.
- Helps readers grasp the details of experimental observations that form the basis for the science of immunology at the molecular, cellular, and whole-organism levels and draw the appropriate conclusions.
- Includes summary boxes that assist with rapid review and mastery of key material.
- Features updates from cover to cover, including tumor immunity (tumor antigens, cancer immunotherapy), immune checkpoints, cytosolic sensors for DNA, non-canonical inflammasomes, prionization as a signaling mechanism, monogenic defects in immunity, and more.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Student Consult | IFC2 | ||
| Cellular and Molecular Immunology | i | ||
| Copyright Page | ii | ||
| Dedication | iii | ||
| Preface | v | ||
| Online Resources for Instructors and Students | vii | ||
| Resources for Instructors | vii | ||
| Image Collection | vii | ||
| Animations | vii | ||
| Test Bank | vii | ||
| Resources for Students | vii | ||
| Textbook online | vii | ||
| Glossary | vii | ||
| Clinical Cases | viii | ||
| Self-Assessment Questions | viii | ||
| Animations | viii | ||
| Table Of Contents | ix | ||
| 1 Properties and Overview of Immune Responses | 1 | ||
| Innate and Adaptive Immunity | 2 | ||
| Innate Immunity: the Early Defense | 3 | ||
| Adaptive Immunity | 4 | ||
| Cardinal Features of Adaptive Immune Responses | 4 | ||
| Overview of Humoral and Cell-Mediated Immunity | 5 | ||
| Initiation and Development of Adaptive Immune Responses | 8 | ||
| Humoral Immunity | 10 | ||
| Cell-Mediated Immunity | 10 | ||
| Summary | 11 | ||
| Selected Readings | 11 | ||
| Historical Ideas | 11 | ||
| Evolution of the Immune System | 11 | ||
| 2 Cells and Tissues of the Immune System | 13 | ||
| Cells of the Immune System | 13 | ||
| Phagocytes | 14 | ||
| Neutrophils | 14 | ||
| Mononuclear Phagocytes | 15 | ||
| Development of Monocytes and Macrophages | 15 | ||
| Subsets of Monocytes | 15 | ||
| Functions of Macrophages | 17 | ||
| Macrophage Receptors and Activation | 17 | ||
| Subsets of Macrophages | 17 | ||
| Mast Cells, Basophils, and Eosinophils | 17 | ||
| Mast Cells | 18 | ||
| Basophils | 18 | ||
| Eosinophils | 18 | ||
| Dendritic Cells (DCs) | 18 | ||
| Development of Dendritic Cells | 18 | ||
| Subsets of Dendritic Cells | 18 | ||
| Lymphocytes | 21 | ||
| Classes of Lymphocytes | 21 | ||
| Subsets of B Lymphocytes | 21 | ||
| Subsets of T Lymphocytes | 21 | ||
| Development of Lymphocytes | 23 | ||
| Populations of Lymphocytes Distinguished by History of Antigen Exposure | 23 | ||
| Naive Lymphocytes | 24 | ||
| Effector Lymphocytes | 25 | ||
| Memory Lymphocytes | 26 | ||
| Natural Killer Cells and Cytokine-Secreting Innate Lymphoid Cells | 27 | ||
| Anatomy and Functions of Lymphoid Tissues | 27 | ||
| Bone Marrow | 28 | ||
| Thymus | 28 | ||
| The Lymphatic System | 30 | ||
| Lymph Nodes | 32 | ||
| Anatomic Organization of B and T Lymphocytes | 33 | ||
| Antigen Transport Through Lymph Nodes | 35 | ||
| Spleen | 35 | ||
| Cutaneous and Mucosal Immune Systems | 36 | ||
| Summary | 36 | ||
| Selected Readings | 37 | ||
| Cells of the Immune System | 37 | ||
| Tissues of the Immune System | 37 | ||
| 3 Leukocyte Circulation and Migration into Tissues | 39 | ||
| Overview of Leukocyte Migration | 39 | ||
| Adhesion Molecules on Leukocytes and Endothelial Cells Involved in Leukocyte Recruitment | 41 | ||
| Selectins and Selectin Ligands | 41 | ||
| Integrins and Integrin Ligands | 42 | ||
| Chemokines and Chemokine Receptors | 43 | ||
| Chemokine Structure, Production, and Receptors | 43 | ||
| Biologic Actions of Chemokines | 44 | ||
| Leukocyte-Endothelial Interactions and Leukocyte Recruitment Into Tissues | 45 | ||
| Migration of Neutrophils and Monocytes to Sites of Infection or Tissue Injury | 46 | ||
| Migration and Recirculation of T Lymphocytes | 47 | ||
| Recirculation of Naive T Lymphocytes Between Blood and Secondary Lymphoid Organs | 47 | ||
| Migration of Naive T Cells Into Lymph Nodes | 47 | ||
| Movement of T Cells Within Secondary Lymphoid Organs | 49 | ||
| Exit of T Cells From Lymph Nodes | 51 | ||
| Recirculation of T Cells Through Other Lymphoid Tissues | 52 | ||
| Migration of Effector T Lymphocytes to Sites of Infection | 52 | ||
| Memory T Cell Migration | 53 | ||
| Migration of B Lymphocytes | 53 | ||
| Summary | 55 | ||
| Selected Readings | 55 | ||
| Adhesion Molecules | 55 | ||
| Chemokines | 56 | ||
| Lymphocyte Migration Through Lymphoid Tissues | 56 | ||
| 4 Innate Immunity | 57 | ||
| Overview of Innate Immunity | 57 | ||
| Functions and Reactions of Innate Immune Responses | 57 | ||
| Comparative Features of Innate and Adaptive Immunity | 58 | ||
| Evolution of Innate Immunity | 58 | ||
| Recognition of Microbes and Damaged Self by the Innate Immune System | 59 | ||
| Cell-Associated Pattern Recognition Receptors and Sensors of Innate Immunity | 62 | ||
| Toll-Like Receptors | 63 | ||
| Cytosolic Receptors for Pathogen-Associated Molecular Patterns and Damage-Associated Molecular Patterns | 66 | ||
| NOD-Like Receptors: NOD1 and NOD2 | 66 | ||
| Cytosolic DNA Sensors and the STING Pathway | 66 | ||
| RIG-Like Receptors | 68 | ||
| Inflammasomes | 68 | ||
| Other Cell-Associated Pattern Recognition Receptors | 71 | ||
| C-Type Lectin Receptors for Microbial Carbohydrates | 71 | ||
| Scavenger Receptors | 72 | ||
| Formyl-Peptide Receptors | 72 | ||
| Cellular Components of the Innate Immune System | 72 | ||
| Epithelial Barriers | 72 | ||
| Phagocytes | 73 | ||
| Dendritic Cells | 74 | ||
| Cytokine-Producing Innate Lymphoid Cells | 74 | ||
| Natural Killer Cells | 75 | ||
| Functions of Natural Killer Cells | 75 | ||
| Activating and Inhibitory Receptors of Natural Killer Cells | 76 | ||
| T and B Lymphocytes With Limited Antigen Receptor Diversity | 78 | ||
| Mast Cells | 79 | ||
| Soluble Effector Molecules of Innate Immunity | 79 | ||
| The Complement System | 79 | ||
| Pentraxins | 80 | ||
| Collectins and Ficolins | 81 | ||
| The Inflammatory Response | 82 | ||
| The Major Proinflammatory Cytokines of Innate Immunity | 82 | ||
| Tumor Necrosis Factor | 83 | ||
| Interleukin-1 | 84 | ||
| Interleukin-6 | 85 | ||
| Other Cytokines Produced During Innate Immune Responses | 85 | ||
| Recruitment of Leukocytes to Sites of Infection | 86 | ||
| Ingestion and Killing of Microbes by Activated Phagocytes | 87 | ||
| Other Functions of Activated Macrophages | 88 | ||
| Systemic and Pathologic Consequences of Inflammation | 88 | ||
| The Antiviral Response | 90 | ||
| Stimulation of Adaptive Immunity | 92 | ||
| Mechanisms That Limit Innate Immune Responses | 93 | ||
| Summary | 93 | ||
| Suggested Readings | 95 | ||
| Pattern Recognition Receptors | 95 | ||
| Cells of the Innate Immune System | 95 | ||
| Effector Molecules and Inflammatory Responses of Innate Immunity | 95 | ||
| Diseases Caused by Innate Immunity | 95 | ||
| 5 Antibodies and Antigens | 97 | ||
| Antibody Structure | 98 | ||
| General Features of Antibody Structure | 98 | ||
| Structural Features of Antibody Variable Regions | 101 | ||
| Structural Features of Antibody Constant Regions | 103 | ||
| Monoclonal Antibodies | 106 | ||
| Synthesis, Assembly, and Expression of Immunoglobulin Molecules | 107 | ||
| Half-Life of Antibodies | 109 | ||
| Antibody Binding of Antigens | 110 | ||
| Features of Biologic Antigens | 110 | ||
| Structural and Chemical Basis of Antigen Binding | 111 | ||
| Structure-Function Relationships in Antibody Molecules | 113 | ||
| Features Related to Antigen Recognition | 113 | ||
| Specificity | 113 | ||
| Diversity | 113 | ||
| Affinity Maturation | 113 | ||
| Features Related to Effector Functions | 114 | ||
| Summary | 115 | ||
| Suggested Readings | 116 | ||
| Structure and Function of Antibodies | 116 | ||
| Therapeutic Applications of Antibodies | 116 | ||
| 6 Antigen Presentation to T Lymphocytes and the Functions of Major Histocompatibility Complex Molecules | 117 | ||
| Properties of Antigens Recognized by T Lymphocytes | 118 | ||
| Antigen Capture and the Functions of Antigen-Presenting Cells | 119 | ||
| General Properties of Antigen-Presenting Cells | 119 | ||
| Role of Dendritic Cells in Antigen Capture and Display | 121 | ||
| Functions of Other Antigen-Presenting Cells | 123 | ||
| The Major Histocompatibility Complex | 123 | ||
| Discovery of the Major Histocompatibility Complex | 123 | ||
| The Mouse Major Histocompatibility Complex (H-2 Complex) | 123 | ||
| The Human Major Histocompatibility Complex (Human Leukocyte Antigen Locus) | 124 | ||
| Immune Response Genes | 124 | ||
| The Phenomenon of MHC Restriction | 124 | ||
| MHC Genes | 124 | ||
| Human and Mouse MHC Gene Loci | 125 | ||
| Expression of MHC Molecules | 127 | ||
| Structure of MHC Molecules | 128 | ||
| General Properties of MHC Molecules | 128 | ||
| Class I MHC Molecules | 129 | ||
| Class II MHC Molecules | 130 | ||
| Binding of Peptides to MHC Molecules | 131 | ||
| Characteristics of Peptide-MHC Molecule Interactions | 131 | ||
| Structural Basis of Peptide Binding to MHC Molecules | 132 | ||
| Processing of Protein Antigens | 133 | ||
| The Class I MHC Pathway for Processing and Presentation of Cytosolic Proteins | 134 | ||
| Sources of Protein Antigens Degraded in Proteasomes | 134 | ||
| Digestion of Proteins in Proteasomes | 135 | ||
| Transport of Peptides From the Cytosol to the Endoplasmic Reticulum | 136 | ||
| Assembly of Peptide–Class I MHC Complexes in the Endoplasmic Reticulum | 136 | ||
| Surface Expression of Peptide–Class I MHC Complexes | 136 | ||
| The Class II MHC Pathway for Presentation of Proteins Degraded in Lysosomes | 136 | ||
| Targeting of Protein Antigens to Lysosomes | 136 | ||
| Proteolytic Digestion of Antigens in Lysosomes | 137 | ||
| Biosynthesis and Transport of Class II MHC Molecules to Endosomes | 138 | ||
| Association of Processed Peptides With Class II MHC Molecules in Vesicles | 138 | ||
| Expression of Peptide–Class II MHC Complexes on the Cell Surface | 139 | ||
| Cross-Presentation | 139 | ||
| Physiologic Significance of MHC-Associated Antigen Presentation | 139 | ||
| Nature of T Cell Responses | 140 | ||
| Immunogenicity of Protein Antigens | 140 | ||
| Presentation of Nonprotein Antigens to T Cells | 141 | ||
| Summary | 142 | ||
| Suggested Readings | 143 | ||
| The Role of Dendritic Cells in Antigen Capture and Presentation | 143 | ||
| Structure of Major Histocompatibility Complex Genes, Major Histocompatibility Complex Molecules, and Peptide-Major Histocompatibility Complex Complexes | 143 | ||
| Protein Antigen Processing and Major Histocompatibility Complex-Associated Presentation of Peptide Antigens | 143 | ||
| Cross-Presentation | 143 | ||
| “Nonclassical” Antigen Presentation | 144 | ||
| 7 Immune Receptors and Signal Transduction | 145 | ||
| Overview of Signal Transduction | 146 | ||
| Modular Signaling Proteins and Adaptors | 148 | ||
| Prion-Like Polymerization and Signaling | 149 | ||
| The Immune Receptor Family | 149 | ||
| General Features of Antigen Receptor Signaling | 150 | ||
| The T Cell Receptor Complex and T Cell Signaling | 151 | ||
| The Structure of the T Cell Receptor for Antigen | 151 | ||
| Signal Initiation by the T Cell Receptor | 153 | ||
| The Role of the CD4 and CD8 Coreceptors in T Cell Activation | 154 | ||
| Activation of Tyrosine Kinases and a Lipid Kinase During T Cell Activation | 156 | ||
| Recruitment and Modification of Adaptor Proteins | 156 | ||
| Formation of the Immune Synapse | 158 | ||
| Mitogen-Activated Protein Kinase Signaling Pathways in T Lymphocytes | 158 | ||
| Calcium- and Protein Kinase C-Mediated Signaling Pathways in T Lymphocytes | 161 | ||
| Activation of Transcription Factors That Regulate T Cell Gene Expression | 161 | ||
| Modulation of T Cell Signaling by Protein Tyrosine Phosphatases | 164 | ||
| Costimulatory Receptor Signaling in T Cells | 164 | ||
| The CD28 Family of Costimulatory Receptors | 164 | ||
| The CD2/Signaling Lymphocytic Activation Molecule Family of Costimulatory Receptors | 165 | ||
| Metabolic Changes During T Cell Activation | 165 | ||
| The B Lymphocyte Antigen Receptor Complex | 165 | ||
| Structure of the B Cell Receptor for Antigen | 165 | ||
| Signal Initiation by the B Cell Receptor | 165 | ||
| Role of the CR2/CD21 Complement Receptor as a Coreceptor for B Cells | 166 | ||
| Signaling Pathways Downstream of the B Cell Receptor | 168 | ||
| The Attenuation of Immune Receptor Signaling | 169 | ||
| Inhibitory Receptors of Natural Killer Cells, B Cells, and T Cells | 169 | ||
| Ubiquitin-Dependent Degradation of Signaling Proteins | 170 | ||
| Cytokine Receptors and Signaling | 170 | ||
| Classes of Cytokine Receptors | 170 | ||
| Type I Cytokine Receptors (Hematopoietin Receptor Family) | 170 | ||
| Type II Cytokine Receptors (Interferon Receptor Family) | 171 | ||
| TNF Receptor Family | 171 | ||
| IL-1 Family | 172 | ||
| IL-17 Family | 173 | ||
| Signaling by Janus Kinases and Signal Transducers and Activators of Transcription | 173 | ||
| Pathways of NF-κB Activation | 175 | ||
| Summary | 177 | ||
| Suggested Readings | 178 | ||
| Signaling by Immune Receptors | 178 | ||
| T Cell Receptor Structure and Signaling | 178 | ||
| B Cell Receptor Structure and Signaling | 178 | ||
| Signal Attenuation in Lymphocytes | 178 | ||
| Cytokine Receptors | 178 | ||
| 8 Lymphocyte Development and Antigen Receptor Gene Rearrangement | 179 | ||
| Overview of Lymphocyte Development | 179 | ||
| Commitment to the B and T Cell Lineages and Proliferation of Progenitors | 180 | ||
| Role of Epigenetic Changes and MicroRNAs in Lymphocyte Development | 181 | ||
| Antigen Receptor Gene Rearrangement and Expression | 182 | ||
| Selection Processes That Shape the B and T Lymphocyte Repertoires | 182 | ||
| Rearrangement of Antigen Receptor Genes in B and T Lymphocytes | 183 | ||
| Germline Organization of Immunoglobulin and T Cell Receptor Genes | 184 | ||
| Organization of Immunoglobulin Gene Loci | 184 | ||
| Organization of T Cell Receptor Gene Loci | 186 | ||
| V(D)J Recombination | 186 | ||
| Recognition Signals That Drive V(D)J Recombination | 187 | ||
| Mechanism of V(D)J Recombination | 189 | ||
| Generation of Diversity in B and T Cells | 191 | ||
| B Lymphocyte Development | 192 | ||
| Stages of B Lymphocyte Development | 193 | ||
| The Pro-B and Pre-B Stages of B Cell Development | 193 | ||
| The Pre-B Cell Receptor | 195 | ||
| Immature B Cells | 196 | ||
| Subsets of Mature B Cells | 197 | ||
| Follicular B Cells | 197 | ||
| B-1 and Marginal Zone B Cells | 198 | ||
| Selection of the Mature B Cell Repertoire | 198 | ||
| T Lymphocyte Development | 199 | ||
| Role of the Thymus in T Cell Maturation | 200 | ||
| Stages of T Cell Maturation | 200 | ||
| Double-Negative Thymocytes | 200 | ||
| Pre-T Cell Receptor | 201 | ||
| Double-Positive Thymocytes | 203 | ||
| Selection Processes in the Maturation of MHC-Restricted αβ T Cells | 203 | ||
| Positive Selection of Thymocytes: Development of the Self MHC–Restricted T Cell Repertoire | 204 | ||
| Negative Selection of Thymocytes: Central Tolerance | 204 | ||
| γδ T Lymphocytes | 205 | ||
| Summary | 205 | ||
| Suggested Readings | 206 | ||
| Early B Cell Development and V(D)J Recombination | 206 | ||
| T Cell Development | 207 | ||
| MicroRNAs and Lymphocyte Development | 207 | ||
| 9 Activation of T Lymphocytes | 209 | ||
| Overview of T Lymphocyte Activation | 209 | ||
| Signals for T Lymphocyte Activation | 211 | ||
| Recognition of Antigen | 211 | ||
| Role of Costimulation in T Cell Activation | 212 | ||
| The B7:CD28 Family of Costimulators | 212 | ||
| Other Costimulatory Pathways | 215 | ||
| Therapeutic Costimulatory Blockade | 215 | ||
| Functional Responses of T Lymphocytes | 216 | ||
| Changes in Surface Molecules During T Cell Activation | 216 | ||
| Cytokines in Adaptive Immune Responses | 217 | ||
| IL-2 Secretion and IL-2 Receptor Expression | 217 | ||
| Functions of IL-2 | 218 | ||
| Clonal Expansion of T Cells | 220 | ||
| Differentiation of Activated T Cells Into Effector Cells | 220 | ||
| Development and Properties of Memory T Cells | 220 | ||
| Properties of Memory T Cells | 221 | ||
| Decline of T Cell Responses | 222 | ||
| Summary | 222 | ||
| Selected Readings | 223 | ||
| T Cell Activation | 223 | ||
| Costimulation: B7, CD28, and More | 223 | ||
| T Cell Cytokines | 223 | ||
| Memory T Cells | 223 | ||
| 10 Differentiation and Functions of CD4+ Effector T Cells | 225 | ||
| Overview of CD4+ T Cell-Mediated Immune Responses | 225 | ||
| Subsets of CD4+ Effector T Cells | 228 | ||
| Properties of Th1, Th2, and Th17 Subsets | 228 | ||
| Development of Th1, Th2, and Th17 Subsets | 230 | ||
| The Th1 Subset | 231 | ||
| Development of Th1 Cells | 231 | ||
| Functions of Th1 Cells | 232 | ||
| Interferon-γ | 232 | ||
| Other Th1 Cytokines | 232 | ||
| Th1-Mediated Classical Macrophage Activation and Killing of Phagocytosed Microbes | 233 | ||
| The Th2 Subset | 234 | ||
| Development of Th2 Cells | 234 | ||
| Functions of Th2 Cells | 235 | ||
| Interleukin-4 | 235 | ||
| Interleukin-13 | 236 | ||
| Interleukin-5 | 236 | ||
| Roles of Th2 Cells in Host Defense | 236 | ||
| The Th17 Subset | 237 | ||
| Development of Th17 Cells | 237 | ||
| Functions of Th17 Cells | 238 | ||
| Interleukin-17 | 238 | ||
| Other Th17 Cytokines | 239 | ||
| Roles of Th17 Cells in Host Defense | 239 | ||
| Functions of Other T Cell Subsets | 240 | ||
| γδ T Cells | 240 | ||
| Natural Killer T Cells | 240 | ||
| Mucosa-Associated Invariant T (MAIT) Cells | 241 | ||
| Summary | 241 | ||
| Suggested Readings | 241 | ||
| Differentiation of CD4+ T Cells into Subsets of Effector Cells: Th1, Th2, and Th17 | 241 | ||
| Activation of Macrophages | 242 | ||
| Other T Cell Populations | 242 | ||
| 11 Differentiation and Functions of CD8+ Effector T Cells | 243 | ||
| Differentiation of CD8+ T Cells Into Cytotoxic T Lymphocytes | 243 | ||
| Nature of Antigen and Antigen-Presenting Cells for Activation of CD8+ T Lymphocytes | 244 | ||
| Role of Helper T Cells | 245 | ||
| Role of Cytokines | 245 | ||
| Inhibition of CD8+ T Cell Responses: T Cell Exhaustion | 246 | ||
| Effector Functions of CD8+ Cytotoxic T Lymphocytes | 246 | ||
| Mechanisms of CTL-Mediated Cytotoxicity | 246 | ||
| Recognition of Antigen and Activation of CTLs | 247 | ||
| Killing of Target Cells by CTLs | 247 | ||
| Cytokine Production by CD8+ Effector T Cells | 249 | ||
| Roles of CD8+ CTLs in Host Defense | 249 | ||
| Summary | 250 | ||
| Selected Readings | 250 | ||
| Activation of CD8+ T Lymphocytes | 250 | ||
| Mechanisms of CTL-Mediated Cytotoxicity | 250 | ||
| 12 B Cell Activation and Antibody Production | 251 | ||
| Overview of Humoral Immune Responses | 251 | ||
| Antigen Recognition and Antigen-Induced B Cell Activation | 254 | ||
| Antigen Capture and Delivery to B Cells | 254 | ||
| Activation of B Cells by Antigens and Other Signals | 255 | ||
| Helper T Cell-Dependent Antibody Responses to Protein Antigens | 256 | ||
| The Sequence of Events During T Cell-Dependent Antibody Responses | 256 | ||
| Initial Activation and Migration of Helper B Cells and T Cells | 256 | ||
| Antigen Presentation by B Cells and the Hapten-Carrier Effect | 257 | ||
| Role of CD40L:CD40 Interaction in T-Dependent B Cell Activation | 259 | ||
| Extrafollicular B Cell Activation | 260 | ||
| The Germinal Center Reaction | 260 | ||
| The Induction and Functions of Follicular Helper T Cells | 261 | ||
| Heavy Chain Isotype (Class) Switching | 263 | ||
| Affinity Maturation: Somatic Mutation of Ig Genes and Selection of High-Affinity B Cells | 266 | ||
| B Cell Differentiation Into Antibody-Secreting Plasma Cells | 269 | ||
| Generation of Memory B Cells | 270 | ||
| Role of Transcriptional Regulators in Determining the Fate of Activated B Cells | 270 | ||
| Antibody Responses to T-Independent Antigens | 271 | ||
| Subsets of B Cells That Respond to T-Independent Antigens | 271 | ||
| Mechanisms of T-Independent Antibody Responses | 271 | ||
| Protection Mediated by T-Independent Antibodies | 272 | ||
| Antibody Feedback: Regulation of Humoral Immune Responses by Fc Receptors | 272 | ||
| Summary | 273 | ||
| Selected Readings | 274 | ||
| B Cell Subsets and B Cell Activation | 274 | ||
| T Follicular Helper Cells and the Germinal Center Reaction | 274 | ||
| Activation-Induced Deaminase, Class Switching, and Somatic Mutation | 274 | ||
| 13 Effector Mechanisms of Humoral Immunity | 275 | ||
| Overview of Humoral Immunity | 275 | ||
| Neutralization of Microbes and Microbial Toxins | 277 | ||
| Antibody-Mediated Opsonization and Phagocytosis | 277 | ||
| Leukocyte Fc Receptors | 278 | ||
| Role of Fcγ Receptors in Phagocytosis and Activation of Phagocytes | 280 | ||
| Inhibitory Signaling by the FcγRIIB Receptor | 281 | ||
| Antibody-Dependent Cell-Mediated Cytotoxicity | 281 | ||
| Antibody-Mediated Clearance of Helminths | 281 | ||
| The Complement System | 281 | ||
| Pathways of Complement Activation | 282 | ||
| The Alternative Pathway | 282 | ||
| The Classical Pathway | 285 | ||
| The Lectin Pathway | 287 | ||
| Late Steps of Complement Activation | 288 | ||
| Receptors for Complement Proteins | 288 | ||
| Regulation of Complement Activation | 290 | ||
| Functions of Complement | 293 | ||
| Opsonization and Phagocytosis | 293 | ||
| Stimulation of Inflammatory Responses | 294 | ||
| Complement-Mediated Cytolysis | 294 | ||
| Other Functions of the Complement System | 295 | ||
| Complement Deficiencies | 296 | ||
| Pathologic Effects of the Complement System | 296 | ||
| Evasion of Complement by Microbes | 297 | ||
| Neonatal Immunity | 297 | ||
| Summary | 298 | ||
| Selected Readings | 298 | ||
| Complement | 298 | ||
| Antibody Effector Functions and Fc Receptors | 298 | ||
| 14 Specialized Immunity at Epithelial Barriers and in Immune Privileged Tissues | 299 | ||
| General Features of Immunity at Epithelial Barriers | 299 | ||
| Immunity in the Gastrointestinal System | 301 | ||
| Innate Immunity in the Gastrointestinal Tract | 301 | ||
| Adaptive Immunity in the Gastrointestinal Tract | 304 | ||
| The Functional Anatomy of the Adaptive Immune System in the Gastrointestinal Tract | 304 | ||
| Humoral Immunity in the Gastrointestinal Tract | 306 | ||
| T Cell–Mediated Immunity in the Gastrointestinal Tract | 310 | ||
| Regulation of Immunity in the Gastrointestinal Tract by Regulatory T Cells and Cytokines | 312 | ||
| Oral Tolerance and Oral Vaccines | 312 | ||
| The Role of the Commensal Microbiome in Immune Regulation | 313 | ||
| Diseases Related to Immune Responses in the Gut | 313 | ||
| Inflammatory Bowel Disease | 313 | ||
| Celiac Disease | 314 | ||
| Other Diseases | 314 | ||
| Immunity in Other Mucosal Tissues | 315 | ||
| Immunity in the Respiratory System | 315 | ||
| Innate Immunity in the Respiratory System | 315 | ||
| Adaptive Immunity in the Respiratory System | 316 | ||
| Immunity in the Genitourinary System | 316 | ||
| The Cutaneous Immune System | 316 | ||
| Innate and Adaptive Immune Responses in the Skin | 316 | ||
| Diseases Related to Immune Responses in the Skin | 318 | ||
| Immune-Privileged Tissues | 320 | ||
| Immune Privilege in the Eye, Brain, and Testis | 320 | ||
| The Eye | 320 | ||
| The Brain | 320 | ||
| The Testis | 321 | ||
| Immune Privilege of the Mammalian Fetus | 321 | ||
| Summary | 322 | ||
| Selected Readings | 323 | ||
| Mucosal Immunity, General | 323 | ||
| Gastrointestinal Immune System | 323 | ||
| Antibody Production in the Gastrointestinal Immune System | 323 | ||
| Diseases of the Gastrointestinal Immune System | 324 | ||
| Respiratory Mucosal Immune System | 324 | ||
| Skin Immune System | 324 | ||
| Other Specialized Immune Systems | 324 | ||
| 15 Immunologic Tolerance and Autoimmunity | 325 | ||
| Overview of Immunologic Tolerance | 325 | ||
| T Lymphocyte Tolerance | 327 | ||
| Central T Cell Tolerance | 327 | ||
| Peripheral T Cell Tolerance | 328 | ||
| Anergy (Functional Unresponsiveness) | 329 | ||
| Regulation of T Cell Responses by Inhibitory Receptors | 330 | ||
| Suppression by Regulatory T Cells | 332 | ||
| Phenotypic Markers and Heterogeneity of Regulatory T Cells | 334 | ||
| Generation and Maintenance of Regulatory T Cells | 334 | ||
| Mechanisms of Action of Regulatory T Cells | 335 | ||
| Inhibitory Cytokines Produced by Regulatory T Cells | 335 | ||
| Roles of Regulatory T Cells in Self-Tolerance and Autoimmunity | 336 | ||
| Deletion of T Cells by Apoptotic Cell Death | 336 | ||
| Factors That Determine the Tolerogenicity of Self Antigens | 338 | ||
| B Lymphocyte Tolerance | 338 | ||
| Central B Cell Tolerance | 339 | ||
| Peripheral B Cell Tolerance | 339 | ||
| Tolerance to Commensal Microbes and Other Foreign Antigens | 340 | ||
| Mechanisms of Autoimmunity | 340 | ||
| General Features of Autoimmune Disorders | 341 | ||
| Immunologic Abnormalities Leading to Autoimmunity | 342 | ||
| Genetic Basis of Autoimmunity | 342 | ||
| Association of MHC Alleles With Autoimmunity | 343 | ||
| Polymorphisms in Non-HLA Genes Associated With Autoimmunity | 344 | ||
| Inherited Single-Gene (Mendelian) Abnormalities That Cause Autoimmunity | 346 | ||
| Role of Infections in Autoimmunity | 346 | ||
| Other Factors in Autoimmunity | 348 | ||
| Summary | 348 | ||
| Selected Readings | 348 | ||
| Immunologic Tolerance, General Mechanisms | 348 | ||
| Central Tolerance | 349 | ||
| Anergy; Inhibitory Receptors | 349 | ||
| Apoptosis | 349 | ||
| Regulatory T Cells | 349 | ||
| Mechanisms of Autoimmunity: General Concepts | 349 | ||
| Mechanisms of Autoimmunity: Genetics | 349 | ||
| Mechanisms of Autoimmunity: Environmental Factors | 350 | ||
| 16 Immunity to Microbes | 351 | ||
| Overview of Immune Responses to Microbes | 351 | ||
| Immunity to Extracellular Bacteria | 354 | ||
| Innate Immunity to Extracellular Bacteria | 354 | ||
| Adaptive Immunity to Extracellular Bacteria | 355 | ||
| Injurious Effects of Immune Responses to Extracellular Bacteria | 356 | ||
| Immune Evasion by Extracellular Bacteria | 356 | ||
| Immunity to Intracellular Bacteria | 357 | ||
| Innate Immunity to Intracellular Bacteria | 357 | ||
| Adaptive Immunity to Intracellular Bacteria | 358 | ||
| Immune Evasion by Intracellular Bacteria | 360 | ||
| Immunity to Fungi | 360 | ||
| Innate and Adaptive Immunity to Fungi | 361 | ||
| Immunity to Viruses | 362 | ||
| Innate Immunity to Viruses | 362 | ||
| Adaptive Immunity to Viruses | 363 | ||
| Immune Evasion by Viruses | 364 | ||
| Immunity to Parasites | 366 | ||
| Innate Immunity to Parasites | 366 | ||
| Adaptive Immunity to Parasites | 366 | ||
| Immune Evasion by Parasites | 368 | ||
| Strategies for Vaccine Development | 368 | ||
| Attenuated and Inactivated Bacterial and Viral Vaccines | 369 | ||
| Purified Antigen (Subunit) Vaccines | 369 | ||
| Synthetic Antigen Vaccines | 370 | ||
| Live Viral Vaccines Involving Recombinant Viruses | 370 | ||
| DNA Vaccines | 370 | ||
| Adjuvants and Immunomodulators | 370 | ||
| Passive Immunization | 370 | ||
| Summary | 371 | ||
| Selected Readings | 371 | ||
| General Principles | 371 | ||
| Immunity to Extracellular and Intracellular Bacteria | 371 | ||
| Immunity to Viruses | 372 | ||
| Immunity to Fungi | 372 | ||
| Immunity to Parasites | 372 | ||
| Vaccines and Adjuvants | 372 | ||
| 17 Transplantation Immunology | 373 | ||
| General Principles of Transplantation Immunology | 373 | ||
| Adaptive Immune Responses to Allografts | 374 | ||
| The Nature of Alloantigens | 374 | ||
| Recognition of Alloantigens by T Cells | 377 | ||
| Direct Recognition of MHC Alloantigens on Donor Cells | 378 | ||
| Indirect Recognition of Alloantigens | 379 | ||
| Activation and Effector Functions of Alloreactive T Lymphocytes | 379 | ||
| Activation of Alloreactive T Lymphocytes | 379 | ||
| Role of Costimulation in T Cell Responses to Alloantigens | 380 | ||
| Effector Functions of Alloreactive T Cells | 381 | ||
| Activation of Alloreactive B Cells and Production and Functions of Alloantibodies | 381 | ||
| Patterns and Mechanisms of Allograft Rejection | 381 | ||
| Hyperacute Rejection | 381 | ||
| Acute Rejection | 382 | ||
| Acute Cellular Rejection | 382 | ||
| Acute Antibody-Mediated Rejection | 383 | ||
| Chronic Rejection and Graft Vasculopathy | 384 | ||
| Prevention and Treatment of Allograft Rejection | 384 | ||
| Methods to Reduce the Immunogenicity of Allografts | 385 | ||
| Immunosuppression to Prevent or to Treat Allograft Rejection | 387 | ||
| Inhibitors of T Cell Signaling Pathways | 387 | ||
| Antimetabolites | 388 | ||
| Function-Blocking or Depleting Anti-Lymphocyte Antibodies | 388 | ||
| Costimulatory Blockade | 389 | ||
| Drugs Targeting Alloantibodies and Alloreactive B Cells | 389 | ||
| Antiinflammatory Drugs | 389 | ||
| Methods to Induce Donor-Specific Tolerance | 390 | ||
| Xenogeneic Transplantation | 391 | ||
| Blood Transfusion and the ABO and Rh Blood Group Antigens | 391 | ||
| ABO Blood Group Antigens | 391 | ||
| Other Blood Group Antigens | 393 | ||
| Lewis Antigen | 393 | ||
| Rhesus (Rh) Antigen | 393 | ||
| Hematopoietic Stem Cell (HSC) Transplantation | 393 | ||
| Indications, Methods, and Immune Barriers in Hematopoietic Stem Cell Transplantation | 393 | ||
| Immunologic Complication of Hematopoietic Stem Cell Transplantation | 394 | ||
| Graft-Versus-Host Disease | 394 | ||
| Immunodeficiency After Hematopoietic Stem Cell Transplantation | 395 | ||
| Summary | 395 | ||
| Selected Readings | 396 | ||
| Recognition and Rejection of Allogeneic Transplants | 396 | ||
| Clinical Transplantation | 396 | ||
| Immunosuppression and Tolerance Induction to Allografts | 396 | ||
| Xenotransplantation | 396 | ||
| 18 Immunity to Tumors | 397 | ||
| Overview of Tumor Immunity | 397 | ||
| Tumor Antigens | 399 | ||
| Neoantigens: Antigens Encoded by Mutated Genes | 399 | ||
| Antigens of Oncogenic Viruses | 399 | ||
| Overexpressed Cellular Proteins | 399 | ||
| Other Antigens of Tumors | 401 | ||
| Immune Responses to Tumors | 402 | ||
| T Lymphocytes | 402 | ||
| Antibodies | 404 | ||
| Natural Killer Cells | 404 | ||
| Macrophages | 404 | ||
| The Role of Innate and Adaptive Immunity in Promoting Tumor Growth | 404 | ||
| Evasion of Immune Responses by Tumors | 405 | ||
| Immune Checkpoints: Inhibition of Immune Responses | 406 | ||
| Loss of Tumor Antigen Expression | 407 | ||
| Immunotherapy for Tumors | 407 | ||
| Checkpoint Blockade: Blocking T Cell Inhibitory Pathways | 408 | ||
| Vaccination With Tumor Antigens | 409 | ||
| Adoptive Cellular Therapy With Antitumor T Cells | 410 | ||
| Chimeric Antigen Receptor T Cell Therapy | 410 | ||
| Adoptive Cellular Therapy With Tumor-Specific T Cells | 412 | ||
| Passive Immunotherapy With Antibodies | 413 | ||
| Other Approaches for Stimulating Antitumor Immunity | 414 | ||
| Cytokine Therapy | 414 | ||
| Nonspecific Inflammatory Stimuli | 414 | ||
| Graft-Versus-Leukemia Effect | 414 | ||
| Summary | 415 | ||
| Selected Readings | 415 | ||
| Immune Responses to Tumors | 415 | ||
| Tumor Immunotherapy | 415 | ||
| 19 Hypersensitivity Disorders | 417 | ||
| Causes of Hypersensitivity Diseases | 417 | ||
| Mechanisms and Classification of Hypersensitivity Reactions | 418 | ||
| Diseases Caused by Antibodies | 419 | ||
| Diseases Caused by Antibodies Against Fixed Cell and Tissue Antigens | 419 | ||
| Immune Complex–Mediated Diseases | 421 | ||
| Experimental Models of Immune Complex–Mediated Diseases | 423 | ||
| Serum Sickness | 423 | ||
| Arthus Reaction | 423 | ||
| Pathogenesis of Immune Complex–Mediated Diseases | 423 | ||
| Diseases Caused by T Lymphocytes | 424 | ||
| Diseases Caused by Cytokine-Mediated Inflammation | 425 | ||
| Delayed-Type Hypersensitivity (DTH) | 426 | ||
| Diseases Caused by Cytotoxic T Lymphocytes | 427 | ||
| Therapeutic Approaches for Immunologic Diseases | 428 | ||
| Broadly Acting Antiinflammatory Agents | 428 | ||
| Anticytokine Therapies | 428 | ||
| Depletion of Cells and Antibodies | 428 | ||
| Other Biologic Agents | 429 | ||
| Intravenous IgG | 429 | ||
| Tolerance-Inducing Therapies | 429 | ||
| Selected Immunologic Diseases: Pathogenesis and Therapeutic Strategies | 430 | ||
| Systemic Lupus Erythematosus (SLE): The Prototypic Immune Complex–Mediated Disease | 430 | ||
| Pathogenesis of Systemic Lupus Erythematosus | 430 | ||
| New Therapies for Systemic Lupus Erythematosus | 430 | ||
| Rheumatoid Arthritis (RA) | 430 | ||
| Pathogenesis of Rheumatoid Arthritis | 431 | ||
| New Therapies for Rheumatoid Arthritis | 432 | ||
| Multiple Sclerosis (MS) | 432 | ||
| Pathogenesis of Multiple Sclerosis | 432 | ||
| New Therapies for Multiple Sclerosis | 433 | ||
| Type 1 Diabetes | 433 | ||
| Pathogenesis of Type 1 Diabetes | 433 | ||
| New Therapies for Type 1 Diabetes | 434 | ||
| Inflammatory Bowel Disease | 434 | ||
| Summary | 434 | ||
| Selected Readings | 434 | ||
| General | 434 | ||
| Antibody and Immune Complex–Mediated Disorders | 434 | ||
| T Cell–Mediated Disorders | 434 | ||
| Systemic Lupus Erythematosus | 435 | ||
| Rheumatoid Arthritis | 435 | ||
| Multiple Sclerosis | 435 | ||
| Type 1 Diabetes | 435 | ||
| 20 Allergy | 437 | ||
| Overview of IgE-Dependent Allergic Reactions | 438 | ||
| Production of IgE | 439 | ||
| The Nature of Allergens | 439 | ||
| Activation of Type 2 Cytokine–Producing Helper T Cells | 440 | ||
| Activation of B Cells and Switching to IgE | 440 | ||
| Cells Involved in Allergic Reactions | 440 | ||
| Role of Th2 Cells and Innate Lymphoid Cells in Allergic Disease | 440 | ||
| Properties of Mast Cells and Basophils | 440 | ||
| Binding of IgE to Mast Cells and Basophils: the Fcε Receptor | 442 | ||
| Activation of Mast Cells | 443 | ||
| Mediators Derived From Mast Cells | 445 | ||
| Vasoactive Amines | 447 | ||
| Granule Enzymes and Proteoglycans | 447 | ||
| Lipid Mediators | 447 | ||
| Cytokines | 448 | ||
| Properties of Eosinophils | 448 | ||
| IgE- and Mast Cell–Dependent Reactions | 448 | ||
| The Immediate Reaction | 448 | ||
| The Late-Phase Reaction | 449 | ||
| Genetic Susceptibility to Allergic Disease | 450 | ||
| Environmental Factors in Allergy | 451 | ||
| Allergic Diseases in Humans: Pathogenesis and Therapy | 452 | ||
| Systemic Anaphylaxis | 452 | ||
| Bronchial Asthma | 452 | ||
| Immediate Hypersensitivity Reactions in the Upper Respiratory Tract, Gastrointestinal Tract, and Skin | 453 | ||
| Specific Immunotherapy (Desensitization) for Allergic Diseases | 455 | ||
| The Protective Roles of IgE- and Mast Cell–Mediated Immune Reactions | 455 | ||
| Summary | 456 | ||
| Selected Readings | 456 | ||
| Mast Cells and Eosinophils | 456 | ||
| Type 2 and IgE Responses | 456 | ||
| Allergic Diseases | 457 | ||
| 21 Congenital and Acquired Immunodeficiencies | 459 | ||
| Overview of Immunodeficiency Diseases | 459 | ||
| Primary (Congenital) Immunodeficiencies | 460 | ||
| Defects in Innate Immunity | 460 | ||
| Defective Microbicidal Activity of Phagocytes: Chronic Granulomatous Disease | 461 | ||
| Leukocyte Adhesion Deficiencies | 462 | ||
| Defects in NK Cells and Phagocytes | 462 | ||
| Inherited Defects in TLR Pathways, Nuclear Factor-κB Signaling, and Type I Interferons | 463 | ||
| Defects in the IL-12/IFN-γ Pathway | 463 | ||
| Defects in Splenic Development | 463 | ||
| Severe Combined Immunodeficiencies | 463 | ||
| The DiGeorge Syndrome and Other Forms of SCID Due to Defective Thymic Epithelial Development | 464 | ||
| ADA Deficiency and Other Forms of SCID Caused by Defects in Nucleotide Metabolism | 464 | ||
| X-Linked SCID | 467 | ||
| Autosomal Recessive Mutations in Cytokine Signaling Components | 467 | ||
| Severe Combined Immunodeficiency Caused by Defects in V(D)J Recombination and Pre-TCR Checkpoint Signaling | 467 | ||
| The Bare Lymphocyte Syndrome and Other Defects in T Cell Positive Selection | 468 | ||
| SCID Caused by Defective T Cell Activation | 468 | ||
| Antibody Deficiencies: Defects in B Cell Development and Activation | 468 | ||
| X-Linked Agammaglobulinemia: An X-linked Pre-BCR Signaling Defect | 468 | ||
| Autosomal Recessive Pre-BCR Checkpoint Defects | 469 | ||
| Selective Immunoglobulin Isotype Deficiencies | 469 | ||
| Defects in B Cell Differentiation: Common Variable Immunodeficiency (CVID) | 470 | ||
| Defects in T Cell–Dependent B Cell Activation: Hyper-IgM Syndromes | 471 | ||
| Defects in T Lymphocyte Activation and Function | 471 | ||
| Defects in TCR Signal Transduction | 471 | ||
| Wiskott-Aldrich Syndrome | 472 | ||
| Hyper-IgE Syndromes | 472 | ||
| The X-Linked Lymphoproliferative Syndrome | 473 | ||
| X-Linked Immunodeficiency-Magnesium Defects-EBV Infection-Neoplasia Syndrome | 473 | ||
| Defective CTL and NK Cell Function: The Familial Hemophagocytic Lymphohistiocytosis Syndromes | 473 | ||
| Multisystem Disorders With Immunodeficiency | 473 | ||
| Ataxia-Telangiectasia | 473 | ||
| Therapeutic Approaches for Congenital Immunodeficiencies | 474 | ||
| Secondary (Acquired) Immunodeficiencies | 474 | ||
| Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome | 475 | ||
| Molecular and Biologic Features of HIV | 475 | ||
| HIV Structure and Genes | 475 | ||
| Viral Life Cycle | 477 | ||
| Pathogenesis of HIV Infection and AIDS | 479 | ||
| Mechanisms of Immunodeficiency Caused by HIV | 480 | ||
| HIV Reservoirs and Viral Turnover | 482 | ||
| Clinical Features of HIV Disease | 482 | ||
| Transmission of HIV and Epidemiology of AIDS | 482 | ||
| Clinical Course of HIV Infection | 483 | ||
| Immune Responses to HIV | 484 | ||
| Innate Immunity to HIV and Host Restriction Factors | 484 | ||
| Adaptive Immune Responses to HIV | 484 | ||
| Mechanisms of Immune Evasion by HIV | 485 | ||
| Elite Controllers and Long-Term Nonprogressors: A Possible Role for Host Genes | 485 | ||
| Treatment and Prevention of AIDS and Vaccine Development | 485 | ||
| Summary | 486 | ||
| Selected Readings | 487 | ||
| Congenital (Primary) Immunodeficiencies | 487 | ||
| HIV and AIDS | 487 | ||
| Glossary | 489 | ||
| Appendices | 519 | ||
| Appendix I Cytokines | 519 | ||
| Appendix II Principal Features of Selected CD Molecules | 523 | ||
| Appendix III Laboratory Techniques Commonly Used in Immunology | 531 | ||
| Laboratory Methods Using Antibodies | 531 | ||
| Quantitation of Antigen by Immunoassays | 531 | ||
| Identification and Purification of Proteins | 533 | ||
| Immunoprecipitation and Immuno-Affinity Chromatography | 533 | ||
| Western Blotting | 533 | ||
| Labeling and Detection of Antigens in Cells and Tissues | 534 | ||
| Flow Cytometry | 534 | ||
| Cytokine Bead Assays | 537 | ||
| Purification of Cells | 537 | ||
| Immunofluorescence and Immunohistochemistry | 537 | ||
| Measurement of Antigen-Antibody Interactions | 538 | ||
| Transgenic Mice and Gene Targeting | 538 | ||
| Methods for Studying T Lymphocyte Responses | 542 | ||
| Polyclonal Activation of T Cells | 542 | ||
| Antigen-Induced Activation of Polyclonal T Cell Populations | 542 | ||
| Antigen-Induced Activation of T Cell Populations With a Single Antigen Specificity | 542 | ||
| Methods to Enumerate and Study Functional Responses of T Cells | 543 | ||
| Methods for Studying B Lymphocyte Responses | 544 | ||
| Activation of Polyclonal B Cell Populations | 544 | ||
| Antigen-Induced Activation of B Cell Populations With a Single Antigen Specificity | 544 | ||
| Assays to Measure B Cell Proliferation and Antibody Production | 544 | ||
| Clinical Diagnostic Applications of Immunologic Assays | 544 | ||
| Flow Cytometry to Determine Numbers of Subsets of Circulating Immune Cells | 545 | ||
| Assays for Innate Immunity | 545 | ||
| Assays for Humoral Immunity | 545 | ||
| Assays for Cellular Immunity | 545 | ||
| Index | 547 | ||
| A | 547 | ||
| B | 549 | ||
| C | 550 | ||
| D | 553 | ||
| E | 553 | ||
| F | 553 | ||
| G | 554 | ||
| H | 554 | ||
| I | 555 | ||
| J | 557 | ||
| K | 558 | ||
| L | 558 | ||
| M | 559 | ||
| N | 560 | ||
| O | 560 | ||
| P | 560 | ||
| R | 561 | ||
| S | 562 | ||
| T | 563 | ||
| U | 564 | ||
| V | 564 | ||
| W | 565 | ||
| X | 565 | ||
| Z | 565 | ||
| Inside Back Cover | ibc1 |