Immunology (eBook)

Richard Coico, SUNY Downstate College of Medicine, Brooklyn, New York Geoffrey Sunshine, Heath Effects Institute, and Tufts University School of Medicine, Boston, Massachusetts

Title Page 5
Copyright Page 6
Contents in Brief 7
Contents 9
About the Authors 17
Contributors 18
Preface and Acknowledgments 19
How to Use Your Textbook 21
About the Companion Website 25
Chapter 1 Overview of the Immune System 27
Introduction 27
Innate and Adaptive Immunity 28
Innate Immunity 28
Adaptive Immunity 28
Clonal Selection Theory 29
Active, Passive, and Adoptive Immunization 31
Major Characteristics of the Adaptive Immune Response 31
Cells Involved in the Adaptive Immune Response 31
Humoral and Cellular Immunity 32
Humoral Immunity 32
Cell-Mediated Immunity 33
Generation of Diversity in the Immune Response 34
Benefits of Immunology 34
Damaging Effects of the Immune Response 35
The Future of Immunology 35
The Short Course Begins Here 36
References and Bibliography 36
Chapter 2 Innate Immunity 37
Introduction 37
Physical and Chemical Barriers of Innate Immunity 37
Origin, Differentiation, and Characterizationof Cells of the Innate Immune System 38
Pattern Recognition: The Hallmark of Innate Immune Responses 41
Pattern Recognition Receptors 41
Complement 44
Intracellular and Extracellular Killing of Microorganisms 45
Inflammation 46
Hallmark Signs of Inflammation 46
Localized Inflammatory Responses 47
Chronic Inflammation 49
Fever 49
References and Bibliography 50
Review Questions 50
Answers to Review Questions 51
Chapter 3 Adaptive Immunity 52
Cells and Organs Involved in Adaptive Immunity 52
The Lymphatic Organs 53
Lymphocyte Migration and Recirculation 55
The Fate of Antigen after Penetration 57
Frequency of Antigen-Specific Naïve Lymphocytes 58
Interrelationship between Innate and Adaptive Immunity 59
Review Questions 60
Answers to Review Questions 60
Chapter 4 Immunogens and Antigens 61
Introduction 61
Requirements for Immunogenicity 61
Foreignness 61
High Molecular Weight 62
Chemical Complexity 62
Degradability 62
Haptens 62
Further Requirements for Immunogenicity 63
Primary and Secondary Responses 64
Antigenicity and Antigen-Binding Site 64
Epitopes Recognized by B Cells and T Cells 65
Major Classes of Antigens 66
Binding of Antigen with Antigen-Specific Antibodies or T Cells 67
Cross-Reactivity 67
Adjuvants 68
References and Bibliography 70
Review Questions 71
Answers to Review Questions 71
Chapter 5 Antibody Structure and Function 73
Introduction 73
Isolation and Characterization of Immunoglobulins 74
Structure of Light and Heavy Chains 74
Domains 77
Hinge Region 77
Variable Region 77
Immunoglobulin Variants 79
Isotypes 79
Allotypes 80
Idiotypes 80
Structural Features of IgG 81
Biologic Properties of IgG 81
Agglutination and Formation of Precipitate 82
Passage through the Placenta and Absorption in Neonates 82
Opsonization 83
Antibody-Dependent Cell-Mediated Cytotoxicity 84
Activation of Complement 84
Neutralization of Toxins 84
Immobilization of Bacteria 84
Neutralization of Viruses 84
Structural Features of IgM 85
Biologic Properties of IgM 85
Complement Fixation 85
Neonatal Immunity and First Line of Humoral Defense 85
Agglutination 86
Isohemagglutinins 86
Structural and Biologic Properties of IgA 86
Biologic Properties of IgA 86
Role in Mucosal Infections 86
Bactericidal Activity 87
Antiviral Activity 87
Structural and Biologic Properties of IgD 87
Structural and Biologic Properties of IgE 88
Importance of IgE in Parasitic Infections and Hypersensitivity Reactions 88
Kinetics of the Antibody Response Following Immunization 88
Primary Response 88
Secondary Response 88
The Immunoglobulin Superfamily 89
References and Bibliography 91
Review Questions 91
Answers to Review Questions 92
Chapter 6 Antigen–Antibody Interactions, Immune Assays, and Experimental Systems 93
Introduction 93
Antigen–Antibody Interactions 93
Primary Interactions Between Antibody and Antigen 94
Association Constant 94
Affinity and Avidity 96
Secondary Interactions between Antibody and Antigen 96
Agglutination Reactions 96
Precipitation Reactions 98
Immunoassays 100
Direct-Binding Immunoassays 100
Solid-Phase Immunoassays 101
Immunofluorescence 102
Direct Immunofluorescence 102
Indirect Immunofluorescence 102
Flow Cytometry 102
Immunoabsorption and Immunoadsorption 104
Cellular Assays 104
Assays of Lymphocyte Function 104
B-Cell and T-Cell Proliferation Assays 104
Antibody Production by B Cells 104
Effector Cell Assays for T Cells and Natural Killer Cells 105
Cell Culture 105
Primary Cell Cultures and Cloned Lymphoid Cell Lines 105
B-Cell Hybridomas and Monoclonal Antibodies 106
T-Cell Hybridomas 106
Genetically Engineered Molecules and Receptors 106
Experimental Animal Models 107
Inbred Strains 107
Adoptive Transfer 108
SCID Mice 108
Thymectomized and Congenitally Athymic (Nude) Mice 108
Transgenic Mice and Gene Targeting 108
Transgenic Mice 108
Knockout and Knock-in Mice 109
Analysis of Gene Expression 109
Microarrays to Assess Gene Expression 109
References and Bibliography 111
Review Questions 112
Answers to Review Questions 112
Chapter 7 The Genetic Basis of Antibody Structure 114
Introduction 114
A Brief Review of Nonimmunoglobulin Gene Structure and Gene Expression 114
Genetic Events in Synthesis of Ig Chains 116
Organization and Rearrangement of Light-Chain Genes 116
?-Chain Synthesis 117
?-Chain Synthesis 118
Organization and Rearrangement of Heavy-Chain Genes 118
Allelic Exclusion and the Regulation of Ig Gene Expression 119
Class or Isotype Switching 120
Generation of Antibody Diversity 121
Presence of Multiple V Genes in the Germline 121
VJ and VDJ Combinatorial Association 121
Random Assortment of H and L Chains 121
Junctional Diversity 121
Somatic Hypermutation 121
Somatic Gene Conversion 122
Role of Activation-Induced Cytidine Deaminase in Generating Antibody Diversity 122
References and Bibliography 124
Review Questions 124
Answers to Review Questions 125
Chapter 8 Biology of the B Lymphocyte 126
Introduction 126
Development of B Lymphocytes 126
Overview 126
Sites of Early B-Cell Differentiation 127
Pro-B and Pre-B Cells: First Ig Rearrangements 127
Immature B Cells 129
Transitional B cells 130
Mature B Cells 130
Plasma Cells 130
Memory B Cells 131
Sites of Antibody Synthesis 131
Interaction of Antigen, B Cells, and Helper T Cells in the Lymph Node 131
Events in the Germinal Center 131
Antibody Synthesis in Mucosal Tissue 133
Thymus-Independent Antibody Responses 135
B-Cell Membrane Proteins 136
Stage-Specific Markers 136
Antigen-Binding Molecules: Membrane Immunoglobulin 137
Signal Transduction Molecules Associated with Membrane Immunoglobulin 137
Molecules Involved in T–B Cell Interactions 137
Homing 138
Intracellular Signaling in B Cells 138
References and Bibliography 141
Review Questions 142
Answers to Review Questions 142
Chapter 9 How T Cells Recognize Antigen: The Role of the Major Histocompatibility Complex 143
Introduction 143
How The MHC Got Its Name 143
MHC Role in Antigen Presentation 144
Different MHC Molecules Are Expressed by Distinct Host Cells and Interact with Different Sets of T Cells 145
MHC Class I 145
MHC Class II 145
Variability of MHC Class I and MHC Class II Molecules 145
Structure of MHC Class I and Class II Molecules 146
MHC Class I 146
Structure of MHC Class II Molecules 148
Antigen Processing and Presentation: How MHC Molecules Bind Peptides and Create Ligands That Interact with T Cells 150
Exogenous Antigens and Generation of MHC Class II–Peptide Complexes 150
Endogenous Antigens: Generation of MHC Class I–Peptide Complexes 152
Cross-Presentation: Exogenous Antigens Presented in the MHC Class I Pathway 153
Which Antigens Trigger Which T-Cell Responses? 154
MHC Molecules Bind Peptides Derived from Self-Molecules 154
Inability to Respond to an Antigen 155
Other Types of Antigen That Activate T-Cell Responses 155
Superantigens 155
Lipids and Glycolipids 155
Multiple Antigens Activate ?? T Cells 156
Genes of the HLA Region 156
Nomenclature of Polymorphic MHC Molecules 157
Regulation of Expression of MHC Genes 157
Codominant Expression 157
Coordinate Regulation 157
Inheritance of MHC Genes 157
MHC in Other Species 158
Diversity of MHC Molecules: MHC Association with Resistance and Susceptibility to Disease 158
References and Bibliography 161
Review Questions 161
Answers to Review Questions 162
Chapter 10 Biology of the T Lymphocyte 163
Introduction 163
The Antigen-Specific T-Cell Receptor 163
Molecules That Interact with Antigen 163
The T-Cell Receptor Complex 165
Co-Receptors 166
Other Important Molecules Expressed on the T-Cell Surface 167
?? T Cells 168
Genes Coding for T-Cell Receptors 169
Generation of T-Cell Receptor Diversity 170
T-Cell Differentiation in the Thymus 170
The Thymus as Primary Organ for T-Cell Differentiation 170
Key Steps in Thymic Differentiation 171
Early T-Cell Receptor Gene Rearrangements: Double-Negative Cells and Splitting Off of ?? T Cells 171
Pre-T Cells 172
Double-Positive Cells 172
Thymic Selection 172
Leaving the Thymus 174
Generation of the T-Cell Repertoire 174
Characteristics of ?? T Cells Emerging from the Thymus 174
Further Differentiation of CD4+ and CD8+ T Cells Outside the Thymus 175
Differentiation of Other Cell Types in the Thymus 175
References and Bibliography 177
Review Questions 177
Answers to Review Questions 178
Chapter 11 Activation and Function of T Cells 179
Introduction 179
A Two-Signal Model for the Activation of T Cells 179
Dendritic Cells Are the Key APC for Naïve T Cells 179
Activation of CD4+ T Cells 181
Paired Interactions at the Surface of the APC and CD4+ T Cell 181
Intracellular Events in CD4+ T-Cell Activation 182
Differentiation to Effector Cells and Migration Out of the Lymph Node 185
Termination of the Response 185
Other Ways to Activate CD4+ T Cells 186
CD4+ T-Cell Function 186
Cytokine Synthesis 187
Major Subsets of Cytokine-Producing CD4+ T Cells 187
Cross-Inhibition of CD4+ T-Cell Subsets 190
Other Sets of Cytokine-Producing CD4+ T Cells 191
Further Points on Cytokine Synthesis 191
Help for B Cell in the Response to TD Antigens 191
Events in the Germinal Center 192
Linked Recognition 193
Activation and Function of CD8+ T Cells 194
Generation of Effector CD8+ T Cells 194
CD8+ T-Cell Killing of Target Cells 195
MHC Restriction and CD8+ T Cell Killer Function 196
Memory T Cells 197
Function of Other Subsets of T Cells 197
NKT Cells 197
?? T Cells 198
Innate Lymphoid Cells 198
References and Bibliography 200
Review Questions 200
Answers to Review Questions 201
Chapter 12 Cytokines 202
Introduction 202
The History of Cytokines 202
Pleiotropic and Redundant Properties of Cytokines 203
General Properties of Cytokines 203
Common Functional Properties 203
Common Systemic Activities 204
Common Cell Sources and Cascading Events 205
Functional Categories of Cytokines 205
Cytokines That Facilitate Innate Immune Responses 205
Cytokines That Regulate Adaptive Immune Responses 207
Cytokines That Induce Differentiation of Distinct T-Cell Lineages 207
Cytokines That Inhibit Lineage-Specific T-Cell Differentiation 208
Cytokines That Promote Inflammatory Responses 209
Cytokines That Affect Leukocyte Movement 209
Cytokines That Stimulate Hematopoiesis 210
Cytokine Receptors 211
Cytokine Receptor Families 211
Common Cytokine Receptor Chains 212
Cytokine Receptor-Mediated Signal Transduction 212
Role of Cytokines and Cytokine Receptors in Disease 214
Toxic Shock Syndrome 214
Bacterial Septic Shock 214
Cancers 215
Autoimmunity and Other Immune-Based Diseases 215
Therapeutic Exploitation of Cytokines and Cytokine Receptors 215
Cytokine Inhibitors/Antagonists 215
Reversing Cellular Deficiencies 216
Treatment of Immunodeficiencies 216
Treatment of Patients with Cancer, Transplanted Organs, and Tissues, and Viral Infections 216
Treatment of Allergies and Asthma 217
References and Bibliography 218
Review Questions 218
Answers to Review Questions 219
Chapter 13 Tolerance and Autoimmunity 220
Introduction 220
Central Tolerance 221
Mechanisms of Central Tolerance: T and B Cells 221
Mechanisms of Central Tolerance: B Cells 222
Peripheral Tolerance 223
Anergy 224
Regulatory T Cells 224
Fas–FasL Interactions 226
Oral Tolerance 226
Immune Privilege 227
Autoimmunity and Disease 227
Genetic Susceptibility 228
Environmental Susceptibility 229
Drug and Hormonal Triggers of Autoimmunity 231
Autoimmune Diseases 231
Autoimmune Diseases in Which Antibodies Play a Predominant Role in Mediating Organ Damage 231
Autoimmune Diseases in Which T Cells Play a Predominant Role in Organ Damage 236
Therapeutic Strategies 238
References and Bibliography 240
Review Questions 241
Answers to Review Questions 242
Chapter 14 Complement 243
Introduction 243
Overview of Complement Activation 243
Classical Pathway 244
Lectin Pathway 245
Alternative Pathway 246
Steps Shared by All Pathways: Activation of C3 and C5 247
Terminal Pathway 248
Regulation of Complement Activity 248
Biologic Activities of Complement 250
Production of Opsonins 250
Production of Anaphylatoxins 251
Lysis 251
Other Important Complement Functions 251
Complement Deficiencies 254
References and Bibliography 256
Review Questions 257
Answers to Review Questions 257
Chapter 15 Hypersensitivity: Type I 259
Introduction 259
Hypersensitivity 259
Coombs–Gell Hypersensitivity Designations 259
General Characteristics of Allergic Reactions 260
Sensitization Phase 260
TH2 Cell Dependency of IgE Antibody Production 260
Activation Phase 261
Effector Phase 263
Preformed Mediators 263
Newly Synthesized Mediators 264
Late-Phase Reaction 264
Clinical Aspects of Allergic Reactions 266
Allergic Rhinitis 266
Food Allergies 267
Atopic Dermatitis 267
Asthma 267
Clinical Tests for Allergies and Clinical Intervention 268
Detection 268
Intervention 268
The Protective Role of IgE 270
References and Bibliography 272
Review Questions 272
Answers to Review Questions 273
Chapter 16 Hypersensitivity: Types II and III 275
Introduction 275
Type II Hypersensitivity 275
Complement-Mediated Reactions 275
Antibody-Dependent Cell-Mediated Cytotoxicity 275
Antibody-Mediated Cellular Dysfunction 276
Examples of Type II Hypersensitivity Reactions 277
Transfusion Reactions 277
Drug-Induced Reactions 277
Rhesus Incompatibility Reactions 277
Reactions Involving Cell Membrane Receptors 278
Reactions Involving Other Cell Membrane Determinants 278
Type III Hypersensitivity 278
Systemic Immune Complex Disease 279
Localized Immune Complex Disease 281
References and Bibliography 283
Review Questions 283
Answers to Review Questions 284
Chapter 17 Hypersensitivity: Type IV 285
Introduction 285
General Characteristics and Pathophysiology of DTH 285
Mechanisms Involved in DTH 286
Examples of DTH 287
Contact Sensitivity 287
Granulomatous Hypersensitivity 288
Tuberculin-Type Hypersensitivity 289
Allograft Rejection 290
Additional Examples of DTH 290
Treatment of DTH 290
References and Bibliography 291
Review Questions 292
Answers to Review Questions 292
Chapter 18 Immunodeficiency Disorders and Neoplasias of the Lymphoid System 294
Introduction 294
Immunodeficiency Syndromes 295
Primary Immunodeficiency Syndromes 296
Immunodeficiency Disorders Associated with T Cells and Cell-Mediated Immunity 300
B-Cell–Associated or Immunoglobulin-Associated Immunodeficiency Disorders 302
Disorders of T–B Interactions 303
Phagocytic Dysfunctions 304
Natural Killer Cell Deficiency 306
Diseases Caused by Abnormalities in the Complement System 306
Secondary Immunodeficiency Diseases 307
Acquired Immunodeficiency Syndrome 308
Initial Description and Epidemiology 308
Human Immunodeficiency Virus 308
Clinical Course 310
Prevention, Control, Diagnosis, and Therapy of HIV Infection 312
Neoplasms of Lymphoid System 313
B-Cell Neoplasms 314
Mature B-Cell Neoplasms 314
Plasma Cell Neoplasms 317
T-Cell Neoplasms 317
Mature T-Cell Neoplasms 318
Immunotherapy 319
References and Bibliography 320
Review Questions 321
Answers to Review Questions 322
Chapter 19 Transplantation 324
Introduction 324
Relationship between Donor and Recipient 324
Immune Mechanisms are Responsible for Allograft Rejection 326
Categories of Allograft Rejection 326
Hyperacute Rejection 326
Acute Rejection 326
Chronic Rejection 327
Role of MHC Molecules in Allograft Rejection 327
Mechanisms of Alloantigen Recognition by T Cells 327
Role of T Cell Lineages and Cytokines in Allograft Rejection 328
Laboratory Tests Used in Tissue Typing 329
Prolongation of Allograft Survival: Immunosuppresive Therapy 330
Anti-Inflammatory Agents 331
Cytotoxic Drugs 331
Agents That Interfere with Cytokine Production and Signaling 332
Immunosuppressive Antibody Therapy 332
New Immunosuppressive Strategies and Frontiers 332
Hematopoietic Stem Cell Transplantation 333
Graft-Versus-Host Disease 334
Xenogeneic Transplantation 334
The Fetus: A Tolerated Allograft 335
References and Bibliography 336
Review Questions 336
Answers to Review Questions 337
Chapter 20 Tumor Immunology 338
Introduction 338
Tumor Antigens 338
Categories of Tumor Antigens 339
Normal Cellular Gene Products 339
Mutant Cellular Gene Products 340
Tumor Antigens Encoded by Oncogenes 341
Immunologic Factors Influencing the Incidence of Cancer 341
Effector Mechanisms in Tumor Immunity 342
B-Cell Responses to Tumors 343
Destruction of Tumor Cells by Opsonization and Phagocytosis 344
Antibody-Mediated Loss of Adhesive Properties of Tumor Cells 344
Cell-Mediated Responses to Tumor Cells 344
Destruction of Tumor Cells by T Lymphocytes 344
Antibody-Dependent Cell-Mediated Cytotoxicity 344
Destruction of Tumor by NK Cells, NK/T Cells, and Cytokine-Activated Killer Cells 344
Destruction of Tumor Cells by Activated Macrophages and Neutrophils 344
Cytokines 345
Limitations of the Effectiveness of The Immune Response Against Tumors 346
Immunodiagnosis 346
Detection of Myeloma Proteins Produced by Plasma Cell Tumors 347
Detection of ?-Fetoprotein 347
Carcinoembryonic Antigen 347
Detection of Prostate-Specific Antigen 347
Cancer Antigen-125 347
Tumor Immunoprophylaxis 347
Immunotherapy 348
Other Immunotherapeutic Strategies in Cancer 349
References And Bibliography 352
Review Questions 352
Answers To Review Questions 353
Chapter 21 Resistance and Immunization to Infectious Diseases 354
Introduction 354
Host Defense Against the Various Classes of Microbial Pathogens 356
Immunity to Viruses 356
Immunity to Bacteria 357
Immunity to Parasites 358
Immunity to Fungi 359
Mechanisms by Which Pathogens Evade the Immune Response 360
Encapsulated Bacteria 360
Toxins 360
Superantigens 361
Antigenic Variation 361
Intracellular Survival 361
Suppression of the Immune System 362
Extracellular Enzymes 362
Expression of Antibody-Binding Proteins 362
Principles of Immunization 362
Objectives of Immunization 363
Active Immunizations 363
Recommended Immunizations 363
Use of Vaccines in Selected Populations 363
Basic Mechanisms of Protection 365
Significance of the Primary and Secondary Responses 365
Age and Timing of Immunizations 365
Vaccine Precautions 367
Site of Administration of Antigen 367
Hazards 367
Recent Approaches to Production of Vaccines 368
Vaccines Produced by Recombinant DNA 368
Conjugated Polysaccharides 368
Synthetic Peptide Vaccines 369
Virus-Carrier Vaccine 369
Bacterium-Carrier Vaccine 369
DNA Vaccines 369
Toxoids 369
Passive Immunization 370
Passive Immunization through Placental Antibody Transfer 370
Passive Immunization via Colostrum 370
Passive Antibody Therapy and Serum Therapy 370
Monoclonal and Polyclonal Preparations 371
Preparation and Properties of Human Immune Serum Globulin 372
Indications for the Use of Immune Globulin 372
Precautions on the Uses of Human Immune Serum Globulin Therapy 373
Colony-Stimulating Factors 373
References and Bibliography 374
Review Questions 375
Answers to Review Questions 376
Glossary 377
Appendix: Partial List of CD Antigens 404
Index 407
EULA 0

Immunology: A Short Course, Seventh Edition introduces all the critical topics of modern immunology in a clear and succinct yet comprehensive fashion. The authors offer uniquely-balanced coverage of classical and contemporary approaches and basic and clinical aspects. The strength of Immunology: A Short Course is in providing a complete review of modern immunology without the burden of excessive data or theoretical discussions. Each chapter is divided into short, self-contained units that address key topics, illustrated by uniformly drawn, full-color illustrations and photographs.

This new edition of Immunology: A Short Course:
* Has been fully revised and updated, with a brand new art program to help reinforce learning
* Includes a new chapter on Innate Immunity to reflect the growth in knowledge in this area
* Highlights important therapeutic successes resulting from targeted antibody therapies
* Includes end of chapter summaries and review questions, a companion website at www.wileyimmunology.com/coico featuring interactive flashcards, USMLE-style interactive MCQs, figures as PowerPoint slides, and case-based material to help understand clinical application. (Journal Investigative Allergol Clinical Immunology, Vol. 26 (1))