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About the Authors xv
Contributors xvi
Preface and Acknowledgments xvii
How to Use Your Textbook xix
About the Companion Website xxiii
1 Overview of the Immune System 1
Introduction 1
Innate and Adaptive Immunity 2
Clonal Selection Theory 3
Active, Passive, and Adoptive Immunization 5
Humoral and Cellular Immunity 6
Cell-Mediated Immunity 7
Generation of Diversity in the Immune Response 8
Benefits of Immunology 8
Damaging Effects of the Immune Response 9
The Future of Immunology 9
The Short Course Begins Here 10
References and Bibliography 10
2 Innate Immunity 11
Introduction 11
Physical and Chemical Barriers of Innate Immunity 11
Pattern Recognition: The Hallmark of Innate Immune Responses 15
Complement 18
Inflammation 20
References and Bibliography 24
Review Questions 24
Answers to Review Questions 25
3 Adaptive Immunity 26
Cells and Organs Involved in Adaptive Immunity 26
The Fate of Antigen after Penetration 31
Interrelationship between Innate and Adaptive Immunity 33
Review Questions 34
Answers to Review Questions 34
4 Immunogens and Antigens 35
Introduction 35
Requirements for Immunogenicity 35
Primary and Secondary Responses 38
Antigenicity and Antigen-Binding Site 38
Epitopes Recognized by B Cells and T Cells 39
Major Classes of Antigens 40
Binding of Antigen with Antigen-Specific Antibodies or T Cells 41
Cross-Reactivity 41
Adjuvants 42
References and Bibliography 44
Review Questions 45
Answers to Review Questions 45
5 Antibody Structure and Function 47
Introduction 47
Isolation and Characterization of Immunoglobulins 48
Structure of Light and Heavy Chains 48
Domains 51
Hinge Region 51
Variable Region 51
Immunoglobulin Variants 53
Structural Features of IgG 55
Structural Features of IgM 59
Biologic Properties of IgM 59
Structural and Biologic Properties of IgA 60
Structural and Biologic Properties of IgD 61
Structural and Biologic Properties of IgE 62
Kinetics of the Antibody Response Following The Immunoglobulin Superfamily 63
References and Bibliography 65
Review Questions 65
Answers to Review Questions 66
6 Antigen–Antibody Interactions, Immune Assays, and Experimental Systems 67
Introduction 67
Antigen–Antibody Interactions 67
Primary Interactions between Antibody and Antigen 68
Secondary Interactions between Antibody and Immunoassays 74
Immunofluorescence 76
Flow Cytometry 76
Immunoabsorption and Immunoadsorption 78
Cellular Assays 78
Cell Culture 79
Experimental Animal Models 81
Transgenic Mice and Gene Targeting 82
Analysis of Gene Expression 83
References and Bibliography 85
Review Questions 86
Answers to Review Questions 86
7 The Genetic Basis of Antibodystructure 88
Introduction 88
A Brief Review of Nonimmunoglobulin Gene Structure and Gene Expression 88
Genetic Events in Synthesis of Ig Chains 90
Class or Isotype Switching 94
Generation of Antibody Diversity 95
Role of Activation-Induced Cytidine Deaminase in Generating Antibody Diversity 96
References and Bibliography 98
Review Questions 98
Answers to Review Questions 99
8 Biology of the B Lymphocyte 100
Introduction 100
Development of B Lymphocytes 100
Sites of Antibody Synthesis 105
B-Cell Membrane Proteins 110
References and Bibliography 115
Review Questions 116
Answers to Review Questions 116
9 How T Cells Recognize Antigen: The Role of the Major Histocompatibility Complex 117
Introduction 117
How the MHC Got Its Name 117
MHC Role in Antigen Presentation 118
Different MHC Molecules Are Expressed by Distinct Variability of MHC Class I and MHC Class II Molecules 119
Structure of MHC Class I and Class II Molecules 120
Antigen Processing and Presentation: How MHC Other Types of Antigen That Activate T-Cell Responses 129
Genes of the HLA Region 130
Nomenclature of Polymorphic MHC Molecules 131
Regulation of Expression of MHC Genes 131
MHC in Other Species 132
Diversity of MHC Molecules: MHC Association with Resistance and Susceptibility to Disease 132
References and Bibliography 135
Review Questions 135
Answers to Review Questions 136
10 Biology of the T Lymphocyte 137
Introduction 137
The Antigen-Specific T-Cell Receptor 137
Genes Coding for T-Cell Receptors 143
Generation of T-Cell Receptor Diversity 144
T-Cell Differentiation in the Thymus 144
References and Bibliography 151
Review Questions 151
Answers to Review Questions 152
11 Activation and Function of T Cells 153
Introduction 153
A Two-Signal Model for the Activation of T Cells 153
Dendritic Cells Are the Key APC for Naïve T Cells 153
Activation of CD4+ T Cells 155
CD4+ T-Cell Function 160
Activation and Function of CD8+ T Cells 168
CD8+ T-Cell Killing of Target Cells 169
Memory T Cells 171
Function of Other Subsets of T Cells 171
References and Bibliography 174
Review Questions 174
Answers to Review Questions 175
12 Cytokines 176
Introduction 176
The History of Cytokines 176
General Properties of Cytokines 177
Functional Categories of Cytokines 179
Cytokine Receptors 185
Cytokine Receptor-Mediated Signal Transduction 186
Role of Cytokines and Cytokine Receptors in Therapeutic Exploitation of Cytokines and Cytokine Receptors 189
References and Bibliography 192
Review Questions 192
Answers to Review Questions 193
13 Tolerance and Autoimmunity 194
Introduction 194
Central Tolerance 195
Peripheral Tolerance 197
Oral Tolerance 200
Immune Privilege 201
Autoimmunity and Disease 201
Autoimmune Diseases 205
References and Bibliography 214
Review Questions 215
Answers to Review Questions 216
14 Complement 217
Introduction 217
Overview of Complement Activation 217
Regulation of Complement Activity 222
Biologic Activities of Complement 224
Complement Deficiencies 228
References and Bibliography 230
Review Questions 231
Answers to Review Questions 231
15 Hypersensitivity: Type I 233
Introduction 233
General Characteristics of Allergic Reactions 234
Sensitization Phase 234
Activation Phase 235
Effector Phase 237
Clinical Aspects of Allergic Reactions 240
Clinical Tests for Allergies and Clinical Intervention 242
Intervention 242
The Protective Role of IgE 244
References and Bibliography 246
Review Questions 246
Answers to Review Questions 247
16 Hypersensitivity: Types II and III 249
Introduction 249
Type II Hypersensitivity 249
Examples of Type II Hypersensitivity Reactions 251
References and Bibliography 257
Review Questions 257
Answers to Review Questions 258
17 Hypersensitivity: Type IV 259
Introduction 259
General Characteristics and Pathophysiology of Examples of DTH 261
Treatment of DTH 264
References and Bibliography 265
Review Questions 266
Answers to Review Questions 266
18 Immunodeficiency Disorders and Neoplasias of the Lymphoid System 268
Introduction 268
Immunodeficiency Syndromes 269
Acquired Immunodeficiency Syndrome 282
Neoplasms of Lymphoid System 287
References and Bibliography 294
Review Questions 295
Answers to Review Questions 296
19 Transplantation 298
Introduction 298
Relationship between Donor and Recipient 298
Immune Mechanisms Are Responsible for Allograft Rejection 300
Categories of Allograft Rejection 300
Role of MHC Molecules in Allograft Rejection 301
Role of T Cell Lineages and Cytokines in Allograft Rejection 302
Laboratory Tests Used in Tissue Typing 303
Prolongation of Allograft Survival: Immunosuppresive Therapy 304
Hematopoietic Stem Cell Transplantation 307
Graft-versus-Host Disease 308
Xenogeneic Transplantation 308
The Fetus: A Tolerated Allograft 309
References and Bibliography 310
Review Questions 310
Answers to Review Questions 311
20 Tumor Immunology 312
Introduction 312
Tumor Antigens 312
Categories of Tumor Antigens 313
Immunologic Factors Influencing the Incidence of Cancer 315
Effector Mechanisms in Tumor Immunity 316
Cell-Mediated Responses to Tumor Cells 318
Cytokines 319
Limitations of the Effectiveness of the Immune Response against Tumors 320
Immunodiagnosis 320
Tumor Immunoprophylaxis 321
Immunotherapy 322
References and Bibliography 326
Review Questions 326
Answers to Review Questions 327
21 Resistance and Immunization to Infectious Diseases 328
Introduction 328
Host Defense against the Various Classes of Microbial Pathogens 330
Mechanisms by Which Pathogens Evade the Immune Response 334
Principles of Immunization 336
Objectives of Immunization 337
Active Immunizations 337
Basic Mechanisms of Protection 339
Vaccine Precautions 341
Recent Approaches to Production of Vaccines 342
Passive Immunization 344
References and Bibliography 348
Review Questions 349
Answers to Review Questions 350
Glossary 351
Appendix: Partial List of CD Antigens 378
Index 381
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