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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