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• Inside Front Cover
• Immunology for Medical Students
• Copyright Page
• Preface
• ■ Preface to the Third Edition
• ■ Preface to the Second Edition
• ■ Preface to the First Edition
• Acknowledgments
• How to Use This Book
• Icons
• Microorganisms Mentioned in This Book
• Table Of Contents
• I Introduction
• 1 Introduction to the Immune System
• Can You Now …
• 2 Basic Concepts and Components of the Immune System
• ■ Innate Immunity
• ■ Adaptive Immunity
• ■ Components of the Immune System
• ■ Active and Passive Immunity
• ■ Phases of an Immune Response
• ■ Types of Immune Response
• Can You Now…
• II Antigen Recognition Molecules
• 3 Introduction to Antigen Recognition
• ■ Antigen Recognition Molecules
• ■ B-Cell and T-Cell Receptors
• ■ Major Histocompatibility Complex Molecules
• Can You Now …
• 4 Antigens and Antibody Structure
• ■ Antigens
• Types of Antigens
• Epitopes
• ■ Antibodies
• Antibody Isolation and Characterization
• Antibody Structure
• Selected Features and Biologic Properties of the Immunoglobulin Classes
• Can You Now…
• 5 Antibody-Antigen Interaction
• ■ Antigen-Binding Sites of Antibodies
• Cross-Reactivity
• ■ Diagnostic Tests for Antibody or Antigen
• Enzyme-Linked Immunosorbent Assay
• Lateral Flow Test
• Immunofluorescence
• Flow Cytometry
• Can You Now….
• 6 Antibody Diversity
• ■ Immunoglobulin Genes
• Assembly of Variable Regions by Somatic Recombination
• Gene Organization and Synthesis
• Human Light Chain
• Human Heavy Chain
• Generation of Antibody Diversity
• ■ Immunoglobulin Classes
• Class Switching
• Membrane-Bound and Secreted Immunoglobulin
• Can You Now…
• 7 The T-Cell Receptor
• ■ Structure of the T-Cell Receptor
• The αβ T-Cell Receptor
• The γδ T-Cell Receptor
• ■ Generation of Diversity of the T-Cell Receptor Genes
• ■ Recognition of Antigen
• ■ Other Accessory Molecules Involved in T-Cell Function
• Can You Now…
• 8 Major Histocompatibility Complex
• ■ Genetic Organization
• ■ Regulation of Gene Expression
• ■ Structure of the Major Histocompatibility Complex Gene Products
• Class I
• Class II
• ■ Restriction of Antigen Recognition
• Models of the Major Histocompatibility Complex–Antigen–T-Cell Receptor Complex
• ■ Population Advantages of Polymorphism in the Major Histocompatibility Complex
• ■ Disease Correlations
• Can You Now …
• 9 Review of Antigen Recognition
• ■ Important Structural Features
• Immunoglobulin Domain Fold
• Antigen Recognition Sites
• ■ Generation of Diversity
• III Physiology
• 10 Antigen Processing and Presentation
• ■ Pathways of Antigen Processing
• ■ Mechanisms of Antigen Processing
• Extracellular (Exogenous) Antigens
• Intracellular (Endogenous) Antigens
• Class I or II Association
• ■ Evasion of Processing Pathways by Pathogens
• Can You Now …
• 11 Lymphocyte Activation
• ■ Antigen Receptors
• B-Cell Receptor
• T-Cell Receptor
• Initiation of B-Cell and T-Cell Activation
• Coreceptor Molecules in B-Cell Activation
• Coreceptor Molecules in T-Cell Activation
• ■ Signaling Events
• ■ Amplification Through Signaling Pathways
• ■ Response
• Can You Now …
• 12 Hematopoiesis
• ■ Three Major Stages of Hematopoiesis
• ■ Lymphoid Cells
• Development
• Lymphoid Cell Types
• Cells
• T Cells
• Natural Killer Cells
• ■ Myeloid Cells
• Development
• Myeloid Cell Types
• Neutrophils
• Mast Cells
• Eosinophils
• Monocytes and Macrophages
• Dendritic Cells
• Can You Now …
• 13 Organs and Tissues of the Immune System
• ■ Primary and Secondary Lymphoid Organs
• Bone Marrow
• Thymus
• Lymph Nodes
• Spleen
• Mucosa-Associated Lymphoid Tissue
• Mucosal Lymphocytes
• Skin: The Cutaneous Immune System
• ■ Lymphocyte Trafficking
• Lymphocyte Recirculation
• Homing
• Lymphocyte Extravasation
• Chemotaxis
• Synapse Formation
• Can You Now…
• 14 B-Cell Development
• ■ Early B-Lymphocyte Development
• Stem Cell to Immature B Cell
• ■ The Mature B Cell
• Additional Tolerance Induction
• Activation and Antibody Production
• ■ Somatic Mutation and Class Switching in Germinal Centers
• ■ Thymus-Independent Antigens
• ■ B1 B Cells and Natural Antibodies
• Can You Now…
• 15 T-Cell Development
• ■ The Thymus
• Overview of the Transition From Thymocyte to Mature T Cell
• Order of T-Cell Receptor Gene Rearrangements
• Major Histocompatibility Complex Self Peptide Expression in the Thymus
• Positive Selection: Establishment of Self-Restriction
• Negative Selection: Establishment of Central Self-Tolerance
• T-Cell Receptor Signaling in Positive and Negative Selection
• ■ The Periphery: Naive T-Cell Activation by Antigen
• Peripheral T-Cell Tolerance
• Mature T-Cell Responses and Functions
• CD4+ T Cells
• CD8+ T Cells: Cytotoxic T Lymphocytes
• The γδ T-Cell Subset
• Can You Now …
• 16 T-Cell Interactions and T-Cell Help
• ■ Generation of Stimulated, or Primed, B and T Cells
• ■ Generation of Effector Cells
• CD4+ T-Helper Interaction With B Cells
• CD4+ T-Helper Interaction With CD8+ T Cells
• ■ Providing the Most Appropriate Immune Response for a Given Pathogen
• Can You Now…
• 17 Immunologic Memory and Homeostasis
• ■ Long-Term Immunologic Memory
• B-Cell Memory
• T-Cell Memory
• ■ Lymphocyte Homeostasis
• ■ Apoptosis
• Can You Now …
• 18 Regulation of the Immune System
• ■ Tolerance
• Central Tolerance
• Peripheral Tolerance
• Immune-Privileged Sites
• Absence of Costimulation or T-Cell Help.
• Activation-Induced Cell Death
• Regulatory T Cells
• Can You Now…
• 19 Brief Review of Immune Physiology
• ■ Integrated Immune System: Connections Between Adaptive and Innate Responses
• IV Innate Immunity
• 20 Constitutive Defenses Including Complement
• ■ Barriers to Infection
• Skin
• Respiratory Tract
• Gastrointestinal Tract
• ■ Extracellular Molecules of the Innate Immune System
• Interferon
• Complement
• Activation of Complement
• Lectin Pathway
• Classical Pathway
• Alternative Pathway
• Summary of Complement Activation
• Amplification Steps
• Complement Effectors
• Anaphylatoxins
• Complement Receptors
• Membrane Attack Complex
• Complement Inhibitors
• Can You Now …
• 21 Phagocytes
• ■ Phagocytic Cell Types
• Neutrophils
• Monocytes/Macrophages
• Tissue Macrophages
• Giant and Epithelioid Cells
• Fixed Macrophages
• Alveolar Macrophages
• Glial Cells
• Osteoclasts
• ■ Phagocyte Production
• ■ Phagocyte Recruitment
• ■ Receptors on Phagocytes
• ■ Molecular Patterns
• Toll-Like Receptors
• C-Lectin Receptors
• Receptors for Complement Components
• Receptors for Immunoglobulin
• ■ Actions of Phagocytes
• Phagocytosis
• Oxidative Burst
• Proteolytic Enzymes
• Inflammatory Signaling
• Acute-Phase Response
• ■ Phagocyte Defects
• ■ Molecular Recognition by the Innate and Adaptive Immune Systems
• Can You Now…
• 22 Killing in the Immune System
• ■ Response to Parasite Worms
• ■ Mast Cells
• Granule Contents
• Mast Cell Enzymes
• Histamine
• Cytokines
• Arachidonic Acid Metabolites
• Eosinophils
• Immediate (Type I) Hypersensitivity
• ■ Natural Killer Cells
• Natural Killer Receptors
• Natural Killer Inhibitor Receptors
• Natural Killer Activating Receptors
• CTLs and Natural Killer Cell Effector Mechanisms
• Perforin
• Granzyme
• Fas Ligand
• ■ Intracellular Mechanisms of Apoptosis
• Apoptosis in the Immune System
• Can You Now…
• 23 Inflammation
• ■ Types of Inflammation
• ■ Cytokine Network in Inflammation
• ■ Tuberculosis
• ■ Hepatitis B Infection
• ■ “Overzealous” Inflammation
• Can You Now…
• 24 Cytokines in the Immune System
• ■ Overview
• ■ Cytokine Receptors and Signaling Molecules
• ■ Review of Some of the Roles of Cytokines in Immune Responses
• Acute Inflammation: Initial Response to Infection
• T-Cell Priming
• Development of Specialized T-Cell Responses
• Gut Immunity
• TH17 Responses
• TH1 Responses
• TH2 Responses
• Regulatory T Cells
• End of the Immune Response
• ■ Clinical Uses for Cytokines and Cytokine Blockade
• Can You Now…
• V Immune System in Health and Disease
• 25 Infections and Vaccines
• ■ How Organisms Evade the Immune Response
• ■ Mechanisms of Immunity
• ■ Types of Vaccines
• Live Vaccines
• Killed Organisms
• Subunit Vaccines
• Adjuvants
• Accessing Intracellular Pathways
• ■ Vaccine Schedules
• Can You Now…
• 26 Hypersensitivity Reactions
• ■ Types of Triggers for Hypersensitivity
• Hypersensitivity to Infectious Agents
• Hypersensitivity to Environmental Substances
• Hypersensitivity to Self Antigens
• ■ Types Of Hypersensitivity Reaction
• Type I
• Type II
• Type III
• Type IV
• ■ Diagnosis and Treatment of Hypersensitivity
• Can You Now…
• 27 Immediate Hypersensitivity (Type I)
• ■ Definitions
• ■ Allergen
• ■ Degranulating Cells
• ■ Antibody
• ■ T-Helper 2 Cells
• ■ Predisposition to Allergy
• Genetics of Allergy
• Environmental Factors and Allergy
• ■ Mediators of Early Phase of Allergy
• ■ Mediators of Late Phase of Allergy
• ■ Treatment
• Drug Treatments
• Allergen Immunotherapy
• Can You Now…
• 28 How Autoimmune Disease Develops
• ■ Some Autoimmunity is Normal
• ■ Initiation of Autoimmune Disease
• ■ T-Cell Tolerance
• ■ Breakdown of T-Cell Tolerance
• Genetic Factors and Loss of Tolerance
• Environmental Factors and Loss of Tolerance
• ■ Tests for Autoimmune Disease
• Can You Now…
• 29 Antibody-Mediated Hypersensitivity (Type II)
• ■ Immune-Mediated Hemolysis
• Red Blood Cell Antigens
• Anti–Red Cell Antibodies
• Types of Immune-Mediated Hemolysis
• Alloimmune Hemolysis
• Autoimmune Hemolysis
• Type II Autoimmune Hypersensitivity Against Solid Tissue
• ■ Type II Hypersensitivity and Antibodies That Affect Cell Function
• Graves Disease
• Can You Now…
• 30 Immune Complex Disease (Type III Hypersensitivity)
• ■ Antigens in Immune Complexes
• Infectious Antigens
• Innocuous Environmental Antigens
• Autoantigens
• ■ Antibodies in Immune Complexes
• ■ Clearance of Immune Complexes
• Complement Breaks Down Large Soluble Complexes
• Complement Receptor 1 Transfers Complexes to Phagocytes
• Failure of Clearance
• ■ Mechanisms of Inflammation in Immune Complex Disease
• ■ Immune Complex Disease in the Kidney
• ■ Treatment of Immune Complex Disease
• Can You Now …
• 31 Delayed Hypersensitivity (Type IV) and Review of Hypersensitivity Reactions
• ■ Delayed Hypersensitivity Reactions are Driven by T-Helper 1 Cells
• ■ Type IV Hypersensitivity Disease
• Rheumatoid Arthritis
• Multiple Sclerosis
• Treatment of Delayed Hypersensitivity Reactions
• Antiinflammatory Drugs
• Immunosuppressive Drugs
• Immunologically Mediated Drug Reactions
• Review of Hypersensitivity Reactions
• Can You Now …
• 32 Primary Immunodeficiency
• ■ Infections Provide Clues to the Type of Immunodeficiency
• ■ Causes of Primary Immunodeficiency
• Mutations and Immunodeficiency
• Polymorphisms and Immunodeficiency
• Polygenic Disorders
• ■ Screening for Severe Combined Immune Deficiency
• ■ Diagnosis of Primary Immunodeficiency
• ■ Treatment
• Gene Therapy
• Can You Now…
• 33 Secondary Immunodeficiency
• ■ HIV Infection
• Entry of HIV Into Host Cells
• Reverse Transcription of the HIV Genome
• HIV Latency and Transcription
• Immune Responses to HIV
• Innate Immune Response
• Antibody Response
• Cytotoxic T-Lymphocyte Response
• How HIV Kills Infected Cells
• Clinical Features of HIV Infection
• Factors That Affect Outcome
• Vaccines
• Treatments for HIV Infection
• ■ Other Secondary Immunodeficiencies
• Extremes of Age
• Immune System in the First Year of Life
• The Aging Immune System
• Miscellaneous Factors
• Drugs
• B-Cell Malignancy
• Kidney and Gut Disease
• Nutrition
• Physiologic Stress
• Infections
• Can You Now…
• 34 Transplantation
• ■ Transplantation Terminology
• ■ Solid Organ Transplantation
• When Transplantation Is Indicated
• Mechanisms of Rejection
• Hyperacute Rejection
• Acute Rejection
• Chronic Rejection
• Tolerance
• ■ Stem Cell Transplantation
• Source of Stem Cells
• Conditioning
• Graft-Versus-Host Disease
• ■ Tissue-Typing Techniques
• Human Leukocyte Antigen Typing
• Human Leukocyte Antigen Cross-Matching
• ■ Immunosuppressive Drugs
• Corticosteroids
• T-Cell Signaling Blockade
• Interleukin-2 Blockade
• Antiproliferatives
• ■ Xenotransplantation
• Can You Now …
• 35 Tumor Immunology
• ■ Lymphoid Tumors
• Oncogenesis
• Chromosomal Translocations
• Pathogens
• Diagnosing Lymphoid Malignancy
• ■ Immunity to Tumors
• Tumor Antigens
• Evidence for Tumor Immunity
• Evasion of the Immune Response by Tumors
• Immunotherapy
• Passive Cancer Immunotherapy
• Active Cancer Immunotherapy
• Can You Now…
• 36 Biopharmaceuticals
• ■ Monoclonal Antibodies
• Historical Approaches to Antibody Therapy
• Monoclonal Antibody Technologies
• Increasing the Effects of Monoclonal Antibodies
• Biospecific Antibodies
• Conjugates
• Some Successes and Failures in Monoclonal Antibody Therapy
• ■ Recombinant Cytokines
• Can You Now…
• Glossary
• Index
• A
• B
• C
• D
• E
• F
• G
• H
• I
• J
• K
• L
• M
• N
• O
• P
• R
• S
• T
• U
• V
• W
• X
• Inside Back Cover