Immunology: A Short Course

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 featuring interactive flashcards, USMLE–style interactive MCQs, figures as PowerPoint slides, and case–based material to help understand clinical applications

About the Authors

Contributors

Preface and Acknowledgments

1 OVERVIEW OF THE IMMUNE SYSTEM

Introduction

Innate and Acquired Immunity

Innate Immunity

Acquired Immunity

Active, Passive, and Adoptive Immunization

Clonal Selection Theory

Humoral and Cellular Immunity

Cell–Mediated Immunity

Generation of Diversity in the Immune Response

Benefits of Immunology

Damaging Effects of the Immune Response

The Future of Immunology

The Short Course Begins Here References

2 INNATE IMMUNITY

Introduction

Innate Immunity

Physical and Chemical Barriers of Innate Immunity

Intracellular and Extracellular Killing of Microorganisms

Cells Involved in the Innate Immune System

Inflammation

Fever

Biologically Active Substances

Receptors Involved in the Innate Immune System

Pattern Recognition Receptors

Acquired Immunity

Cells and Organs Involved in Acquired Immunity

The Lymphatic Organs

Lymphocyte Migration and Recirculation

Fate of Antigen After Penetration

Frequency of Antigen–Specific Naive Lymphocytes

Interrelationship Between Innate and Acquired Immunity

Summary

References

Review

Questions

Answers to Review Questions

3 ADAPTIVE IMMUNITY

4 IMMUNOGENS AND ANTIGENS

Introduction

Requirements for Immunogenicity

Foreignness

High Molecular Weight

Chemical Complexity

Degradability

Haptens

Further Requirements for Immunogenicity

Primary and Secondary Immune Responses

Antigenicity and Antigen–Binding Site

Epitopes Recognized by B and T Cells

Major Classes of Antigens

Binding of Antigen to Antigen–Specific Antibodies or T Cell Receptors

Cross–Reactivity

Adjuvants

Summary

References

Review Questions

Answers to Review Questions

5 ANTIBODY STRUCTURE AND FUNCTION

Introduction

Isolation and Characterization of Immunoglobulins

Structure of Light and Heavy Chains

Immunoglobulin Domains

Immunoglobulin Hinge Region

Immunoglobulin Variable Region

Immunoglobulin Variants

Isotypes

Allotypes

Idiotypes

Structural Features of IgG

Biologic Properties of IgG

Agglutination and Formation of Precipitate

Passage of Ig Through the Placenta and Absorption in Neonates

Opsonization

Antibody–Dependent, Cell–Mediated Cytotoxicity

Activation of Complement

Neutralization of Toxins

Immobilization of Bacteria

Neutralization of Viruses

Structural Features of IgM

Biologic Properties of IgM

Complement Fixation

First

Line of Humoral Defense

Agglutination

Isohemagglutinins

Structural and Biologic Properties of IgA

Biologic Properties of IgA

Role in Mucosal Infections

Bactericidal Activity

Antiviral Activity

Structural and Biologic Properties of IgD

Structural and Biologic Properties of IgE

Importance of IgE in Parasitic Infections and Hypersensitivity Reactions

Kinetics of Antibody Responses Following Immunization

Primary Response

Secondary Response

The Immunoglobulin Superfamily

Summary

References

Review Questions

Answers to Review Questions

6 ANTIGEN ANTIBODY INTERACTIONS, IMMUNE ASSAYS, AND EXPERIMENTAL SYSTEMS

Introduction

Antigen Antibody Interactions

Primary Interactions Between Antibody and Antigen

Association Constant

Affinity and Avidity

Secondary Interactions Between Antibody and Antigen

AgglutinationnReactions

PrecipitationnReactions

Immunoassays

Direct–Binding Immunoassays

Solid–Phase Immunoassays

Immunofluorescence

Direct Immunofluorescence

Indirect Immunofluorescence

Fluorescence–Activated Cell–Sorting Analysis

Immunoabsorption and Immunoadsorption

Cellular Assays

Assays to Assess Lymphocyte Function

B– and T–Cell Proliferation Assays

Assays that Assess Antibody Production by B Cells

Effector Cell Assays for T and NK Cells

Cell Culture

Primary Cell Cultures and Cloned Lymphoid Cell Lines

B–Cell Hybridomas and Monoclonal Antibodies

T–Cell Hybridomas

Genetically Engineered Molecules and Receptors

Experimental Animal Models

Inbred Strains

Adoptive Transfer

SCID Mice

Thymectomized and Congenically Athymic (Nude) Mice

Transgenic Mice and Gene Targeting

Transgenic Mice

Knockout Mice

Analysis of Gene Expression: Microarrays

Summary

References

Review Questions

Answers to Review Questions

7 THE GENETIC BASIS OF ANTIBODY STRUCTURE

Introduction

A Brief Review of Nonimmunoglobulin Gene Structure and Gene Expression

Genetic Events in Synthesis of Ig Chains

Organization and Rearrangement of Light–Chain Genes

Organization and Rearrangement of Heavy–Chain Genes

Regulation of Ig Gene Expression

Class or Isotype Switching

Generation of Antibody Diversity

Presence of Multiple V Genes in the Germline

VJ and VDJ Combinatorial Association

Random Assortment of H and L Chains

Junctional Diversity

Somatic Hypermutation

Somatic Gene Conversion

Receptor Editing

Role of Activation–Induced Cytidine Deaminase in Generating Antibody Diversity

Summary

References

Review Questions

Case Study

Answers to Review Questions

Answer to Case Study

8 BIOLOGY OF THE B LYMPHOCYTE

Introduction

Development of B Lymphocytes

Overview

Sites of Early B–Cell Differentiation

Early Stages of B–Cell Differentiation: Pro–B and Pre–B Cells

Immature B Cells

Mature B Cells

B–Lymphocyte Traffic: Anatomical Distribution of B–Cell Populations

Sites of Antibody Synthesis

Thymus–Dependent Antibody Synthesis in the Germinal Center

Antibody Synthesis in Mucosal Tissue

Thymus–Independent Antibody Responses at Different Sites

B–Cell Membrane Proteins

Stage–Specific Markers

Antigen–Binding Molecules: Membrane Immunoglobulin

Signal Transduction Molecules Associated with Membrane Immunoglobulin

Molecules Involved in T Cell B Cell Interactions

Summary

References

Review Questions

Answers to Review Questions

9 HOW T CELLS RECOGNIZE ANTIGEN: THE ROLE OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

Introduction

How the MHC Got Its Name

Different MHC Molecules Interact with Different Sets of T Cells

Variability of MHC Class I and MHC Class II Molecules

Structure of MHC Class I Molecules

Selectivity of Peptide Binding to MHC Class I Molecules

CD8 Binding to Invariant Region of MHC Class I Molecules

Structure of MHC Class II Molecule

Antigen Processing and Presentation: How MHC Molecules Bind Peptides and Create Ligands that Interact with T Cells

Exogenous Antigens and Generation of MHC Class II Peptide Complexes

Endogenous Antigens: Generation of MHC Class I Peptide Complexes

Decreased MHC Class I Expression in Virus–Infected and Tumor Cells

Cross–Presentation: Exogenous Antigens Presented in the MHC Class I Pathway

Which Antigens Trigger Which T–Cell Responses?

Binding of Peptides Derived from Self–Molecules by MHC Molecules

Inability to Respond to an Antigen

Other Types of Antigen that Activate T–Cell Responses

Lipids and Glycolipids Presented by CD1 to NKT Cells

Genes of the HLA Region

Polymorphic MHC Class I and II Genes

Nomenclature of Polymorphic MHC Molecules

Regulation of Expression of MHC Genes

Codominant Expression

Coordinate Regulation

Inheritance of MHC Genes

Other Genes Within HLA

MHC in Other Species

Diversity of MHC Molecules: MHC Association with Resistance and Susceptibility to Disease

Summary

References

Review Questions

Answers to Review Questions

10 BIOLOGY OF THE T LYMPHOCYTE

Introduction

The Antigen–Specific T–Cell Receptor

Molecules that Interact with Antigen

T–Cell Receptor Complex

Coreceptor Molecules

Other Important Molecules Expressed on the T–Cell Surface

Genes Coding for T–Cell Receptors

Generation of T–Cell Receptor Diversity

T–Cell Differentiation in Thymus

Interactions of Developing T Cells with Nonlymphoid Cells of Thymus

Early T–Cell Receptor Gene Rearrangements: Double–Negative Cells and Splitting Off of T Cells

Pre–T Cells

Double–Positive Cells

Thymic Selection

Role of AIRE Gene Product in Negative Selection

Single–Positive Cells

Generation of the T–Cell Repertoire

Characteristics of T Cells Emerging from Thymus

Further Differentiation of CD4+ and CD8+ T Cells Outside Thymus

Differentiation of Other Sets of Cells in Thymus

Summary

References

Review Questions

Answers to Review Questions

11 ACTIVATION AND FUNCTION OF T CELLS

Introduction

Activation of CD4+ T Cells

Specialized Cells Present Antigen to Naive CD4+ T Cells

Paired Interactions at the Surface of APC and CD4+ T Cells

Intracellular Events in CD4+ T–Cell Activation

Clonal Expansion, Differentiation to Effector Cells, and Migration Out of the Lymph Node

Other Ways to Activate CD4+ T Cells

Superantigens

Plant Proteins and Antibodies to T–Cell Surface Molecules

T–Cell Function

Subsets of CD4+ T Cells Defined by Cytokine Production and Effector Function

CD4+ T Cells

T–Helper–Cell Function: Interaction of CD4+ T Cells with B Cells to Synthesize Antibody

Activation and Function of CD8+ T Cells

Generation of Effector CD8+ T Cells

CD8+ T–Cell Killing of Target Cells

MHC Restriction and CD8+ T Cell Killer Function

Termination of the Response: Induction of Memory Cells

Function of NKT Cells and T Cells

NKT Cells

T Cells

B–Cell Function: Antibody Synthesis in the Absence of T–Cell Help

Conjugate Vaccines

Intracellular Pathways in B–Cell Activation

Modulation of BCR Signal

Summary

References

Review Questions

Answers to Review Questions

12 CYTOKINES

Introduction

The History of Cytokines

Pleiotropic and Redundant Properties of Cytokines

General Properties of Cytokines

Common Functional Properties

Common Systemic Activities

Common Cell Sources and Cascading Events

Functional Categories of Cytokines

Cytokines that Facilitate Innate Immune Responses

Cytokines that Regulate Adaptive Immune Responses

Cytokines that Induce Differentiation of Distinct T–Cell Lineages

Cytokines that Inhibit Lineage–Specific T–Cell Differentiation

Cytokines that Promote Inflammatory Responses

Cytokines that Affect Leukocyte Movement

Cytokines that Stimulate Hematopoiesis

Cytokine Receptors

Cytokine Receptor Families

Common Cytokine Receptor Chains

Cytokine Receptor–Mediated Signal Transduction

Role of Cytokines and Cytokine Receptors in Disease

Toxic–Shock Syndrome

Bacterial Septic Shock

Cancers

Autoimmunity and Other Immune–Based Diseases

Therapeutic Exploitation of Cytokines and Cytokine Receptors

Cytokine Inhibitors/Antagonists

Reversing Cellular Deficiencies

Treatment of Immunodeficiencies

Treatment of Cancer and Transplant Patients

Treatment of Allergies and Asthma

Summary

References

Review Questions

Answers to Review Questions

13 TOLERANCE AND AUTOIMMUNITY

Introduction

Central Tolerance

Anergy, Receptor Editing, Deletion, and Clonal Ignorance

Peripheral Tolerance

Anergy

Fas FasL Interactions

Regulatory/Suppressor T Cells

Oral Tolerance

Immune Privilege

Autoimmunity and Disease

Genetic Susceptibility

Environmental Susceptibility

Drug and Hormonal Triggers of Autoimmunity

Autoimmune Diseases

Autoimmune Diseases in Which Antibodies Play a Predominant Role in Mediating Organ Damage

Autoimmune Diseases in Which T Cells Play a Predominant Role in Organ Damage

Therapeutic Strategies

Summary

References

Review

Questions

Answers to Review Questions

14 COMPLEMENT

Introduction

Overview of Complement Activation

Classical Pathway

Lectin Pathway

Alternative Pathway

Steps Shared by All Pathways: Activation of C3 and C5

Terminal Pathway

Regulation of Complement Activity

Biologic Activities of Complement

Production of Opsonins

Production of Anaphylatoxins

Lysis

Other Important Complement Functions

Complement Deficiencies

Summary

References

Review Questions

Answers to Review Questions

15 HYPERSENSITIVITY: TYPE I

Introduction

Coombs Gell Hypersensitivity Designations

General Characteristics of Allergic Reactions

Sensitization Phase

Activation Phase

Effector Phase

Late–Phase Reaction

Clinical Aspects of Allergic Reactions

Allergic Rhinitis

Food Allergies

Atopic Dermatitis

Asthma

Clinical Tests for Allergies and Clinical Intervention

Detection

Intervention

Protective Role of IgE

Summary

References

Review Questions

Answers to Review Questions

16 HYPERSENSITIVITY: TYPES II AND III

Introduction

Type II Hypersensitivity

Complement–Mediated Reactions

Antibody–Dependent, Cell–Mediated Cytotoxicity

Antibody–Mediated Cellular Dysfunction

Examples of Type II Hypersensitivity Reactions

Transfusion Reactions

Drug–Induced Reactions

Rh Incompatibility Reactions

Reactions Involving Cell Membrane Receptors

Reactions Involving Other Cell Membrane Determinants

Type III Hypersensitivity

Systemic Immune Complex Disease

Localized Immune Complex Disease

Summary

References

Review Questions

Answers to Review Questions

17 HYPERSENSITIVITY: TYPE IV

Introduction

General Characteristics and Pathophysiology of DTH

Mechanisms Involved in DTH

Examples of DTH

Contact Sensitivity

Granulomatous Hypersensitivity

Tuberculin–Type Hypersensitivity

Allograft Rejection

Additional Examples of DTH

Treatment of DTH

Summary

References

Review Questions

Answers to Review Questions

18 IMMUNODEFICIENCY DISORDERS AND NEOPLASIAS OF THE LYMPHOID SYSTEM

Introduction

Immunodeficiency Syndromes

Primary Immunodeficiency Syndromes

Secondary Immunodeficiency Diseases

Acquired Immunodeficiency Syndrome

Initial Description and Epidemiology

Human Immunodeficiency Virus

Clinical Course

Prevention, Control, Diagnosis, and Therapy of HIV Infection

Neoplasms of Lymphoid System

B–Cell Neoplasms

T–Cell Neoplasms

Hodgkin Lymphoma

Immunotherapy

Summary

References

Review Questions

Answers to Review Questions

19 TRANSPLANTATION

Introduction

Relationship Between Donor and Recipient

Immune Mechanisms Responsible for Allograft Rejection

Categories of Allograft Rejection

Hyperacute Rejection

Acute Rejection

Chronic Rejection

Role of MHC Molecules in Allograft Rejection

Mechanisms of Alloantigen Recognition by T Cells

Role of T–Cell Lineages and Cytokines in Allograft Rejection

Laboratory Tests Used in Tissue Typing

Prolongation of Allograft Survival: Immunosuppresive Therapy

Anti–Inflammatory Agents

Cytotoxic Drugs

Agents that Interfere with Cytokine Production and Signaling

Immunosuppressive Antibody Therapy

New Immunosuppressive Strategies and Frontiers

Hematopoietic Stem Cell Transplantation

Graft–Versus–Host Disease

Xenogeneic Transplantation

The Fetus: A Tolerated Allograft

Summary

References

Review Questions

Answers to Review Questions

20 TUMOR IMMUNOLOGY

Introduction

Tumor Antigens

Categories of Tumor Antigens

Normal Cellular Gene Products

Mutant Cellular Gene Products

Tumor Antigens Encoded by Oncogenes

Immunologic Factors Influencing the Incidence of Cancer

Effector Mechanisms in Tumor Immunity

B–Cell Responses to Tumors

Cell–Mediated Responses to Tumor Cells

Cytokines

Limitations of the Effectiveness of Immune Responses Against Tumors

Immunodiagnosis

Detection of Myeloma Proteins Produced by Plasma Cell Tumors

Detection of –Fetoprotein

Carcinoembryonic Antigen

Detection of Prostate–Specific Antigen

Cancer Antigen–125

Radiolabeled Monoclonal Antibody B72.3

Tumor Immunoprophylaxis

Immunotherapy

Summary

References

Review Questions

Answers to Review Questions

21 RESISTANCE AND IMMUNIZATION TO INFECTIOUS DISEASES

Introduction

Host Defense Against Various Classes of Microbial Pathogens

Immunity to Viruses

Immunity to Bacteria

Immunity to Parasites

Immunity to Fungi

Mechanisms by Which Pathogens Evade Immune Responses

Encapsulated Bacteria

Toxins

Superantigens

Antigenic Variation

Intracellular Survival

Suppression of the Immune System

Extracellular Enzymes

Expression of Antibody–Binding Proteins

Principles of Immunization

Objectives of Immunization

Active Immunizations

Recommended Immunizations

Use of Vaccines in Selected Populations

Basic Mechanisms of Protection

Significance of Primary and Secondary

Immune Responses

Age and Timing of Immunizations

Vaccine Precautions

Site of Administration of Antigen

Hazards

Recent Approaches to Production of Vaccines

Vaccines Produced by Recombinant DNA

Conjugated Polysaccharides

Synthetic Peptide Vaccines

Anti–Idiotype Vaccines

Virus–Carrier Vaccine

Bacterium–Carrier Vaccine

DNA Vaccines

Toxoids

Passive Immunization

Passive Immunization Through Placental Antibody

Transfer

Passive Immunization via Colostrum

Passive Antibody Therapy and Serum

Therapy

Monoclonal and Polyclonal Antibodies

Preparation and Properties of Human Immune Serum

Globulin

Indications for Use of Immune Globulin

Precautions About Uses of Human Immune Serum

Globulin Therapy

Colony–Stimulating Factors

Summary

References

Review Questions

Answers to Review Questions

Glossary

Appendix: Partial List of CD Antigens

Index