Оглавление
Richard Coico. Immunology
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
IMMUNOLOGY. A Short Course
ABOUT THE AUTHOR
CONTRIBUTORS
PREFACE AND ACKNOWLEDGMENTS TO THE EIGHTH EDITION
HOW TO USE YOUR TEXTBOOK. FEATURES CONTAINED WITHIN YOUR TEXTBOOK
REVIEW QUESTIONS
ABOUT THE COMPANION WEBSITE
1 OVERVIEW OF THE IMMUNE SYSTEM. INTRODUCTION
INNATE AND ADAPTIVE IMMUNITY
Innate Immunity
Adaptive Immunity
HEMATOPOIESIS AND THE DEVELOPMENT OF THE IMMUNE SYSTEM
CLONAL SELECTION THEORY
ACTIVE, PASSIVE, AND ADOPTIVE IMMUNIZATION
Major Characteristics of the Adaptive Immune Response
Cells Involved in Adaptive Immune Responses
HUMORAL AND CELLULAR IMMUNITY
Humoral Immunity
Cell‐Mediated Immunity
IMMUNE BALANCE
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 AND BIBLIOGRAPHY
2 CELLS AND TISSUES OF THE IMMUNE SYSTEM. INTRODUCTION
THE LYMPHATIC SYSTEM
Primary and Secondary Lymphoid Organs
Thymus Gland
Secondary Lymphoid Organs
The Spleen
Lymph Nodes
MAJOR HEMATOPOIETIC CELLS
Lymphoid Lineage Cell Populations
B Lymphocytes
T Lymphocytes
Naïve Lymphocytes
CTL Effector Cells
Subsets of TH Cells
Natural Killer T Cells
Innate Lymphoid Cells
Myeloid Lineage Immune Cell Populations. Polymorphonuclear Leukocytes
Macrophages
Dendritic Cells
LYMPHOCYTE MIGRATION AND RECIRCULATION
THE FATE OF ANTIGEN AFTER PENETRATION
Frequency of Antigen‐Specific Naïve Lymphocytes
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
3 CELLS OF THE INNATE IMMUNITY. INTRODUCTION
PHYSICAL AND CHEMICAL BARRIERS OF INNATE IMMUNITY
CELLS OF THE INNATE IMMUNE SYSTEM
PATTERN RECOGNITION: A MAJOR FEATURE OF INNATE IMMUNE RESPONSES
Pattern Recognition Receptors
Toll‐Like Receptors
C‐Type Lectin Receptors
f‐Met‐Leu‐Phe Receptors
NOD‐Like Receptors
RIG‐I‐Like Receptors
COMPLEMENT
Intracellular and Extracellular Killing of Microorganisms
Phagocytosis
THE INFLAMMATORY RESPONSE
Transendothelial Migration of Leukocytes
Localized Inflammatory Responses: Roles of Kinins and the Coagulation Pathway
The Acute Phase Response
Fever
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
4 COMPLEMENT. INTRODUCTION
OVERVIEW OF COMPLEMENT ACTIVATION
Classical Pathway
Activators
Early Steps in the Classical Complement Pathway That Lead to C3 Cleavage
Lectin Pathway. Activators
Early Steps in the Lectin Pathway That Lead to C3 Cleavage
Alternative Pathway. Activators
Early Steps in the Alternative Pathway That Lead to C3 Cleavage
Steps Shared by All Pathways: Activation of C3 and C5
Terminal Pathway
REGULATION OF COMPLEMENT ACTIVITY
BIOLOGICAL ACTIVITIES OF COMPLEMENT
Production of Opsonins
Production of Anaphylatoxins
Lysis
Other Important Complement Functions. Enhancing B‐Cell Responses to Antigens
Controlling Formation and Clearance of Immune Complexes
Removing Dead or Dying Cells
Responses to Viruses
COMPLEMENT DEFICIENCIES
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
5 IMMUNOGENS AND ANTIGENS. INTRODUCTION
REQUIREMENTS FOR IMMUNOGENICITY
Foreignness
High Molecular Weight
Chemical Complexity
Degradability
Haptens
Further Requirements for Immunogenicity
PRIMARY AND SECONDARY RESPONSES
ANTIGENICITY AND ANTIGEN‐BINDING SITE
EPITOPES RECOGNIZED BY B CELLS AND T CELLS
MAJOR CLASSES OF ANTIGENS
BINDING OF ANTIGEN WITH ANTIGEN‐SPECIFIC ANTIBODIES OR T CELLS
CROSS‐REACTIVITY
ADJUVANTS
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
6 ANTIBODY STRUCTURE, FUNCTION, AND INTERACTIONS WITH ANTIGEN. INTRODUCTION
ISOLATION AND CHARACTERIZATION OF IMMUNOGLOBULINS
STRUCTURE OF LIGHT AND HEAVY CHAINS
DOMAINS
HINGE REGION
VARIABLE REGION
IMMUNOGLOBULIN VARIANTS. Isotypes
Allotypes
Idiotypes
STRUCTURAL AND BIOLOGICAL PROPERTIES OF IGG
Biological Properties of gG
Agglutination and Formation of Precipitate
Passage 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 AND BIOLOGICAL PROPERTIES OF IGM
Biological Properties of IgM
Complement Fixation
Neonatal Immunity and First Line of Humoral Defense
Agglutination
Isohemagglutinins
STRUCTURAL AND BIOLOGICAL PROPERTIES OF IGA
Biological Properties of IgA
Role in Mucosal Infections
Bactericidal Activity
Antiviral Activity
STRUCTURAL AND BIOLOGICAL PROPERTIES OF IGD
STRUCTURAL AND BIOLOGICAL PROPERTIES OF IGE
Importance of IgE in Parasitic Infections and Hypersensitivity Reactions
KINETICS OF THE ANTIBODY RESPONSE FOLLOWING IMMUNIZATION. Primary Response
Secondary Response
THE IMMUNOGLOBULIN SUPERFAMILY
ANTIGEN–ANTIBODY INTERACTIONS
Primary Interactions Between Antibody and Antigen
Association Constant
Affinity and Avidity
SECONDARY INTERACTIONS BETWEEN ANTIBODY AND ANTIGEN. Agglutination Reactions
Titer
Zeta Potential
Coombs Test
Passive Agglutination
Precipitation Reactions. Reaction in Solutions
Precipitation Reactions in Gels
Radial Immunodiffusion
Immunoelectrophoresis
Western Blots (Immunoblots )
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
7 ORGANIZATION AND EXPRESSION OF LYMPHOCYTE ANTIGEN RECEPTOR GENES. INTRODUCTION
A BRIEF REVIEW OF GENE STRUCTURE AND GENE EXPRESSION
Shared and Unique Features of Lymphocyte Antigen‐Specific Receptors
B‐CELL ANTIGEN‐SPECIFIC RECEPTORS AND RECEPTOR GENES
Gene Expression
GENETIC EVENTS IN SYNTHESIS OF Ig CHAINS
Organization and Rearrangement of Ig Light‐Chain Genes. General Features
κ‐Chain Synthesis
λ‐Chain Synthesis
Organization and Rearrangement of Ig Heavy‐Chain Genes
Allelic Exclusion and the Regulation of Ig Gene Expression
IMMUNOGLOBULIN CLASS 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
ROLE OF ACTIVATION-INDUCED CYTIDINE DEAMINASE IN GENERATING ANTIBODY DIVERSITY
T‐CELL ANTIGEN‐SPECIFIC RECEPTORS AND RECEPTOR GENES
The αβ TCR
Comparison of the αβ TCR and Ig
TCR Antigen Recognition
Valence and Conformation
Secretion of Receptor
No Change in TCR During Response to Antigen
The T‐Cell Receptor Complex
Co‐Receptors
GENES CODING FOR T‐CELL RECEPTORS
GENERATION OF T‐CELL RECEPTOR DIVERSITY
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
8 THE MAJOR HISTOCOMPATIBILITY COMPLEX AND ANTIGEN PRESENTATION. INTRODUCTION
HOW THE MHC GOT ITS NAME
MHC ROLE IN ANTIGEN PRESENTATION
DIFFERENT MHC MOLECULES ARE EXPRESSED BY DISTINCT HOST CELLS AND INTERACT WITH DIFFERENT SETS OF T CELLS
MHC Class I
MHC Class II
VARIABILITY OF MHC CLASS I AND MHC CLASS II MOLECULES
STRUCTURE OF MHC CLASS I AND CLASS II MOLECULES
MHC Class I
Selectivity of Peptide Binding to MHC Class I Molecules
CD8 Binding to Invariant Region of MHC Class I Molecules
Structure of MHC Class II Molecules
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: Role of NK Cells
Cross‐Presentation: Exogenous Antigens Presented in the MHC Class I Pathway
Which Antigens Trigger Which T‐Cell Responses?
MHC Molecules Bind Peptides Derived from Self‐Molecules
Inability to Respond to an Antigen
OTHER TYPES OF ANTIGEN THAT ACTIVATE T‐CELL RESPONSES. Superantigens
Lipids and Glycolipids
Multiple Antigens Activate γδ T Cells
GENES OF THE HLA REGION
NOMENCLATURE OF POLYMORPHIC MHC MOLECULES
REGULATION OF EXPRESSION OF MHC GENES. Co‐Dominant Expression
Coordinate Regulation
Inheritance of MHC Genes
MHC IN OTHER SPECIES
DIVERSITY OF MHC MOLECULES: MHC ASSOCIATION WITH RESISTANCE AND SUSCEPTIBILITY TO DISEASE
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
9 B‐CELL DEVELOPMENT AND ACTIVATION. INTRODUCTION
DEVELOPMENT OF B LYMPHOCYTES. Overview
GENETICS OF IMMUNOGLOBULIN GENE REARRANGEMENTS
Sites of Early B‐Cell Differentiation
Pro‐B cell: D to J Rearrangement
Pre‐B Cell: V‐DJ Rearrangement
NEGATIVE SELECTION AND THE DEVELOPMENT OF CENTRAL TOLERANCE
Transitional B cells
B‐CELL ACTIVATION
Interaction of Antigen, B Cells, and Helper T Cells in the Lymph Node
Events in the Germinal Center
Somatic Hypermutation
Selection of B Cells with Higher Affinity for Antigen
Class Switch Recombination—Development of Plasma Cells and Memory Cells
Antibody Synthesis in Mucosal Tissue
IgA Synthesis in Mucosa
Thymus‐Independent Antibody Responses
Marginal‐Zone B Cells
B‐1 Cells
B‐CELL MEMBRANE PROTEINS
Stage‐Specific Markers
Antigen‐Binding Molecules: Membrane Immunoglobulin
Signal Transduction Molecules Associated with Membrane Immunoglobulin. Igα and Igβ
B‐Cell Co‐Receptor
Molecules Involved in T–B‐Cell Interactions
Major Histocompatibility Complex Class II Molecules
Co‐Stimulator Molecules
Receptors for Cytokines
Homing
Intracellular Signaling in B Cells
Activation by Antigen
Enhancement of B‐Cell Signaling
Negative Regulation of B‐Cell Signaling
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
10 T‐CELL DEVELOPMENT AND ACTIVATION. INTRODUCTION
THE ANTIGEN‐SPECIFIC T‐CELL RECEPTOR. Molecules That Interact with Antigen
The αβ TCR
Comparison of the αβ TCR and Ig
Antigen Recognition
Valence and Conformation
Secretion of Receptor
No Change in TCR During Response to Antigen
The T‐Cell Receptor Complex
Co‐Receptors
Other Important Molecules Expressed on the T‐Cell Surface
Co‐Stimulator Ligands
Molecules Involved in Adhesion and Homing. Adhesion
Homing
γδ T Cells
GENES CODING FOR T‐CELL RECEPTORS
GENERATION OF T‐CELL RECEPTOR DIVERSITY
T‐CELL DIFFERENTIATION IN THE THYMUS. The Thymus as Primary Organ for T‐Cell Differentiation
Thymic Nonlymphoid Cells in T‐Cell Development
Key Steps in Thymic Differentiation
Early T‐Cell Receptor Gene Rearrangements: Double‐Negative Cells and Splitting Off of γδ T Cells
Pre‐T Cells
Double‐Positive Cells
Thymic Selection
Positive Selection
Negative Selection
Role of AIRE Gene Product in Negative Selection
Leaving the Thymus
Generation of the T‐Cell Repertoire
Characteristics of αβ T Cells Emerging from the Thymus
Further Differentiation of CD4+ and CD8+ T Cells Outside the Thymus
Differentiation of Other Cell Types in the Thymus
Natural Killer T (NKT) Cells
Treg Cells
NK Cells
ACTIVATION AND FUNCTION OF T CELLS
A TWO‐SIGNAL MODEL FOR THE ACTIVATION OF T CELLS
DENDRITIC CELLS ARE THE KEY APC FOR NAÏVE T CELLS
ACTIVATION OF CD4+ T CELLS
Paired Interactions at the Surface of the APC and CD4+ T Cell. Peptide/MHC and TCR
MHC Class II with CD4 Co‐Receptor
Co‐Stimulator Pairs
B7–CD28
CD40–CD40L
Adhesion Molecules
Intracellular Events in CD4+ T‐Cell Activation
Formation of the Immunological Synapse
Initial Signal
Activation of Kinases, Phosphorylation of ITAMs, and Assembly and Activation of Signaling Complexes at the Cell Membrane
Activation of Intracellular Signaling Pathways
B7–CD28 Interaction
Proliferation
Differentiation to Effector Cells and Migration Out of the Lymph Node
Termination of the Response
Other Ways to Activate CD4+ T Cells
Superantigens
Plant Proteins, Antibodies to T‐Cell Surface Molecules, and Other T‐Cell Activators
CD4+ T‐CELL FUNCTION
Cytokine Synthesis
Major Subsets of Cytokine‐Producing CD4+ T Cells
Cross‐Inhibition of CD4+ T‐Cell Subsets
Other Sets of Cytokine‐Producing CD4+ T Cells. T helper cells
TH9
Further Points on Cytokine Synthesis
Help for B Cell in the Response to TD Antigens
The B Cell Captures Antigen and Presents It to the Activated TH
Development of the TFH and the Germinal Center
Events in the Germinal Center
Co‐Stimulator Pairs and Cytokines Are Critical in TFH Cell‐Dependent Antibody Synthesis and Class Switching
Linked Recognition
Conjugate Vaccines: Help for Thymus‐Independent Antigens
ACTIVATION AND FUNCTION OF CD8+ T CELLS
Generation of Effector CD8+ T Cells
Activation
CD8+ T‐Cell Killing of Target Cells
MHC Restriction and CD8+ T Cell Killer Function
MEMORY T CELLS
FUNCTION OF OTHER SUBSETS OF T CELLS
NKT Cells
γδ T Cells
Innate Lymphoid Cells
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
11 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. TH1 and TH2 Cell Lineages
The TH17 T‐Cell Lineage
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 Deficimencies
Treatment of Immunodeficiencies
Treatment of Patients with Cancer, and Viral Infections
Treatment of Allergies and Asthma
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
12 TOLERANCE AND AUTOIMMUNITY
INTRODUCTION
Discovery of Tolerance
CENTRAL TOLERANCE
Mechanisms of Central Tolerance: T and B Cells. Deletion
Mechanisms of Central Tolerance: B Cells
Anergy
Receptor Editing
Importance of Receptor Avidity in Tolerance
PERIPHERAL TOLERANCE
Anergy: The Two‐Signal Hypothesis
Regulatory T Cells
Fas–FasL Interactions
ORAL TOLERANCE
IMMUNE PRIVILEGE
AUTOIMMUNITY VERSUS AUTOIMMUNE DISEASE
Genetic Susceptibility
Autoantigen Sequestration and Molecular Mimicry
The Microbiome and Autoimmunity
Role of Sex in Autoimmune Susceptibility
Chemical Triggers of Autoimmunity
The Environment and Autoimmunity
Type I Interferons and Systemic Autoimmunity
AUTOIMMUNE DISEASES
Autoimmune Diseases in Which Antibodies Play a Predominant Role in Mediating Organ Damage. Autoimmune Hemolytic Anemia
Myasthenia Gravis
Graves’ Disease
Systemic Lupus Erythematosus
Other Antibody‐Mediated Diseases
Hashimoto’s Thyroiditis
Autoimmune Diseases in Which T Cells Play a Predominant Role in Organ Damage. Multiple Sclerosis
Type I Diabetes Mellitus
Rheumatoid Arthritis
Psoriasis
Therapeutic Strategies
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
13 HYPERSENSITIVITY: TYPE I. INTRODUCTION. Hypersensitivity
Coombs–Gell Hypersensitivity Designations
Type I
Type II
Type III
Type IV
GENERAL CHARACTERISTICS OF ALLERGIC REACTIONS
SENSITIZATION PHASE
TH2 Cell Dependency of IgE Antibody Production
ACTIVATION PHASE
EFFECTOR PHASE
Preformed Mediators. Histamine
Serotonin
Chemotactic Factors
Heparin
Newly Synthesized Mediators. Leukotrienes
Thromboxanes and Prostaglandins
Late‐Phase Reaction
CLINICAL ASPECTS OF ALLERGIC REACTIONS
Allergic Rhinitis
Food Allergies
Atopic Dermatitis
Asthma
CLINICAL TESTS FOR ALLERGIES AND CLINICAL INTERVENTION. Detection
Intervention. Environmental Intervention
Pharmacological Intervention
Immunological Intervention
THE PROTECTIVE ROLE OF IgE
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
14 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
Rhesus Incompatibility Reactions
Reactions Involving Cell Membrane Receptors
Reactions Involving Other Cell Membrane Determinants
TYPE III HYPERSENSITIVITY
Systemic Immune Complex Disease
Serum Sickness
Infection‐Associated Immune Complex Disease
Complement Deficiency
Localized Immune Complex Disease
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
15 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 AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
16 IMMUNODEFICIENCY DISORDERS AND NEOPLASIAS OF THE LYMPHOID SYSTEM
INTRODUCTION
IMMUNODEFICIENCY SYNDROMES
Primary Immunodeficiency Syndromes
Severe Combined Immunodeficiency Diseases (SCID)
T–B+ Subgroup. X‐linked SCID
Autosomal Recessive SCID
T–B− Subgroup. Adenosine Deaminase Deficiency
Purine Nucleoside Phosphorylase Deficiency
Recombinase Deficiencies and Radiosensitivity SCID
Anhidriotic Ectodermal Dysplasia with Immunodeficiency
T+B– Subgroup. Omenn Syndrome
T+B+ Subgroup. Bare Lymphocyte Syndrome
ZAP‐70 Mutation
Other Rare Causes
Other Multisystem Disorders
Wiskott–Aldrich Syndrome
Ataxia Telangiectasia
Summary
Immunodeficiency Disorders Associated with T Cells and Cell‐Mediated Immunity
22q11.2 Deletion Syndrome (Congenital Thymic Aplasia; DiGeorge Syndrome)
T‐Cell Deficiencies with Normal Peripheral T‐Cell Numbers
Chronic Mucocutaneous Candidiasis/Th17 cells
Defects in Control of T‐Cell Function
Autoimmune Lymphoproliferative Syndrome
B‐Cell‐Associated or Immunoglobulin‐Associated Immunodeficiency Disorders
X‐Linked Agammaglobulinemia
IL‐21/IL‐21Receptor Mutations
Transient Hypogammaglobulinemia
Common Variable Immunodeficiency Disease
Selective Immunoglobulin Deficiencies
Disorders of T–B Interactions
Hyper‐IgM Syndrome
X‐Linked Lymphoproliferative Syndrome (Duncan Syndrome)
Disorders of the Innate Immune System
Phagocytic Dysfunctions
Leukocyte Adhesion Deficiency
Chédiak–Higashi Syndrome
Chronic Granulomatous Disease
Pattern Recognition Receptors and Their Signaling Pathways
Natural Killer Cell Deficiency
Abnormalities of Macrophage/Monocytes (Histiocytes) and Dendritic Cells
Cytokine/Cytokine Receptor Deficiencies
IL‐12/23‐Interferon‐γ Deficiency
Diseases Caused by Abnormalities in the Complement System
Deficiencies of Early Complement Components
Deficiencies of Late Complement Components
Defective Control of Complement Components. Hereditary Angioedema
Glycosyl Phosphatidyl Inositol (GPI) Protein Deficiencies
Secondary Immunodeficiency Diseases
ACQUIRED IMMUNODEFICIENCY SYNDROME. Initial Description and Epidemiology
Human Immunodeficiency Virus
Clinical Course
Acute Infection
Chronic Latent Phase
Crisis Phase
Prevention, Control, Diagnosis, and Therapy of HIV Infection
NEOPLASMS OF LYMPHOID SYSTEM
B‐Cell Neoplasms. Precursor B‐Cell Lymphoblastic Leukemia/ Lymphoma
Mature B‐Cell Neoplasms. Burkitt Lymphoma/Leukemia
Follicular Lymphoma
Mantle Cell Lymphoma
Marginal Zone Lymphoma
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Diffuse Large B‐Cell Lymphoma
Plasma Cell Neoplasms
Lymphoplasmacytic Lymphoma (Waldenström Macroglobulinemia)
T‐Cell Neoplasms. Precursor T‐Cell Acute Lymphoblastic Leukemia/Lymphoma
Mature T‐Cell Neoplasms
Cutaneous T‐Cell Lymphoma
Adult T‐Cell Leukemia/Lymphoma
Hodgkin Lymphoma
Therapy
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
17 TRANSPLANTATION. INTRODUCTION
RELATIONSHIP BETWEEN DONOR AND RECIPIENT
IMMUNE MECHANISMS ARE 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: IMMUNOSUPPRESSIVE THERAPY
Antiinflammatory 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 AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
18 TUMOR IMMUNOLOGY
INTRODUCTION
TUMOR ANTIGENS
TUMOR IMMUNITY. The Body’s Normal Response
Innate Immunity. Macrophages: Whom Are They Helping?
Neutrophils: What is Their Role?
Innate Lymphoid Cells: Which Ones Contribute to Tumor Immunity?
Adaptive Immunity. B Cells
T Cells: TH1/CTL Partnership
THE IMMUNOSUPPRESSIVE ACTIONS OF TUMOR CELLS
IMMUNOTHERAPY
Therapeutic Antibodies Against Cancer Cell Markers
IL‐2 and Tumor Infiltrating Lymphocytes (TILs)
CTLA‐4/PD‐1 Approach
CAR‐T Cells
Vaccination
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
19 RESISTANCE AND IMMUNIZATION TO INFECTIOUS DISEASES. INTRODUCTION
HOST DEFENSE AGAINST THE VARIOUS CLASSES OF MICROBIAL PATHOGENS
Immunity to Viruses
Immunity to Bacteria
Gram‐Positive Bacteria
Gram‐Negative Bacteria
Mycobacteria
Spirochetes
Immunity to Parasites
Protozoa
Helminths
Immunity to Fungi
MECHANISMS BY WHICH PATHOGENS EVADE THE IMMUNE RESPONSE
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 the Primary and Secondary Responses
Age and Timing of Immunizations
VACCINE PRECAUTIONS. Site of Administration of Antigen
Hazards
RECENT APPROACHES TO PRODUCTION OF VACCINES
Nucleic Acid Vaccines
Conjugated Polysaccharides
Synthetic Peptide 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 Preparations
Preparation and Properties of Human Immune Serum Globulin
Indications for the Use of Immune Globulin
Precautions on the Uses of Human Immune Serum Globulin Therapy
Colony‐Stimulating Factors
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
20 EXPERIMENTAL SYSTEMS AND METHODS. INTRODUCTION
IMMUNOASSAYS. Direct‐Binding Immunoassays
Solid‐Phase Immunoassays
Immunoblotting (Western Blotting)
IMMUNOFLUORESCENCE
Direct Immunofluorescence
Indirect Immunofluorescence
FLOW CYTOMETRY
IMMUNOABSORPTION AND IMMUNOADSORPTION
CELLULAR ASSAYS
Assays of Lymphocyte Function
B‐Cell and T‐Cell Proliferation Assays
Antibody Production by B Cells
Effector Cell Assays for T Cells and Natural Killer 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
Assays of Cell Death
EXPERIMENTAL ANIMAL MODELS
INBRED STRAINS
Adoptive Transfer
SCID Mice
Thymectomized and Congenitally Athymic (Nude) Mice
TRANSGENIC MICE AND GENE TARGETING. Transgenic Mice
Knockout and Knock‐in Mice
ANALYSIS OF GENE EXPRESSION. Microarrays to Assess Gene Expression
SUMMARY
REFERENCES AND BIBLIOGRAPHY
REVIEW QUESTIONS
ANSWERS TO REVIEW QUESTIONS
GLOSSARY
APPENDIX Partial List of CD Antigens
Index
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