Clinical Immunology

Principles and Practice

6th Edition - August 23, 2022
Imprint: Elsevier
Editors: Robert R. Rich, Thomas A. Fleisher, Harry W. Schroeder Jr., Cornelia M. Weyand, David B. Corry, Jennifer M. Puck
Language: English
Hardback ISBN:
9 7 8 - 0 - 7 0 2 0 - 8 1 6 5 - 1
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 2 8 5 2 2 - 6

Offering unique, comprehensive coverage of both basic science and clinical scenarios, Clinical Immunology: Principles and Practice, 6th Edition, brings you up to date with every… Read more

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Offering unique, comprehensive coverage of both basic science and clinical scenarios, Clinical Immunology: Principles and Practice, 6th Edition, brings you up to date with every aspect of this fast-changing field. It examines the molecular, cellular, and immunologic bases of immunologic diseases and their broader systemic implications; it also includes complete coverage of common and uncommon immunologic disorders. Updated with all the latest immunologic research and clinical implications, including breakthrough immunotherapies and molecular-based treatment protocols, this fully revised edition provides authoritative guidance from some of the most respected global leaders in immunology in one complete, well-illustrated volume.

Cover image
Title page
Table of Contents
Copyright
Preface to the First Edition
Preface to the Sixth Edition
List Of Contributors
Dedication
Part I: Principles of Immune Response
1. The Human Immune Response
Abstract
The Host-Microbe Interaction
Cells of the Immune System
Basis Of Adaptive Immunity
Antigen-Binding Molecules
Antigen Presentation
Lymphocyte Adhesion and Trafficking
Lymphocyte Activation
Cell-Mediated Immune Responses
Antibody-Mediated Immune Responses
Apoptosis and Immune Homeostasis
Mechanisms of Immunologic Diseases
Host Immune Defenses Summarized
References
2. Organization of the Immune System
Abstract
Hematopoiesis and Lymphopoiesis
Major Lymphoid Organs
Secondary Lymphoid Organs
Acknowledgments
References
3. Innate Immunity
Abstract
Barriers To Infection
Humoral Innate Immunity
Cellular Innate Immunity
Activating Innate Immunity
Innate Immunity In Clinical Practice
References
4. Antigen Receptor Genes, Gene Products, and Co-Receptors
Abstract
Paratopes and Epitopes
The B-Cell and T-Cell Receptor Antigen Recognition Complex
Immunoglobulins and T-Cell Receptor Structures
Immunoglobulin Classes and Subclasses
T-Cell Receptor αβ and γδ
Immunoglobulin Gene Organization
B-Cell Receptor Complex: Structure and Function
The T-Cell Receptor/CD3 Complex
T-Cell Co-Receptors: CD4 and CD8
Co-Stimulatory and Inhibitory T-Cell Molecules: The CD28 Family
REFERENCES
5. The Major Histocompatibility Complex
Abstract
Genomic Organization of the Major Histocompatibility Complex
Structure And Function Of The Human Leukocyte Antigen Molecules
Generation and Selection of Polymorphisms; Biological Consequences
Human Leukocyte Antigens in Infections, Transplantation, Autoimmunity, and Cancer
Human Leukocyte Antigen and Disease Associations
Drug Hypersensitivity and Pharmacogenomics
Methods of Detecting Human Leukocyte Antigen Polymorphisms. The Human Leukocyte Antigen Typing Problem
Human Leukocyte Antigen Nomenclature
Future Learning and Resources
References
6. Antigens and Antigen Presentation
Abstract
Antigens
Antigen-Presenting Cells
Antigen Processing
Antigen Presentation
Clinical Relevance
References
7. B-Cell Development and Differentiation
Abstract
Generation of a Functioning Antigen Receptor Is Key to the Viability of a B Cell
Tyrosine Kinases Play Key Roles in B-Cell Development
Cell-Surface Antigens Associated with B-Cell Development
Transcription Factors and Epigenetic Mechanisms Controlling B-Cell Differentiation
MicroRNAs, Long Noncoding RNAs, and B-Cell Development
Modulation of B-Cell Development by Chemokines, Cytokines, and Hormones
Organization of the Peripheral Lymphoid Organs
The Spleen
B-Cell Development in the Periphery
Differentiation and the Response to Antigen
Molecular Mechanism of Somatic Hypermutation and Class Switch Recombination
B-Cell Memory
Ectopic Lymphoid Tissue and B-Cell Development
B-Cell Functions in Addition to Antibody Production
References
8. Immunoglobulin Function
Abstract
Antigen Binding and Molecular Identity
Immunological Specificity
Protein Epitopes
Carbohydrate Epitopes
Immune Complexes in Vivo
Correlations between CH Region Structure and Antibody Function
Functions Mediated by Antibody Alone
Functions Mediated by Antibody and Additional Molecules or Cells
Antibodies as Surrogate Ligands
Functional Properties of Engineered Antibody Molecules
References
9. T-Cell Development
Abstract
T-Cell Development
Thymus: The Site of T-Cell Development
Early T-Cell Development
T-Cell Receptor Gene Rearrangement Begins at DN2
Positive and Negative Selection
CD4 and CD8 T-Cell Characteristics are set in the Thymus
Tolerance
Migration of Thymocytes into the Periphery
Thymic Atrophy
References
10. T-Cell Activation and Tolerance
Abstract
The T-Cell Antigen Receptor Complex
Integration of Second-Messenger Pathways by Adaptor Proteins
Tolerance
Summary And Future Directions
References
11. Helper T-Cell Subsets and Control of the Inflammatory Response
Abstract
Activation
Clonal Expansion
Trafficking
Differentiation of CD4 Th Subsets
Effector Cell Phenotypes
Regulatory T Cells
Follicular Helper T Cells
Memory T Cells
General Considerations in Effector T-Cell Differentiation
Termination of T-Cell Responses
Cell Death Pathways in T-Cell Homeostasis
Action of Inhibitory Receptors
Cytokine-Mediated Inhibition
Summary of Therapeutic Regulation of T-Cell Responses for Treatment of Immune-Mediated Diseases
References
12. Cytotoxic T Lymphocytes and Natural Killer Cells
Abstract
Effector Functions/Mechanisms
Cytotoxic T Cells
The Cytotoxic T-Lymphocyte Response
CD4 T-Cell Help
Detection and Analysis of Cytotoxic T-Lymphocyte Function
Natural Killer Cells
Cytokine Regulation of Natural Killer–Cell Activation, Function, and Homeostasis
Natural Killer–Cell Receptors
Natural Killer Receptors That Recognize Major Histocompatibility Complex Class I Molecules
Natural Killer–Cell Receptors That Recognize Non–Major Histocompatibility Complex I Molecules
Natural Killer–Cell Licensing and Self-Tolerance
Specific Natural Killer–Cell Functions
Interactions of Cytotoxic T Lymphocyte and Natural Killer Cells in the Immune Response
Evasion of the Cytotoxic Response
References
13. Regulatory Immune Cells
Abstract
Other Subsets of FOXP3− Regulatory T Cells
Clinical Relevance of Regulatory T Cells
Translational Research
References
14. Cytokines and Cytokine Receptors
Abstract
Cytokine Classification
Type I and II Cytokine Receptors (Hematopoietin Family and Interferon Receptors)
The TNF Cytokine and Receptor Superfamily
Interleukin-1/Toll-like Receptor Family
Interleukin-17 Receptors
Cytokines Activating Receptor Tyrosine Kinases
Transforming Growth Factor-b Ligand and Receptor Families
Other Cytokines
Conclusions and Summary
References
15. Chemokines and Chemokine Receptors
Abstract
Chemokines
Chemokine Receptors
Atypical Chemokine System Components
Chemokine Presentation Mechanisms
Chemokine Activation of Chemotactic Signaling Pathways
Regulation of Chemokine Action
Leukocyte Responses to Chemokines
Chemokine Regulation of Hematopoiesis
Chemokine Regulation of the Immune Response
Clinical Correlates
Therapeutic Applications
Conclusion
Acknowledgments
References
16. Lymphocyte Adhesion and Trafficking
Abstract
Early Lymphocyte Precursor Trafficking to the Primary Lymphoid Organs
Migration of Naive Mature Lymphocytes from Blood to the Secondary Lymphoid Organs
Activated Lymphocytes Display Selective Tissue Homing Patterns
Distinct Recirculation Routes in the Spleen
Inflammation-Induced Changes in Leukocyte Trafficking
Molecular Mechanisms Involved in Leukocyte Extravasation from Blood Into Tissues
Receptors and Their Ligands in Leukocyte–Endothelial Cell Interaction
Intraorgan Lymphocyte Localization
Cell Trafficking Within Lymphatics
Clinical Implications
Adhesion Molecules as Diagnostic Targets
Therapeutic Applications of Adhesion-Modulating Therapies
References
17. Death Pathways and Immunogenicity
Abstract
Cell Death and Damage-Associated Molecular Patterns—The Concept of Necroinflammation
Regulated Cell Death Regulates its Immunogenicity in an Active Manner
Signaling Pathways of Regulated Cell Death
Concluding Remarks and Implications for Solid-Organ Transplantations
Acknowledgments and Conflict of Interest Statement
References
Part II: Fundamentals of Host-Environmental Interactions
18. Human Genomics in Immunology
Abstract
Genome Annotation
Human Variation
Clinical Impact of Human Variation
Comparative Genomics
Functional Genomics
Applying Human Genomics to Discovery of Disorders of the Human Immune System
Finding Disease-Causing Variants by Analyzing Deep Sequence Data
Interpreting Variants Discovered Through Gene Sequencing
Future Directions
References
19. Regulatory RNA in Immunologic Diseases
Abstract
Classes of Regulatory RNAs
lncRNAs and the Development and Function of the Immune System
lncRNAs and Immune-Mediated Disease
Links between IFNG-AS1 and Brucellosis, Inflammatory Bowel Disease, and Systemic Lupus Erythematosus
GATA3-AS1 and Allergy
lncRNAs, NUCLEAR FACTOR KAPPA B (NF-κB), and the Pathogenesis of Rheumatoid Arthritis
lncRNAs and Systemic Lupus Erythematosus
miRNAs
Genome-Wide Association Studies
References
20. Immunometabolism
Abstract
Glycolysis and Pentose Phosphate Pathway
Glutaminolysis
Fatty Acid Oxidation and Fatty Acid Synthesis
Tricarboxylic Acid Cycle and Electron Transport Chain
Conclusions and Future Directions
References
21. Immune Deficiencies at the Extremes of Age
Abstract
Infancy and the Generation of an Immune System
Innate Immune Development
Adaptive Immune Development
Infancy and Functional Differentiation of Adaptive Immune Cells
Infant Immune Development and the Microbiome
Clinical Consequences for Childhood Vaccination
Older age and Immune Cell Generation
T-cell Population Homeostasis
Inflammation, Aging, and the Aging Host Environment
Cellular Defects in Immune Aging
Clinical Consequences of Immune Aging—Immunodeficiency, Autoimmunity, and Accelerated Degenerative Diseases
Strategies and Interventions on the Horizon
References
22. The Microbiota in Immunity and Inflammation
Abstract
Overview of Our Nonmammalian “Self”
The Immune System Facilitates Microbial Colonization
Microbiota-Dependent Maturation of The Intestinal Immune System
Immune Consequences of Early Microbial Manipulation
Immune System—Microbiota CROSSTALK in Intestinal Inflammation
Extraintestinal Manifestations of Gut Microbiota–Immune System Interaction
Cancer and the Microbiota
The Skin Microbiota and The Immune System
The Respiratory Tract Microbiota In Health And Disease
Microbes as Therapy
Summary
References
Part III: Host Defenses to Infectious Agents
23. Immunology of the Skin
Abstract
Molecules Primarily Associated with Innate Immunity and Skin
Cytokine Signaling
Cellular Components of the Cutaneous Adaptive Immune Response
Dendritic Cells
T-Cell Subpopulations and the Skin
Mast Cells
Events Involved in the Generation of a Prototypic Innate and Adaptive Immune Response in the Skin
Antibodies and Skin
Environmental Challenges and the Skin-Associated Lymphoid Tissue
References
24. Immunology of Mucosal Surfaces
Abstract
The Innate Mucosal Defense System
The Common Mucosal Immune System
Lymphocyte Homing into Mucosal Compartments
Induction of Mucosal Immunity
Vaccine Development And Mucosal Immune Responses
Synthesis and Functions of Secretory Antibodies
Mucosal Cytotoxic T Lymphocytes
Mucosal Immune Responses in Early Life and Aging
References
25. Host Defenses to Viruses
Abstract
Viral Entry and Infection
Innate Immunity to Viruses
Adaptive Immunity to Viruses
Immunological Memory
Immune Evasion and Immunity to Chronic Viral Infections
Outcomes of Virus Infection: Immunity or Immunopathology
Immunopathology and Autoimmunity
Translational Research Opportunities
Conclusions
Acknowledgments
References
26. Host Defenses to Intracellular Bacteria
Abstract
Balance of Protection and Pathology Defines the Chronic Nature of Intracellular Bacterial Infection
Intracellular Bacterial Infections of Clinical Relevance
Granuloma Pathology as Hallmark of Intracellular Bacterial Infection
Role of the Facultative Intracellular Niche in Sepsis and Pneumonia
The Interdependence of Innate and Adaptive Immunity in Protection Against Intracellular Bacteria
Concluding Remarks
Acknowledgments
References
27. Host Defenses to Extracellular Bacteria Including Spirochetes
Abstract
Clearance and Nonspecific Host Defenses at Mucosal Epithelial Surfaces
Host Defenses to Extracellular Bacteria Including Spirochetes
Host Risk Factors for Local and Systemic Invasion by Extracellular Pathogens and Spirochetes
Deleterious Host Responses
Translational Research Opportunities
References
28. Host Defenses to Fungi
Abstract
Fungal Recognition Pathways and their Contribution to Human Antifungal Host Defense
Immune Responses to Yeast Fungi
Patients AT RISK for Yeast Infections due to Genetic or PHARMACOLOGICAL Factors
Patients AT RISK for Invasive Mold Infections due to Genetic or PHARMACOLOGICAL Factors
Immune Responses to Dimorphic Fungi
Patients AT RISK for Endemic Mycoses due to Genetic or PHARMACOLOGICAL Factors
Acknowledgments
References
29. Host Defenses to Protozoa
Abstract
Plasmodium SPP.
Toxoplasma gondii
Leishmania SPP.
Trypanosoma cruzi
Entamoeba histolytica
Giardia duodenalis
Cryptosporidium SPP.
Trichomonas vaginalis
References
30. Host Defenses to Helminth Infection
Abstract
Spectrum of Host–Parasite Interactions
Prototypical Host Responses to Helminths
Protective Immunity Against Helminths
Pathology Associated with Immune Responses in Parasitic Helminth Infection
Mechanisms of Evasion and Immune Regulation by Helminth Parasites
Helminths and the Microbiota
Regulation of Allergy, Autoimmunity, and Metabolic Diseases in Helminth Infection
Helminth Therapy for Inflammatory Diseases
Vaccines Against Helminth Parasites
References
31. Emerging Pandemic Infectious Disease Threats
Abstract
Introduction
Human Betacoronavirus
Flaviviruses—Dengue and Zika Virus Disease
Treatment and Prevention
Ebola
Alphainfluenzavirus—Pandemic Influenza
Emerging Bacterial Threats
References
Part IV: Immune Deficiency and Immune Regulatory Disorders
32. Approach to the Evaluation of the Patient With Suspected Immunodeficiency
Abstract
Evaluating Suspected Defects in Antibody Response
Evaluating Suspected T-Cell Defects
Newborn Screening for Severe Combined Immune Deficiency
Evaluating Suspected Natural Killer Defects
Evaluating Immune Defects Involving Macrophage Activation
Evaluating Suspected Toll-Like Receptor Defects
Evaluating Suspected Phagocyte Dysfunction Syndromes
Evaluating Suspected Complement Disorders
Conclusions
References
33. Primary Antibody Deficiencies
Abstract
Clinical Manifestations
Principles of Diagnosis and Treatment
X-Linked Agammaglobulinemia
Autosomal Agammaglobulinemia
Hyper-Immunoglobulin Syndrome
Selective Immunoglobulin a Deficiency
Common Variable Immunodeficiency and Common Variable Immunodeficiency-Like Disorders
Selective Immunoglobulin G Subclass Deficiencies
Antibody Deficiency with Normal Serum Immunoglobulin Levels
Selective Light Chain Deficiency
Transient Hypogammaglobulinemia of Infancy
Frontiers in Research
References
34. Primary T-Cell Immunodeficiencies
Abstract
Severe Combined Immune Deficiency—General Considerations
Scid Due to Metabolic Defects Affecting Survival of T-Cell Progenitors
Scid Due to Defects of Cytokine-Mediated Signaling
Scid Due to Defects of V(D)J Recombination
Scid Due to Defects of the Cd3/Tcr Complex
Scid Due to Other Hematopoietic Defects
Scid Due Non-Hematopoietic Defects
Combined Immune Deficiency—Definition
Cid Due to Metabolic Defects
Cid Due to Defects of Major Histocompatibility Complex Molecule Expression
CID Due to Defects of Dna Repair and DNA Replication
CID Associated With Cytoskeletal Defects
CID Due to Defects of Clathrin-Mediated Endocytosis and Iron Internalization
CID Associated With Prominent Immune Dysregulation
Other Forms of Cid Due to Defects of Transcription Factors
Management of Patients with CID
References
35. Genetic Disorders of Interferons-, Interleukin-17, Interleukin-18, and Nuclear Factor-κB-Mediated Immunity
Abstract
Genetic Disorders of Interferon-γ-Dependent Immunity and Mendelian Susceptibility to Mycobacterial Disease
Genetic Disorders Predisposing to Tuberculosis
Genetic Disorders of the TLR3 Pathway in Herpes Simplex Virus-1 Encephalitis
Genetic Disorders of Other Interferon-Inducing Pathways in Other Severe Viral Infections
Genetic Etiologies of Life-Threatening Influenza Pneumonitis
Genetic Etiologies in Human Papillomaviruses
Human Genetic Basis of Fulminant Viral Hepatitis
Hypomorphic Mutations of IKBKG/NEMO
Genetic Disorders of IKKα/IKKβ
Hypermorphic Mutations of Nuclear factor-κB Inhibitor Alpha (NFKBIA/IκBα)
LUBAC Deficiency: HOIL1/RBCK1 and HOIP/RNF31 deficiencies
IRAK4 and MYD88 Deficiency
Conclusion
Acknowledgments
References
36. Hemophagocytic Lymphohistiocytosis
Abstract
Epidemiology
Pathophysiology
Genetics
Diagnosis
Other Manifestations
Distinctive Clinical Contexts
Treatment
Summary
References
37. Autoinflammatory Syndromes
Abstract
Epidemiology
SIGNS and Symptoms
Pathogenesis
Laboratory Tests
Diagnosis
Treatment
Amyloidosis
Conclusions
References
38. Immune Regulatory Disorders
Abstract
Clinical Features of Immune Regulatory Disorders
The Genetics of Immune Regulatory Disorders
General Diagnostic Testing Approach to Immune Regulatory Disorders
Specific Immune Regulatory Disorders
Nonmalignant Lymphoproliferation
Conclusions
References
39. Neutrophils and Neutrophil Disorders
Abstract
Neutrophils
Production of Macrophages and Granulocytes
Evolution of Neutrophil Granules
Disorders of Neutrophil Production
Defects of Leukocyte Adhesion
Chronic Granulomatous Disease
Myeloperoxidase Deficiency
Chediak-Higashi Syndrome
Hyper-IgE Recurrent Infection, or Job Syndrome
Assessment of Neutrophil Function
Translational Research
Acknowledgment
References
40. Complement and Complement Disorders
Abstract
Overview: an Evolutionary and Historical Perspective
Complement Pathways
Membrane Attack Complex
Regulation of Complement Activation
Complement Receptors
Complement in Host Defense and Immunity
Complement Deficiencies
Complement in Disease
Complement-Based Therapeutics
References
41. Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome
Abstract
US Perspective
HIV Immunopathogenesis
Anti-HIV Immunity
Innate Immunity in HIV Infection
Clinical Features
Diagnosis and Monitoring of Hiv Infection
Treatment
Immunoreconstitution After Therapy
Prevention
Hiv Vaccines: Clinical Trials
Translational Research Needs and Conclusions
Acknowledgments
References
42. Autoantibody-Mediated Phenocopies of Primary Immunodeficiency Diseases
Abstract
Overview of Pathophysiology
Anti-GM-CSF Autoantibodies and Pulmonary Alveolar Proteinosis
Anti IFN-Γ Autoantibodies and Susceptibility to Intracellular Pathogens
Anti-IL-17 and Anti-IL-22 Autoantibodies and Chronic Mucocutaneous Candidiasis
Anti-IL-6 Autoantibodies and Bacterial Infections
Management
Conclusions
Acknowledgments
References
Part V: Allergic Diseases
43. Allergic Airway Diseases
Abstract
Clinical Presentation of Allergic Airway Disease
Other Airway Allergic Disease Syndromes
Immunologic Mechanisms of Allergic Airway Disease
Novel Pathways to Therapy in Inflammatory Airway Disease
References
44. Mast Cells and Mast Cell Disorders
Abstract
Mast Cell Biology
Mast Cell Activation
Mast Cell Mediators
Normal Mast Cell Function
Mast Cell Related Disease
Mast Cell Disorders
Basophils and Related Disorders
References
45. Eosinophils and Eosinophilic Disorders
Abstract
Eosinophil Biology
Role of Eosinophils in Homeostasis
Eosinophilia and Eosinophilic Disorders
Therapy of Eosinophil-Associated Disorders
Eosinophilic Gastrointestinal Disorders
Eosinophilic Granulomatosis with Polyangiitis
References
46. Urticaria, Angioedema, and Anaphylaxis
Abstract
Definition
Epidemiology
Genetics
Clinical Patterns
Etiopathophysiology
Clinical Classification
Differential Diagnosis of Urticaria
Work-up in Patients with Urticaria
Management of Urticaria
Management of Hereditary Angioedema
Translational Research Opportunities
References
47. Allergic Reactions to Stinging and Biting Insects
Abstract
Entomological Aspects,
Allergens in Hymenoptera Venoms
Clinical Picture
Epidemiological Aspects
Diagnosis
Prevention
ReferenceS
48. Atopic and Contact Dermatitis
Abstract
Clinical Aspects of Atopic Dermatitis
Pathogenesis of Atopic Dermatitis
Management of Atopic Dermatitis
Recalcitrant Disease
Prevention
Contact Dermatitis
Pathogenesis of Allergic Contact Dermatitis
Pathogenesis of Irritant Contact Dermatitis
Clinical Manifestations of Contact Dermatitis
Management of Allergic Contact Dermatitis
Perspectives in Atopic Dermatitis and Allergic Contact Dermatitis
References
49. Food Allergy
Abstract
Prevalence
Spectrum of Disease
Pathophysiology
Properties of Food Allergens
Diagnosis
Management
Treatment of a Reaction
Prevention of Food Allergy
Experimental Interventional Therapies
References
50. Drug Hypersensitivity
Abstract
Epidemiology
Immune System Recognition of Drugs
Risk Factors for Drug Allergy
Hypersensitivity Reactions
Diagnosis
Management
Specific Drug Hypersensitivity
Conclusion
References
Part VI: Systemic Immune Diseases
51. Mechanisms of Autoimmunity
Abstract
The Distinct Phases in the Development of Autoimmunity
Phase 2: Initiation
Phase 3: Propagation
Translational Research
References
52. Systemic Lupus Erythematosus
Abstract
Epidemiology
Immunopathogenesis
Hormonal Influences
Clinical Manifestations
Translational Research
Conclusions
References
53. Rheumatoid Arthritis
Abstract
Epidemiology
Etiology and Pathogenesis
Clinical Features
Treatment
References
54. Juvenile Idiopathic Arthritis
Abstract
Etiology and Pathogenesis
Environmental Factors
Immune Abnormalities
Juvenile Idiopathic Arthritis Clinical Subtypes
Differential Diagnosis
Treatment
Translational Research
References
55. Sjögren’s Syndrome
Abstract
Etiopathogenesis
Pathophysiology
Diagnosis and Classification
Clinical Features
Therapy
References
56. Scleroderma–Systemic Sclerosis
Abstract
Prevalence and Epidemiology
Etiology and Pathogenesis
Clinical Features
References
57. Inflammatory Muscle Diseases
Abstract
Clinical Features
Classification
Etiology
Pathogenesis
Genetics
Natural History
Patient Management
Diagnostic Tools, Evaluation, and Differential Diagnosis
Pitfalls
References
58. Spondyloarthritis
Abstract
Classification of Spondyloarthritis
Epidemiology
Pathogenesis
Pathology of SpA
Clinical Features
Disease Course and Prognosis
Treatment
Conclusions and Research Opportunities
References
59. Small- and Medium-Vessel Primary Vasculitis
Abstract
Epidemiology
Pathogenesis of Antineutrophil Cytoplasmic Antibody-Associated Vasculitides
Genetics
Epigenetics
Environmental and Infectious Triggers
Drug Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitides
Loss of B- and T-Cell Tolerance in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
Role of Neutrophils
Role of Complement
Pathogenesis of Kawasaki Disease
Pathogenesis of Cryoglobulinemic Vasculitis
Pathogenesis of Eosinophilic Glomerulonephritis with Polyangiitis
Classification of Vasculitides
Diagnosis
Assessment
Treatment
Outcomes
Acknowledgments
References
60. Large Vessel Vasculitides
Abstract
Epidemiology
Etiology and Pathogenesis
Innate Immune System Defects
Adaptive Immune System Defects
Clinical Features in Giant Cell Arteritis
Clinical Features in Polymyalgia Rheumatica
Clinical Features in Takayasu Arteritis
Diagnosis
Therapeutic Management
References
61. Antiphospholipid Syndrome
Abstract
Epidemiology
Etiopathogenesis
Diagnosis
Treatment
Conclusions and Translational Research
References
Part VII: Organ-Specific Inflammatory Disease
62. Immunohematologic Disorders
Abstract
Introduction
Immune-Mediated Hemolytic Anemia
Immune-Mediated Neutropenia
Immune-Mediated Thrombocytopenias
Autoimmune MULTILINEAGE Cytopenias
References
63. Bullous Diseases of the Skin and Mucous Membranes
Abstract
Introduction
Target Antigens and Disease Entities
Epidemiology
Clinical Presentations
Diagnosis
Pathophysiology
Treatment
Acknowledgments
References
64. Immunology of Psoriasis
Abstract
Clinical and Histologic Features of Psoriasis
Immune-Related Genetic Factors Predisposing to Psoriasis
Effector Cells and Immune Mechanisms Operating in Psoriasis
Conclusions
References
65. Myasthenia Gravis
Abstract
Disease Diagnosis and Classification
Neuromuscular Transmission
Autoantigens in Myasthenia Gravis and Their Roles in Neuromuscular Transmission
Experimental Models to Study Myasthenia Gravis
Mechanisms of Immunopathogenesis
Treatment
Acetylcholinesterase Inhibitors
Corticosteroids
Thymectomy
Immunosuppressants
Intravenous Immunoglobulin and Plasma Exchange
Eculizumab
Therapies Under Development
Reducing Effector Activity: Moderation of Autoantibody Levels and Complement Inhibition
Moderating Proinflammatory Signals
Future Studies
References
66. Multiple Sclerosis
Abstract
Clinical Subsets and Phenomonology
Diagnosis
Risk Factors
Pathologic Features of Multiple Sclerosis
Immunopathogenesis
Disease-Modifying Therapies
Future Directions
References
67. Autoimmune Peripheral Neuropathies
Abstract
Acute Inflammatory Polyneuropathy: Guillain-Barré Syndrome(s)
Diagnosis
Antecedent Events
Immunopathology of Guillain-Barré Syndrome
Chronic Inflammatory Demyelinating Polyneuropathy
Multifocal Motor Neuropathy with Conduction Block
Polyneuropathies Associated with Monoclonal Gammopathies of Undetermined Significance
Antibodies to Myelin-Associated Glycoprotein (MAG) in Patients with IgM MGUS (Anti-MAG Neuropathy)
Polyneuropathy, Organomegaly, Endocrinopathy, Myeloma, and Skin Changes (Poems Syndrome)
Paraneoplastic Peripheral Neuropathies WITH Anti-HU OR CRMP-5 Antibodies
Autoimmune Autonomic Neuropathies
Possibly Autoimmune Small Fiber Sensory Neuropathies, Neuropathic Pain, and Neural Antibodies
Mononeuropathy Multiplex and Localized, Isolated Vasculitis of the Peripheral Nerves
Neuropathy with Viruses
Treatment
Multifocal Motor Neuropathy
Acknowledgments
References
68. Immunologic Renal Diseases
Abstract
Hematuria
Proteinuria
Nephrotic Syndrome
Acute Nephritic Syndrome
Renal Biopsy
Minimal Change Disease
Focal Segmental Glomerulosclerosis
Membranous Nephropathy
Membranoproliferative Glomerulonephritis
Postinfectious Nephropathies
References
69. Immunologic Mechanisms ofAtherosclerosis and Myocarditis
Abstract
Immunological Mechanisms that Contribute to Atherosclerosis
Myocarditis: Immune Response that Damages the Heart
Clinical Implications of Cardiac Inflammation
References
70. Autoimmune Thyroid Diseases
Abstract
Graves Hyperthyroidism
Graves Ophthalmopathy
Future Developments for Graves Hyperthyroidism and Ophthalmopathy
Autoimmune Hypothyroidism
Future Developments
Other Forms of Thyroiditis
Postpartum Thyroiditis
Immunomodulation and Thyroid Dysfunction
Translational Research
References
71. Type 1 Diabetes
Abstract
Epidemiology and Natural History of T1DA
Pathogenesis: Nature and Nurture
Genes
β Cells
Environment—Outside and Inside
Treatment and Prevention
References
72. Immunologic Lung Diseases
Abstract
Inflammation of Interstitial Lung Diseases
Idiopathic Interstitial Pneumonias
Lung Involvement in Connective Tissue Diseases
Conclusions
References
73. Chronic Obstructive Pulmonary Disease and Emphysema
Abstract
Chronic Obstructive Pulmonary Disease Definition and Epidemiology
Chronic Obstructive Pulmonary Disease Clinical Subphenotypes
References
74. Immunologic Ocular Disease
Abstract
The Ocular Immune System
Inflammatory Diseases of the Eye
Uveitis and Intraocular Immune-mediated Inflammation
Neuro-Ophthalmic Immune-Mediated Diseases
Paraneoplastic Syndromes
Extraocular Immune-mediated Inflammation
Corneal Transplant and Transplant Rejection
Emerging Topics in Immunologic Ocular Diseases
Summary
References
75. Immunologic Diseases of the Gastrointestinal Tract
Abstract
Gastritis
Celiac Disease
Crohn Disease
Ulcerative Colitis
Other Idiopathic Inflammatory Bowel Diseases
Gastrointestinal Complications of Primary Immunodeficiencies
References
76. Inflammatory Hepatobiliary Diseases
Abstract
Autoimmune Hepatitis
Primary Biliary Cholangitis
Primary Sclerosing Cholangitis
Overlap/Variant Syndromes
Immunoglobulin 4-Related Sclerosing Cholangitis
References
Part VIII: Immunology and Immunotherapy of Neoplasia
77. Lymphoid Leukemias
Abstract
Acute Lymphoblastic Leukemia
Chronic Lymphocytic Leukemia
Conclusions
References
78. Lymphomas
Abstract
Mature B-Cell Neoplasms
T-Cell and NK-Cell Neoplasms
Hodgkin Lymphomas
References
79. Monoclonal Gammopathies
Abstract
Diagnosing a Monoclonal Gammopathy
Monoclonal Gammopathy of Undetermined Significance
Smoldering Multiple Myeloma
Multiple Myeloma
Plasma Cell Leukemia
Plasmacytoma
Immunoglobulin Light-Chain Amyloidosis
WaldenstrÖm Macroglobulinemia and Smoldering WaldenstrÖm Macroglobulinemia
Monoclonal Gammopathy of Clinical Significance
References
80. Immune Responses to Solid Tumors and Immune Checkpoint Therapy
Abstract
Immune Checkpoints
References
81. CAR T-Cell Therapy
Abstract
Car Structure
Car T-Cell Toxicity
Antigen Loss and Heterogeneity
Targeting Hematologic Malignancies
Solid Tumors and Their Immunosuppressive Microenvironment
Combating the Tme by Gene Modification of Car T Cells
The Differentiation State and Subset Origin of the Infused T Cells is Important
Intrapatient Comparative Studies Can Best Identify Optimal Car T Cells
Off-the-Shelf Car T Cells
Summary
References
Part IX: Medical Management of Immunological Diseases
82. Immunoglobulin Therapy: Replacement and Immunomodulation
Abstract
Replacement Therapy with Intravenous Immunoglobulin
Adverse Events Associated With Intravenous Immunoglobulin Therapy
Mechanisms of Action of Immunoglobulin Therapy in Autoimmune and Inflammatory Diseases
References
83. Glucocorticoids
Abstract
Mechanisms of Action
Glucocorticoid Effects on Immune Cells
The Role of Endogenous Glucocorticoids in Inflammatory Arthritis
Therapeutic Use
Glucocorticoid Treatment Regimens: General Aspects
Timing of Glucocorticoid Administration Matters
New Glucocorticoid Receptor Ligands on the Horizon
References
84. Immunomodulating Drugs
Abstract
Methotrexate
Sulfasalazine
Azathioprine
Cyclophosphamide
Leflunomide
Mycophenolate Mofetil
Hydroxyurea
Oral Cyclosporine and Tacrolimus (FK506)
Topical Pimecrolimus and Tacrolimus (FK506)
Sirolimus
Imiquimod
5-Fluorouracil
Glatiramer
Fingolimod (FTY720)
Conclusions
References
85. Protein Kinase Antagonists
Abstract
Structure and Function of Protein Kinases
A Short History of the Generation of Kinase Inhibitors
Targeting Cytokine Signaling
Jakinibs and the Type I/II Cytokine Receptor Family
Targeting Kinases Involved in TNFR Signaling
Targeting Antigen- and Related Receptor Signaling
Conclusions
References
86. Biologic Response Modifiers
Abstract
Immunomodulatory Cytokines
Inhibitors of Inflammatory Cytokines
Inhibitors of Mast Cell Activation
Inhibitors of Eosinophil Activation
B-Cell and T-Cell Depleting Agents
References
87. Vaccines
Abstract
Introduction
History of Vaccination
Accomplishments of Vaccination
Acknowledgments
References
88. Allergen Immunotherapy for Allergic Diseases
Abstract
Historical Perspective
Allergen Immunotherapy for Allergic Rhinoconjunctivitis and Asthma: Place in Therapy
References
Part X: Transplantation
89. Solid Organ Transplantation: Rejection, Immunosuppression, and Tolerance
Abstract
The Immune Response in Organ Transplantation
How Are Grafts Destroyed: The Host Effector Immune Response
Immunosuppressive Management
Tolerance
New Frontiers in Organ Supply for Transplantation: Xenotransplantation
References
90. Allogeneic Transplantation for Immunodeficiency
Abstract
Hematopoietic Stem Cell Transplantation: General Considerations
Future Directions for Hematopoietic Stem Cell Transplantation in the Treatment of Primary Immune Deficiency
References
91. Gene Therapy for Primary Immune Deficiency Diseases
Abstract
Gene Transfer to Hematopoietic Stem Cells
Clinical Trials of Gene Therapy for Primary Immune Deficiencies
Wiskott-Aldrich Syndrome (Chapter 34)
Gene Therapy Considerations for other Primary Immune Deficiencies
Gene Editing for Gene Therapy of Primary Immune Deficiencies
Use of Pluripotent Stem Cells as a Source of Hematopoietic Stem Cells for Gene Therapy of Primary Immune Deficiencies
Gene Therapy for Primary Immune Deficiencies Involving Serum Protein Deficiencies
Advancing Gene Therapy for Primary Immune Deficiencies from Experimental to Standard of Care
Conclusion
References
92. Hematopoietic Stem Cell Transplantation for Malignant Diseases
Abstract
Immune Mechanisms Related to Allo-Hematopoietic Stem Cell Transplantation
Clinical Hematopoietic Stem Cell Transplantation
Conditioning Regimens
Hematopoietic Stem Cell Transplantation for Individual Diseases
Future Directions
References
Part XI: Diagnostic Immunology
93. Flow Cytometry
Abstract
Instrumentation
Fluorescence Reagents
Data Analysis
Methods
Practical Applications of Flow Cytometry
Conclusion
Acknowledgment
References
94. Assessment of Functional Immune Responses in Lymphocytes
Abstract
T-Cell Response
Measurement of T-Cell Function Via Activation Markers
Assessment of Cellular Viability In Lymphocytes
Measurement of Cell-Mediated Cytotoxicity
Natural Killer Cell Activation and Function
Natural Killer Cell Cytotoxicity
Evaluation of Regulatory T-Cell Function
Assessment of Signaling and Dna Repair Pathways In Lymphocytes Via Phosphoflow Cytometry
Assessment of B-Cell Function
Summary
References
95. Assessment of Neutrophil Function
Abstract
Isolation of Neutrophils
Histochemical Analysis of Neutrophils
Analysis of Granule Constituents
Neutrophil Adherence
Neutrophil Chemotaxis
Expression of Surface Antigens
Neutrophil Degranulation
Generation of Reactive Oxygen Species
Western Blot Analysis of Nadph Oxidase Protein Subunits
Conclusions
Acknowledgment
References
96. Assessment of Human Allergic Diseases
Abstract
Biological Properties of Immunoglobulin E
Clinical Importance of Total Serum Immunoglobulin E
Clinical Importance of Allergen-Specific Immunoglobulin E
Clinical History
Diagnostic Methods
Initial Clinical Laboratory Tests
In Vivo Provocation Testing
In Vitro Testing
References
Appendix 1. Selected CD Molecules and Their Characteristics
Appendix 2. Laboratory Reference Values
Index

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