Clinical Immunology E-Book: Principles and Practice

Section 1: Principles Of Immune Response. The Human Immune Response -- Organization Of The Immune System -- Innate Immunity -- Antigen Receptor Genes, Gene Products, And Co-receptors -- The Major Histocompatibility Complex -- Antigens And Antigen Presentation -- B-cell Development And Differentiation -- T-cell Development -- Cytokines And Cytokine Receptors -- Chemokines And Chemokine Receptors -- Lymphocyte Adhesion And Trafficking -- T-cell Activation And Tolerance -- Regulated Cell Death -- The Microbiota In Immunity And Inflammation -- Section 2: Host Defense Mechanisms And Inflammation. Immunoglobulin Function -- Helper T-cell Subsets And Control Of The Inflammatory Response -- Cytotoxic T Lymphocytes And Natural Killer Cells -- Regulatory Immune Cells -- Host Defenses In The Skin -- Host Defenses At Mucosal Surfaces -- Complement In Host Deficiencies And Diseases -- Phagocyte Deficiencies -- Mast Cells, Basophils, And Mastocytosis -- Eosinophils And Eosinophilia-- Section 3: Host Defenses To Infectious Agents. Host Defenses To Viruses -- Host Defenses To Intracellular Bacteria -- Host Defenses To Extracellular Bacteria -- Host Defenses To Spirochetes -- Host Defenses To Fungi -- Host Defenses To Protozoa -- Host Defenses To Helminths -- Section 4: Immunologic Deficiencies. Approach To The Evaluation Of The Immunodeficient Patient -- Human Genomics In Immunology -- Primary Antibody Deficiencies -- Primary T-cell Immunodeficiencies -- Immunodeficiencies At The Interface Of Innate And Adaptive Immunity -- Infections In The Immunocompromised Host -- Immune Deficiencies At The Extremes Of Age -- Hiv Infection And Acquired Immunodeficiency Syndrome -- Autoantibody Mediated Phenocopies Of Primary Immunodeficiency Diseases -- Section 5: Allergic Diseases. Immunological Mechanisms Of Airway Diseases And Pathways To Therapy -- Urticaria, Angioedema, And Anaphylaxis -- Allergic Reactions To Stinging And Biting Insects -- Atopic And Contact Dermatitis-- Food Allergy -- Eosinophil-associated Gastrointestinal Disorders -- Allergic Disorders Of The Eye -- Drug Hypersensitivity -- Occupational Respiratory Allergies Section 6: Systemic Immune Diseases. Mechanisms Of Autoimmunity -- Systemic Lupus Erythematosus -- Rheumatoid Arthritis -- Juvenile Idiopathic Arthritis -- Sjögren's Syndrome -- Scleroderma-systemic Sclerosis -- Inflammatory Muscle Diseases -- Spondyloarthritis -- Small And Medium Vessel Primary Vasculitis -- Large-vessel Vasculitides -- Systemic Autoinflammatory Syndromes -- Antiphospholipid Syndrome -- Section 7: Organ-specific Inflammatory Disease. Immunohematologic Disorders -- Bullous Diseases Of The Skin And Mucous Membranes -- Immunology Of Psoriasis -- Myasthenia Gravis -- Multiple Sclerosis -- Autoimmune Peripheral Neuropathies -- Immunologic Renal Diseases -- Inflammation And Atherothrombosis -- Autoimmune Thyroid Diseases -- Diabetes And Related Autoimmune Diseases -- Immunologic Lung Diseases -- Sarcoidosis -- Immunologic Ocular Disease -- Immunologic Diseases Of The Gastrointestinal Tract -- Inflammatory Hepatobiliary Diseases-- Section 8: Immunology Of Neoplasia. Tumor Immunotherapy -- Lymphoid Leukemias -- Lymphomas -- Monoclonal Gammopathies -- Section 9: Transplantation. Concepts And Challenges In Organ Transplantation: Rejection, Immunosuppression, And Tolerance -- Immune Reconstitution Therapy For Immunodeficiency -- Hematopoietic Stem Cell Transplantation For Malignant Diseases -- Section 10: Prevention And Therapy Of Immunologic Diseases. Immunoglobulin Therapy: Replacement And Immunomodulation -- Gene Therapy -- Glucocorticoids -- Immunomodulating Pharmaceuticals -- Protein Kinase Antagonists As Therapeutic Agents For Immunological And Inflammatory Disorders -- Biological Modifiers Of Inflammation -- Vaccines -- Immunotherapy Of Allergic Disease -- Section 11: Diagnostic Immunology. Flow Cytometry -- Assessment Of Functional Immune Responses -- Assessment Of Neutrophil Function -- Assessment Of Human Allergic Diseases -- Molecular Methods-- Appendices. Selected Cd Molecules And Their Characteristics -- Laboratory Reference Values -- Vaccine Schedules. Edited By Robert Rich, Md [and Five Others]. Includes Bibliographical References And Index. Cover Clinical Immunology Copyright Page Preface to the First Edition Preface to the Fifth Edition List of Contributors Dedication Part One: Principles of Immune Response Chapter 1: The Human Immune Response The Host–Microbe Interaction Adaptive and Innate Immunity Cells of the Immune System Granulocytes Lymphocytes Antigen-Presenting Cells Basis of Adaptive Immunity Clonal Basis of Immunological Memory Antigen-Binding Molecules Immunoglobulins and T-Cell Receptors Receptor Selection Immunoglobulin Class Switching Major Histocompatibility Complex Antigen Presentation Lymphocyte Adhesion and Trafficking Lymphocyte Activation Cell-Mediated Immune Responses T-Cell Subsets CD4 T Cells, Cytokines, and Chemokines CD8 T Cells Antibody-Mediated Immune Responses Complement and Immune Complexes Apoptosis and Immune Homeostasis Mechanisms of Immunological Diseases Host Immune Defenses Summarized Multiple-Choice Questions References Chapter 2: Organization of the Immune System Immune Cell Development Ontogeny of the Cells of the Immune System Tools Essential to an Understanding of Immune Cell Biology Hematopoiesis and Lymphopoiesis Characteristics of Hematopoietic Stem Cells Regulation of Hematopoietic and Lymphopoietic Cell Growth and Differentiation Cytokines That Affect the Growth and Maintenance of Pluripotent and Multipotent Stem Cells Cytokines That Inhibit Hematopoietic Stem Cell Growth Cytokines Affecting Development and Differentiation of Specific Cell Lineages Mature Cells of the Immune System Antigen-Presenting Cells Monocytes–Macrophages Dendritic Cells Polymorphonuclear Granulocytes Neutrophils Eosinophils Basophils and Mast Cells Platelets and Erythrocytes Lymphocytes T Lymphocytes Subpopulations of T Cells B Cells and Plasma Cells Innate Lymphoid Cells Natural Killer Cells Noncytotoxic Innate Immune Cells Major Lymphoid Organs Bone Marrow Thymus Development of Hematopoietic and Lymphoid Cells Secondary Lymphoid Organs Systemic Immune System Spleen Lymph Nodes and Lymphatics Adipose Tissue Mucosal Immune System Gastrointestinal Tract Respiratory Tract Genital Tract Skin Commensal Organisms/Toll-Like Receptors Acknowledgments References Multiple-Choice Questions Chapter 3: Innate Immunity Barriers to Infection Skin and Mucosa Antimicrobial Proteins and Peptides Humoral Innate Immunity The Acute Phase Response The Complement System Complement Deficiency Diseases Cellular Innate Immunity Polymorphonuclear Leukocytes Intraepithelial Lymphocytes, Innate Lymphoid Cells, B1 and MZ B Cells, and Mast Cells Activating Innate Immunity Pattern Recognition Receptors Toll-Like Receptors NOD-Like Receptors RIG-I–Like Receptors C-Type Lectin Receptors Scavenger Receptors Inflammasomes Innate Immunity in Clinical Practice Multiple-Choice Questions References Chapter 4: Antigen Receptor Genes, Gene Products, and Coreceptors Paratopes and Epitopes The BCR and TCR Antigen Recognition Complex Immunoglobulins and TCR Structures The Ig Domain, the Basic IgSF Building Block Idiotypes and Isotypes The V Domain Antigen Recognition and Fab Effector Function and Fc Gm Allotype System Ig Classes and Subclasses IgM IgG IgA IgE IgD TCR αβ and γδ TCR αβ TCR γδ Ligand Recognition Binding to pMHC TCR Binding Affinity Atypical Antigens Superantigens Immunoglobulin Gene Organization The κ Locus The λ Locus The H Chain Locus Class-Switch Recombination Somatic Hypermutation Activation-Induced Cytidine Deaminase Diversity and Constraints on Immunoglobulin Sequence The TCR αδ Chain Locus The TCR β Chain Locus The TCR γ Chain Locus Allelic Exclusion B Cell Receptor Complex: Structure and Function Membrane-Bound Immunoglobulin Signal Transduction and the Ig-α/β (CD79a/CD79b) Heterodimer Clinical Consequences of Disruptions in BCR Signaling BCR Coreceptors Coreceptors That Positively Regulate BCR Signaling CD21 CD19 CD21–CD19 Coreceptor Complex Coreceptors That Negatively Regulate BCR Signaling FcγRIIB CD22 The TCR–CD3 Complex CD3 Proteins Stoichiometry of the TCR–CD3 Complex Assembly and Cell-Surface Expression of the TCR–CD3 Complex Early Events in TCR–CD3 Signaling T-Cell Coreceptors: CD4 and CD8 CD4: Structure and Binding to MHC Class II Molecules CD8: Structure and Binding to MHC Class I Molecules Costimulatory and Inhibitory T-Cell Molecules: the CD28 Family CD28 and CTLA-4 PD-1 Multiple-Choice Questions References Chapter 5: The Major Histocompatibility Complex Genomic Organization of the MHC Structure and Function of the HLA Molecules Classic HLA Class I Molecules MICA and MICB Nonclassic HLA-E, HLA-F, and HLA-G Classic Class II HLA Molecules Nonclassic HLA-DM and HLA-DO Proteosome Elements Within the Class II Region Principles of Peptide Presentation Selection by Self Peptides in the Thymus Evolutionary Considerations Driving the Separate Functions of Class I and Class II Generation and Selection of Polymorphisms: Biological Consequences Hlas in Infections, Transplantation, Autoimmunity, and Cancer HLA in Infections HLA in Transplantation HLA in Autoimmunity HLA in Cancer HLA and Disease Associations Ankylosing Spondylitis Narcolepsy Type 1 Diabetes Rheumatoid Arthritis Multiple Sclerosis Celiac Disease Drug Hypersensitivity and Pharmacogenomics Carbamazepine Nevirapine Abacavir Methods of Detecting HLA Polymorphisms: HLA Typing DNA-Based Typing Techniques: SSO, SSP, and SBT Next-Generation Sequencing HLA Nomenclature Future Learning and Resources Multiple-Choice Questions References Chapter 6: Overview of T-Cell Recognition Antigens Antibodies and T-Cell Receptors Recognize Antigens Innate Receptors Recognize Pathogen-Associated Molecular Patterns or Danger Signal Ligands The Nature of Antigen Recognition by Immunoglobulin and T-Cell Receptor Differs Antigens for B Cells Coupling of B-Cell and T-Cell Epitopes Permits Highly Focused Adaptive Responses Superantigens Antigen-Presenting Cells Cells That Present Antigens to B Cells: Follicular Dendritic Cells Cells That Present Antigens to T Cells MHC-Restricted Recognition of Antigen Class I MHC Class II MHC MHC Class II Antigen Presentation Invariant Chain Class II Peptide Loading HLA-DM and Peptide Exchange Selection of Immunodominant Peptides HLA-DO Targeting of Antigen into the MHC Class II Processing Pathway MHC Class I–Restricted Antigen Presentation The Proteasome Import of Antigenic Peptides Into the Endoplasmic Reticulum and Final Trimming The Peptide Loading Complex Cross-Presentation of Antigens for Recognition by CD8 T Cells The MHC-Presented Peptidome Cryptic Viral or Tumor-Associated Peptides Presented by MHC Class I Molecules Pathogen Evasion Strategies Tumor Escape From Immune Surveillance Potential Role of “Peptide Editing” of Presented Peptides on Self Tolerance and Autoimmunity Summary Acknowledgement Multiple-Choice Questions References Chapter 7: B-Cell Development and Differentiation B-Cell Development Begins in the Primary Lymphoid Organs 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 Controlling B-Cell Differentiation MicroRNAs and B-Cell Development Modulation of B-Cell Development by Chemokines, Cytokines, and Hormones B-Cell Development in the Periphery BAFF and APRIL Can Play Key Roles in the Development of Mature B Cells B Cells and the Response to Antigen T Cell–Independent Antigens T Cell–Dependent Antigens Organization of Peripheral Lymphoid Tissues The Spleen B-1 Cells Germinal Centers B-Cell Functions in Addition to Antibody Production Molecular Mechanism of Somatic Hypermutation and Class-Switch Recombination Somatic Hypermutation Class-Switch Recombination Both SHM and CSR Require Activation-Induced Cytidine Deaminase B-Cell Memory Memory B Cells Plasma Cells Ectopic Lymphoid Tissue and B-Cell Development Multiple-Choice Questions References Chapter 8: T-Cell Development Thymus: the Site of T-Cell Development Lineage Commitment The Common Lymphoid Progenitor The Early Thymic Progenitor Double-Negative Thymocytes Fate Commitment Transcriptional Regulation of Commitment to T-Cell Lineage Notch Notch Ligand T-Cell Factor 7 Enhancer Binding Protein GATA-3 B-Cell Chronic Lymphocytic Lymphoma/ Lymphoma 11B (Bcl11b) T-Cell Receptor Rearrangement and β Selection γδ T cells αβ T cells β Selection and the Appearance of Double-Positive Thymocytes Positive and Negative Selection Positive Selection Negative Selection Role of the Major Histocompatibility Complex in Negative Selection and Positive Selection CD4 and CD8 T-Cell Determination Transition From Double-Positive to Single-Positive CD4 or CD8 Thymocytes Factors That Dictate CD4 Versus CD8 Commitment Migration of Thymocytes Into the Periphery Multiple-Choice Questions References Chapter 9: Cytokines and Cytokine Receptors Cytokine Classification Type I and II Cytokine Receptors (Hematopoietin Family and Interferon Receptors) Ligand and Receptor Structure Family Members and Their Actions Homodimeric Receptors Cytokine Receptors Utilizing gp130 Interleukin-6. Interleukin-11. Interleukin-27. Cytokine Receptors Utilizing the βc Chain Interleukin-3. Interleukin-5. Granulocyte macrophage–colony-stimulating factor. Cytokine Receptors Utilizing the γc Chain Interleukin-2. Interleukin-4. Interleukin-7. Interleukin-9. Interleukin-15. Interleukin-21. Other Heterodimeric Receptors Interleukin-12. Interleukin-23. Interleukin-35. Interleukin-13. Interleukin-31. Thymic stromal lymphopoietin. Interferons Type I Interferons Interferon-α/β. Interferon-γ. Interleukin-10 and related cytokines. Signaling Janus Kinases Signal Transducer and Activator of Transcription (STAT) Attenuation of Type-I and Type-II Cytokine Signaling The TNF Cytokine and Receptor Superfamily Ligand and Receptor Structure Family Members and Their Actions Tumor Necrosis Factor, Lymphotoxin-α, and Receptors Fas Ligand and Its Receptor Fas/APO-1/CD95 CD40 Ligand and CD40 Other TNF-Family Cytokines Signaling Death Domains: TNF Receptor-Associated Death Domain and FAS-Associated Death Domain Clinical Relevance Interleukin-1/Toll-Like Receptor Family Ligand and Receptor Structure Family Members and Their Actions Interleukin-1 Interleukin-18 Interleukin-33 Interleukin-36 Interleukin-37 Interleukin-38 Other Members of the Interleukin-1 Family Signaling Clinical Relevance Interleukin-17 Receptors Ligand and Receptor Structure Signaling Clinical Relevance Cytokines Activating Receptor Tyrosine Kinases Ligand and Receptor Structure Family Members and Their Actions Stem Cell Factor Colony-Stimulating Factor 1 Signaling Transforming Growth Factor-β Ligand and Receptor Families Ligand and Receptor Structure TGF-β Family Members and Their Actions Signaling SMADs R-SMADs. C-SMADs. I-SMADs. SMAD pathways. Other TGF-β–Activated Pathways Clinical Relevance Other Cytokines Interleukin-14 Interleukin-16 Interleukin-32 Therapeutic Targeting of Cytokines and Cytokine Receptors Conclusions and Summary Multiple-Choice Questions References Chapter 10: Chemokines and Chemokine Receptors Introduction Molecular Organization of the Chemokine System Chemokine Receptors Atypical Chemokine System Components Immunological Classification Chemokine Presentation Mechanisms Leukocyte Responses to Chemokines Chemokine Signaling Pathways Regulation of Chemokine Action Chemokine Regulation of Hematopoiesis Bone Marrow Thymus Tissue Chemokine Regulation of the Immune Response Innate Immunity Platelet-Derived Chemokines CXCL8 and CXCR2 Natural Killer Cells Dendritic Cells and Transition to the Adaptive Immune Response Adaptive Immunity Afferent Trafficking to Secondary Lymphoid Tissue Migration Within Lymph Node Microenvironments Efferent Trafficking Tissue-Specific Lymphocyte Homing Chemokines and Disease Opposite Effects of CCR5 in HIV and West Nile Virus Infection Malaria WHIM Syndrome Atherosclerosis Kaposi’s Sarcoma Autoimmunity Acute Neutrophil-Mediated Inflammatory Disorders Transplant Rejection Allergic Airway and Intestinal Disease Cancer Therapeutic Applications Chemokines and Chemokine Receptors as Targets for Drug Development Chemokines as Biological Response Modifiers Conclusion Acknowledgments Multiple-Choice Questions References Chapter 11: Lymphocyte Adhesion and Trafficking 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 The Adhesion Cascade Receptors and Their Ligands in Leukocyte–Endothelial Cell Interaction Selectins and Their Ligands Chemokines and Their Receptors Integrins and Their Immunoglobulin Superfamily Ligands Other Homing-Associated Molecules Intraorgan Lymphocyte Localization Cell Trafficking Within Lymphatics Clinical Implications Immunodeficiencies LAD I LAD II LAD III Autoimmune or Inflammatory Diseases Multiple Sclerosis Inflammatory Bowel Diseases Cancer Adhesion Molecules as Diagnostic Targets Immunodeficiency Disorders Soluble Adhesion Molecules Imaging Therapeutic Applications of Adhesion Modulating Therapies Antibodies and Small-Molecular Drugs Adhesion-Modulating Drugs in Clinical Use Multiple-Choice Questions References Chapter 12: T-Cell Activation and Tolerance The T-Cell Antigen Receptor Complex Activation of Protein Tyrosine Kinases by the TCR and the Role of the ITAMs Second Messenger Cascades Downstream of the TCR-Stimulated PTKs Integration of Second-Messenger Pathways by Adaptor Proteins Coreceptors Transduce Signals That Are Integrated With TCR Signals Counterbalanced Costimulatory and Coinhibitory Signals Determine T-Cell Response Thresholds Spatial and Temporal Distribution of TCR Signaling Proteins Tolerance Central Tolerance/Clonal Deletion Peripheral Mechanisms of Tolerance Immune Privilege T-Cell Anergy Regulation Summary and Future Directions Multiple-Choice Questions References Chapter 13: Regulated Necrosis and Its Immunogenicity 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 Caspase-Dependent Cell Death Apoptosis Pyroptosis Caspase-Independent Regulated Necrosis Necroptosis Ferroptosis Mitochondrial Necrosis MPT-RN Parthanatos Concluding Remarks and Implications for Solid-Organ Transplantations Acknowledgements Multiple-Choice Questions References Chapter 14: The Microbiota in Immunity and Inflammation Overview of Our Nonmammalian “Self” Prokaryotes Viruses Fungi Immune Preparations for Microbial Colonization Prenatal Development of the Immune System Passive Acquisition of Antimicrobial Immunity Microbiota-Dependent Maturation of the Intestinal Immune System Gut-Associated Lymphoid Tissues Innate Lymphoid Cells Invariant Natural Killer T Cells Regulatory T Cells CD4 T-Helper Cells Mucosal B Cells Immune Consequences of Early Microbial Manipulation Immune System—Microbiota Cross-Talk in Intestinal Inflammation Gastrointestinal Infection Inflammatory Bowel Disease Extraintestinal Manifestations of Gut Microbiota–Immune System Interaction Cancer and the Microbiota Microbiota–Immune System Interactions in Cancer Susceptibility and Development The Microbiota in Cancer Immunotherapy The Skin Microbiota and the Immune System Skin Microbes Maintain Barrier Integrity in the Steady State Skin Microbes in Chronic Inflammatory Disease The Respiratory Tract Microbiota in Health and Disease The Shaping of the Healthy Respiratory Microbiota Microbes as Therapy Summary Multiple-Choice Questions References Part Two: Host Defense Mechanisms and Inflammation Chapter 15: Immunoglobulin Function Antigen Binding and Molecular Identity Physical Aspects of Binding Immunological Specificity Protein Epitopes Carbohydrate Epitopes Immune Complexes in vivo Correlations Between CH Region Structure and Antibody Function Functions Mediated by Antibody Alone Virus Neutralization Neutralization of Toxins and Enzymes Functions Mediated by Antibody and Additional Molecules or Cells Complement Activation Receptors for Fc Regions Antibodies as Surrogate Ligands Functional Properties of Engineered Antibody Molecules Monoclonal Antibodies Recombinant Antibodies Multiple-Choice Questions References Chapter 16: Helper T-Cell Subsets and Control of the Inflammatory Response Activation Clonal Expansion Trafficking Differentiation of CD4 Th Subsets Naïve T Cells Effector Cell Phenotypes Th1 Th2 Th17 Th9 Th22 Regulatory T Cells Adaptive Tregs Tr1 Cells Follicular Helper T Cells (Tfh) 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 Multiple-Choice Questions References Chapter 17: Cytotoxic T Lymphocytes and Natural Killer Cells Effector Functions/Mechanisms Cytotoxicity Perforin–Granzyme Pathway Death Receptor–Induced Apoptosis Cytokines Cytotoxic T Cells The Development and Tissue Distribution of CTLs The CTL Response Initial Activation Cross-Presentation and Priming The Contraction of Effector Populations The Long-Term Maintenance of Memory Cells CD4 T-Cell Help Detection and Analysis of CTL Function Natural Killer Cells Properties of NK Cells Tissue Distribution and Diversity of NK Cells Cytokine Regulation of NK-Cell Activation, Function, and Homeostasis NK-Cell Receptors NK-Cell Receptor Signaling NK Receptors That Recognize MHC-I Molecules Killer Cell Immunoglobulin-Like Receptors in Humans The Ly49 Family in Rodents CD94 and NKG2 Family NKG2D NK Cell Receptors That Recognize Non-MHC I Molecules NK-Cell Licensing and Self-Tolerance Specific NK-Cell Functions Control of Viral Infections Control of Malignant Cells Role of NK Cells in Hematopoietic Stem Cell Transplantation NK-Cell Memory Interactions of CTL and NK Cells in the Immune Response Evasion of the Cytotoxic Response Viruses Tumor Cells Multiple-Choice Questions References Chapter 18: Regulatory Immune Cells CD4 Regulatory T Cells Thymus-Derived Regulatory T Cells Thymus-Derived Tregs Express the Transcription Factor Foxp3 Maintenance of Foxp3+ Tregs Suppressive Function of Foxp3+ Tregs Tr1 Cells Other Subsets of Foxp3− Regulatory T Cells Suppressive Non–T Cells Clinical Relevance of Regulatory T Cells Autoimmunity Allergic Disease Transplantation Tumor Immunity Infectious Disease Translational Research Multiple-Choice Questions References Chapter 19: Host Defenses in Skin Innate Immunity and Skin Pattern Recognition Receptors Cutaneous Production of Cytokines and Chemokines Types of Cytokines and Chemokines Phases of Active Cutaneous Cytokine Secretion Initiation. Amplification. Resolution. Antimicrobial Peptides Adaptive Immunity and Skin Dendritic Cells Epidermal Langerhans Cells Dermal Dendritic Cells T Cells and Immune Responses in Skin Phases of the Cell-Mediated Immune Response in Skin Sensitization/immunization phase. Elicitation/effector phase. Skin Resident T-Cell Subpopulations Th1 responses. Th2 responses. Th17 responses. Regulatory T cells. CD8 T-cell immunity. γδ T cells. Cytokines and Chemokines and the Adaptive Immune Response in Skin Mast Cells and Skin Antibodies and Skin Ultraviolet Radiation and Cutaneous Immunity Multiple-Choice Questions References Chapter 20: Host Defenses at Mucosal Surfaces The Innate Mucosal Defense System Epithelial Cells and Other Effectors of the Mucosal Physical Barrier Defensins and Other Mucosal Antimicrobial Peptides Mucosal Innate Lymphoid Cells A Common Mucosal Adaptive Immune System MALT as an Inductive Site Gut-Associated Lymphoreticular Tissues Nasal-Associated Lymphoid Tissues Other Sites for Mucosal Induction of an Immune Response Lymphocyte Homing Into Mucosal Compartments Lymphocyte Homing in the GI Tract Lymphocyte Homing in NALTs and Lung-Associated Tissues The Common Mucosal Immune System Revisited Induction of Mucosal Immunity Mucosal Antigen-Presenting Cells CD4 T-Helper Cell Subsets in Mucosal Immunity B-Cell Isotype Switching and IgA Plasma Cell Differentiation Vaccine Development and Mucosal Immune Responses Lessons From Studies of Bacterial Enterotoxins Cellular Targets of Vaccine Adjuvants Can Shape the Immune Response Central Nervous System Targeting Is a Safety Concern With Nasal Vaccines New Mucosal Adjuvants and Delivery Systems Nontoxic Derivatives of Bacterial Enterotoxins Nucleic Acid Toll-Like Receptor Ligands Mucosal Cytokines and Innate Factors as Adjuvants Transgenic Plants Synthesis and Functions of Secretory Antibodies Polymeric Immunoglobulin Receptor and plgA Transport IgA-Mediated Inhibition of Microbial Adherence Neutralization by sIgA of Viruses, Enzymes, and Toxins Antiinflammatory Actions Mediated by SIgA Antibodies IgA Deficiency Mucosal CTLs Enteric Viruses and Mucosal CTLs Respiratory Viruses and Mucosal CTLs Mucosal AIDS Models for CTL Responses Other Mucosal CTL Systems Mucosal Immune Responses in Early Life and Aging Multiple-Choice Questions Correct Order: References Chapter 21: The Human Complement System: Overview: an Evolutionary and Historical Perspective Complement Pathways Classical Pathway Lectin Pathway Alternative Pathway Membrane Attack Complex Regulation of Complement Activation C1 Esterase Inhibitor Regulators of the C3 and C5 Convertases Factor I Soluble Regulatory Proteins, C4b-Binding Protein, and FH Membrane Regulatory Proteins Properdin Regulators of the Membrane Attack Complex Soluble MAC Inhibitors: Vitronectin and Clusterin Membrane MAC Inhibitor CD59 Complement Receptors C1q Receptors Complement Receptor 1 (CR1, CD35) Complement Receptor 2 (CR2, CD21) Complement Receptors 3 and 4 Complement Receptor of the Immunoglobulin Superfamily (CRIg) C5a and C3a Receptors Complement in Host Defense and Immunity Complement in Host Defense Complement in Inflammation Pathogen Evasion of Complement Role of Complement in Adaptive Immunity Effects of Complement on the Humoral Immune Response Complement and T-Cell Activation Role of Complement in Clearance of Apoptotic Cells Targeted Activation of Complement for Opsonization Complement Deficiencies Genetics and Incidence CP Deficiencies C1 Deficiency C4 Deficiency C2 Deficiency LP Deficiencies AP Deficiencies C3 Deficiencies Acquired C3 Deficiency: Genetic Deficiencies of FH and FI and C3 and C4 Nephritic Factors Deficiencies of Complement Receptors Deficiencies of CR1 (CD35) and CR2 (CD21) Leukocyte Adhesion Deficiency: CR3 and CR4 Deficiency Deficiencies of Regulatory Proteins Hereditary Angioedema: C1-INH Deficiency Paroxysmal Nocturnal Hemoglobinuria: DAF and CD59 Deficiency Control of Localized Complement Activation: Atypical Hemolytic–Uremic Syndrome, Age-Related Macular Degeneration Complement in Disease Measurement of Complement in a Clinical Setting Role of Complement in Specific Immunological Diseases Systemic Lupus Erythematosus (Chapter 51) Antiphospholipid Syndrome (Chapter 61) Rheumatoid Arthritis (Chapter 52) Vasculitis (Chapters 58, 59) Immunological Renal Diseases (Chapter 68) Asthma (Chapter 41) Neurological Disease Ischemia/Reperfusion Injury Complement-Based Therapeutics Multiple-Choice Questions References/Bibliography Chapter 22: Phagocyte Deficiencies Neutrophils Production of Macrophages and Granulocytes Evolution of Neutrophil Granules Disorders of Neutrophil Production Severe Congenital Neutropenia and Cyclic Neutropenia Shwachman-Bodian-Diamond Syndrome Autoimmune Neutropenia Primary Autoimmune Neutropenia Secondary Autoimmune Neutropenia Alloimmune Neonatal Neutropenia Defects of Leukocyte Adhesion Leukocyte Adhesion Defect-1 Leukocyte Adhesion Defect-2 Leukocyte Adhesion Defect-3 Chronic Granulomatous Disease The NADPH Oxidase and Its Activity Mutations Leading to CGD X-Linked CGD Autosomal Recessive CGD Clinical Manifestations of CGD Diagnosis of CGD Treatment of CGD Myeloperoxidase Deficiency Primary MPO Deficiency Secondary or Acquired MPO Deficiency Specific Granule Deficiency Chediak-Higashi Syndrome Hyper-IgE Recurrent Infection, or Job’s Syndrome Facial, Skeletal, and Dental Abnormalities Infections and Immunological Characteristics DOCK8 Deficiency (Autosomal Recessive Hyper-IgE Syndrome) GATA2 Deficiency (Monomac Syndrome) Assessment of Neutrophil Function Isolation of Neutrophils Neutrophil Adherence Neutrophil Chemotaxis Expression of Surface Antigens Neutrophil Degranulation Generation of Reactive Oxygen Species Western Blot for Determination of NADPH Oxidase Defect Translational Research Acknowledgment Multiple-Choice Questions References Chapter 23: Mast Cells, Basophils, and Mastocytosis Development and Distribution of Mast Cells Mast Cell Development and Survival Homing, Distribution, and Heterogeneity of Mast Cells Development and Distribution of Basophils Biological Mediators Produced by Mast Cells and Basophils Preformed Mediators Newly Synthesized Mediators Cytokines, Chemokines, and Growth Factors Mechanisms of Activation of Mast Cells and Basophils FcεRI-Mediated Activation (and Inhibition of IgE-Dependent Activation) Non–IgE-Mediated Activation Mast Cells and Basophils in Disease and Host Defense Allergic Disease Anaphylaxis Asthma Allergic Rhinitis Atopic Dermatitis Mast Cells and Basophils in Immunity Mast Cells in Other Diseases Mast Cell Roles in Normal Physiology Mastocytosis and Other Mast Cell Disorders Epidemiology Pathogenesis Clinical Features Classification Diagnosis Treatment Prognosis Summary and Future Research Directions Multiple-Choice Questions References Chapter 24: Eosinophils and Eosinophilia Production and Distribution of Eosinophils Eosinophilopoiesis Eosinophil Adherence Mechanisms Eosinophil Chemoattractants Structure of Eosinophils Cell-Surface Receptors and Proteins Constituents of Eosinophils Cationic Granule Proteins Cytokines and Chemokines Activated Eosinophils Mechanisms of Eosinophil Degranulation Functions of Eosinophils Roles in Host Defense Roles in Disease Pathogenesis Other Eosinophil Functions Eosinophilia and Eosinophilic Disorders Infectious Diseases Associated With Eosinophilia Helminth Parasites Other Infections: Protozoa and Fungi Human Immunodeficiency Virus and Retroviral Infections Allergic Diseases Associated With Eosinophilia Myeloproliferative and Neoplastic Disease Hypereosinophilic Syndromes Eosinophilia With Tumors or Leukemias Organ System Involvement and Eosinophilia Pulmonary Eosinophilias Skin and Subcutaneous Diseases Gastrointestinal Diseases Rheumatological Disorders Immunological Disorders Endocrine Diseases Other Causes of Eosinophilia Evaluation of Eosinophilia Multiple-Choice Questions References Part Three: Host Defenses to Infectious Agents Chapter 25: Host Defenses to Viruses 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 Multiple-Choice Questions References Chapter 26: Host Defenses to Intracellular Bacteria Balance of Protection and Pathology Defines the Chronic Nature of Intracellular Bacterial Infection Intracellular Bacterial Infections of Clinical Relevance (Table 26.1) Granulomatous Infections Tuberculosis Leprosy Atypical Mycobacterial Infections Typhoid or Enteric Fever Gastroenteritis Listeriosis Brucellosis Lymphogranuloma Venereum Melioidosis Tularemia Nongranulomatous Infections Legionnaires’ Disease or Legionellosis Chlamydial Urethritis, Cervicitis, and Conjunctivitis Trachoma Chlamydia Pneumoniae Typhus Rocky Mountain Spotted Fever, Ehrlichiosis Bartonella Granuloma Pathology as Hallmark of Intracellular Bacterial Infection The Interdependence of Innate and Adaptive Immunity in Protection Against Intracellular Bacteria Innate Immune Mechanisms as First-Line Defense Macrophage Training by Epigenetic Mechanisms Cytokines as Mediators of Defense Against Intracellular Bacteria IFN-γ, TNF-α, IL-12, and IL-18 Proinflammatory Cytokines and Phagocyte Attraction Cytokine-Induced Host-Protective Mechanisms Effector Molecules Apoptosis and Autophagy Nutrient Deprivation Evasion From, Interference With, and Resistance to Microbial Killing Strategies Against Toxic Effector Molecules Intraphagosomal Survival Phenotypic Plasticity of the Infected Cell Escape Into Cytoplasm T Lymphocytes as Specific Mediators of Acquired Resistance CD4 T Cells CD8 T Cells Unconventional T Cells T-Cell Memory and Regulation of Immune Responses B Cells Regulatory T Cells Concluding Remarks Acknowledgments Multiple-Choice Questions References Chapter 27: Host Defenses to Extracellular Bacteria Clearance and Nonspecific Host Defenses at Mucosal Epithelial Surfaces Normal Microbiota as Host Defense Antimicrobial Peptides and Antimicrobial Proteins Recognition of Extracellular Bacteria and Activation of the Immune System Pattern Recognition Receptors Complement Dendritic Cells Macrophages Polymorphonuclear Leukocytes Innate Lymphoid Cells Lymphocytes Immunoglobulins Mechanism of Immune Evasion and Disease by Extracellular Bacteria Host Risk Factors for Local and Systemic Invasion by Extracellular Pathogens Deleterious Host Responses Inflammation and Autoimmunity Sepsis Enhancement of Immune Responses to Extracellular Bacteria (Vaccines and Immunomodulation) Translational Research Opportunities Multiple-Choice Questions References Chapter 28: Host Defenses to Spirochetes Clinical Manifestations Lyme Disease Diagnosis Treatment Venereal Syphilis Diagnosis Treatment Host Defenses to B. burgdorferi Innate Immune Responses Early Pathogen Section 1: Principles Of Immune Response. The Human Immune Response -- Organization Of The Immune System -- Innate Immunity -- Antigen Receptor Genes, Gene Products, And Co-receptors -- The Major Histocompatibility Complex -- Antigens And Antigen Presentation -- B-cell Development And Differentiation -- T-cell Development -- Cytokines And Cytokine Receptors -- Chemokines And Chemokine Receptors -- Lymphocyte Adhesion And Trafficking -- T-cell Activation And Tolerance -- Regulated Cell Death -- The Microbiota In Immunity And Inflammation -- Section 2: Host Defense Mechanisms And Inflammation. Immunoglobulin Function -- Helper T-cell Subsets And Control Of The Inflammatory Response -- Cytotoxic T Lymphocytes And Natural Killer Cells -- Regulatory Immune Cells -- Host Defenses In The Skin -- Host Defenses At Mucosal Surfaces -- Complement In Host Deficiencies And Diseases -- Phagocyte Deficiencies -- Mast Cells, Basophils, And Mastocytosis -- Eosinophils And Eosinophilia-- Section 3: Host Defenses To Infectious Agents. Host Defenses To Viruses -- Host Defenses To Intracellular Bacteria -- Host Defenses To Extracellular Bacteria -- Host Defenses To Spirochetes -- Host Defenses To Fungi -- Host Defenses To Protozoa -- Host Defenses To Helminths -- Section 4: Immunologic Deficiencies. Approach To The Evaluation Of The Immunodeficient Patient -- Human Genomics In Immunology -- Primary Antibody Deficiencies -- Primary T-cell Immunodeficiencies -- Immunodeficiencies At The Interface Of Innate And Adaptive Immunity -- Infections In The Immunocompromised Host -- Immune Deficiencies At The Extremes Of Age -- Hiv Infection And Acquired Immunodeficiency Syndrome -- Autoantibody Mediated Phenocopies Of Primary Immunodeficiency Diseases -- Section 5: Allergic Diseases. Immunological Mechanisms Of Airway Diseases And Pathways To Therapy -- Urticaria, Angioedema, And Anaphylaxis -- Allergic Reactions To Stinging And Biting Insects -- Atopic And Contact Dermatitis-- Food Allergy -- Eosinophil-associated Gastrointestinal Disorders -- Allergic Disorders Of The Eye -- Drug Hypersensitivity -- Occupational Respiratory Allergies Section 6: Systemic Immune Diseases. Mechanisms Of Autoimmunity -- Systemic Lupus Erythematosus -- Rheumatoid Arthritis -- Juvenile Idiopathic Arthritis -- Sjögren's Syndrome -- Scleroderma-systemic Sclerosis -- Inflammatory Muscle Diseases -- Spondyloarthritis -- Small And Medium Vessel Primary Vasculitis -- Large-vessel Vasculitides -- Systemic Autoinflammatory Syndromes -- Antiphospholipid Syndrome -- Section 7: Organ-specific Inflammatory Disease. Immunohematologic Disorders -- Bullous Diseases Of The Skin And Mucous Membranes -- Immunology Of Psoriasis -- Myasthenia Gravis -- Multiple Sclerosis -- Autoimmune Peripheral Neuropathies -- Immunologic Renal Diseases -- Inflammation And Atherothrombosis -- Autoimmune Thyroid Diseases -- Diabetes And Related Autoimmune Diseases -- Immunologic Lung Diseases -- Sarcoidosis -- Immunologic Ocular Disease -- Immunologic Diseases Of The Gastrointestinal Tract -- Inflammatory Hepatobiliary Diseases-- Section 8: Immunology Of Neoplasia. Tumor Immunotherapy -- Lymphoid Leukemias -- Lymphomas -- Monoclonal Gammopathies -- Section 9: Transplantation. Concepts And Challenges In Organ Transplantation: Rejection, Immunosuppression, And Tolerance -- Immune Reconstitution Therapy For Immunodeficiency -- Hematopoietic Stem Cell Transplantation For Malignant Diseases -- Section 10: Prevention And Therapy Of Immunologic Diseases. Immunoglobulin Therapy: Replacement And Immunomodulation -- Gene Therapy -- Glucocorticoids -- Immunomodulating Pharmaceuticals -- Protein Kinase Antagonists As Therapeutic Agents For Immunological And Inflammatory Disorders -- Biological Modifiers Of Inflammation -- Vaccines -- Immunotherapy Of Allergic Disease -- Section 11: Diagnostic Immunology. Flow Cytometry -- Assessment Of Functional Immune Responses -- Assessment Of Neutrophil Function -- Assessment Of Human Allergic Diseases -- Molecular Methods-- Appendices. Selected Cd Molecules And Their Characteristics -- Laboratory Reference Values -- Vaccine Schedules. Edited By Robert Rich, Md [and Five Others]. Includes Bibliographical References And Index. Section 1 - Principles of Immune Response1. The Human Immune Response2. Organization of the Immune System3. Innate Immunity4. Antigen Receptor Genes, Gene Products, and Co-Receptors5. The Major Histocompatibility Complex6. Antigens and Antigen Presentation7. B-Cell Development and Differentiation8. T-Cell Development9. Cytokines and Cytokine Receptors10. Chemokines and Chemokine Receptors11. Lymphocyte Adhesion and Trafficking12. T-Cell Activation and Tolerance13. Regulated Cell Death14. The Microbiota in Immunity and InflammationSection 2 - Host Defense Mechanisms and Inflammation15. Immunoglobulin Function16. Helper T-Cell Subsets and Control of the Inflammatory Response17. Cytotoxic T Lymphocytes and Natural Killer Cells18. Regulatory Immune Cells19. Host Defenses in the Skin20. Host Defenses at Mucosal Surfaces21. Complement in Host Deficiencies And Diseases22. Phagocyte Deficiencies23. Mast Cells, Basophils, and Mastocytosis24. Eosinophils and EosinophiliaSection 3 - Host Defenses to Infectious Agents25. Host Defenses to Viruses26. Host Defenses to Intracellular Bacteria27. Host Defenses to Extracellular Bacteria28. Host Defenses to Spirochetes29. Host Defenses to Fungi30. Host Defenses to Protozoa31. Host Defenses to HelminthsSection 4 - Immunologic Deficiencies32. Approach to the Evaluation of the Immunodeficient Patient33. Human Genomics in Immunology34. Primary Antibody Deficiencies35. Primary T-cell Immunodeficiencies36. Immunodeficiencies at the Interface of Innate and Adaptive Immunity37. Infections in the Immunocompromised Host38. Immune Deficiencies at the Extremes of Age39. HIV Infection and Acquired Immunodeficiency Syndrome40. Autoantibody Mediated Phenocopies of Primary Immunodeficiency DiseasesSection 5 - Allergic Diseases41. Immunological Mechanisms of Airway Diseases and Pathways to Therapy42. Urticaria, Angioedema, and Anaphylaxis43. Allergic Reactions to Stinging and Biting Insects44. Atopic and Contact Dermatitis45. Food Allergy46. Eosinophil-Associated Gastrointestinal Disorders47. Allergic Disorders of the Eye48. Drug Hypersensitivity49. Occupational Respiratory Allergies Section 6 - Systemic Immune Diseases50. Mechanisms of Autoimmunity51. Systemic Lupus Erythematosus52. Rheumatoid Arthritis53. Juvenile Idiopathic Arthritis54. Sjögren's Syndrome55. Scleroderma-Systemic Sclerosis56. Inflammatory Muscle Diseases57. Spondyloarthritis58. Small and Medium Vessel Primary Vasculitis59. Large-Vessel Vasculitides60. Systemic Autoinflammatory Syndromes61. Antiphospholipid SyndromeSection 7 - Organ-Specific Inflammatory Disease62. Immunohematologic Disorders63. Bullous Diseases of the Skin and Mucous Membranes64. Immunology of Psoriasis65. Myasthenia Gravis66. Multiple Sclerosis67. Autoimmune Peripheral Neuropathies68. Immunologic Renal Diseases69. Inflammation and Atherothrombosis70. Autoimmune Thyroid Diseases71. Diabetes and Related Autoimmune Diseases72. Immunologic Lung Diseases73. Sarcoidosis74. Immunologic Ocular Disease75. Immunologic Diseases of the Gastrointestinal Tract76. Inflammatory Hepatobiliary DiseasesSection 8 - Immunology of Neoplasia77. Tumor Immunotherapy78. Lymphoid Leukemias79. Lymphomas80. Monoclonal GammopathiesSection 9 - Transplantation81. Concepts and Challenges in Organ Transplantation: Rejection, Immunosuppression, and Tolerance82. Immune Reconstitution Therapy for Immunodeficiency83. Hematopoietic Stem Cell Transplantation for Malignant DiseasesSection 10 - Prevention and Therapy of Immunologic Diseases84. Immunoglobulin Therapy: Replacement and Immunomodulation85. Gene Therapy86. Glucocorticoids87. Immunomodulating Pharmaceuticals88. Protein Kinase Antagonists as Therapeutic Agents for Immunological and Inflammatory Disorders89. Biological Modifiers of Inflammation90. Vaccines91. Immunotherapy of Allergic DiseaseSection 11 - Diagnostic Immunology92. Flow Cytometry93. Assessment of Functional Immune Responses94. Assessment of Neutrophil Function95. Assessment of Human Allergic Diseases96. Molecular MethodsAppendices97. A1: Selected CD Molecules and their Characteristics98. A2: Laboratory Reference Values99. A3: Vaccine Schedules