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• About this Book
• Cover Page
• Halftitle Page
• Icons Used in This Book
• Title Page
• Copyright Page
• Dedication
• About the Authors
• Brief Contents
• Feature Boxes in Kuby Immunology, Eighth Edition
• Contents
• Preface
• Acknowledgments
• Chapter 1: Overview of the Immune System
• A Historical Perspective of Immunology
• Early Vaccination Studies Led the Way to Immunology
• Vaccination Is an Ongoing, Worldwide Enterprise
• Immunology Is about More than Just Vaccines and Infectious Disease
• Immunity Involves Both Humoral and Cellular Components
• How Are Foreign Substances Recognized by the Immune System?
• Important Concepts for Understanding the Mammalian Immune Response
• Pathogens Come in Many Forms and Must First Breach Natural Barriers
• The Immune Response Quickly Becomes Tailored to Suit the Assault
• Pathogen Recognition Molecules Can Be Encoded as Genes or Generated by DNA Rearrangement
• Tolerance Ensures That the Immune System Avoids Destroying the Host
• The Immune Response Is Composed of Two Interconnected Arms: Innate Immunity and Adaptive Immunity
• Immune Cells and Molecules Can Be Found in Many Places
• Adaptive Immune Responses Typically Generate Memory
• The Good, Bad, and Ugly of the Immune System
• Inappropriate or Dysfunctional Immune Responses Can Result in a Range of Disorders
• The Immune Response Renders Tissue Transplantation Challenging
• Cancer Presents a Unique Challenge to the Immune Response
• Conclusion
• References
• Study Questions
• Chapter 2: Cells, Organs, and Microenvironments of the Immune System
• Hematopoiesis and Cells of the Immune System
• Hematopoietic Stem Cells Differentiate into All Red and White Blood Cells
• HSCs Differentiate into Myeloid and Lymphoid Blood Cell Lineages
• Cells of the Myeloid Lineage Are the First Responders to Infection
• Cells of the Lymphoid Lineage Regulate the Adaptive Immune Response
• Primary Lymphoid Organs: Where Immune Cells Develop
• The Site of Hematopoiesis Changes during Embryonic Development
• The Bone Marrow Is the Main Site of Hematopoiesis in the Adult
• The Thymus Is the Primary Lymphoid Organ Where T Cells Mature
• Secondary Lymphoid Organs: Where the Immune Response Is Initiated
• Secondary Lymphoid Organs Are Distributed throughout the Body and Share Some Anatomical Features
• Blood and Lymphatics Connect Lymphoid Organs and Infected Tissue
• The Lymph Node Is a Highly Specialized Secondary Lymphoid Organ
• The Spleen Organizes the Immune Response against Blood-Borne Pathogens
• Barrier Organs Also Have Secondary Lymphoid Tissue
• Tertiary Lymphoid Tissues Also Organize and Maintain an Immune Response
• Conclusion
• References
• Study Questions
• Chapter 3: Recognition and Response
• General Properties of Immune Receptor-Ligand Interactions
• Receptor-Ligand Binding Occurs via Multiple Noncovalent Bonds
• How Do We Describe the Strength of Receptor-Ligand Interactions?
• Interactions between Receptors and Ligands Can Be Multivalent
• Combinatorial Expression of Protein Chains Can Increase Ligand-Binding Diversity
• Adaptive Immune Receptor Genes Undergo Rearrangement in Individual Lymphocytes
• Levels of Receptor and Ligand Expression Can Vary during an Immune Response
• Local Concentrations of Ligands May Be Extremely High during Cell-Cell Interactions
• Many Immune Receptors Include Immunoglobulin Domains
• Immune Antigen Receptors Can Be Transmembrane, Cytosolic, or Secreted
• Immune Antigen Receptor Systems
• The B-Cell Receptor Has the Same Antigen Specificity as Its Secreted Antibodies
• T-Cell Antigen Receptors Recognize Antigen in the Context of MHC Proteins
• Receptors of Innate Immunity Bind to Conserved Molecules on Pathogens
• Cytokines and Their Receptors
• Cytokines Are Described by Their Functions and the Distances at Which They Act
• Cytokines Exhibit the Attributes of Pleiotropy, Redundancy, Synergism, Antagonism, and Cascade Induction
• Cytokines of the IL-1 Family Promote Proinflammatory Signals
• Class 1 Cytokines Share a Common Structural Motif But Have Varied Functions
• Class 2 Cytokines Are Grouped into Three Families of Interferons
• TNF Family Cytokines May Be Soluble or Membrane-Bound
• The IL-17 Family of Cytokines and Receptors Is the Most Recently Identified
• Chemokines Induce the Directed Movement of Leukocytes
• A Conceptual Framework for Understanding Cell Signaling
• Ligand Binding Can Induce Dimerization or Multimerization of Receptors
• Ligand Binding Can Induce Phosphorylation of Tyrosine Residues in Receptors or Receptor-Associated Molecules
• Src-Family Kinases Play Important Early Roles in the Activation of Many Immune Cells
• Intracellular Adapter Proteins Gather Members of Signaling Pathways
• Common Sequences of Downstream Effector Relays Pass the Signal to the Nucleus
• Not All Ligand-Receptor Signals Result in Transcriptional Alterations
• Immune Responses: The Outcomes of Immune System Recognition
• Changes in Protein Expression Facilitate Migration of Leukocytes into Infected Tissues
• Activated Macrophages and Neutrophils May Clear Pathogens without Invoking Adaptive Immunity
• Antigen Activation Optimizes Antigen Presentation by Dendritic Cells
• Cytokine Secretion by Dendritic Cells and T Cells Can Direct the Subsequent Immune Response
• Antigen Stimulation by T and B Cells Promotes Their Longer-Term Survival
• Antigen Binding by T Cells Induces Their Division and Differentiation
• Antigen Binding by B Cells Induces Their Division and Differentiation
• Conclusion
• References
• Study Questions
• Chapter 4: Innate Immunity
• Anatomical Barriers to Infection
• Epithelial Barriers Prevent Pathogen Entry into the Body’s Interior
• Antimicrobial Proteins and Peptides Kill Would-Be Invaders
• Cellular Innate Response Receptors and Signaling
• Toll-Like Receptors Initiate Responses to Many Types of Molecules from Extracellular Pathogens
• C-Type Lectin Receptors Bind Carbohydrates on the Surfaces of Extracellular Pathogens
• NOD-Like Receptors Bind PAMPs from Cytosolic Pathogens
• ALRs Bind Cytosolic DNA
• RLRs Bind Cytosolic Viral RNA
• cGAS and STING Are Activated by Cytosolic DNA and Dinucleotides
• Induced Innate Immunity Effector Mechanisms
• Expression of Innate Immunity Proteins Is Induced by PRR Signaling
• Phagocytosis Is an Important Mechanism for Eliminating Pathogens
• Regulated Cell Death Contributes to Pathogen Elimination
• Local Inflammation Is Triggered by Innate Immune Responses
• Innate Lymphoid Cells
• Natural Killer Cells Are ILCs with Cytotoxic Activity
• ILC Populations Produce Distinct Cytokines and Have Different Roles
• Regulation and Evasion of Innate and Inflammatory Responses
• Innate and Inflammatory Responses Can Be Harmful
• Innate and Inflammatory Responses Are Regulated Both Positively and Negatively
• Pathogens Have Evolved Mechanisms to Evade Innate and Inflammatory Responses
• Interactions between the Innate and Adaptive Immune Systems
• The Innate Immune System Activates Adaptive Immune Responses
• Recognition of Pathogens by Dendritic Cells Influences Helper T-Cell Differentiation
• Some Antigens Containing PAMPs Can Activate B Cells Independent of Helper T Cells
• Adjuvants Activate Innate Immune Responses That Increase the Effectiveness of Immunizations
• Some Pathogen Clearance Mechanisms Are Common to Both Innate and Adaptive Immune Responses
• Ubiquity of Innate Immunity
• Some Innate Immune System Components Occur across the Plant and Animal Kingdoms
• Invertebrate and Vertebrate Innate Immune Responses Show Both Similarities and Differences
• Conclusion
• References
• Study Questions
• Chapter 5: The Complement System
• The Major Pathways of Complement Activation
• The Classical Pathway Is Initiated by Antibody Binding to Antigens
• The Lectin Pathway Is Initiated When Soluble Proteins Recognize Microbial Antigens
• The Alternative Pathway Is Initiated in Three Distinct Ways
• The Three Complement Pathways Converge at the Formation of C5 Convertase and Generation of the MAC
• The Diverse Functions of Complement
• Complement Receptors Connect Complement-Tagged Pathogens to Effector Cells
• Complement Enhances Host Defense against Infection
• Complement Acts at the Interface between Innate and Adaptive Immunities
• Complement Aids in the Contraction Phase of the Immune Response
• The Regulation of Complement Activity
• Complement Activity Is Passively Regulated by Short Protein Half-Lives and Host Cell Surface Composition
• The C1 Inhibitor, C1INH, Promotes Dissociation of C1 Components
• Decay-Accelerating Factor Promotes Decay of C3 Convertases
• Factor I Degrades C3b and C4b
• CD59 (Protectin) Inhibits the MAC Attack
• Carboxypeptidases Can Inactivate the Anaphylatoxins C3a and C5a
• Complement Deficiencies
• Microbial Complement Evasion Strategies
• The Evolutionary Origins of the Complement System
• Conclusion
• References
• Study Questions
• Chapter 6: The Organization and Expression of Lymphocyte Receptor Genes
• The Puzzle of Immunoglobulin Gene Structure
• Investigators Proposed Two Early Theoretical Models of Antibody Genetics
• Breakthrough Experiments Revealed That Multiple Gene Segments Encode the Immunoglobulin Light Chain
• Multigene Organization of Immunoglobulin Genes
• κ Light-Chain Genes Include V, J, and C Segments
• λ Light-Chain Genes Include Paired J and C Segments
• Heavy-Chain Gene Organization Includes VH, D, JH, and CH Segments
• The Antibody Genes Found in Mature B Cells Are the Product of DNA Recombination
• The Mechanism of V(D)J Recombination
• V(D)J Recombination in Lymphocytes Is a Highly Regulated Sequential Process
• Recombination Is Directed by Recombination Signal Sequences
• Gene Segments Are Joined by a Diverse Group of Proteins
• V(D)J Recombination Occurs in a Series of Well-Regulated Steps
• Five Mechanisms Generate Antibody Diversity in Naïve B Cells
• The Regulation of V(D)J Gene Recombination Involves Chromatin Alteration
• B-Cell Receptor Expression
• Each B Cell Synthesizes only one Heavy Chain and One Light Chain
• Receptor Editing of Potentially Autoreactive Receptors Occurs in Light Chains
• mRNA Splicing Regulates the Expression of Membrane-Bound versus Secreted Ig
• T-Cell Receptor Genes and Their Expression
• Understanding the Protein Structure of the TCR Was Critical to the Process of Discovering the Genes
• The β-Chain Gene Was Discovered Simultaneously in Two Different Laboratories
• A Search for the α-Chain Gene Led to the γ-Chain Gene Instead
• TCR Genes Are Arranged in V, D, and J Clusters of Gene Segments
• Recombination of TCR Gene Segments Proceeds at a Different Rate and Occurs at Different Stages of Development in αβ versus γδ T Cells
• The Process of TCR Gene Segment Rearrangement Is Very Similar to Immunoglobulin Gene Recombination
• TCR Expression Is Controlled by Allelic Exclusion
• Conclusion
• References
• Study Questions
• Chapter 7: The Major Histocompatibility Complex and Antigen Presentation
• The Structure and Function of MHC Class I and II Molecules
• Class I Molecules Consist of One Large Glycoprotein Heavy Chain Plus a Small Protein Light Chain
• Class II Molecules Consist of Two Nonidentical Membrane-Bound Glycoprotein Chains
• Class I and II Molecules Exhibit Polymorphism in the Region That Binds to Peptides
• The Organization and Inheritance of MHC Genes
• The MHC Locus Encodes the Three Major Classes of MHC Molecules
• Allelic Forms of MHC Genes Are Inherited in Linked Groups Called Haplotypes
• MHC Molecules Are Codominantly Expressed
• Class I and Class II Molecules Exhibit Diversity at Both the Individual and Species Levels
• MHC Polymorphism Is Primarily Limited to the Antigen-Binding Groove
• The Role and Expression Pattern of MHC Molecules
• MHC Molecules Present Both Intracellular and Extracellular Antigens
• MHC Class I Expression Is Found Throughout the Body
• Expression of MHC Class II Molecules Is Primarily Restricted to Antigen-Presenting Cells
• MHC Expression Can Change with Changing Conditions
• MHC Alleles Play a Critical Role in Immune Responsiveness
• Seminal Studies Demonstrate That T Cells Recognize Peptide Presented in the Context of Self-MHC Alleles
• Evidence Suggests Distinct Antigen Processing and Presentation Pathways
• The Endogenous Pathway of Antigen Processing and Presentation
• Peptides Are Generated by Protease Complexes Called Proteasomes
• Peptides Are Transported from the Cytosol to the Rough Endoplasmic Reticulum
• Chaperones Aid Peptide Assembly with MHC Class I Molecules
• The Exogenous Pathway of Antigen Processing and Presentation
• Peptides Are Generated from Internalized Antigens in Endocytic Vesicles
• The Invariant Chain Guides Transport of MHC Class II Molecules to Endocytic Vesicles
• Peptides Assemble with MHC Class II Molecules by Displacing CLIP
• Unconventional Antigen Processing and Presentation
• Dendritic Cells Can Cross-Present Exogenous Antigen via MHC Class I Molecules
• Cross-Presentation by APCs Is Essential for the Activation of Naïve CD8+ T Cells
• Presentation of Nonpeptide Antigens
• Conclusion
• References
• Study Questions
• Chapter 8: T-Cell Development
• Early Thymocyte Development
• Thymocytes Progress through Four Double-Negative Stages
• Thymocytes Express Either αβ or γδ T Cell Receptors
• DN Thymocytes Undergo β-Selection, Which Results in Proliferation and Differentiation
• Positive and Negative Selection
• Thymocytes “Learn” MHC Restriction in the Thymus
• T Cells Undergo Positive and Negative Selection
• Positive Selection Ensures MHC Restriction
• Negative Selection (Central Tolerance) Ensures Self-Tolerance
• The Selection Paradox: Why Don’t We Delete All Cells We Positively Select?
• An Alternative Model Can Explain the Thymic Selection Paradox
• Do Positive and Negative Selection Occur at the Same Stage of Development, or in Sequence?
• Lineage Commitment
• Several Models Have Been Proposed to Explain Lineage Commitment
• Transcription Factors Th-POK and Runx3 Regulate Lineage Commitment
• Double-Positive Thymocytes May Commit to Other Types of Lymphocytes
• Exit from the Thymus and Final Maturation
• Other Mechanisms That Maintain Self-Tolerance
• TREG Cells Negatively Regulate Immune Responses
• Peripheral Mechanisms of Tolerance Also Protect against Autoreactive Thymocytes
• Conclusion
• References
• Study Questions
• Chapter 9: B-Cell Development
• B-Cell Development in the Bone Marrow
• Changes in Cell-Surface Markers, Gene Expression, and Immunoglobulin Gene Rearrangements Define the Stages of B-Cell Development
• The Earliest Steps in Lymphocyte Differentiation Culminate in the Generation of a Common Lymphoid Progenitor
• The Later Stages of B-Cell Development Result in Commitment to the B-Cell Phenotype and the Stepwise Rearrangement of Immunoglobulin Genes
• Immature B Cells in the Bone Marrow Are Exquisitely Sensitive to Tolerance Induction through the Elimination of Self-Reactive Cells
• Completion of B-Cell Development in the Spleen
• T1 and T2 Transitional B Cells Form in the Spleen and Undergo Selection for Survival and against Self-Reactivity
• T2 B Cells Give Rise to Mature Follicular B-2 B Cells
• T3 B Cells Are Primarily Self-Reactive and Anergic
• The Properties and Development of B-1 and Marginal Zone B Cells
• B-1a, B-1b, and MZ B Cells Differ Phenotypically and Functionally from B-2 B Cells
• B-1a B Cells Are Derived from a Distinct Developmental Lineage
• Comparison of B- and T-Cell Development
• Conclusion
• References
• Study Questions
• Chapter 10: T-Cell Activation, Helper Subset Differentiation, and Memory
• T-Cell Activation and the Two-Signal Hypothesis
• TCR Signaling Provides Signal 1 and Sets the Stage for T-Cell Activation
• Costimulatory Signals Are Required for Optimal T-Cell Activation Whereas Coinhibitory Signals Prevent T-Cell Activation
• Clonal Anergy Results If a Costimulatory Signal Is Absent
• Cytokines Provide Signal 3
• Antigen-Presenting Cells Provide Costimulatory Ligands and Cytokines to Naïve T Cells
• Superantigens Are a Special Class of T-Cell Activators
• Helper CD4+ T-Cell Differentiation
• Helper T Cells Can Be Divided into Distinct Subsets and Coordinate Type 1 and Type 2 Responses
• The Differentiation of Helper T-Cell Subsets Is Regulated by Polarizing Cytokines
• Each Effector Helper T-Cell Subset Has Unique Properties
• Helper T Cells May Not Be Irrevocably Committed to a Lineage
• Helper T-Cell Subsets Play Critical Roles in Immune Health and Disease
• T-Cell Memory
• Naïve, Effector, and Memory T Cells Can Be Distinguished by Differences in Surface Protein Expression
• Memory Cell Subpopulations Are Distinguished by Their Locale and Effector Activity
• Many Questions Remain Surrounding Memory T-Cell Origins and Functions
• Conclusion
• References
• Study Questions
• Chapter 11: B-Cell Activation, Differentiation, and Memory Generation
• T-Dependent B-Cell Responses: Activation
• Naïve B Cells Encounter Antigen in the Lymph Nodes and Spleen
• B-Cell Recognition of Cell-Bound Antigen Culminates in the Formation of an Immunological Synapse
• Antigen Binding to the BCR Leads to Activation of a Signal Transduction Cascade within the B Cell
• B Cells Also Receive and Propagate Signals through Coreceptors
• B Cells Use More Than One Mechanism to Acquire Antigen from Antigen-Presenting Cells
• Antigen Receptor Binding Induces Internalization and Antigen Presentation
• The Early Phases of the T-Dependent Response Are Characterized by Chemokine-Directed B-Cell Migration
• Specification of the Stimulated B-Cell Fate Depends on Transcription Factor Expression
• T-Dependent B-Cell Responses: Differentiation and Memory Generation
• Some Activated B Cells Differentiate into Plasma Cells That Form the Primary Focus
• Other Activated B Cells Enter the Follicles and Initiate a Germinal Center Response
• The Mechanisms of Somatic Hypermutation and Class Switch Recombination
• Memory B Cells Recognizing T-Dependent Antigens Are Generated Both within and outside the Germinal Center
• Most Newly Generated B Cells Are Lost at the End of the Primary Immune Response
• T-Independent B-Cell Responses
• T-Independent Antigens Stimulate Antibody Production in the Absence of T-Cell Help
• Two Novel Subclasses of B Cells Mediate the Response to T-Independent Antigens
• Negative Regulation of B Cells
• Negative Signaling through CD22 Balances Positive BCR-Mediated Signaling
• Negative Signaling through the Receptor FcγRIIb Inhibits B-Cell Activation
• CD5 Acts as a Negative Regulator of B-Cell Signaling
• B-10 B Cells Act as Negative Regulators by Secreting IL-10
• Conclusion
• References
• Study Questions
• Chapter 12: Effector Responses: Antibody- and Cell-Mediated Immunity
• Antibody-Mediated Effector Functions
• Antibodies Provide Protection against Pathogens, Toxins, and Harmful Cells in a Variety of Ways
• Different Antibody Classes Mediate Different Effector Functions
• Fc Receptors Mediate Many Effector Functions of Antibodies
• Protective Effector Functions Vary among Antibody Classes
• Antibodies Have Many Therapeutic Uses in Treating Diseases
• Cell-Mediated Effector Responses
• Cytotoxic T Lymphocytes Recognize and Kill Infected or Tumor Cells via T-Cell Receptor Activation
• Natural Killer Cell Activity Depends on the Balance of Activating and Inhibitory Signals
• NKT Cells Bridge the Innate and Adaptive Immune Systems
• Conclusion
• References
• Study Questions
• Chapter 13: Barrier Immunity: The Immunology of Mucosa and Skin
• Common Themes in Barrier Immune Systems
• All Barrier Surfaces Are Lined by One or More Layers of Epithelial Cells
• Barrier Organs Are Populated by Innate and Adaptive Immune Cells That Interact with Epithelium and Secondary Lymphoid Tissue
• Barrier Immune Systems Initiate Both Tolerogenic and Inflammatory Responses to Microorganisms
• Intestinal Immunity
• The Gut Is Organized into Different Anatomical Sections and Tissue Layers
• Gut Epithelial Cells Vary in Phenotype and Function
• Setting the Stage: Maintaining Immune Homeostasis in the Intestine
• The Gut Immune System Maintains a Barrier between the Microbiome and the Epithelium
• Antigen Is Delivered from the Intestinal Lumen to Antigen-Presenting Cells in Multiple Ways
• Immune Homeostasis in the Intestine Is Promoted by Several Innate and Adaptive Cell Types
• The Immune Systems in the Small and Large Intestines Differ
• Commensal Microbes Help Maintain Tolerogenic Tone in the Intestine
• Springing into Action: Intestinal Immune System Response to Invasion
• The Gut Immune System Recognizes and Responds to Harmful Pathogens
• The Intestinal Immune System Can Mount Both Type 1 and Type 2 Responses
• Dysbiosis, Inflammatory Bowel Disease, and Celiac Disease
• Other Barrier Immune Systems
• The Respiratory Immune System Shares Many Features with the Intestinal Immune System
• The Skin Is a Unique Barrier Immune System
• Conclusion
• References
• Study Questions
• Chapter 14: The Adaptive Immune Response in Space and Time
• Immune Cells in Healthy Tissue: Homeostasis
• Naïve Lymphocytes Circulate between Secondary and Tertiary Lymphoid Tissues
• Extravasation Is Driven by Sequential Activation of Surface Molecules
• Naïve Lymphocytes Browse for Antigen along the Reticular Network of Secondary Lymphoid Organs
• Immune Cell Response to Antigen: The Innate Immune Response
• Innate Immune Cells Are Activated by Antigen Binding to Pattern Recognition Receptors
• Antigen Travels in Two Different Forms to Secondary Lymphoid Tissue via Afferent Lymphatics
• Antigen-Presenting Cells Presenting Processed Antigen Travel to the T-Cell Zones of Secondary Lymphoid Tissue
• Unprocessed Antigen Travels to the B-Cell Zones
• Blood-Borne Antigen Is Captured by Specialized APCs at the Marginal Zone of the Spleen
• First Contact between Antigen and Lymphocytes
• Naïve CD4+ T Cells Arrest Their Movements after Engaging Antigens
• B Cells Seek Help from CD4+ T Cells at the Border between the Follicle and Paracortex of the Lymph Node
• Dynamic Imaging Adds New Perspectives on B- and T-Cell Behavior in Germinal Centers
• CD8+ T Cells Are Activated in the Lymph Node via a Multicellular Interaction
• A Summary of the Timing of a Primary Response
• Differentiation into Central Memory T Cells Begins Early in the Primary Response
• The Immune Response Contracts within 10 to 14 Days
• The Effector and Memory Cell Response
• Activated Lymphocytes Exit the Lymph Node and Recirculate through Various Tissues
• Chemokine Receptors and Adhesion Molecules Regulate Homing of Memory and Effector Lymphocytes to Peripheral Tissues
• The Immune Response: Case Studies
• CD8+ T-Cell Response to Infection with Toxoplasma gondii
• Resident Memory T-Cell Response to Herpes Simplex Virus Infection
• Host Immune Cell Response to a Tissue Graft
• Dendritic Cell Contribution to Listeria Infection
• T-Cell Response to Tumors
• Regulatory T Cells Inhibit the Immune Response in Multiple Ways
• Conclusion
• References
• Study Questions
• Chapter 15: Allergy, Hypersensitivities, and Chronic Inflammation
• Allergies: Type I Hypersensitivity
• IgE Antibodies Are Responsible for Type I Hypersensitivity
• Many Allergens Can Elicit a Type I Response
• IgE Antibodies Act by Binding Antigen, Resulting in the Cross-Linking of Fcε Receptors
• IgE Receptor Signaling Is Tightly Regulated
• Granulocytes Produce Molecules Responsible for Type I Hypersensitivity Symptoms
• Type I Hypersensitivities Are Characterized by Both Early and Late Responses
• There Are Several Categories of Type I Hypersensitivity Reactions
• Susceptibility to Type I Hypersensitivity Reactions Is Influenced by Both Environmental Factors and Genetics
• Diagnostic Tests and Treatments Are Available for Allergic Reactions
• Why Did Allergic Responses Evolve?
• Antibody-Mediated (Type II) Hypersensitivity
• Transfusion Reactions Are an Example of Type II Hypersensitivity
• Hemolytic Disease of the Newborn Is Caused by Type II Reactions
• Hemolytic Anemia Can Be Drug Induced
• Immune Complex–Mediated (Type III) Hypersensitivity
• Immune Complexes Can Damage Various Tissues
• Immune Complex–Mediated Hypersensitivity Can Resolve Spontaneously
• Auto-Antigens Can Be Involved in Immune Complex–Mediated Reactions
• Arthus Reactions Are Localized Type III Hypersensitivity Reactions
• Delayed-Type (Type IV) Hypersensitivity
• The Initiation of a Type IV DTH Response Involves Sensitization by Antigen
• The Effector Phase of a Classical DTH Response Is Induced by Second Exposure to a Sensitizing Antigen
• The DTH Reaction Can Be Detected by a Skin Test
• Contact Dermatitis Is a Type IV Hypersensitivity Response
• Chronic Inflammation
• Infections Can Cause Chronic Inflammation
• There Are Noninfectious Causes of Chronic Inflammation
• Obesity Is Associated with Chronic Inflammation
• Chronic Inflammation Can Cause Systemic Disease
• Conclusion
• References
• Study Questions
• Chapter 16: Tolerance, Autoimmunity, and Transplantation
• Establishment and Maintenance of Tolerance
• Antigen Sequestration, or Evasion, Is One Means to Protect Self Antigens from Attack
• Central Tolerance Processes Occur in Primary Lymphoid Organs
• Cells That Mediate Peripheral Tolerance Are Generated Outside Primary Lymphoid Organs
• Multiple Immune Cell Types Work in the Periphery to Inhibit Anti-Self Responses
• Autoimmunity
• Some Autoimmune Diseases Target Specific Organs
• Some Autoimmune Diseases Are Systemic
• Both Intrinsic and Extrinsic Factors Can Favor Susceptibility to Autoimmune Disease
• What Causes Autoimmunity?
• Treatments for Autoimmune Disease Range from General Immune Suppression to Targeted Immunotherapy
• Transplantation Immunology
• Demand for Transplants Is High, but Organ Supplies Remain Low
• Antigenic Similarity between Donor and Recipient Improves Transplant Success
• Some Organs Are More Amenable to Transplantation Than Others
• Matching Donor and Recipient Involves Prior Assessment of Histocompatibility
• Allograft Rejection Follows the Rules of Immune Specificity and Memory
• Graft Rejection Takes a Predictable Clinical Course
• Immunosuppressive Therapy Can Be Either General or Target-Specific
• Immune Tolerance to Allografts Is Favored in Certain Instances
• Conclusion
• References
• Study Questions
• Chapter 17: Infectious Diseases and Vaccines
• The Importance of Barriers and Vectors in Infectious Disease
• The Link between Location and Immune Effector Mechanism
• Mucosal or Barrier Infections Are Typically Controlled by TH2-Type Responses
• Extracellular Pathogens Must Be Recognized and Attacked Using Extracellular Tools
• Mechanisms That Recognize Infected Host Cells Are Required to Combat Intracellular Infections
• Viral Infections
• The Antiviral Innate Response Provides Key Instructions for the Later Adaptive Response
• Many Viruses Are Neutralized by Antibodies
• Cell-Mediated Immunity is Important for Viral Control and Clearance
• Viruses Employ Several Strategies to Evade Host Defense Mechanisms
• The Imprinting of a Memory Response Can Influence Susceptibility to Future Viral Infection
• Bacterial Infections
• Immune Responses to Extracellular and Intracellular Bacteria Differ
• Bacteria Can Evade Host Defense Mechanisms at Several Different Stages
• Parasitic Infections
• Protozoan Parasites Are a Diverse Set of Unicellular Eukaryotes
• Parasitic Worms (Helminths) Typically Generate Weak Immune Responses
• Fungal Infections
• Innate Immunity Controls Most Fungal Infections
• Immunity against Fungal Pathogens Can Be Acquired
• Emerging and Re-emerging Infectious Diseases
• Some Noteworthy New Infectious Diseases Have Appeared Recently
• Diseases May Re-emerge for Various Reasons
• Vaccines
• Basic Research and Rational Design Advance Vaccine Development
• Protective Immunity Can Be Achieved by Active or Passive Immunization
• There Are Several Vaccine Strategies, Each with Unique Advantages and Challenges
• Adding a Conjugate or Multivalent Component Can Improve Vaccine Immunogenicity
• Adjuvants Are Included to Enhance the Immune Response to a Vaccine
• Conclusion
• References
• Study Questions
• Chapter 18: Immunodeficiency Diseases
• Primary Immunodeficiencies
• Primary Immunodeficiency Diseases Are Often Detected Early in Life
• Combined Immunodeficiencies Disrupt Adaptive Immunity
• B-Cell Immunodeficiencies Exhibit Depressed Production of One or More Antibody Isotypes
• Disruptions to Innate Immune Components May Also Impact Adaptive Responses
• Complement Deficiencies Are Relatively Common
• NK-Cell Deficiencies Increase Susceptibility to Viral Infections and Cancer
• Immunodeficiency Disorders That Disrupt Immune Regulation Can Manifest as Autoimmunity
• Immunodeficiency Disorders Are Treated by Replacement Therapy
• Animal Models of Immunodeficiency Have Been Used to Study Basic Immune Function
• Secondary Immunodeficiencies
• Secondary Immunodeficiencies May Be Caused by a Variety of Factors
• HIV/AIDS Has Claimed Millions of Lives Worldwide
• The Retrovirus HIV-1 Is the Causative Agent of AIDS
• HIV-1 is Spread by Intimate Contact with Infected Body Fluids
• In Vitro Studies Have Revealed the Structure and Life Cycle of HIV
• HIV Variants with Preference for CCR5 or CXCR4 Coreceptors Play Different Roles in Infection
• Infection with HIV Leads to Gradual Impairment of Immune Function
• Changes over Time Lead to Progression to AIDS
• Antiretroviral Therapy Inhibits HIV Replication, Disease Progression, and Infection of Others
• A Vaccine May Be the Only Way to Stop the HIV/AIDS Pandemic
• Conclusion
• References
• Study Questions
• Chapter 19: Cancer and the Immune System
• Terminology and the Formation of Cancer
• Accumulated DNA Alterations or Translocation Can Induce Cancer
• Genes Associated with Cancer Control Cell Proliferation and Survival
• Malignant Transformation Involves Multiple Steps
• Tumor Antigens
• Tumor-Specific Antigens Contain Unique Sequences
• Tumor-Associated Antigens Are Normal Cellular Proteins with Unique Expression Patterns
• The Immune Response to Cancer
• Immunoediting Can Both Protect Against and Promote Tumor Growth
• Innate and Adaptive Pathways Participate in Cancer Detection and Eradication
• Some Immune Response Elements Can Promote Cancer Survival
• Tumor Cells Evolve to Evade Immune Recognition and Apoptosis
• Anticancer Immunotherapies
• Monoclonal Antibodies Can Be Used to Direct the Immune Response to Tumor Cells
• Tumor-Specific T Cells Can Be Expanded, or Even Created
• Therapeutic Vaccines May Enhance the Antitumor Immune Response
• Manipulation of Comodulatory Signals, Using Checkpoint Blockade
• Conclusion
• References
• Study Questions
• Chapter 20: Experimental Systems and Methods
• Antibody Generation
• Polyclonal Antibodies Are Secreted by Multiple Clones of Antigen-Specific B Cells
• A Monoclonal Antibody Is the Product of a Single Stimulated B Cell
• Monoclonal Antibodies Can Be Modified for Use in the Laboratory or the Clinic
• Immunoprecipitation- and Agglutination-Based Techniques
• Immunoprecipitation Can Be Performed in Solution
• Immunoprecipitation of Soluble Antigens Can Be Performed in Gel Matrices
• Immunoprecipitation Enables Isolation of Specific Molecules from Cell and Tissue Extracts
• Hemagglutination Reactions Can Be Used to Detect Any Antigen Conjugated to the Surface of Red Blood Cells
• Hemagglutination Inhibition Reactions Are Used to Detect the Presence of Viruses and of Antiviral Antibodies
• Bacterial Agglutination Can Be Used to Detect Antibodies to Bacteria
• Antibody Assays Based on Molecules Bound to Solid-Phase Supports
• Radioimmunoassays Are Used to Measure the Concentrations of Biologically Relevant Proteins and Hormones in Body Fluids
• ELISAs Use Antibodies or Antigens Covalently Bound to Enzymes
• ELISPOT Assays Measure Molecules Secreted by Individual Cells
• Western Blotting Is an Assay That Can Identify a Specific Protein in a Complex Protein Mixture
• Methods to Determine the Affinity of Antigen-Antibody Interactions
• Equilibrium Dialysis Can Be Used to Measure Antibody Affinity for Antigen
• Surface Plasmon Resonance Is Now Commonly Used for Measurements of Antibody Affinity
• Antibody-Mediated Microscopic Visualization of Cells and Subcellular Structures
• Immunocytochemistry and Immunohistochemistry Use Enzyme-Conjugated Antibodies to Create Images of Fixed Tissues
• Immunoelectron Microscopy Uses Gold Beads to Visualize Antibody-Bound Antigens
• Immunofluorescence-Based Imaging Techniques
• Fluorescence Can Be Used to Visualize Cells and Molecules
• Confocal Fluorescence Microscopy Provides Three-Dimensional Images of Extraordinary Clarity
• Multiphoton Fluorescence Microscopy Is a Variation of Confocal Microscopy
• Intravital Imaging Allows Observation of Immune Responses in Vivo
• Visualization and Analysis of DNA Sequences in Intact Chromatin
• Flow Cytometry and Cell Sorting
• The Flow Cytometer Measures Scattered and Fluorescent Light from Cells Flowing Past a Laser Beam
• Sophisticated Software Allows the Investigator to Identify Individual Cell Populations within a Sample
• Flow Cytometers and Fluorescence-Activated Cell Sorters Have Important Clinical Applications
• The Analysis of Multicolor Fluorescence Data Has Required the Development of Increasingly Sophisticated Software
• CyTOF Uses Antibodies to Harness the Power of Mass Spectrometry
• Magnets Can Be Used in a Gentle, Sterile Method for Sorting Cells
• Cell Cycle Analysis
• Tritiated Thymidine Uptake Was One of the First Methods Used to Assess Cell Division
• Colorimetric Assays for Cell Division Are Rapid and Eliminate the Use of Radioactive Isotopes
• Bromodeoxyuridine-Based Assays for Cell Division Use Antibodies to Detect Newly Synthesized DNA
• Propidium Iodide Enables Analysis of the Cell Cycle Status of Cell Populations
• Carboxyfluorescein Succinimidyl Ester Can Be Used to Follow Cell Division
• Assays of Cell Death
• The 51Cr Release Assay Was the First Assay Used to Measure Cell Death
• Fluorescently Labeled Annexin A5 Measures Phosphatidylserine in the Outer Lipid Envelope of Apoptotic Cells
• The TUNEL Assay Measures Apoptotically Generated DNA Fragmentation
• Caspase Assays Measure the Activity of Enzymes Involved in Apoptosis
• Analysis of Chromatin Structure
• Chromatin Immunoprecipitation Experiments Characterize Protein-DNA Interactions
• Chromosome Conformation Capture Technologies Analyze Long-Range Chromosomal DNA Interactions
• CRISPR-Cas9
• Whole-Animal Experimental Systems
• Animal Research Is Subject to Federal Guidelines That Protect Nonhuman Research Species
• Inbred Strains Reduce Experimental Variation
• Congenic Strains Are Used to Study the Effects of Particular Gene Loci on Immune Responses
• Adoptive Transfer Experiments Allow in Vivo Examination of Isolated Cell Populations
• Transgenic Animals Carry Genes That Have Been Artificially Introduced
• Knock-in and Knockout Technologies Replace an Endogenous with a Nonfunctional or Engineered Gene Copy
• The Cre/lox System Enables Inducible Gene Deletion in Selected Tissues
• References
• Study Questions
• Appendix I: CD Antigens
• Appendix II: Cytokines and Associated JAK-STAT Signaling Molecules
• Appendix III: Chemokines and Chemokine Receptors
• Glossary
• Answers to Study Questions
• Index