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About this Book<br/>Cover Page<br/>Accessibility<br/>Halftitle Page<br/>Icons Used in This Book<br/>Title Page<br/>Copyright Page<br/>Dedication<br/>About the Authors<br/>Brief Contents<br/>Feature Boxes in Kuby Immunology, Eighth Edition<br/>Contents<br/>Preface<br/>Acknowledgments<br/>Chapter 1: Overview of the Immune System<br/>1.1 A Historical Perspective of Immunology<br/>Early Vaccination Studies Led the Way to Immunology<br/>Vaccination Is an Ongoing, Worldwide Enterprise<br/>Immunology Is about More than Just Vaccines and Infectious Disease<br/>Immunity Involves Both Humoral and Cellular Components<br/>How Are Foreign Substances Recognized by the Immune System?<br/>1.2 Important Concepts for Understanding the Mammalian Immune Response<br/>Pathogens Come in Many Forms and Must First Breach Natural Barriers<br/>The Immune Response Quickly Becomes Tailored to Suit the Assault<br/>Pathogen Recognition Molecules Can Be Encoded as Genes or Generated by DNA Rearrangement<br/>Tolerance Ensures That the Immune System Avoids Destroying the Host<br/>The Immune Response Is Composed of Two Interconnected Arms: Innate Immunity and Adaptive Immunity<br/>Immune Cells and Molecules Can Be Found in Many Places<br/>Adaptive Immune Responses Typically Generate Memory<br/>1.3 The Good, Bad, and Ugly of the Immune System<br/>Inappropriate or Dysfunctional Immune Responses Can Result in a Range of Disorders<br/>The Immune Response Renders Tissue Transplantation Challenging<br/>Cancer Presents a Unique Challenge to the Immune Response<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 2: Cells, Organs, and Microenvironments of the Immune System<br/>2.1 Hematopoiesis and Cells of the Immune System<br/>Hematopoietic Stem Cells Differentiate into All Red and White Blood Cells<br/>HSCs Differentiate into Myeloid and Lymphoid Blood Cell Lineages<br/>Cells of the Myeloid Lineage Are the First Responders to Infection<br/>Cells of the Lymphoid Lineage Regulate the Adaptive Immune Response<br/>2.2 Primary Lymphoid Organs: Where Immune Cells Develop<br/>The Site of Hematopoiesis Changes during Embryonic Development<br/>The Bone Marrow Is the Main Site of Hematopoiesis in the Adult<br/>The Thymus Is the Primary Lymphoid Organ Where T Cells Mature<br/>2.3 Secondary Lymphoid Organs: Where the Immune Response Is Initiated<br/>Secondary Lymphoid Organs Are Distributed throughout the Body and Share Some Anatomical Features<br/>Blood and Lymphatics Connect Lymphoid Organs and Infected Tissue<br/>The Lymph Node Is a Highly Specialized Secondary Lymphoid Organ<br/>The Spleen Organizes the Immune Response against Blood-Borne Pathogens<br/>Barrier Organs Also Have Secondary Lymphoid Tissue<br/>Tertiary Lymphoid Tissues Also Organize and Maintain an Immune Response<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 3: Recognition and Response<br/>3.1 General Properties of Immune Receptor-Ligand Interactions<br/>Receptor-Ligand Binding Occurs via Multiple Noncovalent Bonds<br/>How Do We Describe the Strength of Receptor-Ligand Interactions?<br/>Interactions between Receptors and Ligands Can Be Multivalent<br/>Combinatorial Expression of Protein Chains Can Increase Ligand-Binding Diversity<br/>Adaptive Immune Receptor Genes Undergo Rearrangement in Individual Lymphocytes<br/>Levels of Receptor and Ligand Expression Can Vary during an Immune Response<br/>Local Concentrations of Ligands May Be Extremely High during Cell-Cell Interactions<br/>Many Immune Receptors Include Immunoglobulin Domains<br/>Immune Antigen Receptors Can Be Transmembrane, Cytosolic, or Secreted<br/>3.2 Immune Antigen Receptor Systems<br/>The B-Cell Receptor Has the Same Antigen Specificity as Its Secreted Antibodies<br/>T-Cell Antigen Receptors Recognize Antigen in the Context of MHC Proteins<br/>Receptors of Innate Immunity Bind to Conserved Molecules on Pathogens<br/>3.3 Cytokines and Their Receptors<br/>Cytokines Are Described by Their Functions and the Distances at Which They Act<br/>Cytokines Exhibit the Attributes of Pleiotropy, Redundancy, Synergism, Antagonism, and Cascade Induction<br/>Cytokines of the IL-1 Family Promote Proinflammatory Signals<br/>Class 1 Cytokines Share a Common Structural Motif But Have Varied Functions<br/>Class 2 Cytokines Are Grouped into Three Families of Interferons<br/>TNF Family Cytokines May Be Soluble or Membrane-Bound<br/>The IL-17 Family of Cytokines and Receptors Is the Most Recently Identified<br/>Chemokines Induce the Directed Movement of Leukocytes<br/>3.4 A Conceptual Framework for Understanding Cell Signaling<br/>Ligand Binding Can Induce Dimerization or Multimerization of Receptors<br/>Ligand Binding Can Induce Phosphorylation of Tyrosine Residues in Receptors or Receptor-Associated Molecules<br/>Src-Family Kinases Play Important Early Roles in the Activation of Many Immune Cells<br/>Intracellular Adapter Proteins Gather Members of Signaling Pathways<br/>Common Sequences of Downstream Effector Relays Pass the Signal to the Nucleus<br/>Not All Ligand-Receptor Signals Result in Transcriptional Alterations<br/>3.5 Immune Responses: The Outcomes of Immune System Recognition<br/>Changes in Protein Expression Facilitate Migration of Leukocytes into Infected Tissues<br/>Activated Macrophages and Neutrophils May Clear Pathogens without Invoking Adaptive Immunity<br/>Antigen Activation Optimizes Antigen Presentation by Dendritic Cells<br/>Cytokine Secretion by Dendritic Cells and T Cells Can Direct the Subsequent Immune Response<br/>Antigen Stimulation by T and B Cells Promotes Their Longer-Term Survival<br/>Antigen Binding by T Cells Induces Their Division and Differentiation<br/>Antigen Binding by B Cells Induces Their Division and Differentiation<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 4 Innate Immunity<br/>4.1 Physical and Chemical Barriers to Infection<br/>Physical Barriers Prevent Pathogen Entry into the Body’s Interior<br/>Antimicrobial Proteins and Peptides Kill Potential Microbial Invaders<br/>4.2 The Cells of Innate Immunity<br/>Myeloid Cells are Often the First to Respond<br/>Innate Cells of the Lymphoid Lineage are also Early Responders<br/>4.3 The Receptors of Innate Immunity<br/>Toll-Like Receptors Are Expressed on the Endosomal and Plasma Membranes<br/>C-Type Lectin Receptors Bind Carbohydrates on the Surfaces of Extracellular Pathogens<br/>RLRs Bind Cytosolic Viral RNA<br/>cGAS and STING Are Activated by Cytosolic DNA and Dinucleotides<br/>NOD-Like Receptors Bind PAMPs from Cytosolic Pathogens<br/>ALRs Bind Cytosolic DNA<br/>4.4 The Effector Mechanisms of Induced Innate Immunity<br/>Inflammation and Extravasation Focus Innate Immune Cells at the Site of Infection<br/>Expression of Innate Immunity Proteins Is Induced by PRR Signaling<br/>Phagocytosis is an Important Mechanism for Eliminating Pathogens<br/>4.5 Modulation of Innate Responses<br/>Innate and Inflammatory Responses Are Regulated Both Positively and Negatively<br/>Trained Immunity Is a Manifestation of Innate Immune Memory<br/>Pathogens Can Evade Innate and Inflammatory Responses<br/>4.6 Interactions between the Innate and Adaptive Immune Systems<br/>The Innate Immune System Activates Adaptive Immune Responses<br/>Recognition of Pathogens by Dendritic Cells Customizes Helper T-Cell Differentiation<br/>4.7 Ubiquity of Innate Immunity<br/>Some Innate Immune System Components Occur across the Plant and Animal Kingdoms<br/>Invertebrate and Vertebrate Innate Immune Responses Show Both Similarities and Differences<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 5: The Complement System<br/>5.1 The Major Pathways of Complement Activation<br/>The Classical Pathway Is Initiated by Antibody Binding to Antigens<br/>The Lectin Pathway Is Initiated When Soluble Proteins Recognize Microbial Antigens<br/>The Alternative Pathway Is Initiated in Three Distinct Ways<br/>The Three Complement Pathways Converge at the Formation of C5 Convertase and Generation of the MAC<br/>5.2 The Diverse Functions of Complement<br/>Complement Receptors Connect Complement-Tagged Pathogens to Effector Cells<br/>Complement Enhances Host Defense against Infection<br/>Complement Acts at the Interface between Innate and Adaptive Immunities<br/>Complement Aids in the Contraction Phase of the Immune Response<br/>5.3 The Regulation of Complement Activity<br/>Complement Activity Is Passively Regulated by Short Protein Half-Lives and Host Cell Surface Composition<br/>The C1 Inhibitor, C1INH, Promotes Dissociation of C1 Components<br/>Decay-Accelerating Factor Promotes Decay of C3 Convertases<br/>Factor I Degrades C3b and C4b<br/>CD59 (Protectin) Inhibits the MAC Attack<br/>Carboxypeptidases Can Inactivate the Anaphylatoxins C3a and C5a<br/>5.4 Complement Deficiencies<br/>5.5 Microbial Complement Evasion Strategies<br/>5.6 The Evolutionary Origins of the Complement System<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 6: The Organization and Expression of Lymphocyte Receptor Genes<br/>6.1 The Puzzle of Immunoglobulin Gene Structure<br/>Investigators Proposed Two Early Theoretical Models of Antibody Genetics<br/>Breakthrough Experiments Revealed That Multiple Gene Segments Encode the Immunoglobulin Light Chain<br/>6.2 Multigene Organization of Immunoglobulin Genes<br/>κ Light-Chain Genes Include V, J, and C Segments<br/>λ Light-Chain Genes Include Paired J and C Segments<br/>Heavy-Chain Gene Organization Includes VH, D, JH, and CH Segments<br/>The Antibody Genes Found in Mature B Cells Are the Product of DNA Recombination<br/>6.3 The Mechanism of V(D)J Recombination<br/>V(D)J Recombination in Lymphocytes Is a Highly Regulated Sequential Process<br/>Recombination Is Directed by Recombination Signal Sequences<br/>Gene Segments Are Joined by a Diverse Group of Proteins<br/>V(D)J Recombination Occurs in a Series of Well-Regulated Steps<br/>Five Mechanisms Generate Antibody Diversity in Naïve B Cells<br/>The Regulation of V(D)J Gene Recombination Involves Chromatin Alteration<br/>6.4 B-Cell Receptor Expression<br/>Each B Cell Synthesizes only one Heavy Chain and One Light Chain<br/>Receptor Editing of Potentially Autoreactive Receptors Occurs in Light Chains<br/>mRNA Splicing Regulates the Expression of Membrane-Bound versus Secreted Ig<br/>6.5 T-Cell Receptor Genes and Their Expression<br/>Understanding the Protein Structure of the TCR Was Critical to the Process of Discovering the Genes<br/>The β-Chain Gene Was Discovered Simultaneously in Two Different Laboratories<br/>A Search for the α-Chain Gene Led to the γ-Chain Gene Instead<br/>TCR Genes Are Arranged in V, D, and J Clusters of Gene Segments<br/>Recombination of TCR Gene Segments Proceeds at a Different Rate and Occurs at Different Stages of Development in αβ versus γδ T Cells<br/>The Process of TCR Gene Segment Rearrangement Is Very Similar to Immunoglobulin Gene Recombination<br/>TCR Expression Is Controlled by Allelic Exclusion<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 7: The Major Histocompatibility Complex and Antigen Presentation<br/>7.1 The Structure and Function of MHC Class I and II Molecules<br/>Class I Molecules Consist of One Large Glycoprotein Heavy Chain Plus a Small Protein Light Chain<br/>Class II Molecules Consist of Two Nonidentical Membrane-Bound Glycoprotein Chains<br/>Class I and II Molecules Exhibit Polymorphism in the Region That Binds to Peptides<br/>7.2 The Organization and Inheritance of MHC Genes<br/>The MHC Locus Encodes the Three Major Classes of MHC Molecules<br/>Allelic Forms of MHC Genes Are Inherited in Linked Groups Called Haplotypes<br/>MHC Molecules Are Codominantly Expressed<br/>Class I and Class II Molecules Exhibit Diversity at Both the Individual and Species Levels<br/>MHC Polymorphism Is Primarily Limited to the Antigen-Binding Groove<br/>7.3 The Role and Expression Pattern of MHC Molecules<br/>MHC Molecules Present Both Intracellular and Extracellular Antigens<br/>MHC Class I Expression Is Found Throughout the Body<br/>Expression of MHC Class II Molecules Is Primarily Restricted to Antigen-Presenting Cells<br/>MHC Expression Can Change with Changing Conditions<br/>MHC Alleles Play a Critical Role in Immune Responsiveness<br/>Seminal Studies Demonstrate That T Cells Recognize Peptide Presented in the Context of Self-MHC Alleles<br/>Evidence Suggests Distinct Antigen Processing and Presentation Pathways<br/>7.4 The Endogenous Pathway of Antigen Processing and Presentation<br/>Peptides Are Generated by Protease Complexes Called Proteasomes<br/>Peptides Are Transported from the Cytosol to the Rough Endoplasmic Reticulum<br/>Chaperones Aid Peptide Assembly with MHC Class I Molecules<br/>7.5 The Exogenous Pathway of Antigen Processing and Presentation<br/>Peptides Are Generated from Internalized Antigens in Endocytic Vesicles<br/>The Invariant Chain Guides Transport of MHC Class II Molecules to Endocytic Vesicles<br/>Peptides Assemble with MHC Class II Molecules by Displacing CLIP<br/>7.6 Unconventional Antigen Processing and Presentation<br/>Dendritic Cells Can Cross-Present Exogenous Antigen via MHC Class I Molecules<br/>Cross-Presentation by APCs Is Essential for the Activation of Naïve CD8+ T Cells<br/>7.7 Presentation of Nonpeptide Antigens<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 8: T-Cell Development<br/>8.1 Early Thymocyte Development<br/>Thymocytes Progress through Four Double-Negative Stages<br/>Thymocytes Express Either αβ or γδ T Cell Receptors<br/>DN Thymocytes Undergo β-Selection, Which Results in Proliferation and Differentiation<br/>8.2 Positive and Negative Selection<br/>Thymocytes “Learn” MHC Restriction in the Thymus<br/>T Cells Undergo Positive and Negative Selection<br/>Positive Selection Ensures MHC Restriction<br/>Negative Selection (Central Tolerance) Ensures Self-Tolerance<br/>The Selection Paradox: Why Don’t We Delete All Cells We Positively Select?<br/>An Alternative Model Can Explain the Thymic Selection Paradox<br/>Do Positive and Negative Selection Occur at the Same Stage of Development, or in Sequence?<br/>8.3 Lineage Commitment<br/>Several Models Have Been Proposed to Explain Lineage Commitment<br/>Transcription Factors Th-POK and Runx3 Regulate Lineage Commitment<br/>Double-Positive Thymocytes May Commit to Other Types of Lymphocytes<br/>8.4 Exit from the Thymus and Final Maturation<br/>8.5 Other Mechanisms That Maintain Self-Tolerance<br/>Regulatory T Cells Negatively Regulate Immune Responses<br/>Peripheral Mechanisms of Tolerance Also Protect against Autoreactive Thymocytes<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 9: B-Cell Development<br/>9.1 B-Cell Development in the Bone Marrow<br/>Changes in Cell-Surface Markers, Gene Expression, and Immunoglobulin Gene Rearrangements Define the Stages of B-Cell Development<br/>The Earliest Steps in Lymphocyte Differentiation Culminate in the Generation of a Common Lymphoid Progenitor<br/>The Later Stages of B-Cell Development Result in Commitment to the B-Cell Phenotype and the Stepwise Rearrangement of Immunoglobulin Genes<br/>Immature B Cells in the Bone Marrow Are Exquisitely Sensitive to Tolerance Induction through the Elimination of Self-Reactive Cells<br/>9.2 Completion of B-Cell Development in the Spleen<br/>T1 and T2 Transitional B Cells Form in the Spleen and Undergo Selection for Survival and against Self-Reactivity<br/>T2 B Cells Give Rise to Mature Follicular B-2 B Cells<br/>T3 B Cells Are Primarily Self-Reactive and Anergic<br/>9.3 The Properties and Development of B-1 and Marginal Zone B Cells<br/>B-1a, B-1b, and MZ B Cells Differ Phenotypically and Functionally from B-2 B Cells<br/>B-1a B Cells Are Derived from a Distinct Developmental Lineage<br/>9.4 Comparison of B- and T-Cell Development<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 10: T-Cell Activation, Helper Subset Differentiation, and Memory<br/>10.1 T-Cell Activation and the Two-Signal Hypothesis<br/>TCR Signaling Provides Signal 1 and Sets the Stage for T-Cell Activation<br/>Costimulatory Signals Are Required for Optimal T-Cell Activation Whereas Coinhibitory Signals Prevent T-Cell Activation<br/>Clonal Anergy Results If a Costimulatory Signal Is Absent<br/>Cytokines Provide Signal 3<br/>Antigen-Presenting Cells Provide Costimulatory Ligands and Cytokines to Naïve T Cells<br/>Superantigens Are a Special Class of T-Cell Activators<br/>10.2 Helper CD4+ T-Cell Differentiation<br/>Helper T Cells Can Be Divided into Distinct Subsets and Coordinate Type 1 and Type 2 Responses<br/>The Differentiation of Helper T-Cell Subsets Is Regulated by Polarizing Cytokines<br/>Each Effector Helper T-Cell Subset Has Unique Properties<br/>Helper T Cells May Not Be Irrevocably Committed to a Lineage<br/>Helper T-Cell Subsets Play Critical Roles in Immune Health and Disease<br/>10.3 T-Cell Memory<br/>Naïve, Effector, and Memory T Cells Can Be Distinguished by Differences in Surface Protein Expression<br/>Memory Cell Subpopulations Are Distinguished by Their Locale and Effector Activity<br/>Many Questions Remain Surrounding Memory T-Cell Origins and Functions<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 11: B-Cell Activation, Differentiation, and Memory Generation<br/>11.1 T-Dependent B-Cell Responses: Activation<br/>Naïve B Cells Encounter Antigen in the Lymph Nodes and Spleen<br/>B-Cell Recognition of Cell-Bound Antigen Culminates in the Formation of an Immunological Synapse<br/>Antigen Binding to the BCR Leads to Activation of a Signal Transduction Cascade within the B Cell<br/>B Cells Also Receive and Propagate Signals through Coreceptors<br/>B Cells Use More Than One Mechanism to Acquire Antigen from Antigen-Presenting Cells<br/>Antigen Receptor Binding Induces Internalization and Antigen Presentation<br/>The Early Phases of the T-Dependent Response Are Characterized by Chemokine-Directed B-Cell Migration<br/>Specification of the Stimulated B-Cell Fate Depends on Transcription Factor Expression<br/>11.2 T-Dependent B-Cell Responses: Differentiation and Memory Generation<br/>Some Activated B Cells Differentiate into Plasma Cells That Form the Primary Focus<br/>Other Activated B Cells Enter the Follicles and Initiate a Germinal Center Response<br/>The Mechanisms of Somatic Hypermutation and Class Switch Recombination<br/>Memory B Cells Recognizing T-Dependent Antigens Are Generated Both within and outside the Germinal Center<br/>Most Newly Generated B Cells Are Lost at the End of the Primary Immune Response<br/>11.3 T-Independent B-Cell Responses<br/>T-Independent Antigens Stimulate Antibody Production in the Absence of T-Cell Help<br/>Two Novel Subclasses of B Cells Mediate the Response to T-Independent Antigens<br/>11.4 Negative Regulation of B Cells<br/>Negative Signaling through CD22 Balances Positive BCR-Mediated Signaling<br/>Negative Signaling through the Receptor FcγRIIb Inhibits B-Cell Activation<br/>CD5 Acts as a Negative Regulator of B-Cell Signaling<br/>B-10 B Cells Act as Negative Regulators by Secreting IL-10<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 12: Effector Responses: Antibody- and Cell-Mediated Immunity<br/>12.1 Antibody-Mediated Effector Functions<br/>Antibodies Provide Protection against Pathogens, Toxins, and Harmful Cells in a Variety of Ways<br/>Different Antibody Classes Mediate Different Effector Functions<br/>Fc Receptors Mediate Many Effector Functions of Antibodies<br/>Protective Effector Functions Vary among Antibody Classes<br/>Antibodies Have Many Therapeutic Uses in Treating Diseases<br/>12.2 Cell-Mediated Effector Responses<br/>Cytotoxic T Lymphocytes Recognize and Kill Infected or Tumor Cells via T-Cell Receptor Activation<br/>Natural Killer Cell Activity Depends on the Balance of Activating and Inhibitory Signals<br/>NKT Cells Bridge the Innate and Adaptive Immune Systems<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 13: Barrier Immunity: The Immunology of Mucosa and Skin<br/>13.1 Common Themes in Barrier Immune Systems<br/>Barrier Epithelial Cells Generate a Healthy Distance from Microbiota<br/>Immune Cells Interact with the Barrier Epithelium and Lymphoid Tissue<br/>Barrier Immune Systems Initiate Both Tolerogenic and Inflammatory Responses to Microorganisms<br/>13.2 The Immune System of the Skin<br/>The Skin and Its Epithelium Are Multilayered<br/>Skin Immune Cells Are Present in Both the Epidermis and Dermis<br/>The Interaction between Skin Immune System and Skin Microbes Generates Both Protective and Inflammatory Responses<br/>13.3 The Immune System of the Intestine<br/>The Gut Is Organized into Anatomical Sections and Tissue Layers<br/>Gut Epithelial Cells Vary in Phenotype and Function<br/>Immune Homeostasis in the Intestine Is Regulated by Both Innate and Adaptive Cells<br/>Commensal Microbes Help Maintain Tolerance in the Intestine<br/>The Gut Immune System Recognizes and Responds to Harmful Pathogens<br/>13.4 The Immune System of the Respiratory Tract<br/>The Respiratory Immune System Shares Many Features with the Intestinal Immune System<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 14: The Immune Response in Space and Time<br/>14.1 Immune Cells in Healthy Tissue: Homeostasis<br/>Naïve Lymphocytes Circulate between Secondary and Tertiary Lymphoid Tissues<br/>Naïve Lymphocytes Browse for Antigen along the Reticular Network of Secondary Lymphoid Organs<br/>14.2 The Innate Immune Response to Antigen in Tissues<br/>Innate Immune Cells Are Activated by Antigen Binding to Pattern Recognition Receptors<br/>Antigen Travels in Two Different Forms to Secondary Lymphoid Tissue via Afferent Lymphatics<br/>Antigen-Presenting Cells That Present Processed Antigen Travel to the T-Cell Zones of Secondary Lymphoid Tissue<br/>Unprocessed Antigen Travels to the B-Cell Zones<br/>14.3 First Contact between Antigen and Lymphocytes<br/>Naïve CD4+ T Cells Arrest Their Movements after Engaging Antigens<br/>B Cells Seek Help from CD4+ T Cells at the Border between the Follicle and Paracortex of the Lymph Node<br/>B and T Cells Behave Differently in Germinal Centers<br/>CD8+ T Cells Are Activated in the Lymph Node via a Multicellular Interaction<br/>A Summary of the Timing of a Primary Response<br/>Differentiation into Memory T Cells Begins Early in the Primary Response<br/>14.4 The Effector and Memory Cell Responses in the Periphery<br/>Chemokine Receptors and Adhesion Molecules Coordinate Lymphocyte Homing<br/>Both Effector and Memory Lymphocytes Contribute to Clearing Infection in Tissues<br/>The Immune Response Contracts after Two to Four Weeks<br/>Memory Cells Position Themselves to Mount a Secondary Response to Re-Infection<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 15: Allergy, Hypersensitivities, and Chronic Inflammation<br/>15.1 Allergies: Type I Hypersensitivity<br/>IgE Antibodies Are Responsible for Type I Hypersensitivity<br/>Many Allergens Can Elicit a Type I Response<br/>IgE Antibodies Act by Binding Antigen, Resulting in the Cross-Linking of Fcε Receptors<br/>IgE Receptor Signaling Is Tightly Regulated<br/>Granulocytes Produce Molecules Responsible for Type I Hypersensitivity Symptoms<br/>Type I Hypersensitivities Are Characterized by Both Early and Late Responses<br/>There Are Several Categories of Type I Hypersensitivity Reactions<br/>Susceptibility to Type I Hypersensitivity Reactions Is Influenced by Both Environmental Factors and Genetics<br/>Diagnostic Tests and Treatments Are Available for Allergic Reactions<br/>Why Did Allergic Responses Evolve?<br/>15.2 Antibody-Mediated (Type II) Hypersensitivity<br/>Transfusion Reactions Are an Example of Type II Hypersensitivity<br/>Hemolytic Disease of the Newborn Is Caused by Type II Reactions<br/>Hemolytic Anemia Can Be Drug Induced<br/>15.3 Immune Complex–Mediated (Type III) Hypersensitivity<br/>Immune Complexes Can Damage Various Tissues<br/>Immune Complex–Mediated Hypersensitivity Can Resolve Spontaneously<br/>Auto-Antigens Can Be Involved in Immune Complex–Mediated Reactions<br/>Arthus Reactions Are Localized Type III Hypersensitivity Reactions<br/>15.4 Delayed-Type (Type IV) Hypersensitivity<br/>The Initiation of a Type IV DTH Response Involves Sensitization by Antigen<br/>The Effector Phase of a Classical DTH Response Is Induced by Second Exposure to a Sensitizing Antigen<br/>The DTH Reaction Can Be Detected by a Skin Test<br/>Contact Dermatitis Is a Type IV Hypersensitivity Response<br/>15.5 Chronic Inflammation<br/>Infections Can Cause Chronic Inflammation<br/>There Are Noninfectious Causes of Chronic Inflammation<br/>Obesity Is Associated with Chronic Inflammation<br/>Chronic Inflammation Can Cause Systemic Disease<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 16: Tolerance, Autoimmunity, and Transplantation<br/>16.1 Establishment and Maintenance of Tolerance<br/>Antigen Sequestration, or Evasion, Is One Means to Protect Self Antigens from Attack<br/>Central Tolerance Processes Occur in Primary Lymphoid Organs<br/>Cells That Mediate Peripheral Tolerance Are Generated Outside Primary Lymphoid Organs<br/>Multiple Immune Cell Types Work in the Periphery to Inhibit Anti-Self Responses<br/>16.2 Autoimmunity<br/>Some Autoimmune Diseases Target Specific Organs<br/>Some Autoimmune Diseases Are Systemic<br/>Both Intrinsic and Extrinsic Factors Can Favor Susceptibility to Autoimmune Disease<br/>What Causes Autoimmunity?<br/>Treatments for Autoimmune Disease Range from General Immune Suppression to Targeted Immunotherapy<br/>16.3 Transplantation Immunology<br/>Demand for Transplants Is High, But Organ Supplies Remain Low<br/>Antigenic Similarity between Donor and Recipient Improves Transplant Success<br/>Some Organs Are More Amenable to Transplantation Than Others<br/>Matching Donor and Recipient Involves Prior Assessment of Histocompatibility<br/>Allograft Rejection Follows the Rules of Immune Specificity and Memory<br/>Graft Rejection Takes a Predictable Clinical Course<br/>Immunosuppressive Therapy Can Be Either General or Target-Specific<br/>Immune Tolerance to Allografts Is Favored in Certain Instances<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 17: Infectious Disease and Public Health<br/>17.1 The Chain of Infection<br/>Infectious Agents Reside in Reservoirs<br/>Infection Can Occur via Various Modes of Transmission<br/>Successful Infection Requires a Susceptible Host<br/>17.2 Factors Contributing to Human Infectious Disease Patterns<br/>Emerging and Re-Emerging Infectious Diseases Are on the Rise<br/>Zoonotic Infections Arise from Contact with Animals<br/>Anthropogenic Factors Contribute to the Emergence and Spread of Infectious Disease<br/>Public Health Infrastructure Can Help Identify and Respond to Infectious Outbreaks<br/>Human Nature, History, and Culture Also Play a Role<br/>17.3 The Link Between Timing, Location, and Immune Effector Mechanisms<br/>Earlier Infectious Exposures May Influence Innate Responses to Another Infectious Agent<br/>Extracellular Infections at Barrier Surfaces Are Typically Controlled by Type 2 Responses<br/>Extracellular Pathogens Are Targeted by Extracellular Tools and Type 3 Responses<br/>Type 1 Responses Dominate During Intracellular Infections<br/>Systemic Inflammatory Responses Can Be Life-Threatening<br/>17.4 Viral Infections<br/>The Antiviral Innate Response Provides Key Instructions for the Later Adaptive Response<br/>Many Viruses Are Neutralized by Antibodies<br/>Cell-Mediated Immunity Is Important for Viral Control and Clearance<br/>Viruses Employ Several Strategies to Evade Host Defense Mechanisms<br/>The Imprinting of a Memory Response Can Influence Susceptibility to Future Viral Infection<br/>17.5 Bacterial Infections<br/>Immune Responses to Extracellular and Intracellular Bacteria Differ<br/>Bacteria Can Evade Host Defense Mechanisms at Several Stages<br/>17.6 Parasitic Infections<br/>Protozoan Parasites Are a Diverse Set of Unicellular Eukaryotes<br/>Parasitic Worms (Helminths) Typically Generate Weak Immune Responses<br/>17.7 Fungal Infections<br/>Innate Immunity Controls Most Fungal Infections<br/>Immunity against Fungal Pathogens Can Be Acquired<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 18: Immunization and Vaccines<br/>18.1 Passive Versus Active Immunity<br/>Passive Immunity Is Temporary and Enacted by Preexisting Antibodies<br/>Active Immunization Stimulates Immune Cells and Generates Memory Responses<br/>18.2 Vaccine Research and Design Principles<br/>Years of Basic Research Precede Each New Vaccine<br/>Vaccine Design Begins with Defining the Immune Correlates of Protection<br/>Vaccines Are Tightly Regulated and Monitored<br/>Immunization Programs Must Consider the Human Context<br/>18.3 Vaccine Formulations<br/>Whole Pathogen Vaccines Contain Live or Killed Microbes<br/>Subunit Vaccines Include Pieces of the Pathogen<br/>Particle- or Membrane-Based Vaccines Include an Outer Envelope<br/>Vectored Vaccines Replicate Without the Risk of Reversion<br/>Nucleic Acid Vaccines Provide Instructions for Pathogen-Associated Proteins<br/>18.4 Vaccine Adjuvants, Schedules, and Delivery Methods<br/>Adjuvants Increase Vaccine Effectiveness by Activating Innate Response Elements<br/>Full Immune Protection May Require Multiple Exposures or Boosters<br/>Several Novel Vaccine Delivery Methods Are Under Investigation<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 19: Immunodeficiency Diseases<br/>19.1 Primary Immunodeficiencies<br/>Primary Immunodeficiency Diseases Are Often Detected Early in Life<br/>Combined Immunodeficiencies Disrupt Adaptive Immunity<br/>B-Cell Immunodeficiencies Exhibit Depressed Production of One or More Antibody Isotypes<br/>Disruptions to Innate Immune Components May Also Impact Adaptive Responses<br/>Complement Deficiencies Are Relatively Common<br/>NK-Cell Deficiencies Increase Susceptibility to Viral Infections and Cancer<br/>Immunodeficiency Disorders That Disrupt Immune Regulation Can Manifest as Autoimmunity<br/>Immunodeficiency Disorders Are Treated by Replacement Therapy<br/>Animal Models of Immunodeficiency Have Been Used to Study Basic Immune Function<br/>19.2 Secondary Immunodeficiencies<br/>Secondary Immunodeficiencies May Be Caused by a Variety of Factors<br/>HIV/AIDS Has Claimed Millions of Lives Worldwide<br/>The Retrovirus HIV-1 Is the Causative Agent of AIDS<br/>HIV-1 is Spread by Intimate Contact with Infected Body Fluids<br/>In Vitro Studies Have Revealed the Structure and Life Cycle of HIV<br/>HIV Variants with Preference for CCR5 or CXCR4 Coreceptors Play Different Roles in Infection<br/>Infection with HIV Leads to Gradual Impairment of Immune Function<br/>Changes over Time Lead to Progression to AIDS<br/>Antiretroviral Therapy Inhibits HIV Replication, Disease Progression, and Infection of Others<br/>A Vaccine May Be the Only Way to Stop the HIV/AIDS Pandemic<br/>Conclusion<br/>References<br/>Study Questions<br/>Chapter 20: Cancer and the Immune System<br/>20.1 Cancer Development and Key Characteristics<br/>Cancer Arises from Progressive DNA Changes in a Self Cell<br/>Cancer-Associated Genes Regulate Cell Proliferation and Survival<br/>Blood-Cell Cancers Arise from Various Stages of Hematopoietic Stem Cell Development<br/>Several Key Characteristics Define All Cancers<br/>Distinct Antigen Expression by Cancer Cells Can Aid Detection and Eradication<br/>20.2 The Immune Response to Cancer<br/>The Immune Response Has Pro-Tumor and Anti-Tumor Actions<br/>Innate and Adaptive Mechanisms Detect and Eradicate Cancer<br/>Some Immune Response Elements Promote Cancer Survival<br/>Tumor Cells Evolve to Evade Immune Recognition and Apoptosis<br/>20.3 Anticancer Immunotherapies<br/>Early Physicians Observed the Immune Response to Cancer<br/>Evaluating the Immune Microenvironment Provides Prognostic and Therapeutic Value<br/>Antibodies Can Direct the Immune Response to Tumor Cells<br/>Immune Checkpoint Blockades Can Manipulate Comodulatory Signals<br/>Anti-Tumor Lymphocyte Populations Can Be Expanded or Enhanced to Treat Cancer<br/>Prophylactic and Therapeutic Anticancer Vaccines May Enhance the Anti-Tumor Response<br/>Oncolytic Viruses Can Treat Cancer<br/>Conclusion<br/>References<br/>Study Questions<br/>Appendix A: CD Antigens<br/>Appendix B: Cytokines<br/>Appendix C: Chemokines and Chemokine Receptors<br/>Appendix D: Signal Transduction in the Immune System<br/>Appendix E: Experimental Systems and Methods<br/>Appendix F: An Extended List of CD Antigens<br/>Glossary<br/>Answers to Study Questions<br/>Index<br/>Notes<br/>Extended Descriptions<br/>Icons Used in This Book<br/>Herd immunity threshold for five viruses<br/>The rapid antigen tests for COVID-19 are based on a sandwich E L I S A<br/>Immune response pathways<br/>Engineered B i T E antibodies<br/>Online assignment<br/>Sample page of a PowerPoint presentation<br/>Starting screen for an animation<br/>LaunchPad<br/>Figure 1-3 Drawing by Elie Metchnikoff of phagocytic cells surrounding a foreign particle<br/>Passive Antibodies and the Iditarod<br/>Figure 1-4 Representation of Paul Ehrlich’s side-chain theory to explain antibody formation<br/>Figure 1-5 An Outline for the Humoral and Cell-Mediated (Cellular) Branches of the Immune System.<br/>Figure 1-6 Generation of diversity and clonal selection in T and B lymphocytes<br/>Figure 1-7 Collaboration between Innate and Adaptive Immunity in Resolving an Infection<br/>Figure 1-8 Differences in the primary and secondary adaptive immune response to injected antigen reflect the phenomenon of immunologic memory<br/>Figure 1-11 The proposed role of the microbiome in regulating immune, metabolic, and neurologic function<br/>Figure 2-1 Hematopoiesis<br/>Figure 1 Panning for stem cells<br/>Figure 2 Current approaches for enrichment of pluripotent stem cells from bone marrow<br/>Figure 2-2 Regulation of hematopoiesis by transcription factors<br/>Figure 2-3 An example of lineage commitment during hematopoiesis: the development of B cells from HSCs<br/>Figure 2-4 Examples of granulocytes<br/>Figure 2-5 Examples of monocytes, macrophages, dendritic cells, and megakaryocytes<br/>Figure 2-6 Examples of lymphocytes<br/>Figure 2-7 Structure of the B-cell and T-cell antigen receptors<br/>Figure 2-8 T-cell recognition of antigen<br/>Figure 1 The general strategy used to correct a defective gene by autologous H S C transplantation<br/>Figure 2-9 Sites of hematopoiesis during fetal development<br/>Figure 2-10 The bone marrow microenvironment<br/>Figure 2-11 Structure of the thymus<br/>Figure 1 (b) the first page of the Lancet article (1961) describing his discovery of the function of the thymus<br/>Figure 2-12 The human lymphatic system<br/>Figure 2-13 Structure of a lymph node<br/>Figure 2-14 Stromal cell networks in secondary lymphoid tissue<br/>Figure 2-15 Structure of the spleen<br/>Figure 2-16 Example of secondary lymphoid tissue in barrier organs: gut-associated lymphoid tissue (G A L T)<br/>Figure 1 Evolutionary distribution of lymphoid tissues<br/>Figure 2 Thymic tissue in the lamprey eel<br/>Figure 3 The avian bursa<br/>Recognition and response<br/>Figure 3-1 Receptor-ligand binding obeys the rules of chemistry<br/>Figure 3-2 Univalent and bivalent (or multivalent) binding<br/>Figure 3-3 Cell surface receptors cluster on binding multivalent antigens<br/>Figure 3-4 Combining one receptor chain with different partners allows increased receptor diversity and affinity while minimizing the need for new genetic information<br/>Figure 3-5 Comparison of the three forms of the IL-2 receptor<br/>Figure 3-6 Polarized secretion of I L-12 (pink) by dendritic cells (blue) in the direction of a bound T cell (green)<br/>Figure 3-7 Some examples of proteins bearing immunoglobulin domains<br/>Figure 3-8 The immunoglobulin domain is made up of amino acid residues arranged in beta sheets that are connected by variable loops<br/>Figure 3-9 The B C R exists in both membrane-bound (a) and soluble (b) forms<br/>Figure 1 Experimental demonstration that most antibodies are in the gamma-globulin fraction of serum proteins<br/>Figure 2 Prototype structure of I g G, showing chain structure and interchain disulfide bonds<br/>Figure 3-10 The structure of antibodies<br/>Figure 3-11 The presence of hypervariable regions in the amino acid sequences of antibody V L and V H domain complementarity-determining regions (C D Rs)<br/>Figure 3-12 General structures of the five major classes of antibodies<br/>Figure 3-13 General structure of the four subclasses of human I g G<br/>Figure 3-14 B-cell coreceptors require receptor-associated molecules and coreceptors for signal transduction<br/>Figure 3-15 The three-dimensional structure of the alpha beta T C R<br/>Figure 1 The generation of antibodies specific for the T C R<br/>Figure 3-16 Structure of the C D 4 and C D 8 coreceptors<br/>Figure 3-17 The T-cell receptor and coreceptor complex<br/>Interleukin-1 family<br/>Class 1 hematopoietin cytokine family<br/>Class 2 (interferon) cytokine family<br/>Tumor necrosis factor<br/>Interleukin-17 family<br/>Chemokines<br/>Figure 3-18 Cytokine attributes of (a) pleiotropy, redundancy, synergism, antagonism, and (b) cascade induction<br/>Figure 3-19 Ligands and receptors of the I L-1 family<br/>Figure 3-21 Binding of T N F to T N F R-1 induces trimerization and activation of downstream events<br/>Figure 3-22 The I L-17 family of cytokines and their associated receptors<br/>Figure 3-23 Disulfide bridges in chemokine structures<br/>Concepts in lymphocyte signaling<br/>Figure 3-25 General model of signal transduction mediated by most class 1 and class 2 cytokine receptors<br/>Figure 3-26 The role of lipid raft regions within membranes<br/>Figure 3-27 Activation of S r c-family kinases<br/>Figure 1 Fluorescence-activated cell-sorting (F A C S) profi les of a normal individual and a patient with X L A<br/>Innate Immunity<br/>Figure 4-2 The structure of the mucus layer varies along the length of the gastrointestinal tract<br/>Figure 4-3 Psoriasin prevents colonization of the skin by Escherichia coli (E. coli)<br/>Figure 4-4 Innate Lymphoid Cells<br/>Pattern Recognition Receptors<br/>Figure 4-6 Toll-like receptor (T L R) structure and binding of P A M P ligands<br/>Figure 4-7 Cellular location of T L Rs<br/>Figure 4-8 Cell wall components of gram-negative and gram-positive bacteria<br/>Figure 4-9 L P S binding by T L R 4 complex on host cells<br/>Figure 4-10 The R I G-I-like receptor family<br/>Figure 4-11 The N L R P 3 inflammasome and its activators<br/>Figure 4-12 Activation of inflammasomes<br/>Effectors of innate immune response to infection<br/>Figure 4-14 The steps of leukocyte extravasation<br/>Figure 4-15 Inside-out signaling results in a high affinity form of L F A-1<br/>Figure 4-16 Initiation of a local inflammatory response<br/>Figure 4-17 Induction of antiviral activities by type Roman numeral 1 interferons<br/>Figure 4-18 Phagocytosis<br/>Figure 4-19 Generation of antimicrobial reactive oxygen and nitrogen species<br/>Figure 1 Neutrophil extracellular traps (N E Ts) and N E Tosis<br/>Figure 1 Evasion of type Roman numeral 1 interferon-mediated immunity by S A R S Co V-2<br/>Figure 4-20 Pathogens induce differential signaling through D C P R Rs, influencing helper T-cell functions<br/>Figure 1 Induced closure of leaf stomata following exposure to bacterial P A M Ps<br/>Complement Proteins<br/>Generation of C 3 and C 5 convertases by the three major pathways of complement activation<br/>Figure 5-3 Structure of the C 1 macromolecular complex<br/>Figure 5-4 Models of pentameric I g M and hexameric I g G derived from x-ray crystallographic data<br/>Classical Pathway of Complement Activation<br/>Figure 5-6 Binding of C 4 b to the microbial membrane surface occurs through a thioester bond via an exposed amino or hydroxyl group<br/>Figure 5-7 Initiation of the lectin pathway relies on lectin receptor recognition of microbial cell surface carbohydrates<br/>Figure 5-8 Initiation of the alternative tickover pathway of complement<br/>Figure 2 Pillemer’s experiments<br/>Figure 5-9 Initiation of the alternative pathway by specific, noncovalent binding of properdin to the target membrane<br/>Figure 5-10 Formation of the membrane attack complex (M A C)<br/>Complement and the Visual System<br/>Figure 2 Fluorescence images of the lateral geniculate nucleus, analyzed by array tomography<br/>Figure 5-11 Coligation of antigen to B cells<br/>Figure 5-12 Anaphylatoxins and inflammatory response<br/>Figure 5-13 Opsonization of microbial cells<br/>Figure 5-14 C 1 q colocalizes with annexin A 5 on the surface of apoptotic cells<br/>Figure 5-15 Clearance of circulating immune complexes<br/>Figure 5-16 Regulation of complement activity<br/>Figure 1 Treatment of P N H patients with eculizumab relieves hemoglobinuria<br/>Figure 5-17 Evolution of complement components<br/>Biochemistry of the membrane proteins<br/>Flow cytometric histogram<br/>Heavy chain locus and nuclear lamina<br/>Figure 6-1 Sequencing studies of the variable and constant regions of immunoglobulin<br/>Figure 6-2 Dreyer and Bennett hypothesis<br/>Figure 6-3 The kappa light-chain gene is formed by D N A recombination between variable and constant region gene segments<br/>Figure 6-4 The antibody kappa light-chain locus is composed of three families of D N A segments<br/>Hozumi and Tonegawa’s classic experiment<br/>Figure 6-5 Variable region of antibody heavy chains is encoded in three segments—V, D, and J<br/>Figure 6-6 Organization of immunoglobulin germ-line gene segments in the mouse<br/>Figure 6-7 Pre-B C R and B C R complexes<br/>Figure 6-8 Two conserved sequences in light-chain and heavy-chain D N A function as recombination signal sequences (R S Ss)<br/>Figure 6-9 Recombination between gene segments is required to generate complete variable region light- and heavy-chain genes<br/>Figure 6-10 Structural features of the R A G 1/2 recombinase proteins<br/>Recombnation of immunoglobulin variable region genes<br/>Figure 6-12 Mechanism of V (D) J recombination, illustrated for V kappa-to-J kappa joining<br/>Figure 1 Elements of the recombination substrate used by Carmona and colleagues<br/>Figure 2 Evolution of the R A G 1/2 recombinase<br/>Figure 6-13 Three-dimensional organization of chromosomal regions containing V, D, and J segments changes during B-cell development<br/>Figure 6-14 Nuclear positioning of I g H and I g kappa loci alters during B-cell development<br/>Figure 6-15 Generation of a functional immunoglobulin receptor requires productive rearrangement of heavy- and light-chain gene segments<br/>Figure 6-16 Kappa light-chain receptor editing<br/>Figure 6-17 Differential expression of the secreted and membrane-bound forms of immunoglobulin mu and delta chains is regulated by alternative R N A processing<br/>Figure 6-18 Production and identification of a c D N A clone encoding the T-cell receptor beta gene<br/>Figure 6-19 Germ-line organization of the mouse T C R alpha-, beta-, gamma-, and delta-chain gene segments<br/>Figure 6-20 Locations R S S spacers in T C R genes<br/>Figure 6-21 The pre-T C R: the T C R beta chain is expressed on the T-cell surface in combination with the pre-T alpha chain<br/>D N A with V domain and D domain<br/>Recombination of two gene segments<br/>Position of genes in germ-line D N A and D N A from antibody-producing cells<br/>Schematic diagrams of M H C class Roman numeral 1 (a) and M H C class Roman numeral 2 (b) molecules, showing the external domains, transmembrane segments, cytoplasmic tails, and peptide-binding groove<br/>Figure 7-3 Peptide-binding groove of M H C class Roman numeral 1 and class Roman numeral 2 molecules, with bound peptides<br/>Figure 7-4 Examples of anchor residues (blue) in nonameric peptides eluted from two different M H C class Roman numeral 1 molecules<br/>Figure 7-5 Conformation of peptides bound to M H C class Roman numeral 1 molecules<br/>Figure 7-6 Comparison of the organization of the major histocompatibility complex (M H C) in mice and humans<br/>Figure 7-7 Simplified map of the mouse and human M H C loci<br/>Figure 7-8 Illustration of inheritance of MHC haplotypes in inbred mouse strains and in humans<br/>Figure 7-9 Diagram illustrating the various M H C molecules expressed on antigen-presenting cells of a heterozygous H 2 k/d mouse<br/>Figure 7-10 Variability in the amino acid sequences of allelic H L A class Roman numeral 1 molecules<br/>Figure 1 Experimental demonstration of self-M H C restriction in cells<br/>Figure 2 Experimental demonstration that antigen recognition by T C cells exhibits M H C restriction<br/>Figure 7-11 Experimental demonstration that antigen processing is necessary for<br/>Figure 7-12 Overview of endogenous and exogenous pathways for processing antigen<br/>Figure 7-13 Proteolytic system for degradation of intracellular proteins<br/>Figure 7-14 T A P (transporter associated with antigen processing)<br/>Figure 7-15 Assembly and stabilization of M H C class I molecules<br/>Figure 7-16 Generation of antigenic peptides and assembly of M H C class Roman numeral 2 molecules in the exogenous processing pathway<br/>Antigen-presenting pathways<br/>Figure 7-18 Activation of naïve T c cells by exogenous antigen requires D C licensing and cross-presentation<br/>Figure 7-19 Lipid antigen binding to the C D 1 molecule<br/>Specificity of T cells against the M C M V and tum peptide<br/>Development of T Cells in the Thymus<br/>Figure 8-2 Development of T cells from hematopoietic stem cells on bone marrow stromal cells expressing the Notch ligand<br/>T-cell receptor expression and function<br/>Figure 8-4 Time course of appearance of gamma delta thymocytes and alpha beta thymocytes during mouse fetal development<br/>Positive and negative selection of thymocytes in the mouse<br/>Figure 8-6 Experimental demonstration that the thymus selects for maturation only those T cells whose T-cell receptors recognize antigen presented on target cells with the haplotype of the thymus<br/>Figure 1 Experimental demonstration that negative selection of thymocytes requires both self antigen and self-M H C, and positive selection requires self-M H C<br/>Figure 2 Primary data from experiments summarized in Figure 1<br/>Figure 8-7 Relationship between T C R affinity and selection<br/>Figure 8-8 Experimental support for the role of T C R affinity in thymic selection<br/>Figure 8-9 A N D Accompanying Video 8-9v Imaging live d p thymocytes undergoing selection in the thymus<br/>Figure 8-10 Proposed models of lineage commitment, the decision of double-positive thymocytes to become helper C D 4 plus or cytotoxic C D 8 plus T cells<br/>Figure 8-11 How regulatory T cells (T R E G s) inactivate traditional T cells<br/>Fluorescence activated cell sorting plots<br/>Stages of B-cell development<br/>B-Cell Development<br/>Figure 9-2 H S Cs and B-cell progenitors<br/>Figure 1 Factors regulating B-cell development<br/>Figure 9-3 Transcription factors during early B-cell development<br/>Figure 9-4 Immunoglobulin gene rearrangements and expression of marker proteins during B-cell development<br/>Figure 1 Experimental approach for the isolation of Hardy’s fractions from bone marrow<br/>Figure 2 Flow cytometric characterization of the stages of B-cell development in the bone marrow<br/>Figure 9-5 The pre-B-cell receptor<br/>Figure 9-6 Experimental evidence for negative selection (clonal deletion) and light-chain editing of self-reactive immature B cells in the bone marrow<br/>Figure 9-7 T 2, but not T 1, transitional B cells can enter splenic B-cell follicles and recirculate<br/>Figure 9-8 Transitional B cells undergo positive and negative selection in the spleen<br/>Figure 9-9 Goodnow’s experimental system for demonstrating clonal anergy in mature peripheral B cells<br/>Figure 9-10 The three major populations of mature B cells in the periphery<br/>Levels of antigens in wild-type and Dicer knockout mice<br/>Staining of Pro-B and Pre-B cells with Annexin V<br/>Figure 10-1 T-Cell Activation and Differentiation<br/>Figure 10-2 Three Signals Are Required for Activation of a Naïve T Cell<br/>Figure 10-3 Surface interactions responsible for T-cell activation<br/>Figure 10-4 Schematic of T-cell receptor signaling<br/>Figure 1 Evidence that C D 28 is costimulatory ligand for T cell proliferation<br/>Figure 1 How the checkpoint inhibitor ipilimumab works<br/>Figure 10-5 Signals that lead to clonal anergy versus clonal expansion<br/>Figure 10-6 Comparison of professional antigen-presenting cells that induce T-cell activation<br/>Figure 10-7 Superantigen-mediated cross-linkage of T-cell receptor and M H C class Roman numeral 2 molecules<br/>Figure 10-8 Activation and differentiation of naïve T cells into effector and memory T cells<br/>Figure 10-9 T Helper Subset Differentiation<br/>Figure 10-10 General events and factors that drive T H subset polarization<br/>Figure 10-11 Initiation of T H 1 and T H 2 responses by pathogens<br/>Figure 10-12 Cross-regulation of T helper cell subsets by transcriptional regulators<br/>Figure 1 C D 4 + T cells from patients with hyper-I g E syndrome do not differentiate into T H 17 cells<br/>Figure 1 The anatomy and cell biology of the human placenta<br/>Figure 2 Genetic differences between the F o x P 3 enhancer in placental (eutherian) and nonplacental animals<br/>Figure 10-13 Examples of how T F H and T H 1 T cells provide help in the immune response<br/>Figure 10-14 Correlation between type of leprosy and relative T H 1 or T H 2 activity<br/>Figure 10-15 One possible model for the development of memory T-cell subsets<br/>Fluorescence-activated cell-sorting (F A C S) profiles<br/>Figure 11-2 Maturation and clonal selection of B lymphocytes<br/>Figure 11-3 Different types of antigens signal through different receptor units<br/>Figure 11-4 Adoptive transfer experiments demonstrated the need for two cell populations during the generation of antibodies to T-dependent antigens<br/>Figure 11-5 Alternative Fates of B Cells following T-Dependent Antigen Stimulation<br/>Figure 11-6 Antigen presentation to follicular B cells in the lymph node<br/>Figure 11-7 Antigen recognition by the B C R triggers membrane spreading<br/>Figure 11- 8 The B- cell immunological synapse includes a central core of receptor, surrounded by adhesion molecules, and is corralled by an actin ring<br/>Figure 11-9 Signal Transduction Pathways Emanating from the B C R<br/>Figure 11-10 B cells extract antigen from the antigen-presenting cell membrane, using active contractions of the actomyosin skeleton<br/>Figure 1 Visualization of antigen-specific B cell movements in the germinal center<br/>Figure 11-11 Differential chemokine receptor expression controls B-cell migration during the T-dependent immune response<br/>Figure 11-12 Movement of antigen-specific T and B cells within the lymph node after antigen encounter<br/>Figure 11-13 Experiment showing that a single B cell can give rise to plasmablasts, germinal center B cells, or memory B cells<br/>Figure 11-14 A regulatory network of transcription factors controls the germinal center B cell/plasma cell decision point<br/>Figure 11-15 Terminology describing antibody-secreting cells<br/>Figure 11-16 The germinal center<br/>Figure 11-17 B-Cell Differentiation Events Occur in Different Anatomical Locations<br/>Figure 11-18 Activation-induced cytidine deaminase (A I D) mediates the deamination of deoxycytidine and the formation of deoxyuridine<br/>Figure 11-19 The generation of somatic cell mutations in I g genes by A I D. A I D deaminates a deoxycytidine residue, creating a uridine-guanosine (U-G) mismatch<br/>Figure 11-20 Class switch recombination from a C mu to a C gamma 1 heavy-chain constant region gene<br/>Figure 11-21 The bone marrow niche occupied by plasma cells is supported by eosinophils and megakaryocytes, as well as by mesenchymal stromal cells<br/>Figure 11-22 Temporal separation of recall responses from I g G 1 and I g M 1 memory responses<br/>Figure 11-24 The marginal zone of the mouse spleen<br/>I g M levels<br/>B cells and their flow cytometric data<br/>Figure 12-1 The Six Broad Categories of Antibody Effector Functions<br/>FIgure 12-3 Agglutination of Streptococcus pneumoniae by antibodies in nasal secretions<br/>Figure 12-4 Structure of human F c receptors<br/>Figure 12-5 Functions of F c receptors. F c receptors (F c Rs) come in a variety of types and are expressed by many different cell types<br/>Figure 12-6 Generation of effector C T Ls<br/>Figure 12-7 Localizing antigen-specific C D 8 plus T-cell populations in vivo<br/>Figure 1 M H C-peptide tetramers<br/>Figure 12-8 Stages in C T L-mediated killing of target cells<br/>Figure 12-9 Effect of antigen activation on the ability of C T Ls to bind to the intercellular cell adhesion molecule I C A M-1<br/>Figure 12-10 Formation of a conjugate between a C T L and a target cell and reorientation of C T L cytoplasmic granules as recorded by time-lapse photography<br/>Figure 12-11 C T L-mediated pore formation in target cell membrane<br/>Figure 12-12 Experimental demonstration that C T Ls use F a s and perforin pathways<br/>Figure 12-13 Two pathways of C T L-activated target cell apoptosis<br/>Figure 12-14 Time course of responses to viral infection<br/>Figure 12-15 How N K cytotoxicity is restricted to altered self cells: missing self model and balanced signals model<br/>Figure 12-16 Structures of N K inhibitory and activating receptors bound to their ligands<br/>Figure 1 The investigators’ experimental approach<br/>Figure 2 Experimental results<br/>Figure 13.1 Barrier immune tissues<br/>Figure 13.2 Major cell types in barrier immune systems<br/>Figure 13.3 Major barrier tissue immune cells interact to produce type 1, type 2, and type 3 responses<br/>Figure 13.4 Lymphoid tissues associated with barrier organs<br/>Figure 13.5 Secondary lymphoid tissue associated with the small intestine<br/>Figure 13.6 Common themes in barrier immune responses<br/>Figure 13.7 Skin anatomy and associated immune cells<br/>Figure 13.8 Developmental regulation of T R E G cells in the skin<br/>Figure 13.9 Immune responses in the skin<br/>Figure 13.10 Gross anatomy of the gastrointestinal (G I) tract<br/>Figure 13.11 Cellular anatomy of the small and large intestines<br/>Figure 13.12 How antigen is delivered from the lumen to antigen-presenting cells<br/>Figure 13.13 Maintaining homeostasis and tolerance to the microbiome at the intestinal surface<br/>Figure 13.14 Transcytosis of I g A to the lumen of the intestine<br/>Figure 13.15 Effect of commensal bacteria on intestinal immune responses<br/>Figure 13.16 Conditions that cause a switch from homeostatic (a) to inflammatory (b) immune responses<br/>Figure 1 Maintaining germ-free mice<br/>Figure 2 Mice from different laboratories harbor different microorganisms<br/>S F B colonization affects I L-17 production by intestinal T H cells<br/>Figure 1 Examples of the communication between the gut microbiota, immune system, and nervous system<br/>Figure 13.17 Intestinal immune system response to Salmonella bacterial infection: an example of a type 1 response<br/>Figure 13.18 Intestinal immune system response to worm infection: an example of a type 2 response<br/>Figure 13.19 Gross and cellular anatomy of the respiratory tract<br/>Figure 13.20 Immune responses in the respiratory tract<br/>Figure 14-1 Lymphocyte recirculation routes<br/>Figure 14-2 Lymphocyte migration through H E Vs<br/>Figure 14-3 Lymphocyte migration in the spleen<br/>Figure 1 The four families of cell-adhesion molecules<br/>Figure 14-4 Lung associated lymphoid tissue<br/>Cell traffic in a resting lymph node<br/>Figure 14-6 Two-photon imaging of live T and B cells within a mouse lymph node<br/>Figure 14-7 Antigen-presenting cells are present in all lymph-node microenvironments<br/>Figure 14-8 Lymphocytes exit the lymph node through portals in the cortical and medullary sinuses<br/>Figure 14-9 A successful immune response to a viral lung infection (S A R S-C o V-2)<br/>Figure 14-10 How antigen travels into a lymph node<br/>Figure 14-11 Migration of antigen-presenting cells from tissue to lymph node through efferent lymphatics<br/>Figure 14-12 Antigen entry to lymph nodes and the spleen<br/>Figure 14-13 Activation of C D 4 plus T cells and B cells in a lymph node during a primary immune response<br/>Figure 14-14 B-cell activity in the germinal center<br/>Figure 14-16 The formation of a tricellular complex in a lymph node during C D 8 plus T-cell activation<br/>Figure 14-17 A summary of the nature and timing of events during T- and B-cell activation in a lymph node after the introduction of antigen<br/>Figure 14-18 Effector and memory lymphocytes leave the lymph node via efferent lymphatics and circulate to infection sites<br/>Figure 14-19 Examples of the homing receptors and addressins involved in trafficking naïve and effector T cells<br/>Figure 14-20 The contraction of an immune response<br/>Figure 14-21 Memory lymphocytes distribute themselves throughout the body, following cues provided by chemokines and cell adhesion molecules<br/>Level of I g G against the spike protein<br/>Level of I g M against the spike protein<br/>Level of anti-spike I g G<br/>Figure 15-1 The four types of hypersensitivity reactions<br/>Figure 15-2 General mechanism underlying an immediate type 1 hypersensitivity reaction<br/>Figure 15-3 Schematic diagrams of the high-affinity F c e R 1 and low-affinity F c e R 2 receptors that bind the F c region of I g E<br/>Figure 15-4 Signaling pathways initiated by I g E allergen cross-linking of F c E R 1 receptors<br/>Figure 15-5 Effects of mast cell activation<br/>Figure 15-6 The early and late inflammatory responses in asthma<br/>Figure 15-7 Environmental factors and genetics influence predisposition to allergies<br/>Figure 15-8 Induction of I g E-mediated food allergy response<br/>Figure 15-9 Skin testing for hypersensitivity<br/>Figure 15-10 Mechanisms underlying immunotherapy-induced desensitization<br/>Figure 15-11 A B O (A B H) blood groups<br/>Figure 15-12 Destruction of R h-positive red blood cells during erythroblastosis fetalis<br/>Figure 15-15 The D T H response<br/>Figure 15-16 A prolonged D T H response can lead to formation of a granuloma, a nodule-like mass<br/>Figure 15-17 Tuberculin skin test<br/>Figure 15-18 Poison ivy causes contact dermatitis due to its toxin, urushiol<br/>Figure 15-19 Induction of contact dermatitis by urushiol can be mediated by T H 1, T H 17, and C T L effector T cells<br/>Figure 15-20 Causes and consequences of chronic inflammation<br/>Figure 1 Signaling events that link obesity and inflammation to insulin resistance<br/>Association between exposure to various bacterial species and the development of allergies<br/>Figure 16-1 Central and peripheral tolerance<br/>Figure 16-2 C T L A-4–mediated inhibition of A P Cs by T R E G cells<br/>Figure 16-3 Linked suppression mediated by T R E G cells<br/>Figure 16-5 Insulitis in Type 1 diabetes<br/>Figure 16-6 Mechanism of myasthenia gravis induction<br/>Figure 16-11 Schematic diagrams of the process of graft acceptance and rejection<br/>Figure 16-12 Solid organ transplant numbers for 2020<br/>Figure 16-13 Steps in the hyperacute rejection of a kidney graft<br/>Figure 16-14 Direct versus indirect presentation of allogeneic M H C<br/>Figure 16-15 Experimental demonstration that T cells can transfer allograft rejection<br/>Figure 16-16 The role of C D 4 plus and C D 8 plus T cells in allograft rejection is demonstrated by the curves showing survival times of skin grafts between mice mismatched at the M H C<br/>Figure 16-17 Effector mechanisms involved in allograft rejection<br/>Figure 16-18 Blocking costimulatory signals at the time of transplantation can cause anergy instead of activation of T cells reactive against a graft<br/>Figure 16-19 Site of action for various immunotherapy agents used in clinical transplantation<br/>Figure 17-1 Causes of death worldwide, 2019<br/>Figure 17-2 An increase in U.S. deaths in 2020 linked to COVID-19<br/>Figure 17-3 Chain of infection<br/>Figure 1 Characteristics of cytokine release syndrome (C R S) in COVID-19<br/>Figure 1 A tubercle formed in pulmonary tuberculosis<br/>Figure 1 Two mechanisms generate variations in influenza surface antigens<br/>Figure 17-4 Transmission of respiratory infections<br/>Figure 17-5 Vector-borne infectious diseases<br/>Figure 17-6 Examples of global emerging and re-emerging infectious diseases<br/>Figure 1 Structure of a typical coronavirus<br/>Figure 2 Potential transmission route of the S A R S-Co V-2 precursor between hosts<br/>Figure 1 Herd immunity explained<br/>Figure 2 Herd immunity threshold as a function of R0<br/>Figure 17-7 Progress with polio eradication<br/>Figure 17-8 The five stages of infectious disease evolution from animals to humans<br/>Figure 17-9 The Entry Points and in Vivo Microenvironments of Infectious Agents<br/>Figure 17-10 The three major immune response pathways: type 1, 2, and 3<br/>Figure 1 Two pathways to variation in influenza surface antigens<br/>Figure 17-11 The presence of preformed antibody inhibits primary responses to a pathogen<br/>Figure 17-12 Antibody-mediated mechanisms to combat infections by extracellular bacteria<br/>Figure 17-14 Malarial life cycle<br/>An advertisement for smallpox inoculation that was distributed in the early 1800s in Boston, M A<br/>Figure 18-1 Return on investment from childhood immunizations in low- and middle-income countries, 2011 to 2020<br/>Figure 18-2 Immune response pathways induced by vaccination<br/>Recommended childhood immunization schedule in the United States, 2022<br/>Figure 18-3 Pertussis cases in the United States, 1922 to 2019<br/>Figure 1. Strategies used to design COVID-19 vaccines<br/>Figure 18-5 Sequence of clinical trial phases in the United States<br/>Figure 18-6 Vaccine formulations<br/>Figure 18-8 Mucosal administration of a live, attenuated vaccine<br/>Figure 18-9 Subunit vaccines<br/>Figure 18-10 Multivalent subunit polysaccharide vaccines protect young children from bacterial pneumonia<br/>Figure 18-11 Particle- and membrane-based vaccines<br/>Figure 18-12 Viral- and bacterial-based vaccine vectors<br/>Figure 18-13 Nucleic acid–based vaccines<br/>Figure 18-14 A 2012 promotion for the pertussis booster<br/>Figure 1 A prime-and-pull vaccine strategy protects mice against lethal challenge with H S V<br/>Figure 18-15 Smallpox vaccination<br/>A figure shows 9 graphs that depict E7-specific C D 8 plus T-cell response in mice<br/>Two graphs show E7-specific CD8+ T lymphocyte response in wild type mice and C D 4 knockout mice<br/>Primary immunodeficiencies resulting from inherited defects affect specific cell types<br/>Figure 19-2 Primary immunodeficiency warning signs<br/>Figure 19-3 Defects in lymphocyte development and signaling can lead to severe combined immunodeficiency (S C I D) in humans<br/>Figure 19-4 Defects in C D 40 L on T cells or C D 40 on B cells and other A P Cs can give rise to the primary immunodeficiency known as hyper-I g M syndrome<br/>Figure 19-5 Genetic defects resulting in Mendelian susceptibility to mycobacterial diseases (M S M Ds)<br/>Figure 19- 7 Global AIDS epidemic<br/>Figure 19-8 Trends in the H I V/ AIDS epidemic<br/>Figure 19-9 Structure of H I V<br/>Figure 19-11 Genetic organization of H I V-1 (a) and functions of encoded proteins (b)<br/>H I V infection of target cells and virus replication<br/>Figure 19-13 Budding of new virus particles from the surface of an infected T cell<br/>Figure 19-14 C X C R 4 and C C R 5 serve as coreceptors for H I V infection of different cell types<br/>Figure 19-15 Typical course of H I V infection in an untreated patient<br/>Figure 19-16 Endoscopic and histologic evidence for depletion of C D 4 plus T cells in the G I tract of patients with A I D S<br/>Figure 19-17 Stages in viral replication cycle that provide targets for therapeutic antiretroviral drugs<br/>E 7-specific C D 8 plus T-cell response<br/>Figure 1 New H I V infections worldwide among children with and without the provision of antiretroviral medicines to prevent mother-to-child transmission, from 1995 to 2020<br/>Figure 2 Most countries are providing lifelong antiretroviral therapy to pregnant and breastfeeding women living with H I V<br/>Figure 1 Neutralizing antibodies to H I V<br/>Figure 2 Neutralizing antibodies to H I V<br/>Figure 3 An immunization approach for stimulating production of broadly neutralizing antibodies to the H I V-1 E n v spike<br/>Effect of C V I D on the immune response<br/>Figure 19-2 Chromosomal translocations resulting in Burkitt’s lymphoma<br/>Figure 19-3 Model of sequential genetic alterations leading to metastatic colon cancer<br/>Figure 19-4 Hallmarks of cancer<br/>Figure 19-5 Different mechanisms generate tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs)<br/>Figure 19-7 Down-regulation of MHC class I expression on tumor cells may allow for tumor escape mutants<br/>Figure 19-9 Development of a monoclonal antibody specific for idiotypic determinants on B-lymphoma cells<br/>Figure 1<br/>Figure 2<br/>Figure 19-10 Mechanism of action of sipuleucel-T, a prostate cancer vaccine<br/>Figure 19-11 Use of CD80 (B7.1)-transfected tumor cells for cancer immunotherapy<br/>Figure 19-12 Using checkpoint blockade therapy to treat cancer<br/>Figure 20-1 Tumor growth and metastasis<br/>Figure 20-2 Hallmarks of cancer<br/>Figure 20-3 Mechanisms that generate tumor-specific antigens (T S As) and tumor-associated antigens (T A As)<br/>Figure 1 Age of vaccination against H P V and the future risk of cervical cancer in women<br/>Figure 20-4 The three stages of cancer immunoediting<br/>Figure 20-5 The immunosuppressive, pro-tumor microenvironment<br/>Figure 20-6 Immune contexture and immunoscores used in cancer staging and prognosis<br/>Figure 20-7 Types of immunotherapy available to treat cancer<br/>Figure 20-8 Bispecific T-cell engagers (B i T Es) used in cancer immunotherapy<br/>Figure 20-9 Using checkpoint blockade therapy to treat cancer<br/>Figure 20-10 The sipuleucel-T mechanism of action, a prostate cancer vaccine<br/>Figure 1 Driving Cancer Away with CAR T Cells<br/>Figure 2 Examples of the specialized accessories included in C A Rs<br/>Figure 20-11 The NeoVax cancer vaccine platform<br/>Figure 20-12 Using oncolytic viruses to treat cancer<br/>Figure 1 Optical properties of the three types of filters<br/>A photo shows an 8 by 8 micro-titre plate that is used for a hemagglutination inhibition assay<br/>Stimulated and unstimulated T cells<br/>C D 46 graph<br/>Apoptotic and healthy cells<br/>An illustration shows the formation of a recombined v j gene in a B cell from a germ-line light-chain (kappa) D N A<br/>An illustration shows the formation of a recombined V D J gene from a germ-line heavy-chain (H) D N A in two steps<br/>Recombined V D J B gene in T cell<br/>Recombined V J gene<br/>Comparing thymus and lymph nodes of normal and knockout mice<br/>Different B cells<br/>Activation-induced cytidine deaminase<br/>Figure C-1 The chemokine system: an overview<br/>Figure D-1 Icons used in this Appendix<br/>Figure D-3 G protein activation<br/>Figure D-4 The M A P kinase pathway<br/>Figure D-5 Downstream components of the canonical and noncanonical pathways of N F-kappa B activation<br/>Figure D-6 Upstream portion of the canonical N F-kappa B pathway<br/>Figure D-7 Upstream portion of the noncanonical N F-kappa B pathway<br/>Figure D-8 Integration of common signaling pathways<br/>Figure D-9 Signaling through plasma membrane T L Rs<br/>Figure D-10 Signaling through endosomal T L Rs<br/>Figure D-11 Signaling through C L Rs<br/>Figure D-12 Signaling through N L R and R L R receptors<br/>Figure D-13 Signaling through c G A S and S T I N G<br/>Figure D-14 The J A K-S T A T pathway of cytokine activation<br/>Figure D-15 Signal transduction pathways from G protein–coupled receptors<br/>Figure D-16 Signaling through T N F-R 1<br/>Figure D-17 Pathways that regulate apoptosis<br/>Figure D-18 Signaling through the Notch receptor<br/>Figure D-19 Signaling through the T-cell receptor<br/>Figure D-20 Signaling through the B-cell receptor<br/>Figure D-21 Activation of S r c-family kinases<br/>Figure E-1 The generation of polyclonal and monoclonal antibodies<br/>Figure E-2 Immunoprecipitation in solution<br/>Figure E-6 Competitive, solid-phase radioimmunoassay (R I A) to measure cytokine concentrations in serum<br/>Figure E-7 Variations in the enzyme-linked immunosorbent assay (E L I S A) technique allow for the determination of antibody or antigen<br/>Figure E-8 E L I S P O T measurements of interferon (I F N)- gamma secretion by N K T cells<br/>Figure E-9 Western blotting uses antibodies to identify protein bands after gel electrophoresis<br/>Figure E-10 Determining antibody affinity with equilibrium dialysis<br/>Figure E-11 Surface plasmon resonance (S P R)<br/>Figure E-14 Fluorescently labeled cells and the passage of light through a fluorescence microscope<br/>Figure E-16 The principle of confocal microscopy<br/>Figure E-17 Fluorescence excitation by one-photon versus two-photon laser excitation<br/>Figure E-18 Three-dimensional fluorescence in situ hybridization (3-D F I S H)<br/>Figure E-19 A simple flow cytometry setup<br/>Figure E-20 Optical properties of the three types of filters<br/>Figure E-21 Nature of the voltage pulse is determined by the shape of the emitting structure<br/>Figure E-22 Typical dot plots of cytometric data<br/>Figure E-23 Analysis of multicolor fluorescence data<br/>Figure E-24 The emission spectra of commonly used dyes have considerable overlap<br/>Figure E-25 Spectral cytometry collects the entire emission spectra of all fluorochromes<br/>Figure E-26 C y T O F enables the measurement of up to 45 different parameters<br/>Figure E-27 The M T T assay is used to measure the number of viable cells in a suspension<br/>Figure E-28 Bromodeoxyuridine replaces deoxythymidine during D N A synthesis<br/>Figure E-29 Propidium iodide intercalates into D N A and is a cell cycle and apoptosis indicator<br/>Figure E-30 C F S E labeling can determine the frequency of cells that have divided a defined number of times<br/>Figure E-31 Assessment of apoptosis, using a T U N E L assay<br/>Figure E-32 D N A Hi-C detects regions of D N A that interact in three-dimensional space in situ<br/>Figure E-33 Sanger dideoxy sequencing<br/>Figure E-34 Next-generation sequencing<br/>Figure E-35 The C R I S P R-Cas 9 system can be applied to problems that require targeted D N A manipulations<br/>Figure E-36 Quantitative P C R detects the frequency of a viral sequence using fluorescence detection<br/>Figure E-37 L A M P-P C R operates under isothermal conditions to amplify viral sequences<br/>Figure E-38 C R I S P R-Cas 12 a can detect S A R S-Co V-2<br/>Figure E-39 Antibody-based rapid detection test for viral antigens<br/>Figure E-40 General procedure for generating transgenic mice<br/>Figure E-41 Gene targeting with C r e / l o x<br/>Back cover of the Kuby Immunology textbook<br/>Back Cover<br/> |
