000			69377nam a22003615i 4500
003			CUTN
005			20250813160648.0
008			220309s2022 nyu 000 0 eng
020			_a9781319495282
020			_z9781319440930
020			_z9781319498658
041			_aEnglish
042			_apcc
082			_a616.079 _bSTR
100	1		_aStranford, Sharon A.,
100	1		_eauthor.
245	1	0	_aKuby immunology : _bCovid-19 and digital update / _cSharon A. Stranford, Judith A. Owen, Jenni Punt, Patricia P. Jones.
250			_aEighth edition.
260			_aNew York : _bW.H Freeman and Company, _c2023.
263			_a2208
300			_apages cm
505			_tAbout this Book Cover Page Accessibility 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 1.1 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? 1.2 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 1.3 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 2.1 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 2.2 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 2.3 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 3.1 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 3.2 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 3.3 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 3.4 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 3.5 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 4.1 Physical and Chemical Barriers to Infection Physical Barriers Prevent Pathogen Entry into the Body’s Interior Antimicrobial Proteins and Peptides Kill Potential Microbial Invaders 4.2 The Cells of Innate Immunity Myeloid Cells are Often the First to Respond Innate Cells of the Lymphoid Lineage are also Early Responders 4.3 The Receptors of Innate Immunity Toll-Like Receptors Are Expressed on the Endosomal and Plasma Membranes C-Type Lectin Receptors Bind Carbohydrates on the Surfaces of Extracellular Pathogens RLRs Bind Cytosolic Viral RNA cGAS and STING Are Activated by Cytosolic DNA and Dinucleotides NOD-Like Receptors Bind PAMPs from Cytosolic Pathogens ALRs Bind Cytosolic DNA 4.4 The Effector Mechanisms of Induced Innate Immunity Inflammation and Extravasation Focus Innate Immune Cells at the Site of Infection Expression of Innate Immunity Proteins Is Induced by PRR Signaling Phagocytosis is an Important Mechanism for Eliminating Pathogens 4.5 Modulation of Innate Responses Innate and Inflammatory Responses Are Regulated Both Positively and Negatively Trained Immunity Is a Manifestation of Innate Immune Memory Pathogens Can Evade Innate and Inflammatory Responses 4.6 Interactions between the Innate and Adaptive Immune Systems The Innate Immune System Activates Adaptive Immune Responses Recognition of Pathogens by Dendritic Cells Customizes Helper T-Cell Differentiation 4.7 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 5.1 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 5.2 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 5.3 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 5.4 Complement Deficiencies 5.5 Microbial Complement Evasion Strategies 5.6 The Evolutionary Origins of the Complement System Conclusion References Study Questions Chapter 6: The Organization and Expression of Lymphocyte Receptor Genes 6.1 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 6.2 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 6.3 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 6.4 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 6.5 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 7.1 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 7.2 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 7.3 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 7.4 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 7.5 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 7.6 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 7.7 Presentation of Nonpeptide Antigens Conclusion References Study Questions Chapter 8: T-Cell Development 8.1 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 8.2 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? 8.3 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 8.4 Exit from the Thymus and Final Maturation 8.5 Other Mechanisms That Maintain Self-Tolerance Regulatory T Cells Negatively Regulate Immune Responses Peripheral Mechanisms of Tolerance Also Protect against Autoreactive Thymocytes Conclusion References Study Questions Chapter 9: B-Cell Development 9.1 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 9.2 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 9.3 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 9.4 Comparison of B- and T-Cell Development Conclusion References Study Questions Chapter 10: T-Cell Activation, Helper Subset Differentiation, and Memory 10.1 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 10.2 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 10.3 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 11.1 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 11.2 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 11.3 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 11.4 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 12.1 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 12.2 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 13.1 Common Themes in Barrier Immune Systems Barrier Epithelial Cells Generate a Healthy Distance from Microbiota Immune Cells Interact with the Barrier Epithelium and Lymphoid Tissue Barrier Immune Systems Initiate Both Tolerogenic and Inflammatory Responses to Microorganisms 13.2 The Immune System of the Skin The Skin and Its Epithelium Are Multilayered Skin Immune Cells Are Present in Both the Epidermis and Dermis The Interaction between Skin Immune System and Skin Microbes Generates Both Protective and Inflammatory Responses 13.3 The Immune System of the Intestine The Gut Is Organized into Anatomical Sections and Tissue Layers Gut Epithelial Cells Vary in Phenotype and Function Immune Homeostasis in the Intestine Is Regulated by Both Innate and Adaptive Cells Commensal Microbes Help Maintain Tolerance in the Intestine The Gut Immune System Recognizes and Responds to Harmful Pathogens 13.4 The Immune System of the Respiratory Tract The Respiratory Immune System Shares Many Features with the Intestinal Immune System Conclusion References Study Questions Chapter 14: The Immune Response in Space and Time 14.1 Immune Cells in Healthy Tissue: Homeostasis Naïve Lymphocytes Circulate between Secondary and Tertiary Lymphoid Tissues Naïve Lymphocytes Browse for Antigen along the Reticular Network of Secondary Lymphoid Organs 14.2 The Innate Immune Response to Antigen in Tissues 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 That Present Processed Antigen Travel to the T-Cell Zones of Secondary Lymphoid Tissue Unprocessed Antigen Travels to the B-Cell Zones 14.3 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 B and T Cells Behave Differently 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 Memory T Cells Begins Early in the Primary Response 14.4 The Effector and Memory Cell Responses in the Periphery Chemokine Receptors and Adhesion Molecules Coordinate Lymphocyte Homing Both Effector and Memory Lymphocytes Contribute to Clearing Infection in Tissues The Immune Response Contracts after Two to Four Weeks Memory Cells Position Themselves to Mount a Secondary Response to Re-Infection Conclusion References Study Questions Chapter 15: Allergy, Hypersensitivities, and Chronic Inflammation 15.1 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? 15.2 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 15.3 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 15.4 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 15.5 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 16.1 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 16.2 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 16.3 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 Disease and Public Health 17.1 The Chain of Infection Infectious Agents Reside in Reservoirs Infection Can Occur via Various Modes of Transmission Successful Infection Requires a Susceptible Host 17.2 Factors Contributing to Human Infectious Disease Patterns Emerging and Re-Emerging Infectious Diseases Are on the Rise Zoonotic Infections Arise from Contact with Animals Anthropogenic Factors Contribute to the Emergence and Spread of Infectious Disease Public Health Infrastructure Can Help Identify and Respond to Infectious Outbreaks Human Nature, History, and Culture Also Play a Role 17.3 The Link Between Timing, Location, and Immune Effector Mechanisms Earlier Infectious Exposures May Influence Innate Responses to Another Infectious Agent Extracellular Infections at Barrier Surfaces Are Typically Controlled by Type 2 Responses Extracellular Pathogens Are Targeted by Extracellular Tools and Type 3 Responses Type 1 Responses Dominate During Intracellular Infections Systemic Inflammatory Responses Can Be Life-Threatening 17.4 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 17.5 Bacterial Infections Immune Responses to Extracellular and Intracellular Bacteria Differ Bacteria Can Evade Host Defense Mechanisms at Several Stages 17.6 Parasitic Infections Protozoan Parasites Are a Diverse Set of Unicellular Eukaryotes Parasitic Worms (Helminths) Typically Generate Weak Immune Responses 17.7 Fungal Infections Innate Immunity Controls Most Fungal Infections Immunity against Fungal Pathogens Can Be Acquired Conclusion References Study Questions Chapter 18: Immunization and Vaccines 18.1 Passive Versus Active Immunity Passive Immunity Is Temporary and Enacted by Preexisting Antibodies Active Immunization Stimulates Immune Cells and Generates Memory Responses 18.2 Vaccine Research and Design Principles Years of Basic Research Precede Each New Vaccine Vaccine Design Begins with Defining the Immune Correlates of Protection Vaccines Are Tightly Regulated and Monitored Immunization Programs Must Consider the Human Context 18.3 Vaccine Formulations Whole Pathogen Vaccines Contain Live or Killed Microbes Subunit Vaccines Include Pieces of the Pathogen Particle- or Membrane-Based Vaccines Include an Outer Envelope Vectored Vaccines Replicate Without the Risk of Reversion Nucleic Acid Vaccines Provide Instructions for Pathogen-Associated Proteins 18.4 Vaccine Adjuvants, Schedules, and Delivery Methods Adjuvants Increase Vaccine Effectiveness by Activating Innate Response Elements Full Immune Protection May Require Multiple Exposures or Boosters Several Novel Vaccine Delivery Methods Are Under Investigation Conclusion References Study Questions Chapter 19: Immunodeficiency Diseases 19.1 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 19.2 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 20: Cancer and the Immune System 20.1 Cancer Development and Key Characteristics Cancer Arises from Progressive DNA Changes in a Self Cell Cancer-Associated Genes Regulate Cell Proliferation and Survival Blood-Cell Cancers Arise from Various Stages of Hematopoietic Stem Cell Development Several Key Characteristics Define All Cancers Distinct Antigen Expression by Cancer Cells Can Aid Detection and Eradication 20.2 The Immune Response to Cancer The Immune Response Has Pro-Tumor and Anti-Tumor Actions Innate and Adaptive Mechanisms Detect and Eradicate Cancer Some Immune Response Elements Promote Cancer Survival Tumor Cells Evolve to Evade Immune Recognition and Apoptosis 20.3 Anticancer Immunotherapies Early Physicians Observed the Immune Response to Cancer Evaluating the Immune Microenvironment Provides Prognostic and Therapeutic Value Antibodies Can Direct the Immune Response to Tumor Cells Immune Checkpoint Blockades Can Manipulate Comodulatory Signals Anti-Tumor Lymphocyte Populations Can Be Expanded or Enhanced to Treat Cancer Prophylactic and Therapeutic Anticancer Vaccines May Enhance the Anti-Tumor Response Oncolytic Viruses Can Treat Cancer Conclusion References Study Questions Appendix A: CD Antigens Appendix B: Cytokines Appendix C: Chemokines and Chemokine Receptors Appendix D: Signal Transduction in the Immune System Appendix E: Experimental Systems and Methods Appendix F: An Extended List of CD Antigens Glossary Answers to Study Questions Index Notes Extended Descriptions Icons Used in This Book Herd immunity threshold for five viruses The rapid antigen tests for COVID-19 are based on a sandwich E L I S A Immune response pathways Engineered B i T E antibodies Online assignment Sample page of a PowerPoint presentation Starting screen for an animation LaunchPad Figure 1-3 Drawing by Elie Metchnikoff of phagocytic cells surrounding a foreign particle Passive Antibodies and the Iditarod Figure 1-4 Representation of Paul Ehrlich’s side-chain theory to explain antibody formation Figure 1-5 An Outline for the Humoral and Cell-Mediated (Cellular) Branches of the Immune System. Figure 1-6 Generation of diversity and clonal selection in T and B lymphocytes Figure 1-7 Collaboration between Innate and Adaptive Immunity in Resolving an Infection Figure 1-8 Differences in the primary and secondary adaptive immune response to injected antigen reflect the phenomenon of immunologic memory Figure 1-11 The proposed role of the microbiome in regulating immune, metabolic, and neurologic function Figure 2-1 Hematopoiesis Figure 1 Panning for stem cells Figure 2 Current approaches for enrichment of pluripotent stem cells from bone marrow Figure 2-2 Regulation of hematopoiesis by transcription factors Figure 2-3 An example of lineage commitment during hematopoiesis: the development of B cells from HSCs Figure 2-4 Examples of granulocytes Figure 2-5 Examples of monocytes, macrophages, dendritic cells, and megakaryocytes Figure 2-6 Examples of lymphocytes Figure 2-7 Structure of the B-cell and T-cell antigen receptors Figure 2-8 T-cell recognition of antigen Figure 1 The general strategy used to correct a defective gene by autologous H S C transplantation Figure 2-9 Sites of hematopoiesis during fetal development Figure 2-10 The bone marrow microenvironment Figure 2-11 Structure of the thymus Figure 1 (b) the first page of the Lancet article (1961) describing his discovery of the function of the thymus Figure 2-12 The human lymphatic system Figure 2-13 Structure of a lymph node Figure 2-14 Stromal cell networks in secondary lymphoid tissue Figure 2-15 Structure of the spleen Figure 2-16 Example of secondary lymphoid tissue in barrier organs: gut-associated lymphoid tissue (G A L T) Figure 1 Evolutionary distribution of lymphoid tissues Figure 2 Thymic tissue in the lamprey eel Figure 3 The avian bursa Recognition and response Figure 3-1 Receptor-ligand binding obeys the rules of chemistry Figure 3-2 Univalent and bivalent (or multivalent) binding Figure 3-3 Cell surface receptors cluster on binding multivalent antigens Figure 3-4 Combining one receptor chain with different partners allows increased receptor diversity and affinity while minimizing the need for new genetic information Figure 3-5 Comparison of the three forms of the IL-2 receptor Figure 3-6 Polarized secretion of I L-12 (pink) by dendritic cells (blue) in the direction of a bound T cell (green) Figure 3-7 Some examples of proteins bearing immunoglobulin domains Figure 3-8 The immunoglobulin domain is made up of amino acid residues arranged in beta sheets that are connected by variable loops Figure 3-9 The B C R exists in both membrane-bound (a) and soluble (b) forms Figure 1 Experimental demonstration that most antibodies are in the gamma-globulin fraction of serum proteins Figure 2 Prototype structure of I g G, showing chain structure and interchain disulfide bonds Figure 3-10 The structure of antibodies 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) Figure 3-12 General structures of the five major classes of antibodies Figure 3-13 General structure of the four subclasses of human I g G Figure 3-14 B-cell coreceptors require receptor-associated molecules and coreceptors for signal transduction Figure 3-15 The three-dimensional structure of the alpha beta T C R Figure 1 The generation of antibodies specific for the T C R Figure 3-16 Structure of the C D 4 and C D 8 coreceptors Figure 3-17 The T-cell receptor and coreceptor complex Interleukin-1 family Class 1 hematopoietin cytokine family Class 2 (interferon) cytokine family Tumor necrosis factor Interleukin-17 family Chemokines Figure 3-18 Cytokine attributes of (a) pleiotropy, redundancy, synergism, antagonism, and (b) cascade induction Figure 3-19 Ligands and receptors of the I L-1 family Figure 3-21 Binding of T N F to T N F R-1 induces trimerization and activation of downstream events Figure 3-22 The I L-17 family of cytokines and their associated receptors Figure 3-23 Disulfide bridges in chemokine structures Concepts in lymphocyte signaling Figure 3-25 General model of signal transduction mediated by most class 1 and class 2 cytokine receptors Figure 3-26 The role of lipid raft regions within membranes Figure 3-27 Activation of S r c-family kinases Figure 1 Fluorescence-activated cell-sorting (F A C S) profi les of a normal individual and a patient with X L A Innate Immunity Figure 4-2 The structure of the mucus layer varies along the length of the gastrointestinal tract Figure 4-3 Psoriasin prevents colonization of the skin by Escherichia coli (E. coli) Figure 4-4 Innate Lymphoid Cells Pattern Recognition Receptors Figure 4-6 Toll-like receptor (T L R) structure and binding of P A M P ligands Figure 4-7 Cellular location of T L Rs Figure 4-8 Cell wall components of gram-negative and gram-positive bacteria Figure 4-9 L P S binding by T L R 4 complex on host cells Figure 4-10 The R I G-I-like receptor family Figure 4-11 The N L R P 3 inflammasome and its activators Figure 4-12 Activation of inflammasomes Effectors of innate immune response to infection Figure 4-14 The steps of leukocyte extravasation Figure 4-15 Inside-out signaling results in a high affinity form of L F A-1 Figure 4-16 Initiation of a local inflammatory response Figure 4-17 Induction of antiviral activities by type Roman numeral 1 interferons Figure 4-18 Phagocytosis Figure 4-19 Generation of antimicrobial reactive oxygen and nitrogen species Figure 1 Neutrophil extracellular traps (N E Ts) and N E Tosis Figure 1 Evasion of type Roman numeral 1 interferon-mediated immunity by S A R S Co V-2 Figure 4-20 Pathogens induce differential signaling through D C P R Rs, influencing helper T-cell functions Figure 1 Induced closure of leaf stomata following exposure to bacterial P A M Ps Complement Proteins Generation of C 3 and C 5 convertases by the three major pathways of complement activation Figure 5-3 Structure of the C 1 macromolecular complex Figure 5-4 Models of pentameric I g M and hexameric I g G derived from x-ray crystallographic data Classical Pathway of Complement Activation 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 Figure 5-7 Initiation of the lectin pathway relies on lectin receptor recognition of microbial cell surface carbohydrates Figure 5-8 Initiation of the alternative tickover pathway of complement Figure 2 Pillemer’s experiments Figure 5-9 Initiation of the alternative pathway by specific, noncovalent binding of properdin to the target membrane Figure 5-10 Formation of the membrane attack complex (M A C) Complement and the Visual System Figure 2 Fluorescence images of the lateral geniculate nucleus, analyzed by array tomography Figure 5-11 Coligation of antigen to B cells Figure 5-12 Anaphylatoxins and inflammatory response Figure 5-13 Opsonization of microbial cells Figure 5-14 C 1 q colocalizes with annexin A 5 on the surface of apoptotic cells Figure 5-15 Clearance of circulating immune complexes Figure 5-16 Regulation of complement activity Figure 1 Treatment of P N H patients with eculizumab relieves hemoglobinuria Figure 5-17 Evolution of complement components Biochemistry of the membrane proteins Flow cytometric histogram Heavy chain locus and nuclear lamina Figure 6-1 Sequencing studies of the variable and constant regions of immunoglobulin Figure 6-2 Dreyer and Bennett hypothesis Figure 6-3 The kappa light-chain gene is formed by D N A recombination between variable and constant region gene segments Figure 6-4 The antibody kappa light-chain locus is composed of three families of D N A segments Hozumi and Tonegawa’s classic experiment Figure 6-5 Variable region of antibody heavy chains is encoded in three segments—V, D, and J Figure 6-6 Organization of immunoglobulin germ-line gene segments in the mouse Figure 6-7 Pre-B C R and B C R complexes Figure 6-8 Two conserved sequences in light-chain and heavy-chain D N A function as recombination signal sequences (R S Ss) Figure 6-9 Recombination between gene segments is required to generate complete variable region light- and heavy-chain genes Figure 6-10 Structural features of the R A G 1/2 recombinase proteins Recombnation of immunoglobulin variable region genes Figure 6-12 Mechanism of V (D) J recombination, illustrated for V kappa-to-J kappa joining Figure 1 Elements of the recombination substrate used by Carmona and colleagues Figure 2 Evolution of the R A G 1/2 recombinase Figure 6-13 Three-dimensional organization of chromosomal regions containing V, D, and J segments changes during B-cell development Figure 6-14 Nuclear positioning of I g H and I g kappa loci alters during B-cell development Figure 6-15 Generation of a functional immunoglobulin receptor requires productive rearrangement of heavy- and light-chain gene segments Figure 6-16 Kappa light-chain receptor editing 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 Figure 6-18 Production and identification of a c D N A clone encoding the T-cell receptor beta gene Figure 6-19 Germ-line organization of the mouse T C R alpha-, beta-, gamma-, and delta-chain gene segments Figure 6-20 Locations R S S spacers in T C R genes 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 D N A with V domain and D domain Recombination of two gene segments Position of genes in germ-line D N A and D N A from antibody-producing cells 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 Figure 7-3 Peptide-binding groove of M H C class Roman numeral 1 and class Roman numeral 2 molecules, with bound peptides Figure 7-4 Examples of anchor residues (blue) in nonameric peptides eluted from two different M H C class Roman numeral 1 molecules Figure 7-5 Conformation of peptides bound to M H C class Roman numeral 1 molecules Figure 7-6 Comparison of the organization of the major histocompatibility complex (M H C) in mice and humans Figure 7-7 Simplified map of the mouse and human M H C loci Figure 7-8 Illustration of inheritance of MHC haplotypes in inbred mouse strains and in humans Figure 7-9 Diagram illustrating the various M H C molecules expressed on antigen-presenting cells of a heterozygous H 2 k/d mouse Figure 7-10 Variability in the amino acid sequences of allelic H L A class Roman numeral 1 molecules Figure 1 Experimental demonstration of self-M H C restriction in cells Figure 2 Experimental demonstration that antigen recognition by T C cells exhibits M H C restriction Figure 7-11 Experimental demonstration that antigen processing is necessary for Figure 7-12 Overview of endogenous and exogenous pathways for processing antigen Figure 7-13 Proteolytic system for degradation of intracellular proteins Figure 7-14 T A P (transporter associated with antigen processing) Figure 7-15 Assembly and stabilization of M H C class I molecules Figure 7-16 Generation of antigenic peptides and assembly of M H C class Roman numeral 2 molecules in the exogenous processing pathway Antigen-presenting pathways Figure 7-18 Activation of naïve T c cells by exogenous antigen requires D C licensing and cross-presentation Figure 7-19 Lipid antigen binding to the C D 1 molecule Specificity of T cells against the M C M V and tum peptide Development of T Cells in the Thymus Figure 8-2 Development of T cells from hematopoietic stem cells on bone marrow stromal cells expressing the Notch ligand T-cell receptor expression and function Figure 8-4 Time course of appearance of gamma delta thymocytes and alpha beta thymocytes during mouse fetal development Positive and negative selection of thymocytes in the mouse 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 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 Figure 2 Primary data from experiments summarized in Figure 1 Figure 8-7 Relationship between T C R affinity and selection Figure 8-8 Experimental support for the role of T C R affinity in thymic selection Figure 8-9 A N D Accompanying Video 8-9v Imaging live d p thymocytes undergoing selection in the thymus 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 Figure 8-11 How regulatory T cells (T R E G s) inactivate traditional T cells Fluorescence activated cell sorting plots Stages of B-cell development B-Cell Development Figure 9-2 H S Cs and B-cell progenitors Figure 1 Factors regulating B-cell development Figure 9-3 Transcription factors during early B-cell development Figure 9-4 Immunoglobulin gene rearrangements and expression of marker proteins during B-cell development Figure 1 Experimental approach for the isolation of Hardy’s fractions from bone marrow Figure 2 Flow cytometric characterization of the stages of B-cell development in the bone marrow Figure 9-5 The pre-B-cell receptor Figure 9-6 Experimental evidence for negative selection (clonal deletion) and light-chain editing of self-reactive immature B cells in the bone marrow Figure 9-7 T 2, but not T 1, transitional B cells can enter splenic B-cell follicles and recirculate Figure 9-8 Transitional B cells undergo positive and negative selection in the spleen Figure 9-9 Goodnow’s experimental system for demonstrating clonal anergy in mature peripheral B cells Figure 9-10 The three major populations of mature B cells in the periphery Levels of antigens in wild-type and Dicer knockout mice Staining of Pro-B and Pre-B cells with Annexin V Figure 10-1 T-Cell Activation and Differentiation Figure 10-2 Three Signals Are Required for Activation of a Naïve T Cell Figure 10-3 Surface interactions responsible for T-cell activation Figure 10-4 Schematic of T-cell receptor signaling Figure 1 Evidence that C D 28 is costimulatory ligand for T cell proliferation Figure 1 How the checkpoint inhibitor ipilimumab works Figure 10-5 Signals that lead to clonal anergy versus clonal expansion Figure 10-6 Comparison of professional antigen-presenting cells that induce T-cell activation Figure 10-7 Superantigen-mediated cross-linkage of T-cell receptor and M H C class Roman numeral 2 molecules Figure 10-8 Activation and differentiation of naïve T cells into effector and memory T cells Figure 10-9 T Helper Subset Differentiation Figure 10-10 General events and factors that drive T H subset polarization Figure 10-11 Initiation of T H 1 and T H 2 responses by pathogens Figure 10-12 Cross-regulation of T helper cell subsets by transcriptional regulators Figure 1 C D 4 + T cells from patients with hyper-I g E syndrome do not differentiate into T H 17 cells Figure 1 The anatomy and cell biology of the human placenta Figure 2 Genetic differences between the F o x P 3 enhancer in placental (eutherian) and nonplacental animals Figure 10-13 Examples of how T F H and T H 1 T cells provide help in the immune response Figure 10-14 Correlation between type of leprosy and relative T H 1 or T H 2 activity Figure 10-15 One possible model for the development of memory T-cell subsets Fluorescence-activated cell-sorting (F A C S) profiles Figure 11-2 Maturation and clonal selection of B lymphocytes Figure 11-3 Different types of antigens signal through different receptor units Figure 11-4 Adoptive transfer experiments demonstrated the need for two cell populations during the generation of antibodies to T-dependent antigens Figure 11-5 Alternative Fates of B Cells following T-Dependent Antigen Stimulation Figure 11-6 Antigen presentation to follicular B cells in the lymph node Figure 11-7 Antigen recognition by the B C R triggers membrane spreading 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 Figure 11-9 Signal Transduction Pathways Emanating from the B C R Figure 11-10 B cells extract antigen from the antigen-presenting cell membrane, using active contractions of the actomyosin skeleton Figure 1 Visualization of antigen-specific B cell movements in the germinal center Figure 11-11 Differential chemokine receptor expression controls B-cell migration during the T-dependent immune response Figure 11-12 Movement of antigen-specific T and B cells within the lymph node after antigen encounter Figure 11-13 Experiment showing that a single B cell can give rise to plasmablasts, germinal center B cells, or memory B cells Figure 11-14 A regulatory network of transcription factors controls the germinal center B cell/plasma cell decision point Figure 11-15 Terminology describing antibody-secreting cells Figure 11-16 The germinal center Figure 11-17 B-Cell Differentiation Events Occur in Different Anatomical Locations Figure 11-18 Activation-induced cytidine deaminase (A I D) mediates the deamination of deoxycytidine and the formation of deoxyuridine 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 Figure 11-20 Class switch recombination from a C mu to a C gamma 1 heavy-chain constant region gene Figure 11-21 The bone marrow niche occupied by plasma cells is supported by eosinophils and megakaryocytes, as well as by mesenchymal stromal cells Figure 11-22 Temporal separation of recall responses from I g G 1 and I g M 1 memory responses Figure 11-24 The marginal zone of the mouse spleen I g M levels B cells and their flow cytometric data Figure 12-1 The Six Broad Categories of Antibody Effector Functions FIgure 12-3 Agglutination of Streptococcus pneumoniae by antibodies in nasal secretions Figure 12-4 Structure of human F c receptors 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 Figure 12-6 Generation of effector C T Ls Figure 12-7 Localizing antigen-specific C D 8 plus T-cell populations in vivo Figure 1 M H C-peptide tetramers Figure 12-8 Stages in C T L-mediated killing of target cells 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 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 Figure 12-11 C T L-mediated pore formation in target cell membrane Figure 12-12 Experimental demonstration that C T Ls use F a s and perforin pathways Figure 12-13 Two pathways of C T L-activated target cell apoptosis Figure 12-14 Time course of responses to viral infection Figure 12-15 How N K cytotoxicity is restricted to altered self cells: missing self model and balanced signals model Figure 12-16 Structures of N K inhibitory and activating receptors bound to their ligands Figure 1 The investigators’ experimental approach Figure 2 Experimental results Figure 13.1 Barrier immune tissues Figure 13.2 Major cell types in barrier immune systems Figure 13.3 Major barrier tissue immune cells interact to produce type 1, type 2, and type 3 responses Figure 13.4 Lymphoid tissues associated with barrier organs Figure 13.5 Secondary lymphoid tissue associated with the small intestine Figure 13.6 Common themes in barrier immune responses Figure 13.7 Skin anatomy and associated immune cells Figure 13.8 Developmental regulation of T R E G cells in the skin Figure 13.9 Immune responses in the skin Figure 13.10 Gross anatomy of the gastrointestinal (G I) tract Figure 13.11 Cellular anatomy of the small and large intestines Figure 13.12 How antigen is delivered from the lumen to antigen-presenting cells Figure 13.13 Maintaining homeostasis and tolerance to the microbiome at the intestinal surface Figure 13.14 Transcytosis of I g A to the lumen of the intestine Figure 13.15 Effect of commensal bacteria on intestinal immune responses Figure 13.16 Conditions that cause a switch from homeostatic (a) to inflammatory (b) immune responses Figure 1 Maintaining germ-free mice Figure 2 Mice from different laboratories harbor different microorganisms S F B colonization affects I L-17 production by intestinal T H cells Figure 1 Examples of the communication between the gut microbiota, immune system, and nervous system Figure 13.17 Intestinal immune system response to Salmonella bacterial infection: an example of a type 1 response Figure 13.18 Intestinal immune system response to worm infection: an example of a type 2 response Figure 13.19 Gross and cellular anatomy of the respiratory tract Figure 13.20 Immune responses in the respiratory tract Figure 14-1 Lymphocyte recirculation routes Figure 14-2 Lymphocyte migration through H E Vs Figure 14-3 Lymphocyte migration in the spleen Figure 1 The four families of cell-adhesion molecules Figure 14-4 Lung associated lymphoid tissue Cell traffic in a resting lymph node Figure 14-6 Two-photon imaging of live T and B cells within a mouse lymph node Figure 14-7 Antigen-presenting cells are present in all lymph-node microenvironments Figure 14-8 Lymphocytes exit the lymph node through portals in the cortical and medullary sinuses Figure 14-9 A successful immune response to a viral lung infection (S A R S-C o V-2) Figure 14-10 How antigen travels into a lymph node Figure 14-11 Migration of antigen-presenting cells from tissue to lymph node through efferent lymphatics Figure 14-12 Antigen entry to lymph nodes and the spleen Figure 14-13 Activation of C D 4 plus T cells and B cells in a lymph node during a primary immune response Figure 14-14 B-cell activity in the germinal center Figure 14-16 The formation of a tricellular complex in a lymph node during C D 8 plus T-cell activation 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 Figure 14-18 Effector and memory lymphocytes leave the lymph node via efferent lymphatics and circulate to infection sites Figure 14-19 Examples of the homing receptors and addressins involved in trafficking naïve and effector T cells Figure 14-20 The contraction of an immune response Figure 14-21 Memory lymphocytes distribute themselves throughout the body, following cues provided by chemokines and cell adhesion molecules Level of I g G against the spike protein Level of I g M against the spike protein Level of anti-spike I g G Figure 15-1 The four types of hypersensitivity reactions Figure 15-2 General mechanism underlying an immediate type 1 hypersensitivity reaction 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 Figure 15-4 Signaling pathways initiated by I g E allergen cross-linking of F c E R 1 receptors Figure 15-5 Effects of mast cell activation Figure 15-6 The early and late inflammatory responses in asthma Figure 15-7 Environmental factors and genetics influence predisposition to allergies Figure 15-8 Induction of I g E-mediated food allergy response Figure 15-9 Skin testing for hypersensitivity Figure 15-10 Mechanisms underlying immunotherapy-induced desensitization Figure 15-11 A B O (A B H) blood groups Figure 15-12 Destruction of R h-positive red blood cells during erythroblastosis fetalis Figure 15-15 The D T H response Figure 15-16 A prolonged D T H response can lead to formation of a granuloma, a nodule-like mass Figure 15-17 Tuberculin skin test Figure 15-18 Poison ivy causes contact dermatitis due to its toxin, urushiol 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 Figure 15-20 Causes and consequences of chronic inflammation Figure 1 Signaling events that link obesity and inflammation to insulin resistance Association between exposure to various bacterial species and the development of allergies Figure 16-1 Central and peripheral tolerance Figure 16-2 C T L A-4–mediated inhibition of A P Cs by T R E G cells Figure 16-3 Linked suppression mediated by T R E G cells Figure 16-5 Insulitis in Type 1 diabetes Figure 16-6 Mechanism of myasthenia gravis induction Figure 16-11 Schematic diagrams of the process of graft acceptance and rejection Figure 16-12 Solid organ transplant numbers for 2020 Figure 16-13 Steps in the hyperacute rejection of a kidney graft Figure 16-14 Direct versus indirect presentation of allogeneic M H C Figure 16-15 Experimental demonstration that T cells can transfer allograft rejection 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 Figure 16-17 Effector mechanisms involved in allograft rejection Figure 16-18 Blocking costimulatory signals at the time of transplantation can cause anergy instead of activation of T cells reactive against a graft Figure 16-19 Site of action for various immunotherapy agents used in clinical transplantation Figure 17-1 Causes of death worldwide, 2019 Figure 17-2 An increase in U.S. deaths in 2020 linked to COVID-19 Figure 17-3 Chain of infection Figure 1 Characteristics of cytokine release syndrome (C R S) in COVID-19 Figure 1 A tubercle formed in pulmonary tuberculosis Figure 1 Two mechanisms generate variations in influenza surface antigens Figure 17-4 Transmission of respiratory infections Figure 17-5 Vector-borne infectious diseases Figure 17-6 Examples of global emerging and re-emerging infectious diseases Figure 1 Structure of a typical coronavirus Figure 2 Potential transmission route of the S A R S-Co V-2 precursor between hosts Figure 1 Herd immunity explained Figure 2 Herd immunity threshold as a function of R0 Figure 17-7 Progress with polio eradication Figure 17-8 The five stages of infectious disease evolution from animals to humans Figure 17-9 The Entry Points and in Vivo Microenvironments of Infectious Agents Figure 17-10 The three major immune response pathways: type 1, 2, and 3 Figure 1 Two pathways to variation in influenza surface antigens Figure 17-11 The presence of preformed antibody inhibits primary responses to a pathogen Figure 17-12 Antibody-mediated mechanisms to combat infections by extracellular bacteria Figure 17-14 Malarial life cycle An advertisement for smallpox inoculation that was distributed in the early 1800s in Boston, M A Figure 18-1 Return on investment from childhood immunizations in low- and middle-income countries, 2011 to 2020 Figure 18-2 Immune response pathways induced by vaccination Recommended childhood immunization schedule in the United States, 2022 Figure 18-3 Pertussis cases in the United States, 1922 to 2019 Figure 1. Strategies used to design COVID-19 vaccines Figure 18-5 Sequence of clinical trial phases in the United States Figure 18-6 Vaccine formulations Figure 18-8 Mucosal administration of a live, attenuated vaccine Figure 18-9 Subunit vaccines Figure 18-10 Multivalent subunit polysaccharide vaccines protect young children from bacterial pneumonia Figure 18-11 Particle- and membrane-based vaccines Figure 18-12 Viral- and bacterial-based vaccine vectors Figure 18-13 Nucleic acid–based vaccines Figure 18-14 A 2012 promotion for the pertussis booster Figure 1 A prime-and-pull vaccine strategy protects mice against lethal challenge with H S V Figure 18-15 Smallpox vaccination A figure shows 9 graphs that depict E7-specific C D 8 plus T-cell response in mice Two graphs show E7-specific CD8+ T lymphocyte response in wild type mice and C D 4 knockout mice Primary immunodeficiencies resulting from inherited defects affect specific cell types Figure 19-2 Primary immunodeficiency warning signs Figure 19-3 Defects in lymphocyte development and signaling can lead to severe combined immunodeficiency (S C I D) in humans 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 Figure 19-5 Genetic defects resulting in Mendelian susceptibility to mycobacterial diseases (M S M Ds) Figure 19- 7 Global AIDS epidemic Figure 19-8 Trends in the H I V/ AIDS epidemic Figure 19-9 Structure of H I V Figure 19-11 Genetic organization of H I V-1 (a) and functions of encoded proteins (b) H I V infection of target cells and virus replication Figure 19-13 Budding of new virus particles from the surface of an infected T cell 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 Figure 19-15 Typical course of H I V infection in an untreated patient 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 Figure 19-17 Stages in viral replication cycle that provide targets for therapeutic antiretroviral drugs E 7-specific C D 8 plus T-cell response 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 Figure 2 Most countries are providing lifelong antiretroviral therapy to pregnant and breastfeeding women living with H I V Figure 1 Neutralizing antibodies to H I V Figure 2 Neutralizing antibodies to H I V Figure 3 An immunization approach for stimulating production of broadly neutralizing antibodies to the H I V-1 E n v spike Effect of C V I D on the immune response Figure 19-2 Chromosomal translocations resulting in Burkitt’s lymphoma Figure 19-3 Model of sequential genetic alterations leading to metastatic colon cancer Figure 19-4 Hallmarks of cancer Figure 19-5 Different mechanisms generate tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs) Figure 19-7 Down-regulation of MHC class I expression on tumor cells may allow for tumor escape mutants Figure 19-9 Development of a monoclonal antibody specific for idiotypic determinants on B-lymphoma cells Figure 1 Figure 2 Figure 19-10 Mechanism of action of sipuleucel-T, a prostate cancer vaccine Figure 19-11 Use of CD80 (B7.1)-transfected tumor cells for cancer immunotherapy Figure 19-12 Using checkpoint blockade therapy to treat cancer Figure 20-1 Tumor growth and metastasis Figure 20-2 Hallmarks of cancer Figure 20-3 Mechanisms that generate tumor-specific antigens (T S As) and tumor-associated antigens (T A As) Figure 1 Age of vaccination against H P V and the future risk of cervical cancer in women Figure 20-4 The three stages of cancer immunoediting Figure 20-5 The immunosuppressive, pro-tumor microenvironment Figure 20-6 Immune contexture and immunoscores used in cancer staging and prognosis Figure 20-7 Types of immunotherapy available to treat cancer Figure 20-8 Bispecific T-cell engagers (B i T Es) used in cancer immunotherapy Figure 20-9 Using checkpoint blockade therapy to treat cancer Figure 20-10 The sipuleucel-T mechanism of action, a prostate cancer vaccine Figure 1 Driving Cancer Away with CAR T Cells Figure 2 Examples of the specialized accessories included in C A Rs Figure 20-11 The NeoVax cancer vaccine platform Figure 20-12 Using oncolytic viruses to treat cancer Figure 1 Optical properties of the three types of filters A photo shows an 8 by 8 micro-titre plate that is used for a hemagglutination inhibition assay Stimulated and unstimulated T cells C D 46 graph Apoptotic and healthy cells 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 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 Recombined V D J B gene in T cell Recombined V J gene Comparing thymus and lymph nodes of normal and knockout mice Different B cells Activation-induced cytidine deaminase Figure C-1 The chemokine system: an overview Figure D-1 Icons used in this Appendix Figure D-3 G protein activation Figure D-4 The M A P kinase pathway Figure D-5 Downstream components of the canonical and noncanonical pathways of N F-kappa B activation Figure D-6 Upstream portion of the canonical N F-kappa B pathway Figure D-7 Upstream portion of the noncanonical N F-kappa B pathway Figure D-8 Integration of common signaling pathways Figure D-9 Signaling through plasma membrane T L Rs Figure D-10 Signaling through endosomal T L Rs Figure D-11 Signaling through C L Rs Figure D-12 Signaling through N L R and R L R receptors Figure D-13 Signaling through c G A S and S T I N G Figure D-14 The J A K-S T A T pathway of cytokine activation Figure D-15 Signal transduction pathways from G protein–coupled receptors Figure D-16 Signaling through T N F-R 1 Figure D-17 Pathways that regulate apoptosis Figure D-18 Signaling through the Notch receptor Figure D-19 Signaling through the T-cell receptor Figure D-20 Signaling through the B-cell receptor Figure D-21 Activation of S r c-family kinases Figure E-1 The generation of polyclonal and monoclonal antibodies Figure E-2 Immunoprecipitation in solution Figure E-6 Competitive, solid-phase radioimmunoassay (R I A) to measure cytokine concentrations in serum Figure E-7 Variations in the enzyme-linked immunosorbent assay (E L I S A) technique allow for the determination of antibody or antigen Figure E-8 E L I S P O T measurements of interferon (I F N)- gamma secretion by N K T cells Figure E-9 Western blotting uses antibodies to identify protein bands after gel electrophoresis Figure E-10 Determining antibody affinity with equilibrium dialysis Figure E-11 Surface plasmon resonance (S P R) Figure E-14 Fluorescently labeled cells and the passage of light through a fluorescence microscope Figure E-16 The principle of confocal microscopy Figure E-17 Fluorescence excitation by one-photon versus two-photon laser excitation Figure E-18 Three-dimensional fluorescence in situ hybridization (3-D F I S H) Figure E-19 A simple flow cytometry setup Figure E-20 Optical properties of the three types of filters Figure E-21 Nature of the voltage pulse is determined by the shape of the emitting structure Figure E-22 Typical dot plots of cytometric data Figure E-23 Analysis of multicolor fluorescence data Figure E-24 The emission spectra of commonly used dyes have considerable overlap Figure E-25 Spectral cytometry collects the entire emission spectra of all fluorochromes Figure E-26 C y T O F enables the measurement of up to 45 different parameters Figure E-27 The M T T assay is used to measure the number of viable cells in a suspension Figure E-28 Bromodeoxyuridine replaces deoxythymidine during D N A synthesis Figure E-29 Propidium iodide intercalates into D N A and is a cell cycle and apoptosis indicator Figure E-30 C F S E labeling can determine the frequency of cells that have divided a defined number of times Figure E-31 Assessment of apoptosis, using a T U N E L assay Figure E-32 D N A Hi-C detects regions of D N A that interact in three-dimensional space in situ Figure E-33 Sanger dideoxy sequencing Figure E-34 Next-generation sequencing 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 Figure E-36 Quantitative P C R detects the frequency of a viral sequence using fluorescence detection Figure E-37 L A M P-P C R operates under isothermal conditions to amplify viral sequences Figure E-38 C R I S P R-Cas 12 a can detect S A R S-Co V-2 Figure E-39 Antibody-based rapid detection test for viral antigens Figure E-40 General procedure for generating transgenic mice Figure E-41 Gene targeting with C r e / l o x Back cover of the Kuby Immunology textbook Back Cover
520			_a"It is our goal that students should complete an immunology course not only with a firm grasp of content, but also with a clear sense of how key discoveries were made, what interesting questions remain, and how they might best be answered"--
700	1		_aOwen, Judith A.,
700	1		_aPunt, Jenni,
700	1		_aJones, Patricia P.,
700	1		_eauthor.
700	1		_eauthor.
700	1		_eauthor.
906			_a0 _bibc _corignew _d2 _eepcn _f20 _gy-gencatlg
942			_2ddc _cPROJECT
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