Cellular and Molecular Immunology

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Student Consult
Cellular and Molecular Immunology
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Dedication
Preface
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Table Of Contents
1 Properties and Overview of Immune Responses
	Innate and Adaptive Immunity
	Innate Immunity: the Early Defense
	Adaptive Immunity
		Cardinal Features of Adaptive Immune Responses
		Overview of Humoral and Cell-Mediated Immunity
		Initiation and Development of Adaptive Immune Responses
		Humoral Immunity
		Cell-Mediated Immunity
	Summary
	Selected Readings
		Historical Ideas
		Evolution of the Immune System
2 Cells and Tissues of the Immune System
	Cells of the Immune System
		Phagocytes
			Neutrophils
			Mononuclear Phagocytes
				Development of Monocytes and Macrophages
					Subsets of Monocytes
				Functions of Macrophages
					Macrophage Receptors and Activation
					Subsets of Macrophages
		Mast Cells, Basophils, and Eosinophils
			Mast Cells
			Basophils
			Eosinophils
			Dendritic Cells (DCs)
				Development of Dendritic Cells
				Subsets of Dendritic Cells
		Lymphocytes
			Classes of Lymphocytes
				Subsets of B Lymphocytes
				Subsets of T Lymphocytes
			Development of Lymphocytes
			Populations of Lymphocytes Distinguished by History of Antigen Exposure
				Naive Lymphocytes
				Effector Lymphocytes
				Memory Lymphocytes
		Natural Killer Cells and Cytokine-Secreting Innate Lymphoid Cells
	Anatomy and Functions of Lymphoid Tissues
		Bone Marrow
		Thymus
		The Lymphatic System
		Lymph Nodes
			Anatomic Organization of B and T Lymphocytes
			Antigen Transport Through Lymph Nodes
		Spleen
		Cutaneous and Mucosal Immune Systems
	Summary
	Selected Readings
		Cells of the Immune System
		Tissues of the Immune System
3 Leukocyte Circulation and Migration into Tissues
	Overview of Leukocyte Migration
	Adhesion Molecules on Leukocytes and Endothelial Cells Involved in Leukocyte Recruitment
		Selectins and Selectin Ligands
		Integrins and Integrin Ligands
	Chemokines and Chemokine Receptors
		Chemokine Structure, Production, and Receptors
		Biologic Actions of Chemokines
	Leukocyte-Endothelial Interactions and Leukocyte Recruitment Into Tissues
	Migration of Neutrophils and Monocytes to Sites of Infection or Tissue Injury
	Migration and Recirculation of T Lymphocytes
		Recirculation of Naive T Lymphocytes Between Blood and Secondary Lymphoid Organs
			Migration of Naive T Cells Into Lymph Nodes
			Movement of T Cells Within Secondary Lymphoid Organs
			Exit of T Cells From Lymph Nodes
		Recirculation of T Cells Through Other Lymphoid Tissues
		Migration of Effector T Lymphocytes to Sites of Infection
		Memory T Cell Migration
	Migration of B Lymphocytes
	Summary
	Selected Readings
		Adhesion Molecules
		Chemokines
		Lymphocyte Migration Through Lymphoid Tissues
4 Innate Immunity
	Overview of Innate Immunity
		Functions and Reactions of Innate Immune Responses
		Comparative Features of Innate and Adaptive Immunity
		Evolution of Innate Immunity
	Recognition of Microbes and Damaged Self by the Innate Immune System
	Cell-Associated Pattern Recognition Receptors and Sensors of Innate Immunity
		Toll-Like Receptors
		Cytosolic Receptors for Pathogen-Associated Molecular Patterns and Damage-Associated Molecular Patterns
			NOD-Like Receptors: NOD1 and NOD2
			Cytosolic DNA Sensors and the STING Pathway
			RIG-Like Receptors
			Inflammasomes
		Other Cell-Associated Pattern Recognition Receptors
			C-Type Lectin Receptors for Microbial Carbohydrates
			Scavenger Receptors
			Formyl-Peptide Receptors
	Cellular Components of the Innate Immune System
		Epithelial Barriers
		Phagocytes
		Dendritic Cells
		Cytokine-Producing Innate Lymphoid Cells
			Natural Killer Cells
			Functions of Natural Killer Cells
			Activating and Inhibitory Receptors of Natural Killer Cells
		T and B Lymphocytes With Limited Antigen Receptor Diversity
		Mast Cells
	Soluble Effector Molecules of Innate Immunity
		The Complement System
		Pentraxins
		Collectins and Ficolins
	The Inflammatory Response
		The Major Proinflammatory Cytokines of Innate Immunity
			Tumor Necrosis Factor
			Interleukin-1
			Interleukin-6
			Other Cytokines Produced During Innate Immune Responses
		Recruitment of Leukocytes to Sites of Infection
		Ingestion and Killing of Microbes by Activated Phagocytes
			Other Functions of Activated Macrophages
		Systemic and Pathologic Consequences of Inflammation
	The Antiviral Response
	Stimulation of Adaptive Immunity
	Mechanisms That Limit Innate Immune Responses
	Summary
	Suggested Readings
		Pattern Recognition Receptors
		Cells of the Innate Immune System
		Effector Molecules and Inflammatory Responses of Innate Immunity
		Diseases Caused by Innate Immunity
5 Antibodies and Antigens
	Antibody Structure
		General Features of Antibody Structure
		Structural Features of Antibody Variable Regions
		Structural Features of Antibody Constant Regions
		Monoclonal Antibodies
	Synthesis, Assembly, and Expression of Immunoglobulin Molecules
		Half-Life of Antibodies
	Antibody Binding of Antigens
		Features of Biologic Antigens
		Structural and Chemical Basis of Antigen Binding
	Structure-Function Relationships in Antibody Molecules
		Features Related to Antigen Recognition
			Specificity
			Diversity
			Affinity Maturation
		Features Related to Effector Functions
	Summary
	Suggested Readings
		Structure and Function of Antibodies
		Therapeutic Applications of Antibodies
6 Antigen Presentation to T Lymphocytes and the Functions of Major Histocompatibility Complex Molecules
	Properties of Antigens Recognized by T Lymphocytes
	Antigen Capture and the Functions of Antigen-Presenting Cells
		General Properties of Antigen-Presenting Cells
		Role of Dendritic Cells in Antigen Capture and Display
		Functions of Other Antigen-Presenting Cells
	The Major Histocompatibility Complex
		Discovery of the Major Histocompatibility Complex
			The Mouse Major Histocompatibility Complex (H-2 Complex)
			The Human Major Histocompatibility Complex (Human Leukocyte Antigen Locus)
			Immune Response Genes
			The Phenomenon of MHC Restriction
		MHC Genes
			Human and Mouse MHC Gene Loci
			Expression of MHC Molecules
		Structure of MHC Molecules
			General Properties of MHC Molecules
			Class I MHC Molecules
			Class II MHC Molecules
		Binding of Peptides to MHC Molecules
			Characteristics of Peptide-MHC Molecule Interactions
			Structural Basis of Peptide Binding to MHC Molecules
	Processing of Protein Antigens
		The Class I MHC Pathway for Processing and Presentation of Cytosolic Proteins
			Sources of Protein Antigens Degraded in Proteasomes
			Digestion of Proteins in Proteasomes
			Transport of Peptides From the Cytosol to the Endoplasmic Reticulum
			Assembly of Peptide–Class I MHC Complexes in the Endoplasmic Reticulum
			Surface Expression of Peptide–Class I MHC Complexes
		The Class II MHC Pathway for Presentation of Proteins Degraded in Lysosomes
			Targeting of Protein Antigens to Lysosomes
			Proteolytic Digestion of Antigens in Lysosomes
			Biosynthesis and Transport of Class II MHC Molecules to Endosomes
			Association of Processed Peptides With Class II MHC Molecules in Vesicles
			Expression of Peptide–Class II MHC Complexes on the Cell Surface
		Cross-Presentation
		Physiologic Significance of MHC-Associated Antigen Presentation
			Nature of T Cell Responses
			Immunogenicity of Protein Antigens
	Presentation of Nonprotein Antigens to T Cells
	Summary
	Suggested Readings
		The Role of Dendritic Cells in Antigen Capture and Presentation
		Structure of Major Histocompatibility Complex Genes, Major Histocompatibility Complex Molecules, and Peptide-Major Histocompatibility Complex Complexes
		Protein Antigen Processing and Major Histocompatibility Complex-Associated Presentation of Peptide Antigens
		Cross-Presentation
		“Nonclassical” Antigen Presentation
7 Immune Receptors and Signal Transduction
	Overview of Signal Transduction
		Modular Signaling Proteins and Adaptors
		Prion-Like Polymerization and Signaling
	The Immune Receptor Family
		General Features of Antigen Receptor Signaling
	The T Cell Receptor Complex and T Cell Signaling
		The Structure of the T Cell Receptor for Antigen
		Signal Initiation by the T Cell Receptor
		The Role of the CD4 and CD8 Coreceptors in T Cell Activation
		Activation of Tyrosine Kinases and a Lipid Kinase During T Cell Activation
		Recruitment and Modification of Adaptor Proteins
		Formation of the Immune Synapse
		Mitogen-Activated Protein Kinase Signaling Pathways in T Lymphocytes
		Calcium- and Protein Kinase C-Mediated Signaling Pathways in T Lymphocytes
		Activation of Transcription Factors That Regulate T Cell Gene Expression
		Modulation of T Cell Signaling by Protein Tyrosine Phosphatases
		Costimulatory Receptor Signaling in T Cells
			The CD28 Family of Costimulatory Receptors
			The CD2/Signaling Lymphocytic Activation Molecule Family of Costimulatory Receptors
		Metabolic Changes During T Cell Activation
	The B Lymphocyte Antigen Receptor Complex
		Structure of the B Cell Receptor for Antigen
		Signal Initiation by the B Cell Receptor
		Role of the CR2/CD21 Complement Receptor as a Coreceptor for B Cells
		Signaling Pathways Downstream of the B Cell Receptor
	The Attenuation of Immune Receptor Signaling
		Inhibitory Receptors of Natural Killer Cells, B Cells, and T Cells
		Ubiquitin-Dependent Degradation of Signaling Proteins
	Cytokine Receptors and Signaling
		Classes of Cytokine Receptors
			Type I Cytokine Receptors (Hematopoietin Receptor Family)
			Type II Cytokine Receptors (Interferon Receptor Family)
			TNF Receptor Family
			IL-1 Family
			IL-17 Family
		Signaling by Janus Kinases and Signal Transducers and Activators of Transcription
		Pathways of NF-κB Activation
	Summary
	Suggested Readings
		Signaling by Immune Receptors
		T Cell Receptor Structure and Signaling
		B Cell Receptor Structure and Signaling
		Signal Attenuation in Lymphocytes
		Cytokine Receptors
8 Lymphocyte Development and Antigen Receptor Gene Rearrangement
	Overview of Lymphocyte Development
		Commitment to the B and T Cell Lineages and Proliferation of Progenitors
		Role of Epigenetic Changes and MicroRNAs in Lymphocyte Development
		Antigen Receptor Gene Rearrangement and Expression
		Selection Processes That Shape the B and T Lymphocyte Repertoires
	Rearrangement of Antigen Receptor Genes in B and T Lymphocytes
		Germline Organization of Immunoglobulin and T Cell Receptor Genes
			Organization of Immunoglobulin Gene Loci
			Organization of T Cell Receptor Gene Loci
		V(D)J Recombination
			Recognition Signals That Drive V(D)J Recombination
			Mechanism of V(D)J Recombination
		Generation of Diversity in B and T Cells
	B Lymphocyte Development
		Stages of B Lymphocyte Development
			The Pro-B and Pre-B Stages of B Cell Development
			The Pre-B Cell Receptor
			Immature B Cells
			Subsets of Mature B Cells
				Follicular B Cells
				B-1 and Marginal Zone B Cells
		Selection of the Mature B Cell Repertoire
	T Lymphocyte Development
		Role of the Thymus in T Cell Maturation
		Stages of T Cell Maturation
			Double-Negative Thymocytes
			Pre-T Cell Receptor
			Double-Positive Thymocytes
		Selection Processes in the Maturation of MHC-Restricted αβ T Cells
			Positive Selection of Thymocytes: Development of the Self MHC–Restricted T Cell Repertoire
			Negative Selection of Thymocytes: Central Tolerance
		γδ T Lymphocytes
	Summary
	Suggested Readings
		Early B Cell Development and V(D)J Recombination
		T Cell Development
		MicroRNAs and Lymphocyte Development
9 Activation of T Lymphocytes
	Overview of T Lymphocyte Activation
	Signals for T Lymphocyte Activation
		Recognition of Antigen
		Role of Costimulation in T Cell Activation
			The B7:CD28 Family of Costimulators
			Other Costimulatory Pathways
			Therapeutic Costimulatory Blockade
	Functional Responses of T Lymphocytes
		Changes in Surface Molecules During T Cell Activation
		Cytokines in Adaptive Immune Responses
			IL-2 Secretion and IL-2 Receptor Expression
			Functions of IL-2
		Clonal Expansion of T Cells
		Differentiation of Activated T Cells Into Effector Cells
		Development and Properties of Memory T Cells
			Properties of Memory T Cells
	Decline of T Cell Responses
	Summary
	Selected Readings
		T Cell Activation
		Costimulation: B7, CD28, and More
		T Cell Cytokines
		Memory T Cells
10 Differentiation and Functions of CD4+ Effector T Cells
	Overview of CD4+ T Cell-Mediated Immune Responses
	Subsets of CD4+ Effector T Cells
		Properties of Th1, Th2, and Th17 Subsets
		Development of Th1, Th2, and Th17 Subsets
	The Th1 Subset
		Development of Th1 Cells
		Functions of Th1 Cells
			Interferon-γ
			Other Th1 Cytokines
			Th1-Mediated Classical Macrophage Activation and Killing of Phagocytosed Microbes
	The Th2 Subset
		Development of Th2 Cells
		Functions of Th2 Cells
			Interleukin-4
			Interleukin-13
			Interleukin-5
			Roles of Th2 Cells in Host Defense
	The Th17 Subset
		Development of Th17 Cells
		Functions of Th17 Cells
			Interleukin-17
			Other Th17 Cytokines
			Roles of Th17 Cells in Host Defense
	Functions of Other T Cell Subsets
		γδ T Cells
		Natural Killer T Cells
		Mucosa-Associated Invariant T (MAIT) Cells
	Summary
	Suggested Readings
		Differentiation of CD4+ T Cells into Subsets of Effector Cells: Th1, Th2, and Th17
		Activation of Macrophages
		Other T Cell Populations
11 Differentiation and Functions of CD8+ Effector T Cells
	Differentiation of CD8+ T Cells Into Cytotoxic T Lymphocytes
		Nature of Antigen and Antigen-Presenting Cells for Activation of CD8+ T Lymphocytes
		Role of Helper T Cells
		Role of Cytokines
		Inhibition of CD8+ T Cell Responses: T Cell Exhaustion
	Effector Functions of CD8+ Cytotoxic T Lymphocytes
		Mechanisms of CTL-Mediated Cytotoxicity
			Recognition of Antigen and Activation of CTLs
			Killing of Target Cells by CTLs
		Cytokine Production by CD8+ Effector T Cells
	Roles of CD8+ CTLs in Host Defense
	Summary
	Selected Readings
		Activation of CD8+ T Lymphocytes
		Mechanisms of CTL-Mediated Cytotoxicity
12 B Cell Activation and Antibody Production
	Overview of Humoral Immune Responses
	Antigen Recognition and Antigen-Induced B Cell Activation
		Antigen Capture and Delivery to B Cells
		Activation of B Cells by Antigens and Other Signals
	Helper T Cell-Dependent Antibody Responses to Protein Antigens
		The Sequence of Events During T Cell-Dependent Antibody Responses
		Initial Activation and Migration of Helper B Cells and T Cells
		Antigen Presentation by B Cells and the Hapten-Carrier Effect
		Role of CD40L:CD40 Interaction in T-Dependent B Cell Activation
		Extrafollicular B Cell Activation
		The Germinal Center Reaction
		The Induction and Functions of Follicular Helper T Cells
		Heavy Chain Isotype (Class) Switching
		Affinity Maturation: Somatic Mutation of Ig Genes and Selection of High-Affinity B Cells
		B Cell Differentiation Into Antibody-Secreting Plasma Cells
		Generation of Memory B Cells
		Role of Transcriptional Regulators in Determining the Fate of Activated B Cells
	Antibody Responses to T-Independent Antigens
		Subsets of B Cells That Respond to T-Independent Antigens
		Mechanisms of T-Independent Antibody Responses
		Protection Mediated by T-Independent Antibodies
	Antibody Feedback: Regulation of Humoral Immune Responses by Fc Receptors
	Summary
	Selected Readings
		B Cell Subsets and B Cell Activation
		T Follicular Helper Cells and the Germinal Center Reaction
		Activation-Induced Deaminase, Class Switching, and Somatic Mutation
13 Effector Mechanisms of Humoral Immunity
	Overview of Humoral Immunity
	Neutralization of Microbes and Microbial Toxins
	Antibody-Mediated Opsonization and Phagocytosis
		Leukocyte Fc Receptors
			Role of Fcγ Receptors in Phagocytosis and Activation of Phagocytes
			Inhibitory Signaling by the FcγRIIB Receptor
		Antibody-Dependent Cell-Mediated Cytotoxicity
		Antibody-Mediated Clearance of Helminths
	The Complement System
		Pathways of Complement Activation
			The Alternative Pathway
			The Classical Pathway
			The Lectin Pathway
			Late Steps of Complement Activation
		Receptors for Complement Proteins
		Regulation of Complement Activation
		Functions of Complement
			Opsonization and Phagocytosis
			Stimulation of Inflammatory Responses
			Complement-Mediated Cytolysis
			Other Functions of the Complement System
		Complement Deficiencies
		Pathologic Effects of the Complement System
		Evasion of Complement by Microbes
	Neonatal Immunity
	Summary
	Selected Readings
		Complement
		Antibody Effector Functions and Fc Receptors
14 Specialized Immunity at Epithelial Barriers and in Immune Privileged Tissues
	General Features of Immunity at Epithelial Barriers
	Immunity in the Gastrointestinal System
		Innate Immunity in the Gastrointestinal Tract
		Adaptive Immunity in the Gastrointestinal Tract
			The Functional Anatomy of the Adaptive Immune System in the Gastrointestinal Tract
			Humoral Immunity in the Gastrointestinal Tract
			T Cell–Mediated Immunity in the Gastrointestinal Tract
		Regulation of Immunity in the Gastrointestinal Tract by Regulatory T Cells and Cytokines
		Oral Tolerance and Oral Vaccines
		The Role of the Commensal Microbiome in Immune Regulation
		Diseases Related to Immune Responses in the Gut
			Inflammatory Bowel Disease
			Celiac Disease
			Other Diseases
	Immunity in Other Mucosal Tissues
		Immunity in the Respiratory System
			Innate Immunity in the Respiratory System
			Adaptive Immunity in the Respiratory System
		Immunity in the Genitourinary System
	The Cutaneous Immune System
		Innate and Adaptive Immune Responses in the Skin
		Diseases Related to Immune Responses in the Skin
	Immune-Privileged Tissues
		Immune Privilege in the Eye, Brain, and Testis
			The Eye
			The Brain
			The Testis
		Immune Privilege of the Mammalian Fetus
	Summary
	Selected Readings
		Mucosal Immunity, General
		Gastrointestinal Immune System
		Antibody Production in the Gastrointestinal Immune System
		Diseases of the Gastrointestinal Immune System
		Respiratory Mucosal Immune System
		Skin Immune System
		Other Specialized Immune Systems
15 Immunologic Tolerance and Autoimmunity
	Overview of Immunologic Tolerance
	T Lymphocyte Tolerance
		Central T Cell Tolerance
		Peripheral T Cell Tolerance
			Anergy (Functional Unresponsiveness)
			Regulation of T Cell Responses by Inhibitory Receptors
			Suppression by Regulatory T Cells
				Phenotypic Markers and Heterogeneity of Regulatory T Cells
				Generation and Maintenance of Regulatory T Cells
				Mechanisms of Action of Regulatory T Cells
				Inhibitory Cytokines Produced by Regulatory T Cells
				Roles of Regulatory T Cells in Self-Tolerance and Autoimmunity
			Deletion of T Cells by Apoptotic Cell Death
		Factors That Determine the Tolerogenicity of Self Antigens
	B Lymphocyte Tolerance
		Central B Cell Tolerance
		Peripheral B Cell Tolerance
	Tolerance to Commensal Microbes and Other Foreign Antigens
	Mechanisms of Autoimmunity
		General Features of Autoimmune Disorders
		Immunologic Abnormalities Leading to Autoimmunity
		Genetic Basis of Autoimmunity
			Association of MHC Alleles With Autoimmunity
			Polymorphisms in Non-HLA Genes Associated With Autoimmunity
			Inherited Single-Gene (Mendelian) Abnormalities That Cause Autoimmunity
		Role of Infections in Autoimmunity
		Other Factors in Autoimmunity
	Summary
	Selected Readings
		Immunologic Tolerance, General Mechanisms
		Central Tolerance
		Anergy; Inhibitory Receptors
		Apoptosis
		Regulatory T Cells
		Mechanisms of Autoimmunity: General Concepts
		Mechanisms of Autoimmunity: Genetics
		Mechanisms of Autoimmunity: Environmental Factors
16 Immunity to Microbes
	Overview of Immune Responses to Microbes
	Immunity to Extracellular Bacteria
		Innate Immunity to Extracellular Bacteria
		Adaptive Immunity to Extracellular Bacteria
		Injurious Effects of Immune Responses to Extracellular Bacteria
		Immune Evasion by Extracellular Bacteria
	Immunity to Intracellular Bacteria
		Innate Immunity to Intracellular Bacteria
		Adaptive Immunity to Intracellular Bacteria
		Immune Evasion by Intracellular Bacteria
	Immunity to Fungi
		Innate and Adaptive Immunity to Fungi
	Immunity to Viruses
		Innate Immunity to Viruses
		Adaptive Immunity to Viruses
		Immune Evasion by Viruses
	Immunity to Parasites
		Innate Immunity to Parasites
		Adaptive Immunity to Parasites
		Immune Evasion by Parasites
	Strategies for Vaccine Development
		Attenuated and Inactivated Bacterial and Viral Vaccines
		Purified Antigen (Subunit) Vaccines
		Synthetic Antigen Vaccines
		Live Viral Vaccines Involving Recombinant Viruses
		DNA Vaccines
		Adjuvants and Immunomodulators
		Passive Immunization
	Summary
	Selected Readings
		General Principles
		Immunity to Extracellular and Intracellular Bacteria
		Immunity to Viruses
		Immunity to Fungi
		Immunity to Parasites
		Vaccines and Adjuvants
17 Transplantation Immunology
	General Principles of Transplantation Immunology
	Adaptive Immune Responses to Allografts
		The Nature of Alloantigens
		Recognition of Alloantigens by T Cells
			Direct Recognition of MHC Alloantigens on Donor Cells
			Indirect Recognition of Alloantigens
		Activation and Effector Functions of Alloreactive T Lymphocytes
			Activation of Alloreactive T Lymphocytes
			Role of Costimulation in T Cell Responses to Alloantigens
			Effector Functions of Alloreactive T Cells
		Activation of Alloreactive B Cells and Production and Functions of Alloantibodies
	Patterns and Mechanisms of Allograft Rejection
		Hyperacute Rejection
		Acute Rejection
			Acute Cellular Rejection
			Acute Antibody-Mediated Rejection
		Chronic Rejection and Graft Vasculopathy
	Prevention and Treatment of Allograft Rejection
		Methods to Reduce the Immunogenicity of Allografts
		Immunosuppression to Prevent or to Treat Allograft Rejection
			Inhibitors of T Cell Signaling Pathways
			Antimetabolites
			Function-Blocking or Depleting Anti-Lymphocyte Antibodies
			Costimulatory Blockade
			Drugs Targeting Alloantibodies and Alloreactive B Cells
			Antiinflammatory Drugs
		Methods to Induce Donor-Specific Tolerance
	Xenogeneic Transplantation
	Blood Transfusion and the ABO and Rh Blood Group Antigens
		ABO Blood Group Antigens
		Other Blood Group Antigens
			Lewis Antigen
			Rhesus (Rh) Antigen
	Hematopoietic Stem Cell (HSC) Transplantation
		Indications, Methods, and Immune Barriers in Hematopoietic Stem Cell Transplantation
		Immunologic Complication of Hematopoietic Stem Cell Transplantation
			Graft-Versus-Host Disease
			Immunodeficiency After Hematopoietic Stem Cell Transplantation
	Summary
	Selected Readings
		Recognition and Rejection of Allogeneic Transplants
		Clinical Transplantation
		Immunosuppression and Tolerance Induction to Allografts
		Xenotransplantation
18 Immunity to Tumors
	Overview of Tumor Immunity
	Tumor Antigens
		Neoantigens: Antigens Encoded by Mutated Genes
		Antigens of Oncogenic Viruses
		Overexpressed Cellular Proteins
		Other Antigens of Tumors
	Immune Responses to Tumors
		T Lymphocytes
		Antibodies
		Natural Killer Cells
		Macrophages
		The Role of Innate and Adaptive Immunity in Promoting Tumor Growth
	Evasion of Immune Responses by Tumors
		Immune Checkpoints: Inhibition of Immune Responses
		Loss of Tumor Antigen Expression
	Immunotherapy for Tumors
		Checkpoint Blockade: Blocking T Cell Inhibitory Pathways
		Vaccination With Tumor Antigens
		Adoptive Cellular Therapy With Antitumor T Cells
			Chimeric Antigen Receptor T Cell Therapy
			Adoptive Cellular Therapy With Tumor-Specific T Cells
		Passive Immunotherapy With Antibodies
		Other Approaches for Stimulating Antitumor Immunity
			Cytokine Therapy
			Nonspecific Inflammatory Stimuli
			Graft-Versus-Leukemia Effect
	Summary
	Selected Readings
		Immune Responses to Tumors
		Tumor Immunotherapy
19 Hypersensitivity Disorders
	Causes of Hypersensitivity Diseases
	Mechanisms and Classification of Hypersensitivity Reactions
	Diseases Caused by Antibodies
		Diseases Caused by Antibodies Against Fixed Cell and Tissue Antigens
		Immune Complex–Mediated Diseases
			Experimental Models of Immune Complex–Mediated Diseases
				Serum Sickness
				Arthus Reaction
			Pathogenesis of Immune Complex–Mediated Diseases
	Diseases Caused by T Lymphocytes
		Diseases Caused by Cytokine-Mediated Inflammation
			Delayed-Type Hypersensitivity (DTH)
		Diseases Caused by Cytotoxic T Lymphocytes
	Therapeutic Approaches for Immunologic Diseases
		Broadly Acting Antiinflammatory Agents
		Anticytokine Therapies
		Depletion of Cells and Antibodies
		Other Biologic Agents
		Intravenous IgG
		Tolerance-Inducing Therapies
	Selected Immunologic Diseases: Pathogenesis and Therapeutic Strategies
		Systemic Lupus Erythematosus (SLE): The Prototypic Immune Complex–Mediated Disease
			Pathogenesis of Systemic Lupus Erythematosus
			New Therapies for Systemic Lupus Erythematosus
		Rheumatoid Arthritis (RA)
			Pathogenesis of Rheumatoid Arthritis
			New Therapies for Rheumatoid Arthritis
		Multiple Sclerosis (MS)
			Pathogenesis of Multiple Sclerosis
			New Therapies for Multiple Sclerosis
		Type 1 Diabetes
			Pathogenesis of Type 1 Diabetes
			New Therapies for Type 1 Diabetes
		Inflammatory Bowel Disease
	Summary
	Selected Readings
		General
		Antibody and Immune Complex–Mediated Disorders
		T Cell–Mediated Disorders
		Systemic Lupus Erythematosus
		Rheumatoid Arthritis
		Multiple Sclerosis
		Type 1 Diabetes
20 Allergy
	Overview of IgE-Dependent Allergic Reactions
	Production of IgE
		The Nature of Allergens
		Activation of Type 2 Cytokine–Producing Helper T Cells
		Activation of B Cells and Switching to IgE
	Cells Involved in Allergic Reactions
		Role of Th2 Cells and Innate Lymphoid Cells in Allergic Disease
		Properties of Mast Cells and Basophils
			Binding of IgE to Mast Cells and Basophils: the Fcε Receptor
			Activation of Mast Cells
			Mediators Derived From Mast Cells
				Vasoactive Amines
				Granule Enzymes and Proteoglycans
				Lipid Mediators
				Cytokines
		Properties of Eosinophils
	IgE- and Mast Cell–Dependent Reactions
		The Immediate Reaction
		The Late-Phase Reaction
	Genetic Susceptibility to Allergic Disease
		Environmental Factors in Allergy
	Allergic Diseases in Humans: Pathogenesis and Therapy
		Systemic Anaphylaxis
		Bronchial Asthma
		Immediate Hypersensitivity Reactions in the Upper Respiratory Tract, Gastrointestinal Tract, and Skin
		Specific Immunotherapy (Desensitization) for Allergic Diseases
	The Protective Roles of IgE- and Mast Cell–Mediated Immune Reactions
	Summary
	Selected Readings
		Mast Cells and Eosinophils
		Type 2 and IgE Responses
		Allergic Diseases
21 Congenital and Acquired Immunodeficiencies
	Overview of Immunodeficiency Diseases
	Primary (Congenital) Immunodeficiencies
		Defects in Innate Immunity
			Defective Microbicidal Activity of Phagocytes: Chronic Granulomatous Disease
			Leukocyte Adhesion Deficiencies
			Defects in NK Cells and Phagocytes
			Inherited Defects in TLR Pathways, Nuclear Factor-κB Signaling, and Type I Interferons
			Defects in the IL-12/IFN-γ Pathway
			Defects in Splenic Development
		Severe Combined Immunodeficiencies
			The DiGeorge Syndrome and Other Forms of SCID Due to Defective Thymic Epithelial Development
			ADA Deficiency and Other Forms of SCID Caused by Defects in Nucleotide Metabolism
			X-Linked SCID
			Autosomal Recessive Mutations in Cytokine Signaling Components
			Severe Combined Immunodeficiency Caused by Defects in V(D)J Recombination and Pre-TCR Checkpoint Signaling
			The Bare Lymphocyte Syndrome and Other Defects in T Cell Positive Selection
			SCID Caused by Defective T Cell Activation
		Antibody Deficiencies: Defects in B Cell Development and Activation
			X-Linked Agammaglobulinemia: An X-linked Pre-BCR Signaling Defect
			Autosomal Recessive Pre-BCR Checkpoint Defects
			Selective Immunoglobulin Isotype Deficiencies
			Defects in B Cell Differentiation: Common Variable Immunodeficiency (CVID)
			Defects in T Cell–Dependent B Cell Activation: Hyper-IgM Syndromes
		Defects in T Lymphocyte Activation and Function
			Defects in TCR Signal Transduction
			Wiskott-Aldrich Syndrome
			Hyper-IgE Syndromes
			The X-Linked Lymphoproliferative Syndrome
			X-Linked Immunodeficiency-Magnesium Defects-EBV Infection-Neoplasia Syndrome
			Defective CTL and NK Cell Function: The Familial Hemophagocytic Lymphohistiocytosis Syndromes
		Multisystem Disorders With Immunodeficiency
			Ataxia-Telangiectasia
		Therapeutic Approaches for Congenital Immunodeficiencies
	Secondary (Acquired) Immunodeficiencies
	Human Immunodeficiency Virus and the Acquired Immunodeficiency Syndrome
		Molecular and Biologic Features of HIV
			HIV Structure and Genes
			Viral Life Cycle
		Pathogenesis of HIV Infection and AIDS
			Mechanisms of Immunodeficiency Caused by HIV
			HIV Reservoirs and Viral Turnover
		Clinical Features of HIV Disease
			Transmission of HIV and Epidemiology of AIDS
			Clinical Course of HIV Infection
		Immune Responses to HIV
			Innate Immunity to HIV and Host Restriction Factors
			Adaptive Immune Responses to HIV
			Mechanisms of Immune Evasion by HIV
		Elite Controllers and Long-Term Nonprogressors: A Possible Role for Host Genes
		Treatment and Prevention of AIDS and Vaccine Development
	Summary
	Selected Readings
		Congenital (Primary) Immunodeficiencies
		HIV and AIDS
Glossary
Appendices
	Appendix I Cytokines
	Appendix II Principal Features of Selected CD Molecules
	Appendix III Laboratory Techniques Commonly Used in Immunology
		Laboratory Methods Using Antibodies
			Quantitation of Antigen by Immunoassays
			Identification and Purification of Proteins
			Immunoprecipitation and Immuno-Affinity Chromatography
			Western Blotting
			Labeling and Detection of Antigens in Cells and Tissues
			Flow Cytometry
			Cytokine Bead Assays
			Purification of Cells
			Immunofluorescence and Immunohistochemistry
			Measurement of Antigen-Antibody Interactions
		Transgenic Mice and Gene Targeting
		Methods for Studying T Lymphocyte Responses
			Polyclonal Activation of T Cells
			Antigen-Induced Activation of Polyclonal T Cell Populations
			Antigen-Induced Activation of T Cell Populations With a Single Antigen Specificity
			Methods to Enumerate and Study Functional Responses of T Cells
		Methods for Studying B Lymphocyte Responses
			Activation of Polyclonal B Cell Populations
			Antigen-Induced Activation of B Cell Populations With a Single Antigen Specificity
			Assays to Measure B Cell Proliferation and Antibody Production
		Clinical Diagnostic Applications of Immunologic Assays
			Flow Cytometry to Determine Numbers of Subsets of Circulating Immune Cells
				Assays for Innate Immunity
				Assays for Humoral Immunity
				Assays for Cellular Immunity
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	R
	S
	T
	U
	V
	W
	X
	Z
Inside Back Cover