【0】Janeway’s Immunobiology目录

目录：

Part I: An Introduction to Immunobiology and Innate Immunity

• Chapter 1: Basic Concepts in Immunology
• Chapter 2: Innate Immunity: The First Lines of Defense
• Chapter 3: Cellular Mechanisms of Innate Immunity

Part II: The Recognition of Antigen

• Chapter 4: Antigen Recognition by B-cell and T-cell Receptors
• Chapter 5: The Generation of Lymphocyte Antigen Receptors
• Chapter 6: Antigen Presentation to T Lymphocytes

Part III: The Development of Mature Lymphocyte Receptor Repertoires

• Chapter 7: Lymphocyte Receptor Signaling
• Chapter 8: The Development of B and T Lymphocytes

Part IV: The Adaptive Immune Response

• Chapter 9: T Cell–Mediated Immunity
• Chapter 10: The Humoral Immune Response
• Chapter 11: Integrated Dynamics of Innate and Adaptive Immunity
• Chapter 12: The Barrier Immune System

Part V: The Immune System in Health and Disease

• Chapter 13: Failures of Host Defense Mechanisms
• Chapter 14: Allergic Diseases and Hypersensitvity Reactions
• Chapter 15: Autoimmunity and Transplantation
• Chapter 16: Manipulation of the Immune Response

Appendix I: The Immunologist’s Toolbox

Detailed Contents

Preface iii

1. What’s New in the Tenth Edition iv
2. Resources for Instructors and Students vi
3. Acknowledgments vii
4. About the Authors ix

PART I AN INTRODUCTION TO IMMUNOBIOLOGY AND INNATEIMMUNITY

1.01 Chapter 1 Basic Concepts in Immunology

• 1.02 The origins of vertebrate immune cells

Principles of innate immunity:

• 1.1 Commensal organisms cause little host damage while pathogensdamage host tissues by a variety of mechanisms.
• 1.2 Anatomic and chemical barriers are the first defense againstpathogens.
• 1-3 The immune system is activated by inflammatory inducers that indicatethe presence of pathogens or tissue damage.
• 1-4 The myeloid lineage comprises most of the cells of the innate immunesystem.
• 1-5 Sensor cells express pattern-recognition receptors that provide an initialdiscrimination between self and nonself.
• 1-6 Sensor cells induce an inflammatory response by producing mediatorssuch as chemokines and cytokines.
• 1-7 Innate lymphoid cells and natural killer cells are effector cells that sharesimilarities with lymphoid lineages of the adaptive immune system.
• Summary

Principles of adaptive immunity:

• 1-8 The interaction of antigens with antigen receptors induces lymphocytesto acquire effector and memory activity.
• 1-9 Antibodies and T-cell receptors are composed of constant and variableregions that provide distinct functions.
• 1-10 Antibodies and T-cell receptors recognize antigens by fundamentallydifferent mechanisms.
• 1-11 Antigen-receptor genes are assembled by somatic gene rearrangementsof incomplete receptor gene segments.
• 1-12 Lymphocytes activated by antigen give rise to clones of antigen-specificeffector cells that mediate adaptive immunity.
• 1-13 Lymphocytes with self-reactive receptors are normally eliminatedduring development or are functionally inactivated.
• 1-14 Lymphocytes mature in the bone marrow or the thymus and thencongregate in lymphoid tissues throughout the body.
• 1-15 Adaptive immune responses are initiated by antigen and antigen-presenting cells in peripheral lymphoid tissues.
• 1-16 Lymphocytes encounter and respond to antigen in the peripherallymphoid organs.
• 1-17 Mucosal surfaces have specialized immune structures that orchestrateresponses to environmental microbial encounters.
• 1-18 Lymphocytes activated by antigen proliferate in the peripheral lymphoidorgans, generating effector cells and immunological memory.
• Summary.24

The effector mechanisms of immunity：

• 1-19 Innate immune responses can select from several effector modules toprotect against different types of pathogens.
• 1-20 Antibodies protect against extracellular pathogens and their toxicproducts.
• 1-21 T cells orchestrate cell-mediated immunity and regulate B-cell responsesto most antigens.
• 1-22 Inherited and acquired defects in the immune system result in increasedsusceptibility to infection.
• 1-23 Understanding adaptive immune responses is important for the control ofallergies, autoimmune disease, and the rejection of transplanted organs.
• 1-24 Vaccination is the most effective means of controlling infectiousdiseases.
• 1-25 Emerging pathogens present new challenges for the immune system.3333.
• Summary.34
• Summary to Chapter 1.
• References.

Chapter 2 Innate Immunity: The First Lines of Defense37

Anatomic barriers and initial chemical defenses:

• 2-1 Infectious diseases are caused by diverse living agents that replicate intheir hosts
• 2-2 Epithelial surfaces of the body provide the first barrier againstinfection.
• 2-3 Infectious agents must overcome innate host defenses to establish a focusof infection.
• 2-4 Epithelial cells and phagocytes produce several kinds of antimicrobialmolecules.
• Summary.49

The complement system and innate immunity:

• 2-5 The complement system recognizes features of microbial surfaces andmarks them for destruction by coating them with C3b.
• 2-6 The lectin pathway uses soluble receptors that recognize microbialsurfaces to activate the complement cascade.
• 2-7 The classical pathway is initiated by activation of the C1 complex and ishomologous to the lectin pathway.
• 2-8 Complement activation is largely confined to the surface on which it isinitiated.
• 2-9 The alternative pathway is an amplification loop for C3b formation thatis accelerated by properdin in the presence of pathogens.
• 2-10 Membrane and plasma proteins that regulate the formation and stabilityof C3 convertases determine the extent of complement activation.
• 2-11 Complement developed early in the evolution of multicellularorganisms.
• 2-12 Surface-bound C3 convertase deposits large numbers of C3b fragmentson pathogen surfaces and generates C5 convertase activity.
• 2-13 Ingestion of complement-tagged pathogens by phagocytes is mediatedby receptors for the bound complement proteins.
• 2-14 The small fragments of some complement proteins initiate a localinflammatory response.
• 2-15 The terminal complement proteins polymerize to form pores inmembranes that can kill certain pathogens.
• 2-16 Complement-control proteins regulate all three pathways of complementactivation and protect the host from their destructive effects.
• 2-17 Genetic and acquired disorders in complement regulation can producevarious inflammatory conditions.
• 2-18 Pathogens produce several types of proteins that can inhibit complementactivation.7358. Summary.
• Summary to Chapter 2.
• Discussion questions.
• References.

Chapter 3 Cellular Mechanisms of Innate Immunity

Pathogen recognition by cells of the innate immune system.

• 3-1 After entering tissues, many microbes are recognized, ingested, andkilled by phagocytes.8065.
• 3-2G protein–coupled receptors on phagocytes link microbe recognition withincreased efficiency of intracellular killing.8366.
• 3-3 Microbial recognition and tissue damage initiate an inflammatoryresponse.8767.
• 3-4 Toll-like receptors represent an ancient pathogen-recognition system.9068.
• 3-5 Mammalian Toll-like receptors are activated by many different pathogen-associated molecular patterns.9069.
• 3-6 TLR-4 recognizes bacterial lipopolysaccharide in association with thehost accessory proteins MD-2 and CD14.9470.
• 3-7 TLRs activate NFκB, AP-1, and IRF transcription factors to induce theexpression of inflammatory cytokines and type I interferons.9571.
• 3-8 The RIG-I–like receptors detect cytoplasmic viral RNAs and activateMAVS to induce type I interferon production and pro-inflammatorycytokines.98
• 3-9 Cytosolic DNA activates the cGAS–STING pathway to induceproduction of type I interferons.10073.
• 3-10 NLRs comprise a large family of intracellular sensors with diversefunctions.10274.
• 3-11 Certain NLR proteins react to infection or cellular damage by forming aninflammasome that induces cell death and secretion of inflammatorycytokines.10375.
• 3-12 Activation of innate sensors in macrophages and dendritic cells triggerschanges in gene expression that have far-reaching effects on the immuneresponse.10676.
• 3-13 Toll signaling in Drosophila is downstream of a distinct set of pathogen-recognition molecules.10777.
• 3-14 TLR and NOD genes have undergone extensive diversification in bothinvertebrates and some primitive chordates.10878. Summary.10979. Consequences of innate immune activation.10980.
• 3-15 Cytokines and their receptors fall into distinct families of structurallyrelated proteins.11081
• 3-16 Cytokine receptors of the hematopoietin superfamily are associated withthe JAK family of tyrosine kinases, which activate STAT transcriptionfactors.11282.
• 3-17 Chemokines released by macrophages and dendritic cells recruit effectorcells to sites of infection.11483.
• 3-18 Cell-adhesion molecules control interactions between leukocytes andendothelial cells during an inflammatory response.11684.
• 3-19 Neutrophils make up the first wave of cells that cross the blood vesselwall to enter an inflamed tissue.11885.
• 3-20 TNF-α is an important cytokine that triggers local containment ofinfection but induces shock when released systemically.12086.
• 3-21 Cytokines made by macrophages and dendritic cells induce a systemicreaction known as the acute-phase response.12287.
• 3-22 Interferons induced by viral infection make several contributions to hostdefense.12488.
• 3-23 Several types of innate lymphoid cells provide protection in earlyinfection.12689.
• 3-24 NK cells are activated by type I interferon and macrophage-derivedcytokines.12890.
• 3-25 NK cells express activating and inhibitory receptors to distinguishbetween healthy and infected cells.12991.
• 3-26 NK-cell receptors belong to several structural families.13092.
• 3-27 NK cells express activating receptors that recognize ligands induced oninfected cells or tumor cells.13393.
• Summary.13494.
• Summary to Chapter 3
• Discussion questions.
• References.

PART II THE RECOGNITION OF ANTIGEN1. Chapter 4 Antigen Recognition by B-cell and T-cell Receptors1412. The structure of a typical antibody molecule.1423. 4-1 IgG antibodies consist of four polypeptide chains.1434. 4-2Immunoglobulin heavy and light chains are composed of constant andvariable regions.1445. 4-3The domains of an immunoglobulin molecule have similarstructures.1446. 4-4The antibody molecule can readily be cleaved into functionally distinctfragments.1467. 4-5The hinge region of the immunoglobulin molecule allows flexibility inbinding to multiple antigens.1478. Summary.1479. Structural variation in immunoglobulin constant regions.14810. 4-6Different classes of immunoglobulins are distinguished by the structureof their heavy-chain constant regions.14811. 4-7The constant region confers functional specialization on theantibody.15012. 4-8IgM and IgA can form polymers by interacting with the J chain.15113. Summary.15214. The interaction of the antibody molecule with specific antigen.15215. 4-9Localized regions of hypervariable sequence form the antigen-bindingsite.15216. 4-10 Antibodies bind antigens via contacts in CDRs that are complementaryto the size and shape of the antigen.15317. 4-11 Antibodies bind to conformational shapes on the surfaces of antigensusing a variety of noncovalent forces.15518. 4-12 Antibody interaction with intact antigens is influenced by stericconstraints.15619. 4-13 Some species generate antibodies with alternative structures.15720. Summary.15821. Antigen recognition by T cells.15922. 4-14 The TCRαβ heterodimer is very similar to a Fab fragment ofimmunoglobulin.15923. 4-15 A T-cell receptor recognizes antigen in the form of a complex of aforeign peptide bound to an MHC molecule.16124. 4-16 There are two classes of MHC molecules with distinct subunitcompositions but similar three-dimensional structures.16225. 4-17 Peptides are stably bound to MHC molecules and also serve to stabilizethe MHC molecule on the cell surface.16426. 4-18 MHC class I molecules bind short peptides of 8–10 amino acids by bothends.165

27. 4-19 The length of the peptides bound by MHC class II molecules is notconstrained.16628. 4-20 The crystal structures of several peptide:MHC:T-cell receptor complexesshow a similar orientation of the T-cell receptor over the peptide:MHCcomplex.16829. 4-21 The CD4 and CD8 cell-surface proteins of T cells directly contact MHCmolecules and are required to make an effective response to antigen.16930. 4-22 The two classes of MHC molecules are expressed differentially oncells.17231. 4-23 A distinct subset of T cells bears an alternative receptor made up of γand δ chains.17332. Summary.17433. Summary to Chapter 4.17434. Discussion questions.17535. References.17636. Chapter 5 The Generation of Lymphocyte Antigen Receptors17937. Primary immunoglobulin gene rearrangements and expression.18038. 5-1 Complete immunoglobulin genes are generated by the somaticrecombination of separate gene segments.18039. 5-2Multiple contiguous V gene segments are present at eachimmunoglobulin locus.18240. 5-3Rearrangement of V, D, and J gene segments is guided by flanking DNAsequences.18441. 5-4The reaction that recombines V, D, and J gene segments involves bothlymphocyte-specific and ubiquitous DNA-modifying enzymes.18742. 5-5The diversity of the immunoglobulin repertoire is generated by four mainprocesses.19043. 5-6The multiple inherited gene segments are used in differentcombinations.19144. 5-7Variable addition and subtraction of nucleotides at the junctions betweengene segments contributes to the diversity of the third hypervariable region.19145. 5-8IgM and IgD are derived from the same pre-mRNA transcript and areboth expressed on the surface of mature B cells.19346. 5-9Transmembrane and secreted forms of immunoglobulin are generatedfrom different heavy-chain mRNA transcripts.19447. Summary.19648. T-cell receptor gene rearrangement.19649. 5-10 The T-cell receptor gene segments are arranged in a pattern similar tothat of immunoglobulin gene segments and are rearranged by the sameenzymes.19650. 5-11 T-cell receptors concentrate diversity in the third hypervariableregion.19951. 5-12 γδ T-cell receptors are also generated by gene rearrangement.20052. Summary.201

28. Evolution of the adaptive immune response.20154. 5-13 Some invertebrates generate extensive diversity in a repertoire ofimmunoglobulin-like genes.20255. 5-14 Agnathans possess an adaptive immune system that uses somatic generearrangement to diversify receptors built from LRR domains.20356. 5-15 RAG-dependent adaptive immunity based on a diversified repertoire ofimmunoglobulin-like genes appeared abruptly in the cartilaginous fishes.20557. 5-16 Different species generate immunoglobulin diversity in differentways.20758. 5-17 Both αβ and γδ T-cell receptors are present in cartilaginous fishes.21059. 5-18 MHC class I and class II molecules are also first found in thecartilaginous fishes.21060. Summary.21161. Summary to Chapter 5.21162. Discussion questions.21263. References.21364. Chapter 6 Antigen Presentation to T Lymphocytes21765. The generation of αβ T-cell receptor ligands.21866. 6-1 Antigen presentation functions both in arming effector T cells and intriggering their effector functions to attack pathogen-infected cells.21867. 6-2Peptides are generated from ubiquitinated proteins in the cytosol by theproteasome.22068. 6-3Peptides from the cytosol are transported by TAP into the endoplasmicreticulum and further processed before binding to MHC class I molecules.22269. 6-4Newly synthesized MHC class I molecules are retained in theendoplasmic reticulum until they bind a peptide.22470. 6-5Dendritic cells use cross-presentation to present exogenous proteins onMHC class I molecules so as to prime CD8 T cells.22671. 6-6Peptide:MHC class II complexes are generated in acidified endocyticvesicles from proteins obtained through endocytosis, phagocytosis, andautophagy.22772. 6-7The invariant chain directs newly synthesized MHC class II molecules toacidified intracellular vesicles.22973. 6-8The MHC class II–like molecules HLA-DM and HLA-DO regulateexchange of CLIP for other peptides.23074. 6-9Cessation of MHC class II antigen processing occurs after dendritic-cellactivation through reduced expression of the MARCH-1 E3 ligase.23375. Summary.23476. The major histocompatibility complex and its function.23577. 6-10 Many proteins involved in antigen processing and presentation areencoded by genes within the MHC.23578. 6-11 The protein products of MHC class I and class II genes are highlypolymorphic.23879. 6-12 MHC polymorphism affects antigen recognition by T cells by

influencing both peptide binding and the contacts between the T-cell receptor andMHC molecule.24080. 6-13 Alloreactive T cells recognizing nonself MHC molecules are veryabundant.24381. 6-14 Many T cells respond to superantigens.24582. 6-15 MHC polymorphism extends the range of antigens to which the immunesystem can respond.24683. Summary.24684. Recognition of nonpeptide ligands by unconventional T-cell subsets.24785. 6-16 A variety of genes with specialized functions in immunity are alsoencoded in the MHC.24786. 6-17 Specialized MHC class I molecules act as ligands for the activation andinhibition of NK cells and unconventional T-cell subsets.24987. 6-18 Members of the CD1 family of MHC class I–like molecules presentlipid-based antigens to NKT cells.25188. 6-19 The nonclassical MHC class I molecule MR1 presents microbialriboflavin metabolites to MAIT cells.25389. 6-20 γδ T cells can recognize a variety of diverse ligands.25490. Summary.25591. Summary to Chapter 6.25592. Discussion questions.25693. References.257PART III THE DEVELOPMENT OF MATURE LYMPHOCYTE RECEPTORREPERTOIRES1. Chapter 7 Lymphocyte Receptor Signaling2612. General principles of signal transduction and propagation.2613. 7-1 Transmembrane receptors convert extracellular signals into intracellularbiochemical events.2624. 7-2Intracellular signal propagation is mediated by large multiproteinsignaling complexes.2635. 7-3Small G proteins act as molecular switches in many different signalingpathways.2646. 7-4Signaling proteins are recruited to the membrane by a variety ofmechanisms.2657. 7-5Post-translational modifications of proteins can both activate and inhibitsignaling responses.2668. 7-6The activation of many receptors generates small-molecule secondmessengers.2679. Summary.26810. Antigen receptor signaling and lymphocyte activation.26811. 7-7Antigen receptors consist of variable antigen-binding chains associatedwith invariant chains that carry out the signaling function of the receptor.26812. 7-8Antigen recognition by the T-cell receptor and its co-receptors transducesa signal across the plasma membrane to initiate signaling.270

13. 7-9Antigen recognition by the T-cell receptor and its co-receptors leads tophosphorylation of ITAMs by Src family kinases, generating the first intracellularsignal in a signaling cascade.27214. 7-10 Phosphorylated ITAMs recruit and activate the tyrosine kinase ZAP-70.27315. 7-11 ITAMs are also found in other receptors on leukocytes that signal forcell activation.27416. 7-12 Activated ZAP-70 phosphorylates adaptor proteins and promotes PI 3-kinase activation.27517. 7-13 Activated PLC-γ generates the second messengers diacylglycerol andinositol trisphosphate that lead to transcription factor activation.27618. 7-14 Ca2+ entry activates the transcription factor NFAT.27719. 7-15 Ras activation stimulates the mitogen-activated protein kinase (MAPK)relay and induces expression of the transcription factor AP-1.27820. 7-16 Protein kinase C activates the transcription factors NFκB and AP-1.28021. 7-17 PI 3-kinase activation up-regulates cellular metabolic pathways via theserine/threonine kinase Akt.28122. 7-18 T-cell receptor signaling leads to enhanced integrin-mediated celladhesion.28323. 7-19 T-cell receptor signaling induces cytoskeletal reorganization byactivating the small GTPase Cdc42.28324. 7-20 The logic of B-cell receptor signaling is similar to that of T-cell receptorsignaling, but some of the signaling components are specific to B cells.28525. 7-21 Antigen receptor signaling is a dynamic process that evolves overtime.28726. Summary.28827. Co-stimulatory and inhibitory receptors modulate antigen receptor signaling in Tand B lymphocytes.28828. 7-22 The cell-surface protein CD28 is a required co-stimulatory signalingreceptor for naive T-cell activation.28929. 7-23 Maximal activation of PLC-γ, which is important for transcription factoractivation, requires a co-stimulatory signal induced by CD28.29030. 7-24 TNF receptor superfamily members augment T-cell and B-cellactivation.29131. 7-25 Inhibitory receptors on lymphocytes down-regulate immune responsesby interfering with co-stimulatory signaling pathways.29232. 7-26 Inhibitory receptors on lymphocytes down-regulate immune responsesby recruiting protein or lipid phosphatases.29333. 7-27 Knowledge of lymphocyte receptor signaling pathways can be exploitedto engineer chimeric antigen receptors.29534. Summary.29635. Summary to Chapter 7.29736. Discussion questions.29737. References.298

14. Chapter 8 The Development of B and T Lymphocytes30139. Development of B lymphocytes.30340. 8-1 Lymphocytes derive from hematopoietic stem cells in the bonemarrow.30341. 8-2Commitment to B cell, T cell, or innate lymphoid cell lineages isregulated by distinct networks of transcription factors.30542. 8-3B-cell development begins by rearrangement of the heavy-chainlocus.30543. 8-4The pre-B-cell receptor tests for successful production of a completeheavy chain and signals for the transition from the pro-B cell to the pre-B cellstage.30844. 8-5Pre-B-cell receptor signaling inhibits further heavy-chain locusrearrangement and enforces allelic exclusion.31045. 8-6Pre-B cells rearrange the light-chain locus and express cell-surfaceimmunoglobulin.31046. 8-7Immature B cells are tested for autoreactivity before they leave the bonemarrow.31247. 8-8Lymphocytes that encounter sufficient quantities of self antigens in theperiphery are eliminated.31348. 8-9Newly formed B cells arriving in the spleen turn over rapidly and requirecytokines and positive signals through the B-cell receptor for maturation andlong-term survival.31449. 8-10 B-1 B cells are an innate lymphocyte subset that arises early indevelopment.31650. Summary.31751. Development of T lymphocytes.31952. 8-11 T-cell progenitors originate in the bone marrow, but all the importantevents in T-cell development occur in the thymus.32053. 8-12 T-cell precursors proliferate extensively in the thymus, but most diethere.32154. 8-13 Successive stages in the development of thymocytes are marked bychanges in cell-surface molecules.32155. 8-14 Commitment to the T-cell lineage occurs in the thymus after Notchsignaling.32256. 8-15 After T-cell commitment, thymocyte development is regulated by T-cellreceptor rearrangement, expression, and signaling.32557. 8-16 Thymocytes at different developmental stages are found in distinct partsof the thymus.32658. 8-17 T cells with αβ or γδ receptors arise from a common progenitor.32659. 8-18 T cells expressing γδ T-cell receptors arise in two distinct phases duringdevelopment.32760. 8-19 Successful synthesis of a rearranged β chain allows the production of apre-T-cell receptor that triggers cell proliferation and blocks further β-chain generearrangement.329

15. 8-20 T-cell α-chain genes undergo successive rearrangements until positiveselection or cell death intervenes.33162. Summary.33263. Positive and negative selection of T cells.33364. 8-21 Overview of positive and negative selection of αβ lineage T cells.33365. 8-22 Only thymocytes whose receptors interact with self peptide:self MHCcomplexes can survive and mature.33466. 8-23 Positive selection coordinates the expression of CD4 or CD8 with thespecificity of the T-cell receptor and the potential effector functions of the Tcell.33567. 8-24 Thymic cortical epithelial cells mediate positive selection of developingthymocytes.33768. 8-25 T cells that react strongly with self antigens are deleted in thethymus.33869. 8-26 The specificity and/or the strength of signals for negative and positiveselection must differ.33970. 8-27 αβ T cells diverge into multiple lineages at the CD4+ and CD8+ single-positive stage in the thymic medulla.33971. 8-28 Thymic emigration is controlled by signaling through a G protein–coupled receptor.34072. 8-29 T cells that encounter sufficient quantities of self antigens for the firsttime in the periphery are eliminated or inactivated.34173. Summary.34174. Summary to Chapter 8.34175. Discussion questions.34276. References.343PART IV THE ADAPTIVE IMMUNE RESPONSE1. Chapter 9 T Cell–Mediated Immunity3472. Development and function of secondary lymphoid organs—sites for the initiationof adaptive immune responses.3493. 9-1 Secondary lymphoid structures are specialized to facilitate theinteraction of circulating T and B lymphocytes with antigen.3494. 9-2The development of secondary lymphoid tissues is initiated by lymphoidtissue inducer cells and cytokines of the tumor necrosis factor family.3515. 9-3T-cell entry into lymphoid tissues occurs across specialized small bloodvessels and is mediated by the sequential actions of adhesion molecules andchemokine receptors.3536. 9-4T cells are highly motile within T-cell zones as they survey dendriticcells for cognate antigen.3567. 9-5The exit of T cells from T-cell zones of lymphoid tissues is controlled bya chemotactic lipid.3578. 9-6Activation of conventional dendritic cells stimulates their maturation andmigration to T-cell zones to induce naive T-cell activation.3599. 9-7Subsets of conventional dendritic cells are specialized for different

modes of antigen presentation.36410. Summary. 36611. Naive T-cell activation, clonal expansion, and differentiation into effector andmemory T cells.36712. 9-8Conventional dendritic cells deliver multiple signals for the activation ofnaive T cells.36813. 9-9T-cell activation induces metabolic changes that prepare the T cell forrapid clonal expansion and differentiation.36914. 9-10 The rapid expression of interleukin-2 and the high-affinity component ofits receptor allow activated T cells to respond to this cytokine coincident withentry into the cell cycle.37215. 9-11 Additional co-stimulatory and inhibitory receptors are engaged afterinitial T-cell activation to control clonal expansion and contraction.37316. 9-12 Proliferating T cells differentiate into effector T cells that areprogrammed for altered tissue homing and loss of a requirement for co-stimulation to act.37517. 9-13 CD8 T cells can be activated in different ways to become cytotoxiceffector cells.37618. 9-14 CD4 T cells differentiate into several functionally distinct subsets.37819. 9-15 Cytokines play a central role in guiding the differentiation of CD4 Tcells down distinct pathways.38120. 9-16 CD4 T-cell subsets can cross-regulate each other’s differentiationthrough the cytokines they produce.38521. 9-17 Regulatory T cells are a subset of CD4 T cells that restrains immuneresponses to maintain self-tolerance.38622. Summary.38823. General properties of effector T cells and their cytokines.38924. 9-18 An immunological synapse can form between effector T cells and theirtargets to direct the release of effector molecules.38925. 9-19 The effector functions of T cells are determined by the array of effectormolecules they produce, which can act locally or at a distance.39126. 9-20 Effector T cells express several TNF family cytokines.39227. Summary.39428. T cell–mediated cytotoxicity.39429. 9-21 Cytotoxic T cells induce target cells to undergo programmed cell deathvia extrinsic or intrinsic pathways of apoptosis.39430. 9-22 Cytotoxic effector proteins that trigger apoptosis are contained in thegranules of cytotoxic CD8 T cells.39831. 9-23 Cytotoxic T cells are selective serial killers of targets expressing aspecific antigen.39932. 9-24 Cytotoxic T cells also act by releasing cytokines.40033. Summary.40034. Summary to Chapter 9.40035. Discussion questions.401

36. References.40237. Chapter 10 The Humoral Immune Response40538. B-cell activation by antigen and helper T cells.40639. 10-1 Activation of B cells by antigen involves signals from the B-cell receptorand either helper T cells or microbial antigens.40640. 10-2 Linked recognition of antigen by T cells and B cells promotes robustantibody responses.40841. 10-3 B cells that encounter their antigens migrate toward the boundariesbetween B-cell and T-cell areas in secondary lymphoid tissues.40942. 10-4 T cells express surface molecules and cytokines that activate B cells,which in turn promote TFH cell development.41243. 10-5 Some activated B cells differentiate into antibody-secreting plasmablastsand plasma cells.41344. 10-6 The second phase of a primary B-cell immune response occurs whenactivated B cells migrate into follicles and proliferate to form germinalcenters.41445. 10-7 Germinal center B cells undergo V-region somatic hypermutation, andcells with mutations that improve affinity for antigen are selected.41746. 10-8 Positive selection of germinal center B cells involves contact with TFHcells and CD40 signaling.41947. 10-9 Activation-induced cytidine deaminase introduces mutations into genestranscribed in B cells.42048. 10-10 Mismatch and base-excision repair pathways contribute to somatichypermutation after initiation by AID.42149. 10-11 AID initiates class switching to allow the same assembled VH exon to beassociated with different CH genes in the course of an immune response.42350. 10-12 Cytokines made by TH cells direct the choice of isotype for classswitching in T-dependent antibody responses.42551. 10-13 B cells that survive the germinal center reaction eventually differentiateinto either plasma cells or memory cells.42652. 10-14 Some antigens do not require T-cell help to induce antibodyresponses.42753. Summary.42954. The distributions and functions of immunoglobulin classes.43055. 10-15 Antibodies of different classes operate in distinct places and havedistinct effector functions.43156. 10-16 Polymeric immunoglobulin receptor binds to the Fc regions of IgA andIgM and transports them across epithelial barriers.43257. 10-17 The neonatal Fc receptor carries IgG across the placenta and preventsIgG excretion from the body.43358. 10-18 High-affinity IgG and IgA antibodies can neutralize toxins and block theinfectivity of viruses and bacteria.43459. 10-19 Antigen:antibody complexes activate the classical pathway of

complement by binding to C1q.43660. 10-20 Complement receptors and Fc receptors both contribute to removal ofimmune complexes from the circulation.43861. Summary.43962. The destruction of antibody-coated pathogens via Fc receptors.44063. 10-21 The Fc receptors of accessory cells are signaling receptors specific forimmunoglobulins of different classes.44064. 10-22 Fc receptors on phagocytes are activated by antibodies bound to thesurface of pathogens and enable the phagocytes to ingest and destroypathogens.44165. 10-23 Fc receptors activate NK cells to destroy antibody-coated targets.44366. 10-24 Mast cells and basophils bind IgE antibody via the high-affinity Fcεreceptor.44467. 10-25 IgE-mediated activation of accessory cells has an important role inresistance to parasite infection.44568. Summary.44669. Summary to Chapter 10.44670. Discussion questions.44771. References.44872. Chapter 11Integrated Dynamics of Innate and Adaptive Immunity45373. Integration of innate and adaptive immunity in response to specific types ofpathogens.45474. 11-1 The course of an infection can be divided into several distinctphases.45475. 11-2 The effector mechanisms that are recruited to clear an infection can beorganized into immune modules.45876. 11-3 Subsets of ILCs are early responders of the immune response.46077. Summary.46278. Effector CD4 T cells augment the effector functions of innate immune cells.46279. 11-4 Effector T cells are guided to specific tissues and sites of infection bychanges in their expression of adhesion molecules and chemokine receptors.46380. 11-5 Pathogen-specific effector T cells are progressively enriched at sites ofinfection where they may undergo further maturation to acquire full effectorfunction.46781. 11-6 TH1 cells coordinate and amplify the host response to intracellularpathogens through classical activation of macrophages.46782. 11-7 Activation of macrophages by TH1 cells must be tightly regulated toavoid tissue damage.46983. 11-8 Chronic activation of macrophages by TH1 cells mediates the formationof granulomas to contain intracellular pathogens that cannot be cleared.47184. 11-9 Defects in type 1 immunity reveal its important role in the elimination ofintracellular pathogens.47185. 11-10 TH2 cells coordinate type 2 responses to expel intestinal helminths andrepair tissue injury.472

86. 11-11 TH17 cells coordinate type 3 responses to enhance the clearance ofextracellular bacteria and fungi.47587. 11-12 Effector T cells continue to respond to maturational and maintenancesignals as they carry out their effector functions in target tissues.47688. 11-13 Effector T cells can be activated to release cytokines independently ofantigen recognition.47889. 11-14 Effector CD4 T cells demonstrate plasticity and cooperativity thatenable adaptation during antipathogen responses.47990. 11-15 Integration of cell- and antibody-mediated immunity is critical forprotection against many types of pathogens.48091. 11-16 Resolution of an infection is accompanied by the death of most effectorT cells and persistence of a small number of long-lived memory T cells.48292. Summary.48393. Immunological memory.48494. 11-17 Immunological memory is long lived after infection or vaccination.48495. 11-18 MHC tetramers and adoptive transfers of clonal T-cell populations haveenabled the study of T-cell memory.48596. 11-19 The developmental origins of memory T cells parallel those of effectorT cells.48697. 11-20 Memory T cells are heterogeneous and include central memory, effectormemory, and tissue-resident subsets.48898. 11-21 Circulating memory T cells acquire heightened sensitivity to IL-7 and/orIL-15 and undergo metabolic reprogramming to survive long-term.49199. 11-22 CD4 T-cell help is required for CD8 T-cell memory and involves CD40and IL-2 signaling.492100. 11-23 Memory B-cell responses are more rapid and have higher affinity forantigen compared with responses of naive B cells.494101. 11-24 Memory B cells can reenter germinal centers and undergo additionalsomatic hypermutation and affinity maturation during secondary immuneresponses.496102. 11-25 In immune individuals, secondary and subsequent responses are mainlyattributable to memory lymphocytes.496103. Summary.498104. Summary to Chapter 11.498105. Discussion questions.500106. References.500107. Chapter 12 The Barrier Immune System505108. Organization of the mucosal immune system.505109. 12-1 The mucosal immune system protects the internal surfaces of thebody.506110. 12-2 Immune cells of the mucosal immune system are located both within andoutside of specialized lymphoid tissues in proximity to the epithelium.510111. 12-3 Maturation of the gut-associated lymphoid tissue is driven by acquisitionof the commensal microbiota.516

87. Summary.519113. Innate immune defenses of the intestinal immune system.520114. 12-4 The intestines are lined by a diversity of epithelial cell types that developfrom a common progenitor and play distinct roles in mucosal immunity.520115. 12-5 The intestinal epithelium contains conventional and unconventional Tcells that are focused on barrier maintenance and defense.528116. 12-6 Innate lymphoid cells and unconventional lymphocytes are present inGALT and in the lamina propria and are rapid responders to microbes that breachthe epithelium.534117. Summary.535118. The role of adaptive immunity in regulating the intestinal mucosal immunesystem at homeostasis.536119. 12-7 The mucosal immune system must establish and maintain tolerance toharmless foreign antigens.536120. 12-8 Macrophages and dendritic cells have complementary roles in themaintenance of immune tolerance in the intestines.537121. 12-9 The intestines have multiple routes for uptake and delivery of antigen toantigen-presenting cells.540122. 12-10 Intestinal dendritic cells favor the induction of antigen-specific Treg cellsthat are critical for the maintenance of mucosal immune homeostasis.543123. 12-11 Lymphocytes primed within the mucosal immune system are directed toreturn to the mucosal tissue by tissue-specific adhesion molecules and chemokinereceptors.546124. 12-12 Secretory IgA is the dominant class of antibody associated with themucosal immune system at homeostasis.547125. 12-13 T cell–independent processes can contribute to IgA production in somespecies.550126. 12-14 IgA deficiency is relatively common in humans but may be compensatedfor by secretory IgM.551127. 12-15 Large numbers of antigen-experienced T cells are present in theintestinal lamina propria even in the absence of disease.551128. 12-16 Priming of lymphocytes in one mucosal tissue may induce protectiveimmunity at other mucosal surfaces.552129. Summary.553130. The intestinal immune response in host defense and immune-mediateddisease.553131. 12-17 Enteric pathogens elicit ‘danger signals’ by activating pattern-recognition receptors that are sequestered in the intestinal epithelium.554132. 12-18 Pathogens induce inflammatory adaptive immune responses when innatedefenses have been breached.556133. 12-19 Effector T-cell responses in the intestine protect the function of theepithelium.557134. 12-20 Noninvasive and invasive enteric bacterial pathogens use differentstrategies to colonize the intestines.557

88. 12-21 Dysregulated immune responses to commensal bacteria provokeintestinal disease.563136. Summary.564137. Immunity at other barrier tissues.564138. 12-22 Anatomy and mucosal immunity of the airways.564139. 12-23 Respiratory immunity to inhaled pathogens; respiratory viruses.567140. 12-24 Cutaneous immunity.574141. 12-25 The sensory nervous system communicates with the immune system toenhance defense against infections in the skin.577142. Summary.579143. Summary to Chapter 12.580144. Discussion questions.581145. References.581PART V THE IMMUNE SYSTEM IN HEALTH AND DISEASE1. Chapter 13 Failures of Host Defense Mechanisms5872. Immunodeficiency diseases.5883. 13-1 Primary immunodeficiency diseases are caused by inherited genevariants that typically cause recurrent infections early in life.5884. 13-2 Defects in T-cell development can result in severe combined immunedeficiencies.5895. 13-3 SCID can also be due to defects in the purine salvage pathway.5926. 13-4 Defects in antigen receptor gene rearrangement can result in SCID.5937. 13-5 Defects in signaling from T-cell antigen receptors can cause severeimmunodeficiency.5948. 13-6 Genetic defects in thymic development or function that block T-celldevelopment result in combined immunodeficiencies.5949. 13-7 Defects in B-cell development result in deficiencies in antibodyproduction that cause an inability to clear extracellular bacteria.59610. 13-8 Combined immunodeficiencies (CIDs) can be caused by defects in T-cell differentiation and function that impair activation of B cells, dendritic cellsand macrophages, and innate effector cells.59811. 13-9 B cell–specific activation defects cause hyper IgM syndromes that arelimited to defects in the antibody response.60012. 13-10 Common variable immunodeficiency results from a variety of inheriteddefects that cause more limited defects in the antibody response.60013. 13-11 Unidentified genetic defects cause isotype-specific antibodydeficiencies.60114. 13-12 Normal pathways for host defense against different infectious agents arepinpointed by genetic deficiencies of cytokine pathways central to type 1/TH1 andtype 3/TH17 responses.60115. 13-13 Inherited defects in the cytolytic pathway of lymphocytes can causeuncontrolled lymphoproliferation and inflammatory responses to viralinfections.60316. 13-14 X-linked lymphoproliferative syndrome is associated with fatal infection

by Epstein–Barr virus and the development of lymphomas.605

17. 13-15 Immunodeficiency is caused by inherited defects in the development ofdendritic cells.60618. 13-16 Defects in complement components and complement-regulatory proteinscause defective humoral immune function and tissue damage.60719. 13-17 Defects in phagocytic cells result in widespread bacterial infections.60820. 13-18 Mutations in the molecular regulators of inflammation can causeuncontrolled inflammatory responses that result in ‘autoinflammatorydisease.’61221. 13-19 Factor-replacement therapies, hematopoietic stem-cell transplantation,and gene therapy can be used successfully to correct genetic defects.61322. 13-20 Noninherited, secondary immunodeficiencies are major predisposingcauses of infection and death.61523. Summary.61624. Evasion and subversion of immune defenses.61625. 13-21 Extracellular bacterial pathogens have evolved different strategies toavoid detection by pattern-recognition receptors and destruction by antibody,complement, and antimicrobial peptides.61726. 13-22 Intracellular bacterial pathogens can evade the immune system byseeking shelter within phagocytes.62227. 13-23 Immune evasion is also practiced by protozoan parasites.62328. 13-24 Many viruses target type I and type III interferon pathways to impairhost antiviral defense.62529. 13-25 RNA viruses use different mechanisms of antigenic variation to keep astep ahead of the adaptive immune system.62630. 13-26 DNA viruses use multiple mechanisms to subvert CTL and NK-cellresponses.62831. 13-27 Viruses that establish latency persist in vivo by ceasing to replicate untilimmunity wanes.63132. 13-28 DNA and RNA viruses can induce exhaustion of CTL and NK cellresponses, thereby impairing the antiviral response.63333. Summary.63334. Acquired immune deficiency syndrome.63435. 13-29 HIV is a retrovirus that establishes a chronic infection that slowlyprogresses to AIDS.63636. 13-30 HIV infects and replicates within cells of the immune system.63637. 13-31 Activated CD4 T cells are the major source of HIV replication.63838. 13-32 There are several routes by which HIV is transmitted and establishesinfection.64139. 13-33 HIV variants with tropism for different co-receptors play different rolesin transmission and progression of disease.64140. 13-34 A genetic deficiency of the co-receptor CCR5 confers resistance to HIVinfection.64441. 13-35 An immune response controls but does not eliminate HIV.644

18. 13-36 Lymphoid tissue is the major reservoir of HIV infection.64643. 13-37 Genetic variation in the host can alter the rate of HIV diseaseprogression.64744. 13-38 The destruction of immune function as a result of HIV infection leads toincreased susceptibility to opportunistic infection and eventually to death.64945. 13-39 Drugs that block HIV replication lead to a rapid decrease in titer ofinfectious virus and an increase in CD4 T cells.64946. 13-40 In the course of infection, HIV accumulates many mutations, which canresult in the outgrowth of drug-resistant variants.65247. 13-41 HIV treatment and prophylaxis are leading to a decline in the spread ofHIV and AIDS.65248. 13-42 Vaccination against HIV remains an attractive solution but poses manydifficulties.65349. Summary.65550. Summary to Chapter 13.65651. Discussion questions.65652. References.65753. Chapter 14 Allergic Diseases and Hypersensitivity Reactions66354. IgE and IgE-mediated allergic diseases.66455. 14-1 Sensitization involves class switching to IgE production on first contactwith an allergen.66556. 14-2 Although many types of antigens can cause allergic sensitization,proteases are common sensitizing agents.66657. 14-3 Genetic factors contribute to the development of IgE-mediated allergicdisease.66758. 14-4 Environmental factors may interact with genetic susceptibility to causeallergic disease.66959. Summary.67160. Effector mechanisms in IgE-mediated allergic reactions.67161. 14-5 Most IgE is cell-bound and engages effector mechanisms of the immunesystem by pathways different from those of other antibody isotypes.67162. 14-6 Mast cells reside in tissues and orchestrate allergic reactions.67363. 14-7 Eosinophils and basophils cause inflammation and tissue damage inallergic reactions.67564. 14-8 IgE-mediated allergic reactions have a rapid onset but can also lead tochronic responses.67765. 14-9 Allergen introduced into the bloodstream can cause anaphylaxis andurticaria.67966. 14-10 Allergen inhalation is associated with the development of rhinitis andasthma.68167. 14-11 Allergy to particular foods causes systemic reactions as well assymptoms limited to the gut.68268. 14-12 IgE-mediated allergic disease can be treated by inhibiting effectorpathways or by desensitization to restore biological tolerance.684

19. Summary.68670. Non-IgE-mediated allergic diseases.68671. 14-13 Non-IgE-dependent drug-induced hypersensitivity reactions insusceptible individuals occur by binding of the drug to the surface of circulatingblood cells.68772. 14-14 Systemic disease caused by immune-complex formation can follow theadministration of large quantities of poorly catabolized antigens.68773. 14-15 Hypersensitivity reactions can be mediated by TH1 cells and cytotoxicCD8 T cells.68974. 14-16 Celiac disease has features of both an allergic response andautoimmunity.69275. Summary.69476. Summary to Chapter 14.69477. Discussion questions.69578. References.69579. Chapter 15 Autoimmunity and Transplantation69980. The making and breaking of self-tolerance.69981. 15-1 Multiple mechanisms normally contribute to prevent autoimmunity.69982. 15-2 Lymphocytes that bind self antigens with relatively low affinity usuallyignore them but in some circumstances become activated.70283. 15-3 Antigens in immunologically privileged sites do not induce immuneattack but can serve as targets.70384. 15-4 Autoimmune responses can be controlled at various stages by regulatoryT cells.70485. Summary.70586. Autoimmune diseases and pathogenic mechanisms.70687. 15-5 Autoimmunity can be classified into either organ-specific or systemicdisease.70688. 15-6 Multiple components of the immune system are typically recruited inautoimmune disease.70789. 15-7 Chronic autoimmune disease develops through positive feedback frominflammation, inability to clear the self antigen, and a broadening of theautoimmune response.70990. 15-8 Both antibody and effector T cells can cause tissue damage inautoimmune disease.71191. 15-9 Autoantibodies against blood cells promote their destruction.71392. 15-10 The fixation of sublytic doses of complement to cells in tissuesstimulates a powerful inflammatory response.71393. 15-11 Autoantibodies against receptors cause disease by stimulating orblocking receptor function.71494. 15-12 Autoantibodies against extracellular antigens cause inflammatoryinjury.71595. 15-13 T cells specific for self antigens can cause direct tissue injury and sustainautoantibody responses.717

20. Summary.72197. The genetic and environmental basis of autoimmunity.72198. 15-14 Autoimmune diseases have a strong genetic component.72299. 15-15 Monogenic defects of immune tolerance.722100. 15-16 MHC genes have an important role in controlling susceptibility toautoimmune disease.726101. 15-17 Genetic variants that impair innate immune responses can predispose toT cell–mediated chronic inflammatory disease.727102. 15-18 Cross-reactivity between foreign molecules on pathogens and selfmolecules can promote autoimmune disease.730103. Summary.731104. Responses to alloantigens and transplant rejection.732105. 15-19 Transplant rejection is mediated primarily by T-cell responses to MHCmolecules.732106. 15-20 Rejection of MHC-identical grafts is caused by peptides from otheralloantigens bound to graft MHC molecules.734107. 15-21 Alloreactive T cells reject transplanted organs by direct and indirectallorecognition.735108. 15-22 Antibodies that react with endothelium cause hyperacute graftrejection.737109. 15-23 Late failure of transplanted organs is caused by chronic injury to thegraft.737110. 15-24 A variety of organs are transplanted routinely in clinical medicine.738111. 15-25 The converse of graft rejection is graft-versus-host disease.740112. 15-26 The fetus is an allograft that is tolerated repeatedly.741113. Summary.742114. Summary to Chapter 15.743115. Discussion questions.744116. References.744117. Chapter 16 Manipulation of the Immune Response749118. Fighting infectious diseases with vaccination.749119. 16-1 Vaccines can be based on attenuated pathogens or material from killedorganisms.750120. 16-2 Most effective vaccines generate antibodies that prevent damage causedby toxins or that neutralize pathogens and stop infection.752121. 16-3 Effective vaccines must induce long-lasting protection while being safeand inexpensive.753122. 16-4 Live-attenuated viral vaccines are usually more potent than ‘killed’vaccines.753123. 16-5 Live-attenuated viral vaccines can be made safer by the use ofrecombinant DNA technology.754124. 16-6 Vaccines against bacteria or parasites can be developed usingnonpathogenic or disabled bacteria or genetically attenuated parasites(GAPs).755

21. 16-7 Conjugate vaccines rely on linked recognition between T and Bcells.756126. 16-8 Adjuvants enhance the immunogenicity of vaccines, but few areapproved for use in humans.758127. 16-9 Protective immunity can be induced by RNA- and DNA-basedvaccination.759128. 16-10 The route of vaccination is an important determinant of success.760129. 16-11 Bordetella pertussis vaccination illustrates the importance of theperceived safety of a vaccine.761130. 16-12 Peptide-based vaccines can elicit protective immunity, but they requireadjuvants and must be targeted to the appropriate cells and cell compartment tobe effective.762131. 16-13 Vaccination and checkpoint blockade may be useful in controllingexisting chronic infections.763132. Summary.763133. Using the immune response to attack tumors.764134. 16-14 The development of transplantable tumors in mice led to the discoveryof protective immune responses to tumors.764135. 16-15 Tumors are ‘edited’ by the immune system as they evolve and canescape rejection in many ways.765136. 16-16 Tumor-rejection antigens can be recognized by T cells and form thebasis of immunotherapies.769137. 16-17 Checkpoint blockade can augment immune responses to existingtumors.771138. 16-18 T cells expressing chimeric antigen receptors are an effective treatmentin some leukemias.773139. 16-19 Monoclonal antibodies against tumor antigens, alone or linked to toxins,can control tumor growth.774140. 16-20 Enhancing the immune response to tumors by vaccination holds promisefor cancer prevention and therapy.776141. Summary.777142. Treatment of unwanted immune responses.778143. 16-21 Corticosteroids are powerful anti-inflammatory drugs that alter thetranscription of many genes.779144. 16-22 Cytotoxic drugs cause immunosuppression by killing dividing cells andhave serious side effects.780145. 16-23 Cyclosporin A, tacrolimus, and rapamycin are effectiveimmunosuppressive agents that interfere with various T-cell signalingpathways.781146. 16-24 JAK inhibitors can be used to treat autoimmune and inflammatorydiseases.783147. 16-25 Antibodies against cell-surface molecules can be used to eliminatelymphocyte subsets or to inhibit lymphocyte function.783148. 16-26 Antibodies can be engineered to reduce their immunogenicity in

humans.784149. 16-27 Monoclonal antibodies can be used to prevent allograft rejection.785150. 16-28 Depletion of autoreactive lymphocytes can treat autoimmunedisease.787151. 16-29 Biologics that block TNF-α, IL-1, or IL-6 can alleviate autoimmunediseases.788152. 16-30 Biologics can block cell migration to sites of inflammation and reduceimmune responses.789153. 16-31 Blockade of co-stimulatory pathways that activate lymphocytes can beused to treat autoimmune disease.790154. 16-32 Some commonly used drugs have immunomodulatory properties.791155. 16-33 Controlled administration of antigen can be used to manipulate thenature of an antigen-specific response.791156. Summary.792157. Summary to Chapter 16.792158. Discussion questions.794159. References.794160. APPENDICES161. Note: Appendices II–IV are available on digital.wwnorton.com/janeway10 and inthe ebook.162. Appendix I The Immunologist’s ToolboxA-1163. A-1 Immunization.A-1164. A-2 Antibody responses.A-4165. A-3 Affinity chromatography.A-5166. A-4 Radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA),and competitive inhibition assay.A-5167. A-5 Multiplex bead assay for detection of cytokines, antibody responses, orantigens.A-7168. A-6 Hemagglutination and blood typing.A-8169. A-7 Coombs tests and the detection of rhesus incompatibility.A-9170. A-8 Monoclonal antibodies.A-11171. A-9 Phage display libraries for antibody V-region production.A-12172. A-10 Generation of human monoclonal antibodies from vaccinatedindividuals.A-13173. A-11 Microscopy and imaging using fluorescent dyes.A-13174. A-12 Immunoelectron microscopy.A-15175. A-13 Immunohistochemistry.A-15176. A-14 Immunoprecipitation and co-immunoprecipitation.A-16177. A-15 Immunoblotting (western blotting).A-17178. A-16 Use of antibodies in the isolation and characterization of multiproteincomplexes by mass spectrometry.A-18179. A-17 Isolation of peripheral blood lymphocytes by density-gradientfractionation.A-20180. A-18 Isolation of lymphocytes from tissues other than blood.A-20

181. A-19 Flow cytometry and FACS analysis.A-21182. A-20 Lymphocyte isolation using antibody-coated magnetic beads.A-23183. A-21 Isolation of homogeneous T-cell lines.A-24184. A-22 ELISPOT assay.A-24185. A-23 Identification of functional subsets of T cells based on cytokine productionor transcription factor expression.A-25186. A-24 Identification of T or B lymphocytes on the basis of antigen receptorspecificity.A-28187. A-25 Biosensor assays for measuring the rates of association and dissociation ofantigen receptors for their ligands.A-28188. A-26 Assays of lymphocyte proliferation.A-30189. A-27 Measurements of apoptosis.A-32190. A-28 Assays for cytotoxic T cells.A-33191. A-29 Assays for CD4 T cells.A-34192. A-30 Transfer of protective immunity.A-35193. A-31 Adoptive transfer of lymphocytes.A-36194. A-32 Assessment of lymphocyte tissue residency by parabiosis.A-37195. A-33 Hematopoietic stem-cell transfers.A-38196. A-34 In vivo administration of antibodies.A-38197. A-35 Transgenic mice.A-39198. A-36 Gene knockout by targeted disruption.A-40199. A-37 Knockdown of gene expression by RNA interference (RNAi).A-43200. A-38 Cell-lineage tracing techniques.A-44201. A-39 Single-cell analysisA-45202. eAppendix IICD AntigensA-49203. eAppendix III Cytokines and Their ReceptorsA-69204. eAppendix IV Chemokines and Their ReceptorsA-73205. GlossaryG-1206. CreditsC-1207. IndexI-1

参考资料

• Janeway’s Immunobiology 10th edition