xiv 817 foseseectonacoparepetoectLcelreceptors 8-18 sion CD4 349 he p 8-19 I cells mediate positive selection 310 351 820 eact stro y with ubiquitous self antigens Summary. 352 311 8-21 arrow der rived antigen-pre 313 eng3gcogearercelsbypathogen-actiated 353 822 9-10 314 363 Summary. 315 911 354 ion of mhoce inperipheral 9-12 CD28-dependentco- 316 in-2 8-23 36 913 824 914 the 317 8-25 357 319 15 8-26 916 320 g2Lcesecabeactatednderentwastobecome 8.27 917 CD4Tceseentaieintosereralsutsetsoftuncionaly 360 E-cell recer 918 Various forms of si al 3 induce th 8-28 B-1cells a B-cell 362 32 919 or pa 8-29 Summary. to Chanter 8 General their cytokines 366 920 329 921 e10 Section references 329 e9artrerge 367 Part IV THE ADAPTIVE IMMUNE 92 ed by the RESPONSE Cyto anes can act loca or at a distance T Cell-Mediated Immunity Summary. 2 Entry of naiveT cells and antigen-presenting cells into peripheral lymphoid organs. 1 Tcell-mediated cytotoxicity e 925 91 totbaxtcTcescanindtcetargetcelsioundergo 337 926 ctor pro s are t05 92 374 killers o taroet 93 9.28 yreleasing cytokine T-cell eripheral lymphoid 342 95 Macrophage activation by t.1 cells 377 344 0.20 cells haw 96 eng ctivation 378 930 n of ma .ce issue damage. 378
� S-17 Positive selection acts on a repertoire ofT-cell receptors 9-7 Plasmacytoid dendritic cells produce abundant type I with inherent specificity for MHC molecules. 30S interferons and may act as helper cells for antigen S-1S Positive selection coordinates the expression of CD4 presentation by conventional dendritic cells. 349 or CDS with the specificity of the T-cell receptor and 9-S Macrophages are scavenger cells that can be induced the potential effector functions of the T cell. 30S by pathogens to present foreign antigens to naive T cells. 350 S-19 Thymic cortical epithelial cells mediate positive selection 9-9 8 cells are highly efficient at presenting antigens that of developing thymocytes. 310 bind to their surface immunoglobulin. 351 S-20 T cells that react strongly with ubiquitous self antigens Summary. 352 are deleted in the thymus. 311 S-21 Negative selection is driven most efficiently by bone Priming of naive T cells by pathogen-activated marrow derived antigen-presenting cells. 313 dendritic cells. 353 S-22 The specificity and/or the strength of signals for negative 9-10 Cell-adhesion molecules mediate the initial interaction and positive selection must differ. 314 of naive T cells with antigen-presenting cells. 353 Summary. 315 9-11 Antigen-presenting cells deliver three kinds of signals for the clonal expansion and differentiation of naive T cells. 354 Survival and maturation of lymphocytes in peripheral 9-12 CD2S-dependent co-stimulation of activated T cells lymphoid tissues. 316 induces expression of the T-cell growth factor interleukin-2 S-23 Different lymphocyte subsets are found in particular and the high-affinity IL-2 receptor. 355 locations in peripheral lymphoid tissues. 316 9-13 Signal 2 can be modified by additional co-stimulatory S-24 The development of peripheral lymphoid tissues is pathways. 356 controlled by lymphoid tissue inducer cells and proteins 9-14 Antigen recognition in the absence of co-stimulation of the tumor necrosis factor family. 317 leads to functional inactivation or clonal deletion of S-25 The homing of lymphocytes to specific regions of peripheral T cells. 357 peripheral lymphoid tissues is mediated by chemokines. 319 9-15 Proliferating T cells differentiate into effector T cells that S-26 Lymphocytes that encounter sufficient quantities of self do not require co-stimulation to act. 35S antigens for the first time in the periphery are eliminated 9-16 CDS T cells can be activated in different ways to become or inactivated. 320 cytotoxic effector cells. 359 S-27 Immature 8 cells arriving in the spleen turn over rapidly 9-17 CD4 T cells differentiate into several subsets of functionally and require cytokines and positive signals through the different effector cells. 360 8-cell receptor for maturation and survival. 321 9-1S Various forms of signal 3 induce the differentiation of S-2S B-1 cells and marginal zone B cells are distinct B-cell naive CD4 T cells down distinct effector pathways. 362 subtypes with unique antigen receptor specificity. 322 9-19 Regulatory CD4 T cells are involved in controlling S-29 T-cell homeostasis in the periphery is regulated by adaptive immune responses. 364 cytokines and self-MHC interactions. 324 Summary. 365 Summary. 325 General properties of effectorT cells and their cytokines. Summary to Chapter S. 325 366 Questions. 329 9-20 Effector T-cell interactions with target cells are initiated General references. 329 by antigen-nonspecific cell-adhesion molecules. 366 Section references. 329 9-21 An immunological synapse forms between effector T cells and their targets to regulate signaling and to direct the release of effector molecules. 367 I Part IV I 9-22 T he effector functions ofT cells are determined by the THE ADAPTIVE IMMUNE array of effector molecules that they produce. 369 RESPONSE 9-23 Cytokines can act locally or at a distance. 370 9-24 T cells express several TNF-family cytokines as trimeric proteins that are usually associated with the cell surface. 371 Chapter 9 T Cell-Mediated Immunity 335 Summary. 372 Entry of naive T cells and antigen-presenting cells into T cell-mediated cytotoxicity. 372 peripheral lymphoid organs. 337 9-25 Cytotoxic T cells can induce target cells to undergo 9-1 Naive T cells migrate through peripheral lymphoid tissues, programmed cell death. 373 sampling the peptide:MHC complexes on dendritic 9-26 Cytotoxic effector proteins that trigger apoptosis are cell surfaces. 337 contained in the granules of CDS cytotoxic T cells. 374 9-2 Lymphocyte entry into lymphoid tissues depends on 9-27 Cytotoxic T cells are selective and serial killers of targets chemokines and adhesion molecules. 33S expressing a specific antigen. 376 9-3 Activation of integrins by chemokines is responsible for 9-2S Cytotoxic T cells also act by releasing cytokines. 377 the entry of naive T cells into lymph nodes. 339 9-4 T-cell responses are initiated in peripheral lymphoid Summary. 377 organs by activated dendritic cells. 342 Macrophage activation by T H 1 cells. 377 9-5 Dendritic cells process antigens from a wide array of pathogens. 344 9-29 T H 1 cells have a central role in macrophage activation. 37S 9-6 Pathogen-induced TLR signaling in immature dendritic 9-30 Activation of macrophages by T 1 cells promotes cells induces their migration to lymphoid organs and microbial killing and must be tig�tly regulated to avoid enhances antigen processing. 347 tissue damage. 37S
379 eeporionofantbody-coatedpathogensVia 417 Summary. 10-21 Summary to Chapter 380 10-22 and en beheodies Section references 382 10-23 NK cells to antody-coated 419 Chapter 10 The Humoral Immune Response 387 10-24 nd hann igh-ainiyreErecept 421 B-cell activation by helperT cells 388 10-25 10-1 Summary. 389 Summary to Chapter10. ion of the B-cell antigen and complement General references 389 10-3 HeperTcells activate Bcells thatei thesame Section references. 426 390 rane-bound and se reted moecules 391 Chapter 11 Dynamics of Adaptive Immunity 429 105 Bcesha60toe0eeangeaaseosen8e Thecourse of the immune to infecion. 430 392 11-1 tion can be divded into several 10-6 ting plasma cells differentiate from 395 11-2 10-7 432 11-3 396 10-8 ninal center B 11-4 mprove affinity 435 oranigenareselected 398 1-5 SRcel6bescamcoseguaeachoters 10-9 形 11-6 400 g 10-10 11-7 402 10-11 ogngeominalcegnwerBsoelsdierentiaienioeher 402 11-8 10-12 he3SOc582aapathogensam6oaw 42 404 11-9 Antibody respo 10-13 444 11-10 Antibody re are sustained in medullary cords Summary. 1-11 Th edtoclearanintfecion Imesenbutioasandtuncionsofimmunoglobum 408 11-12 emory cel 403 10-15 Summary nological memory 448 10-16 412 1-13 1017 449 413 11-14 10-18 Antibodies can block the adherence of bacteria to host 413 11-15 Repe3tedinmnzationleatoncreasingaiyod 10-19 414 10-20 11-16 416 Summary. 417
E 9-31 T H 1 cells coordinate the host response to intracellular The destruction of antibody-coated pathogens via pathogens. 379 Fe receptors. 417 Summary. 380 10-21 The Fe receptors of accessory cells are signaling receptors Summary to Chapter 9. 381 specific for immunoglobulins of different classes. 418 Questions. 382 10-22 Fe receptors on phagocytes are activated by antibodies General references. 382 bound to the surface of pathogens and enable the Section references. 382 phagocytes to ingest and destroy pathogens. 419 10-23 Fe receptors activate NK cells to destroy antibody-coated targets. 420 Chapter 10 The Humoral Immune Response 387 10-24 Mast cells and basophils bind lgE antibody via the high-affinity Fee receptor. 421 B-cell activation by helperT cells. 388 10-25 lgE-mediated activation of accessory cells has an 10-1 T he humoral immune response is initiated when B cells important role in resistance to parasite infection. 422 that bind antigen are signaled by helper T cells or by certain Summary. 423 microbial antigens alone. 389 Summary to Chapter 10. 424 10-2 B-cell responses are enhanced by co-ligation of the B-cell Questions. 425 receptor and B-cell co-receptor by antigen and complement General references. 426 fragments on microbial surfaces. 389 Section references. 426 10-3 Helper T cells activate B cells that recognize the same antigen. 390 10-4 T cells make membrane-bound and secreted molecules Chapter 11 Dynamics of Adaptive Immunity 429 that activate B cells. 391 10-5 B cells that encounter their antigens migrate toward the The course of the immune response to infection. 430 boundaries between B-cell and T-cell areas in secondary 11-1 The course of an infection can be divided into several lymphoid tissues. 392 distinct phases. 430 10-6 Antibody-secreting plasma cells differentiate from 11-2 The nonspecific responses of innate immunity are activated B cells. 395 necessary for an adaptive immune response to be initiated. 432 10-7 T he second phase of a primary B-cell immune response 11-3 Cytokines made during infection can direct differentiation occurs when activated B cells migrate into follicles and of CD4 T cells toward the T H 17 subset. 434 proliferate to form germinal centers. 396 10-8 Germinal center B cells undergo V-region somatic 11-4 T H 1 and T H2 cells are induced by cytokines generated hypermutation, and cells with mutations that improve affinity in response to different pathogens. 435 for antigen are selected. 398 11-5 CD4 T-cell subsets can cross-regulate each other's 10-9 Class switching in thymus-dependent antibody responses differentiation. 437 requires expression of CD40 ligand by helper T cells and 11-6 Effector T cells are guided to sites of infection by is directed by cytokines. 400 chemokines and newly expressed adhesion molecules. 439 10-10 Ligation of CD40 and prolonged contact with T follicular 11-7 Differentiated effector T cells are not a static population helper cells is required to sustain germinal center B cells. 402 but continue to respond to signals as they carry out their 10-11 Surviving germinal center B cells differentiate into either effector functions. 441 plasma cells or memory cells. 402 11-8 Primary CDS T-cell responses to pathogens can occur 10-12 Some bacterial antigens do not require T-cell help to in the absence of CD4 T-cell help. 442 induce B-cell responses. 404 11-9 Antibody responses develop in lymphoid tissues under 10-13 B-cell responses to bacterial polysaccharides do not the direction ofT F H cells. 444 require peptide-specific T-cell help. 405 11-10 Antibody responses are sustained in medullary cords Summary. 407 and bone marrow. 445 11-11 The effector mechanisms used to clear an infection The distributions and functions of immunoglobulin depend on the infectious agent. 445 classes. 408 11-12 Resolution of an infection is accompanied by the death of most of the effector cells and the generation of 10-14 Antibodies of different classes operate in distinct places memory cells. 447 and have distinct effector functions. 408 Summary. 448 10-15 Transport proteins that bind to the Fe regions of antibodies carry particular isotypes across epithelial barriers. 409 Immunological memory. 448 10-16 High-affinity lgG and lgA antibodies can neutralize 11-13 Immunological memory is long-lived after infection bacterial toxins. 412 or vaccination. 449 10-17 High-affinity lgG and lgA antibodies can inhibit the 11-14 Memory B-cell responses differ in several ways from infectivity of viruses. 413 those of naive B cells. 450 10-18 Antibodies can block the adherence of bacteria to host 11-15 Repeated immunization leads to increasing affinity of cells. 413 antibody due to somatic hypermutation and selection 10-19 Antibody:antigen complexes activate the classical by antigen in germinal centers. 451 pathway of complement by binding to C1q. 414 11-16 Memory T cells are increased in frequency compared with 10-20 Complement receptors are important in the removal naive T cells specific for the same antigen, and have of immune complexes from the circulation. 416 distinct activation requirements and cell-surface proteins Summary. 417 that distinguish them from effector T cells. 452
xvi Summary. 11-18 Summary to Chapter 12. 11-1g to Chapter 11. PartV THE IMMUNE SYSTEM IN Section references HEALTH AND DISEASE Chapter 12 The Mucosal Immune System 465 Chapter 13 Failures of Host Defense Mechanisms 509 The organization of the mucosal system. 465 Evasion and subversion of immune detenses 509 12.1 sthe intea 13-1 menwesgparsithiotyceasngtoepicaeuri o 122 13-2 123 512 133 468 124 mechanismso 134 canconlniteopes9stenSeaeemmuneesponses 515 12-5 13-5 473 518 12-6 13-6 Regulatory afiect the inetious and chemokine receptors Summary 127 475 519 12-8 13-7 520 点p 476 13-8 478 520 12.10 13-9 479 an result in severe ed 522 12-11 13-10 lsobe due to defects in the purine salvage 52g 12-12 13-11 Detecstnanigenreceptorgenerearangementcam 524 Summary 486 13-12 524 eeoglnePeepoe8sgtonandreglaion of muc 486 13-13 harblocdtTcel evere immunodet 12-13 1314 s in 486 12-14 527 13-15 dby defects in B-cell 489 12.15 13-16 49 532 12.16 The btdoasnot 13-17 mit widespread bacteria 1316 12.17 536 12.18 Intestinal helminths provoke strong T.2-mediated immune 13-19 potnledbygeneticdeicienctesofFy 12-19 538 13-20 1220 nent of homas 539
� 11-17 Memory T cells are heterogeneous and include central Summary. 502 memory and effector memory subsets. 455 Summary to Chapter 12. 503 11-18 CD4 T-cell help is required for COB T-cell memory and Questions. 504 involves CD40 and IL-2 signaling. 456 General references. 504 11-19 In immune individuals, secondary and subsequent Section references. 504 responses are mainly attributable to memory lymphocytes. 458 Summary. 459 Summary to Chapter 11. 460 Questions. 461 I PartV I THE IMMUNE SYSTEM IN Section references. 462 HEALTH AND DISEASE Chapter 12 The Mucosal Immune System 465 Chapter 13 Failures of Host Defense Mechanisms 509 The organization of the mucosal system. 465 Evasion and subversion of immune defenses. 509 12-1 The mucosal immune system protects the internal 13-1 Antigenic variation allows pathogens to escape from surfaces of the body. 465 immunity. 510 12-2 The mucosal immune system may be the original 13-2 Some viruses persist in vivo by ceasing to replicate until vertebrate immune system. 468 immunity wanes. 512 12-3 Cells of the mucosal immune system are located both 13-3 Some pathogens resist destruction by host defense in anatomically defined compartments and scattered mechanisms or exploit them for their own purposes. 514 throughout mucosal tissues. 468 13-4 Immunosuppression or inappropriate immune responses 12-4 The intestine has distinctive routes and mechanisms of can contribute to persistent disease. 515 antigen uptake. 472 13-5 Immune responses can contribute directly to 12-5 The mucosal immune system contains large numbers of pathogenesis. 518 effector lymphocytes even in the absence of disease. 473 13-6 Regulatory T cells can affect the outcome of infectious 12-6 The circulation of lymphocytes within the mucosal immune disease. 518 system is controlled by tissue-specific adhesion molecules Summary. 519 and chemokine receptors. 474 12-7 Priming of lymphocytes in one mucosal tissue can induce Immunodeficiency diseases. 519 protective immunity at other mucosal surfaces. 475 12-8 Unique populations of dendritic cells control mucosal 13-7 A history of repeated infections suggests a diagnosis of immune responses. 476 immunodeficiency. 520 12-9 The intestinal lamina propria contains antigen-experienced 13-8 Primary immunodeficiency diseases are caused by T cells and populations of unusual innate-type lymphocytes. 478 inherited gene defects. 520 12-10 The intestinal epithelium is a unique compartment of the 13-9 Defects in T-cell development can result in severe immune system. 479 combined immunodeficiencies. 522 12-11 Secretory lgA is the class of antibody associated with the 13-10 SCID can also be due to defects in the purine salvage mucosal immune system. 482 pathway. 523 12-12 lgA deficiency is common in humans but may be 13-11 Defects in antigen receptor gene rearrangement can compensated for by secretory lgM. 485 result in SCI D. 524 Summary. 486 13-12 Defects in signaling from T-cell antigen receptors can cause severe immunodeficiency. 524 The mucosal response to infection and regulation 13-13 Genetic defects in thymic function that block T-cell of mucosal immune responses. 486 development result in severe immunodeficiencies. 525 12-13 Enteric pathogens cause a local inflammatory response 13-14 Defects in B-cell development result in deficiencies in and the development of protective immunity. 486 antibody production that cause an inability to clear 12-14 The outcome of infection by intestinal pathogens is extracellular bacteria. 527 determined by a complex interplay between the 13-15 Immune deficiencies can be caused by defects in B-cell microorganism and the host immune response. 489 orT-cell activation and function. 528 12-15 The mucosal immune system must maintain a balance 13-16 Defects in complement components and complementbetween protective immunity and homeostasis to a large regulatory proteins cause defective humoral immune number of different foreign antigens. 491 function and tissue damage. 532 12-16 The healthy intestine contains large quantities of bacteria 13-17 Defects in phagocytic cells permit widespread bacterial but does not generate potentially harmful immune infections. 533 responses against them. 493 13-18 Mutation in the molecular regulators of inflammation can 12-17 Full immune responses to commensal bacteria provoke cause uncontrolled inflammatory responses that result in intestinal disease. 497 'autoinflammatory disease: 536 12-18 Intestinal helminths provoke strong T H 2 -mediated immune 13-19 The normal pathways for host defense against intracellular responses. 498 bacteria are pinpointed by genetic deficiencies of IFN-y 12-19 Other eukaryotic parasites provoke protective immunity and IL-12 and their receptors. 538 and pathology in the gut. 501 13-20 X-linked lymphoproliferative syndrome is associated with 12-20 The mucosal immune system has to compromise between fatal infection by Epstein-Barr virus and with the suppression and activation of an immune response. 501 development of lymphomas. 539
xvii 1321 148 ses to v alinectiors 585 539 14-9 13-2 ergic reactions have a rapid onset but 541 14-10 13-23 s are major 589 542 1411 Summary. 543 20aa3rnssocedwmteeetepmey 591 1412 Acquired immune deficiency syndrome 592 13-4oeme 1413 545 龙 13-25 14-14 547 at lead to 13-26 eetceeieanetehoscanaertheaeod 549 597 13-27 Summary. ceptor CCR5 confers 549 13-28 Non-IgE-mediated allergic diseases. 598 551 14-15 鸣 14-16 1.3 ult of Hly isti 1417 556 % 1333 DnushatblocktHYeicaonleedtnarapdeceas 1418 13-34 Summary. Summary to Chapter 14 559 13-35 Gen 560 607 13-36 speadtHandhoSanbe28on which the 561 Chapter 15 Autoimmunity and Transplantation 611 to Chapter 13 The making and breaking of self-tolerance 611 General reterences 564 151 Section references. 564 62 15-2 613 Chapter14 Allergy and Allergic Diseases 571 15-3 614 and IgE-mediated allergic diseases 573 15-4 141 573 616 15-5 14-2 ucosally at low AnigensnnunoogicayDpmiegeisnesdonotindce 55 re 61 143 15-6 tive T cells oment of lgE 144 tal fa 15-7 579 gasbyTeg629ceontoledtvaious 145 Regulatory T cells can control allergic responses 581 Summary 621 Summary 582 582 Autoimmune diseases and pathogenic mechanisms. 鸟 15-8 Specicatapnemmuneresponsestosefanigens 14-6 622 15-9 ther ant isotype 583 sedntoctsters n-sp 15-10 nt th 583 624
E 13-21 Genetic abnormalities in the secretory cytotoxic pathway of 14-8 Eosinophils and basophils cause inflammation and tissue lymphocytes cause uncontrolled lymphoproliferation damage in allergic reactions. 585 and inflammatory responses to viral infections. 539 14-9 lgE-mediated allergic reactions have a rapid onset but 13-22 Hematopoietic stem cell transplantation or gene therapy can also lead to chronic responses. 587 can be useful to correct genetic defects. 541 14-10 Allergen introduced into the bloodstream can cause 13-23 Secondary immunodeficiencies are major predisposing anaphylaxis. 589 causes of infection and death. 542 14-11 Allergen inhalation is associated with the development Summary. 543 of rhinitis and asthma. 591 14-12 A genetically determined defect in the skin's barrier Acquired immune deficiency syndrome. 543 function increases the risk of atopic eczema. 592 13-24 Most individuals infected with HIV progress over time 14-13 Allergy to particular foods causes systemic reactions as to AIDS. 545 well as symptoms limited to the gut. 594 13-25 HIV is a retrovirus that infects CD4 T cells, dendritic cells, 14-14 lgE-mediated allergic disease can be treated by inhibiting and macrophages. 547 the effector pathways that lead to symptoms or by desensitization techniques that aim at restoring tolerance 13-26 Genetic variation in the host can alter the rate of to the allergen. 595 progression of disease. 549 Summary. 597 13-27 A genetic deficiency of the co-receptor CCR5 confers resistance to HIV infection in vivo. 549 Non-lgE-mediated allergic diseases. 598 13-28 HIV RNA is transcribed by viral reverse transcriptase 14-15 Innocuous antigens can cause type II hypersensitivity into DNA that integrates into the host-cell genome. 551 reactions in susceptible individuals by binding to the 13-29 Replication of HIV occurs only in activated T cells. 551 surfaces of circulating blood cells. 598 13-30 Lymphoid tissue is the major reservoir of HIV infection. 554 14-16 Systemic disease caused by immune-complex formation 13-31 An immune response controls but does not eliminate HIV. 554 can follow the administration of large quantities of poorly 13-32 The destruction of immune function as a result of HIV catabolized antigens. 598 infection leads to increased susceptibility to opportunistic 14-17 Hypersensitivity reactions can be mediated by T H 1 cells infection and eventually to death. 556 and CDS cytotoxic T cells. 600 13-33 Drugs that block HIV replication lead to a rapid decrease 14-18 Celiac disease has features of both an allergic response in titer of infectious virus and an increase in CD4 T cells. 557 and autoimmunity. 603 13-34 HIV accumulates many mutations in the course of infection, Summary. 605 and drug treatment is soon followed by the outgrowth of Summary to Chapter 14. 606 drug-resistant variants. 559 Questions. 606 13-35 Vaccination against HIV is an attractive solution but General references. 607 poses many difficulties. 560 Section references. 607 13-36 Prevention and education are one way in which the spread of HIV and AIDS can be controlled. 561 Summary. 562 Chapter 15 Autoimmunity and Transplantation 611 Summary to Chapter 13. 562 Questions. 563 The making and breaking of self-tolerance. 611 General references. 564 15-1 A critical function of the immune system is to discriminate Section references. 564 self from nonself. 612 15-2 Multiple tolerance mechanisms normally prevent autoimmunity. 613 Chapter 14 Allergy and Allergic Diseases 571 15-3 Central deletion or inactivation of newly formed lymphocytes is the first checkpoint of self-tolerance. 614 lgE and lgE-mediated allergic diseases. 573 15-4 Lymphocytes that bind self antigens with relatively low 14-1 Sensitization involves class switching to lgE production affinity usually ignore them but in some circumstances become activated. 616 on first contact with an allergen. 573 15-5 Antigens in immunologically privileged sites do not induce 14-2 Allergens are usually delivered transmucosally at low immune attack but can serve as targets. 617 dose, a route that favors lgE production. 575 15-6 Autoreactive T cells that express particular cytokines 14-3 Genetic factors contribute to the development of lgE- may be nonpathogenic or may suppress pathogenic mediated allergic disease. 577 lymphocytes. 619 14-4 Environmental factors may interact with genetic 15-7 Autoimmune responses can be controlled at various susceptibility to cause allergic disease. 579 stages by regulatory T cells. 619 14-5 Regulatory T cells can control allergic responses. 581 Summary. 621 Summary. 582 Autoimmune diseases and pathogenic mechanisms. 622 Effector mechanisms in lgE-mediated allergic reactions. 582 15-8 Specific adaptive immune responses to self antigens 14-6 Most lgE is cell-bound and engages effector mechanisms can cause autoimmune disease. 622 of the immune system by different pathways from those 15-9 Autoimmune diseases can be classified into clusters of other antibody isotypes. 583 that are typically either organ-specific or systemic. 623 14-7 Mast cells reside in tissues and orchestrate allergic 15-10 Multiple components of the immune system are typically reactions. 583 recruited in autoimmune disease. 624
xvili 15-11 hrrcaomnmnedseaeeebcshrohpos9 15-38 The fetus is an allograft that is tolerated repeatedly 15-12 629 1513 ieoctbodesagainbloodcelspromolethet 1514 hetatianotstblhtcdosesofcomplementiocelbs Chapter 16 Manipulation of the Immune Response 669 15-15 g2 632 Treatment of unwanted immune responses. 669 15-16 16-1 farseratsepoweantintammaorydgs ype量 162 se immun on by killing 1517 Tcells s cause direct tissue 671 Summa 838 163 (FK506).an 67 The genetic and environm tbasis ofautoimmunity 16-4 1519 function. 16-5 netc t 640 mmneg8nnvtengneredioreducethei 15-20 16-6 地caohnalanitodsGaneeadtopeamalbgah 674 642 675 15-21 cause autoimmune 167 eactive lymphocyes can treat 643 677 15.22 16-8 lock TNF-orcan alleviate 644 678 15-23 169 Boogcaensncanileecemgratonnaeso 679 64 16-10 Blockadeof ays that activate 15-24 mpn cytes can be usec 680 15.25 1611 e m tory ymphocyt 649 681 15-26 16-12 can lead toanti-sef 681 6 Summary. 682 15-27 Drugs and toxins can cause autoimmune syndromes 6 1528 nts may be required for the initiation o Using the immune response to attack tumors. 682 Summary. 1 6-13 Responses to alloantigens and transplant rejection. 16-14 m as they evolve 684 652 16-15 s can be r cognized by T cells and 15-30 687 16-16 153 691 h 16-17 15-32 16-18 can n ponses 694 15-33 ct with hyperacute Summary 696 657 15-34 nsplantedans is caused by chronic Fighting infectious diseases with vaccination 697 1535 fogansaeenpbneuimeynehea 6-19 material from kild organisms. nuated pathogens 698 16-20 15-3 Ccseaeret 659 699 15-37 67 16-21
� 15-11 Chronic autoimmune disease develops through positive 15-38 T he fetus is an allograft that is tolerated repeatedly. 661 feedback from inflammation, inability to clear the self Summary. 663 antigen, and a broadening of the autoimmune response. 625 15-12 Both antibody and effector T cells can cause tissue Summary to Chapter 15. 663 damage in autoimmune disease. 629 Questions. 664 15-13 Autoantibodies against blood cells promote their Section references. 665 destruction. 631 15-14 The fixation of sublytic doses of complement to cells in tissues stimulates a powerful inflammatory response. 632 Chapter 16 Manipulation of the Immune Response 669 15-15 Autoantibodies against receptors cause disease by Treatment of unwanted immune responses. stimulating or blocking receptor function. 632 669 15-16 Autoantibodies against extracellular antigens cause 16-1 Corticosteroids are powerful anti-inflammatory drugs inflammatory injury by mechanisms akin to type II and that alter the transcription of many genes. 670 type Ill hypersensitivity reactions. 632 16-2 Cytotoxic drugs cause immunosuppression by killing 15-17 T cells specific for self antigens can cause direct tissue dividing cells and have serious side-effects. 671 injury and sustain autoantibody responses. 635 16-3 Cyclosporin A, tacrolimus (FK506), and rapamycin Summary. 638 (sirolimus) are powerful immunosuppressive agents that interfere with T-cell signaling. 671 T he genetic and environmental basis of autoimmunity. 639 16-4 Antibodies against cell-surface molecules can be used to 15-18 Autoimmune diseases have a strong genetic component. 639 eliminate lymphocyte subsets or to inhibit lymphocyte function. 674 15-19 Several approaches have given us insight into the genetic basis of autoimmunity. 640 16-5 Antibodies can be engineered to reduce their 15-20 Many genes that predispose to autoimmunity fall into immunogenicity in humans. 674 categories that affect one or more of the mechanisms of 16-6 Monoclonal antibodies can be used to prevent allograft tolerance. 642 rejection. 675 15-21 A defect in a single gene can cause autoimmune 16-7 Depletion of auto reactive lymphocytes can treat disease. 643 autoimmune disease. 677 15-22 MHC genes have an important role in controlling 16-8 Biologic agents that block TN F-a or IL-1 can alleviate susceptibility to autoimmune disease. 644 autoimmune diseases. 678 15-23 Genetic variants that impair innate immune responses 16-9 Biologic agents can block cell migration to sites of can predispose toT cell-mediated chronic inflammatory inflammation and reduce immune responses. 679 disease. 647 16-10 Blockade of co-stimulatory pathways that activate 15-24 External events can initiate autoimmunity. 648 lymphocytes can be used to treat autoimmune disease. 680 15-25 Infection can lead to autoimmune disease by providing 16-11 Some commonly used drugs have immunomodulatory an environment that promotes lymphocyte activation. 649 properties. 681 15-26 Cross-reactivity between foreign molecules on 16-12 Controlled administration of antigen can be used to pathogens and self molecules can lead to anti-self manipulate the nature of an antigen-specific response. 681 responses and autoimmune disease. 649 Summary. 682 15-27 Drugs and toxins can cause autoimmune syndromes. 651 15-28 Random events may be required for the initiation of Using the immune response to attack tumors. 682 autoimmunity. 651 16-13 T he development of transplantable tumors in mice led Summary. 651 to the discovery of protective immune responses to tumors. 684 Responses to alloantigens and transplant rejection. 652 16-14 Tumors are 'edited' by the immune system as they evolve 15-29 Graft rejection is an immunological response mediated and can escape rejection in many ways. 684 primarily by T cells. 652 16-15 Tumor-specific antigens can be recognized byT cells and 15-30 !ransplant rejection is caused primarily by the strong form the basis of immunotherapies. 687 1mmune response to nonself MHC molecules. 653 16-16 Monoclonal antibodies against tumor antigens, alone or 15-31 In MHC-identical grafts, rejection is caused by peptides from linked to toxins, can control tumor grow1h. 691 other alloantigens bound to graft MHC molecules. 654 16-17 Enhancing the immune response to tumors by vaccination 15-32 There are two ways of presenting alloantigens on the holds promise for cancer prevention and therapy. 693 transplanted donor organ to the recipient's 16-18 Checkpoint blockade can augment immune responses T lymphocytes. 655 to existing tumors. 694 15-33 Antibodies that react with endothelium cause hyperacute Summary. 696 graft rejection. 657 15-34 Late failure of transplanted organs is caused by chronic Fighting infectious diseases with vaccination. 697 injury to the graft. 658 16-19 Vaccines can be based on attenuated pathogens or 15-35 A variety of organs are transplanted routinely in clinical material from killed organisms. 698 medicine. 659 16-20 Most effective vaccines generate antibodies that prevent 15-36 The converse of graft rejection is graft-versus-host the damage caused by toxins or that neutralize the disease. 659 pathogen and stop infection. 699 15-37 Regulatory T cells are involved in alloreactive immune 16-21 Effective vaccines must induce long-lasting protection responses. 661 while being safe and inexpensive. 700