病理學(xué)課件：第四章 炎癥

第四章炎癥概述炎癥的概念具有血管系統(tǒng)的活體組織對各種損傷因子所發(fā)生的一種防御性反應(yīng)。變質(zhì)、滲出和增生血管反應(yīng)是炎癥過程的中心環(huán)節(jié)。Thecomponentsofacuteandchronicinflammatoryresponses:circulatingcellsandproteins,cellsofbloodvessels,andcellsandproteinsoftheextracellularmatrix.Celsus,aRomanwriterofthefirstcenturyAD,firstlistedthefourcardinalsignsofinflammation:rubor,tumor,calor,anddolor(redness,swelling,heat,andpain).Afifthclinicalsign,lossoffunction(functiolaesa),waslateraddedbyVirchow-localmanifestationofinflammationJuliusCohnheim(1839-1884)firstusedthemicroscopetoobserveinflamedbloodvesselsinthin,transparentmembranes.Hewrotedescriptionsofinflammationthatcanhardlybeimprovedon.Inthe1880s,theRussianbiologistElieMetchnikoffdiscoveredtheprocessofphagocytosis.MetchnikoffandPaulEhrlich(whodevelopedthehumoraltheoryofimmunity)sharedtheNobelPrizein1908.SirThomasLewis,who,onthebasisofsimpleexperimentsstudyingtheinflammatoryresponseinskin,establishedtheconceptthatchemicalsubstances,suchashistaminelocallyinducedbyinjury,mediatethevascularchangesofinflammation.

炎癥的原因致炎因子：引起組織和細胞損傷，誘發(fā)炎癥反應(yīng)的因素。物理性因子化學(xué)性因子生物性因子-感染壞死組織變態(tài)反應(yīng)或異常免疫反應(yīng)炎癥的基本病理變化變質(zhì)、滲出和增生早期以變質(zhì)和滲出為主，后期以增生為主。三者相互聯(lián)系變質(zhì)（alteration）炎癥局部組織或細胞發(fā)生變性和壞死。是致炎因子引起的損傷過程常見的變質(zhì)性變化：細胞水腫、脂肪變性、細胞凝固性壞死或液化性壞死-實質(zhì)細胞粘液變性和纖維素樣變性或壞死-間質(zhì)細胞滲出（exudation）炎癥局部組織血管內(nèi)的液體和細胞成分，通過血管壁進入組織間質(zhì)、體腔、體表和粘膜表面的過程。是炎癥最具特征性的變化滲出液和漏出液的區(qū)別在炎癥早期或急性炎癥時表現(xiàn)特別明顯ExudateandtransudateCauseinflammationnon-inflammationGrosscloudyclearGravity>1.018<1.018Protein>30g/L<30g/LCellno.>100/mm3<100/mm3Coagulation+-Mucoprotein+-滲出液與漏出液

蛋白含量>30g/L<30g/L

白細胞數(shù)0.5×109/L0.1×109/L

比重>1.018<1.018Rivalta試驗陽性陰性(漿液粘蛋白定性實驗)

凝固性自凝不自凝透明度混濁澄清滲出的作用稀釋中和毒素白細胞吞噬搬運壞死組織，清除致病因子帶來營養(yǎng)物質(zhì)帶走代謝產(chǎn)物抗體補體消滅病原體纖維素交織成網(wǎng)，限制病原微生物擴散，有利白細胞吞噬，后期成為修復(fù)支架，促進成纖維細胞產(chǎn)生膠原纖維滲出物中病原微生物和毒素隨淋巴液到達淋巴結(jié)，刺激細胞免疫和體液免疫。壓迫、阻塞和粘連、硬化增生（proliferation）炎癥局部組織內(nèi)的細胞增生或再生，使細胞數(shù)目增多。實質(zhì)細胞的增生（上皮、腺體等）間質(zhì)細胞的增生（巨噬細胞、成纖維細胞、血管內(nèi)皮細胞）炎癥的臨床局部表現(xiàn)和全身反應(yīng)局部臨床特征：紅、腫、熱、痛和功能障礙。全身反應(yīng)：細胞因子（IL-1,IL-6,TNF)發(fā)熱末梢血白細胞計數(shù)的變化（類白血病反應(yīng)，核左移）急性期反應(yīng)蛋白（CRP,纖維蛋白原，血清淀粉樣蛋白）合成增多慢波睡眠增加厭食，肌肉蛋白降解加速炎癥分類根據(jù)致炎因子性質(zhì)和機體對損傷刺激的反應(yīng)，分為急性炎癥和慢性炎癥。急性炎癥：反應(yīng)迅速，持續(xù)時間短，以滲出性病變?yōu)橹?，浸潤炎癥細胞以中性粒細胞為主慢性炎癥：持續(xù)時間長，以增殖性病變?yōu)橹鳎櫻装Y細胞以淋巴和單核細胞為主。亞急性炎癥急性炎癥血管反應(yīng)白細胞反應(yīng)炎癥介質(zhì)Themajorlocalmanifestationsofacuteinflammation:(1)vasculardilation;(2)extravasationofplasmafluidandprotein;(3)leukocyteemigrationandaccumulationinthesiteofinjury血管反應(yīng)-血流動力學(xué)變化血流量和血管口徑的改變首先是細動脈短暫收縮；繼而發(fā)生血管擴張、血流加快、此時局部代謝增強、發(fā)紅、發(fā)熱。血流速度減慢，血液粘稠度增加。炎癥早期的血管形態(tài)學(xué)改變血管反應(yīng)-血管通透性增加血管內(nèi)流體靜力壓增高血漿膠體滲透壓下降間質(zhì)膠體滲透壓增加內(nèi)皮細胞的病理變化BloodpressureandplasmacolloidosmoticforcesA,Normalhydrostaticpressure(redarrows)isabout32mmHgatthearterialendofacapillarybedand12mmHgatthevenousend;themeancolloidosmoticpressureoftissuesisapproximately25mmHg(greenarrows),whichisequaltothemeancapillarypressure.B,Acuteinflammation.Arteriolepressureisincreasedto50mmHg,themeancapillarypressureisincreasedbecauseofarteriolardilation,andthevenouspressureincreasestoapproximately30mmHg.Atthesametime,osmoticpressureisreduced(averaging20mmHg)becauseofproteinleakageacrossthevenule.Thenetresultisanexcessofextravasatedfluid.Formationoftransudatesandexudates.A,Normalhydrostaticpressure(bluearrows)isabout32mmHgatthearterialendofacapillarybedand12mmHgatthevenousend;themeancolloidosmoticpressureoftissuesisapproximately25mmHg(greenarrows),whichisequaltothemeancapillarypressure.Therefore,thenetflowoffluidacrossthevascularbedisalmostnil.B,Atransudateisformedwhenfluidleaksoutbecauseofincreasedhydrostaticpressureordecreasedosmoticpressure.C,Anexudateisformedininflammationbecausevascularpermeabilityincreasesasaresultofincreasedinterendothelialspaces.內(nèi)皮的完整性1.內(nèi)皮細胞收縮-毛細血管后靜脈2.內(nèi)皮細胞穿胞作用

細靜脈3.內(nèi)皮細胞損傷脫落

累及所有微循環(huán)血管，包括毛細血管、細動脈和細靜脈炎癥早期白細胞黏附4.新生毛細血管壁的高通透性血管反應(yīng)-血管通透性增加血管通透性增加的作用稀釋毒素帶來營養(yǎng)物質(zhì)，帶走有害物質(zhì)帶來大量抗體、補體用以消滅病原體纖維素有利于吞噬和修復(fù)有利于產(chǎn)生體液和細胞免疫壓迫、阻塞和粘連、硬化淋巴管炎癥環(huán)境中淋巴回流增加炎癥刺激因子擴散淋巴管炎，引流至淋巴結(jié)-反應(yīng)性淋巴結(jié)炎臨床皮膚創(chuàng)口的硬性條索edema,orfluidcollectionwithintissues.Thisexampleofedemawithinflammationisnottrivialatall:thereismarkedlaryngealedemasuchthattheairwayisnarrowed.Thisislife-threatening.Thus,fluidcollectionscanbeseriousdependingupontheirlocation.Hereisanexampleoffluidcollectionintoabodycavity,oraneffusion.Thisisarightpleuraleffusion(inababy).Notetheclear,paleyellowappearanceofthefluid.Thisisaserouseffusion.Seenhereisvasodilationwithexudationthathasledtoanoutpouringoffluidwithfibrinintothealveolarspaces,alongwithPMN's.HereisanexampleofthefibrinmeshinfluidwithPMN'sthathasformedintheareaofacuteinflammation.Itisthisfluidcollectionthatproducesthe"tumor"orswellingaspectofacuteinflammation.Thediagramshownhereillustratestheprocessofexudation,aidedbyendothelialcellcontractionandvasodilation,whichtypicallyismostpronouncedinvenules.Chemicalmediatorsproducingendothelialcontractioninclude:histamine,leukotrienes,bradykinin,plateletactivatingfactor,andtheC3aandC5acomponentsfromcomplementactivation.Mediatorsofthisprocessoveralongertermincludetumornecrosisfactorandinterleukin-1.Chemicalmediatorsthatpromotevasodilationinclude:histamine,prostaglandins,andnitricoxide.急性炎癥中的白細胞反應(yīng)Themajorlocalmanifestationsofacuteinflammation,comparedtonormal.(1)Vasculardilationandincreasedbloodflow(causingerythemaandwarmth),(2)extravasationanddepositionofplasmafluidandproteins(edema),and(3)leukocyteemigrationandaccumulationinthesiteofinjury.HereisanexampleofthefibrinmeshinfluidwithPMN'sthathasformedintheareaofacuteinflammation.Itisthisfluidcollectionthatproducesthe"tumor"orswellingaspectofacuteinflammation.Thisanimationdemonstratestheactionsofneutrophilsintheacuteinflammatoryprocess.白細胞游出的過程白細胞邊集離開血管中心的軸流，到達血管的邊緣，沿著內(nèi)皮細胞表面滾動、附壁。白細胞粘著依靠細胞表面的黏附分子的作用來完成。Themultistepprocessofleukocytemigrationthroughbloodvessels,shownhereforneutrophils.Theleukocytesfirstroll,thenbecomeactivatedandadheretoendothelium,thentransmigrateacrosstheendothelium,piercethebasementmembrane,andmigratetowardchemoattractantsemanatingfromthesourceofinjury.Differentmoleculesplaypredominantrolesindifferentstepsofthisprocess-selectinsinrolling;chemokinesinactivatingtheneutrophilstoincreaseavidityofintegrins(ingreen);integrinsinfirmadhesion;andCD31(PECAM-1)intransmigration.白細胞游出阿米巴運動的形式早期以中性粒細胞為主，此后是單核細胞。根據(jù)致炎因子的不同，分別以中性粒細胞、淋巴細胞和嗜酸性粒細胞為主。Regulationofendothelialandleukocyteadhesionmolecules內(nèi)皮的活化白細胞在內(nèi)皮細胞上的滾動Increasedbindingavidityofintegrins整合素（Integrins）為跨膜異二聚體糖蛋白，由α與β亞單位組成，表達于多種細胞表面，與配體結(jié)合介導(dǎo)白細胞與內(nèi)皮細胞，白細胞之間，以及白細胞與基質(zhì)之間粘附。白細胞與內(nèi)皮的粘附是由整合素與免疫球蛋白超家族分子（ICAM-1、VCAM-1)介導(dǎo)的。β2integrinsLFA-1、Mac-1(CD11a/CD18、CD11b/CD18)結(jié)合ICAM-1,β1integrins(VLA-4)結(jié)合VCAM-1.白細胞附壁白細胞游出白細胞游出是炎癥反應(yīng)最重要的指征Schematicandhistologicsequenceofeventsfollowingacuteinjury.Forsakeofsimplicity,edemaisshownasanacutetransientresponse,althoughsecondarywavesofdelayededemaandneutrophilinfiltrationcanalsooccur.趨化作用和趨化因子白細胞游出是炎癥反應(yīng)最重要的指征趨化作用和趨化因子趨化作用（chemotaxis）是指白細胞向化學(xué)刺激物作定向移動。這些化學(xué)刺激物稱為趨化因子。趨化因子外源性可溶性細菌產(chǎn)物，特別是含有N-甲酰基蛋氨酸末端氨基酸的多肽內(nèi)源性(1)補體成分尤其是C5a(2)白細胞三烯B4(LTB4)(3)細胞因子(如IL-8)趨化因子的作用吸附具有特異性，和細胞受體結(jié)合引起生化反應(yīng)，細胞內(nèi)微絲、微管收縮，細胞移動Seenhereisvasodilationwithexudationthathasledtoanoutpouringoffluidwithfibrinintothealveolarspaces,alongwithPMN's.Asintheprecedingdiagram,herePMN'sthataremarginatedalongthedilatedvenulewall(arrow)aresqueezingthroughthebasementmembrane(theprocessofdiapedesis)andspillingoutintoextravascularspace.白細胞活化白細胞活化相關(guān)的表面受體Toll樣受體(TLRs),10種哺乳類TLRs，識別細菌脂多糖，蛋白多糖，脂類，病毒雙鏈RNA。G蛋白耦連受體，識別含有N-甲酰甲硫氨酸的細菌短肽。細胞因子受體，感染后產(chǎn)生，通過與白細胞表面受體結(jié)合激活白細胞。最為重要的是IFN-γ，激活巨噬細胞。

調(diào)理素受體，包裹微生物，增強吞噬細胞吞噬功能的蛋白質(zhì)，抗體IgGFc段，補體C3b,凝集素。白細胞活化通過磷脂酶A2和鈣離子濃度升高促進花生四烯酸代謝產(chǎn)物產(chǎn)生。脫顆粒和釋放溶酶體酶，活性氧產(chǎn)生。釋放細胞因子，主要從活化的巨噬細胞產(chǎn)生，促進炎癥反應(yīng)。調(diào)節(jié)粘附分子。白細胞在局部的作用吞噬和免疫吞噬作用是指白細胞游出到炎癥灶，吞噬病原體以及組織碎片的過程。主要由嗜中性粒細胞和巨噬細胞完成吞噬過程識別與附著吞入，形成吞噬溶酶體殺傷或降解依賴氧殺菌機制不依賴氧殺菌機制A,Phagocytosisofaparticle(e.g.,bacterium)involvesattachmentandbindingofFcandC3btoreceptorsontheleukocytemembrane,engulfment,andfusionoflysosomeswithphagocyticvacuoles,followedbydestructionofingestedparticleswithinthephagolysosomes.Notethatduringphagocytosis,granulecontentsmaybereleasedintoextracellulartissues.Productionofmicrobicidalreactiveoxygenintermediateswithinphagocyticvesicles.非氧依賴途徑溶酶體內(nèi)細菌通透性增加蛋白-激活磷脂酶降解細胞膜磷脂溶菌酶水解細菌糖肽外衣白細胞特異性顆粒中乳鐵蛋白，吞噬酸性粒細胞主要堿性蛋白-寄生蟲防御素Eventsintheresolutionofinflammation:(1)returntonormalvascularpermeability;(2)drainageofedemafluidandproteinsintolymphaticsor(3)bypinocytosisintomacrophages;(4)phagocytosisofapoptoticneutrophilsand(5)phagocytosisofnecroticdebris;and(6)disposalofmacrophages.Macrophagesalsoproducegrowthfactorsthatinitiatethesubsequentprocessofrepair.Notethecentralroleofmacrophagesinresolution.免疫作用主要有巨噬細胞、淋巴細胞和漿細胞。呈遞抗原產(chǎn)生淋巴因子和抗體抗感染組織損傷作用白細胞活化過程中將產(chǎn)物釋放到細胞外間質(zhì)釋放溶酶體酶、活性氧自由基、前列腺素和白細胞三烯，NETs(neutrophilextracellulartraps)等。引起內(nèi)皮細胞和組織損傷造成組織溶解和破壞NETs組織損傷作用-白細胞釋放機制溶酶體酶釋放：吞噬溶酶體完全封閉前與外界相通不能被吞噬的物質(zhì)引起白細胞胞膜運動表面吞噬作用吞噬的物質(zhì)本身溶解溶酶體膜中性粒細胞脫顆粒白細胞功能缺陷粘附缺陷吞噬溶酶體形成缺陷殺菌活性障礙骨髓白細胞生成障礙白細胞激活障礙導(dǎo)致嚴(yán)重反復(fù)的感染各種炎癥細胞的作用中性粒細胞：急性炎癥早期和化膿性炎單核細胞巨噬細胞：急性炎癥后期、慢性炎癥尤其是肉芽腫性炎癥，某些特殊微生物感染淋巴細胞：T淋巴細胞識別巨噬細胞傳遞的抗原，釋放淋巴因子，產(chǎn)生細胞免疫。B淋巴細胞轉(zhuǎn)化成漿細胞產(chǎn)生多種抗體，參與體液免疫。嗜酸性粒細胞：變態(tài)反應(yīng)、寄生蟲感染Acuteinflammationismarkedbyanincreaseininflammatorycells.Perhapsthesimplestindicatorofacuteinflammationisanincreaseinthewhitebloodcellcountintheperiphealblood,heremarkedbyanincreaseinsegmentedneutrophils(PMN's).Followingengulfment,thebacteriumiscontainedwithinaphagosome,andlysosomalgranulesfusewithit,releasingtheircontentstoformthephagolysosomeseenhere.RapidactivationofNADPHoxidaseleadstogenerationofsuperoxidethatisconvertedtohydrogenperoxidebyspontaneousdismutation.Alongwithmyeloperoxidasefromtheneutrophilazurophilicgranulesandhalideion,hydrogenperoxideisconvertedtoHOCLthatdestroysthebacteriumbyhalogenation.Theredbloodcellsherearenormal,happyRBC's.Theyhaveazoneofcentralpallorabout1/3thesizeoftheRBC.TheRBC'sdemonstrateminimalvariationinsize(anisocytosis)andshape(poikilocytosis).Afewsmallfuzzyblueplateletsareseen.Inthecenterofthefieldareabandneutrophilontheleftandasegmentedneutrophilontheright.Ultrastructureandcontentsofneutrophilgranules,stainedforperoxidaseactivity.Thelargeperoxidase-containinggranulesaretheazurophilgranules;thesmallerperoxidase-negativeonesarethespecificgranules(SG).N,portionofnucleus;BPI,bactericidalpermeabilityincreasingprotein.Maturationofmononuclearphagocytes.Hereisamonocyte.Itisslightlylargerthanalymphocyteandhasafoldednucleus.Monocytescanmigrateoutofthebloodstreamandbecometissuemacrophagesundertheinfluenceofcytokines.NotethemanysmallsmudgyblueplateletsbetweentheRBC's.Inthecenterofthefieldisaneosinophilwithabilobednucleusandnumerousreddishgranulesinthecytoplasm.Justunderneathitisasmalllymphocyte.Eosinophilscanincreasewithallergicreactionsandwithparasiticinfestations.AnormalmaturelymphocyteisseenontheleftcomparedtoasegmentedPMNontheright.AnRBCisseentobeabout2/3thesizeofanormallymphocyte.Athighermagnification,earlyabscessingpneumoniaisshown.Alveolarwallsarenotclearlyseen,onlysheetsofneutrophils.Ofcourse,inflammatoryreactionsarenotneatlycategorizedbycelltype.Avarietyofinflammatorycelltypesmaybepresent,thoughonemaypredominate.Afocusofinflammationshowingnumerouseosinophils.

Amononuclearinflammatorycellinfiltrateextendsfromportalareasanddisruptsthelimitingplateofhepatocyteswhichareundergoingnecrosis,theso-called"piecemeal"necrosisofchronicactivehepatitis.HistopathologyofalymphnodeinacaseofTyphoidFever.Identifythesegmentedneutrophil,bandneutrophil,lymphocyte,monocyte,eosinophil,basophil,andplateletintheimagebelow:DisordersCellsandMoleculesInvolvedinInjuryAcuteAcuterespiratorydistresssyndromeNeutrophilsAcutetransplantrejectionLymphocytes;antibodiesandcomplementAsthmaEosinophils;IgEantibodiesGlomerulonephritisAntibodiesandcomplement;neutrophils,monocytesSepticshockCytokinesVasculitisAntibodiesandcomplement;neutrophilsChronicArthritisLymphocytes,macrophages;antibodiesAsthmaEosinophils,otherleukocytes;IgEantibodiesAtherosclerosisMacrophages;lymphocytes?ChronictransplantrejectionLymphocytes;cytokinesPulmonaryfibrosisMacrophages;fibroblasts炎癥介質(zhì)在炎癥過程中的作用炎癥介質(zhì)（inflammatorymediator)的概念一系列介導(dǎo)炎癥反應(yīng)的化學(xué)因子來自血漿(主要在肝臟合成，前體形式存在，蛋白酶水解激活）和細胞（胞內(nèi)顆粒儲存，需要時釋放或刺激下即刻合成）通過靶細胞表面特異性抗體發(fā)揮作用，或本身具有酶活性或氧化損傷可刺激產(chǎn)生次級炎癥介質(zhì)可作用于一種或多種靶細胞，產(chǎn)生不同作用半衰期短，很快降解滅活或被拮抗因子抑制，清除大多數(shù)對正常組織具有潛在危害Chemicalmediatorsofinflammation.EC,endothelialcells.細胞釋放的炎癥介質(zhì)血管活性胺包括組胺和5－羥色胺，又稱血清素。組胺主要存在于肥大細胞中，使細動脈擴張和細靜脈通透性增加。5－HT主要存在于血小板和腸嗜鉻細胞，作用與組胺類似。Aflatspreadofomentumshowingmastcellsaroundbloodvesselsandintheinterstitialtissue.Stainedwithmetachromaticstaintoidentifythemastcellgranules(darkblueorpurple).Theredstructuresarefatglobulesstainedwithfatstain.花生四烯酸代謝產(chǎn)物，包括前列腺素（PG）、白細胞三烯（LT）和脂質(zhì)素(lipoxins)使炎癥時血管擴張、水腫加劇，引起發(fā)熱和疼痛；血管收縮、支氣管痙攣以及血管通透性增加。脂質(zhì)素炎癥抑制因子臨床上的對癥治療的靶點細胞釋放的炎癥介質(zhì)Generationofarachidonicacidmetabolitesandtheirrolesininflammation.Themoleculartargetsofactionofsomeanti-inflammatorydrugsareindicatedbyaredX.COX,cyclooxygenase;HETE,hydroxyeicosatetraenoicacid;HPETE,hydroperoxyeicosatetraenoicacid.Biosynthesisofleukotrienesandlipoxinsbycell-cellinteraction.ActivatedneutrophilsgenerateLTB4fromarachidonicacid-derivedLTA4bytheactionof5-lipoxygenase,buttheydonotpossessLTC4-synthaseactivityandconsequentlydonotproduceLTC4.Incontrast,plateletscannotformLTC4fromendogenoussubstrates,buttheycangenerateLTC4andlipoxinsfromneutrophil-derivedLTA4.TheNobelPrizeinPhysiologyorMedicine1982"fortheirdiscoveriesconcerningprostaglandinsandrelatedbiologicallyactivesubstances".SuneK.Bergstr?mBengtI.SamuelssonJohnR.Vane主要來自嗜中性粒細胞和單核細胞。活性氧代謝產(chǎn)物，與NO結(jié)合，影響炎癥反應(yīng)，損傷組織。溶酶體成分，促發(fā)炎癥，組織破壞，直接降解C3和C5。細胞釋放的炎癥介質(zhì)-白細胞產(chǎn)物主要由激活的淋巴細胞和單核巨噬細胞產(chǎn)生。調(diào)節(jié)淋巴細胞調(diào)節(jié)自然免疫激活巨噬細胞對不同炎癥細胞有趨化作用刺激造血，調(diào)節(jié)白細胞生長、分化細胞釋放的炎癥介質(zhì)-細胞因子和化學(xué)趨化因子Majoreffectsofinterleukin-1(IL-1)andtumornecrosisfactor(TNF)ininflammation.細胞因子引起巨噬細胞的活化IL-1/TNF在炎癥中的作用血小板激活因子(PAF)來源于多種細胞，參與多方面炎癥過程。影響血流動力學(xué)改變增加血管通透性促使白細胞與內(nèi)皮細胞粘著影響趨化作用促使白細胞脫顆粒一氧化氮(NO)由內(nèi)皮細胞、巨噬細胞和一些特定神經(jīng)細胞產(chǎn)生。作用于血管平滑肌，使血管擴張抑制血小板粘著和聚集抑制肥大細胞引起的炎癥反應(yīng)調(diào)節(jié)、控制白細胞向炎癥灶的集中減少微生物復(fù)制、導(dǎo)致組織的損傷神經(jīng)肽：P物質(zhì)，增加血管通透性Functionsofnitricoxide(NO)inbloodvesselsandmacrophages,producedbytwoNOsynthaseenzymes.NOcausesvasodilation,andNOfreeradicalsaretoxictomicrobialandmammaliancells.NOS,nitricoxidesynthase.MediatorSourcePrincipalActionsCell-DerivedHistamineMastcells,basophils,plateletsVasodilation,increasedvascularpermeability,endothelialactivationSerotoninPlateletsVasodilation,increasedvascularpermeabilityProstaglandinsMastcells,leukocytesVasodilation,pain,feverLeukotrienesMastcells,leukocytesIncreasedvascularpermeability,chemotaxis,leukocyteadhesionandactivationPlatelet-activatingfactorLeukocytes,endothelialcellsVasodilation,increasedvascularpermeability,leukocyteadhesion,chemotaxis,degranulation,oxidativeburstReactiveoxygenspeciesLeukocytesKillingofmicrobes,tissuedamageNitricoxideEndothelium,macrophagesVascularsmoothmusclerelaxation;killingofmicrobesCytokines(e.g.TNF,IL-1)Macrophages,lymphocytes,endothelialcells,mastcellsLocalendothelialactivation(expressionofadhesionmolecules),systemicacute-phaseresponse;insevereinfections,septicshockChemokinesLeukocytes,activatedmacrophagesChemotaxis,leukocyteactivation體液中的炎癥介質(zhì)激肽系統(tǒng)（kininsystem）補體系統(tǒng)（complementsystem)凝血和纖溶系統(tǒng)（coagulationandfibrinolyticsystem)激肽系統(tǒng)（kininsystem）最終產(chǎn)物是緩激肽，增加血管的通透性皮下注射可引起血管擴張、平滑肌收縮、引起疼痛作用時間短暫，易被激肽酶滅活Vascularleakageinducedbychemicalmediators.A,Thisisafixedandclearedpreparationofaratcremastermuscleexaminedunstainedbytransillumination.Onehourbeforesacrifice,bradykininwasinjectedoverthismuscle,andcolloidalcarbonwasgivenintravenously.Plasma,loadedwithcarbon,escaped,butmostofthecarbonparticleswereretainedbythebasementmembraneoftheleakingvessels,withtheresultthatthesebecame"labeled"black.Notethatnotallthevesselsleak-onlythevenules.InB,ahigherpower,thecapillarynetworkisfaintlyvisibleinthebackground.補體系統(tǒng)由20種蛋白質(zhì)組成是機體抵抗病原微生物的重要因子增加血管通透性、促使化學(xué)趨化作用和調(diào)理素化作用C3a和C5a具有引起血管擴張、增加血管通透性的影響C3b調(diào)理素化作用Theactivationandfunctionsofthecomplementsystem.ActivationofcomplementbydifferentpathwaysleadstocleavageofC3.ThefunctionsofthecomplementsystemaremediatedbybreakdownproductsofC3andothercomplementproteins,andbythemembraneattackcomplex(MAC).補體系統(tǒng)的活化可分為早期和晚期兩個階段。早期階段由經(jīng)典、替代，凝集素途徑三條通路導(dǎo)致C3蛋白水解。

晚期階段為活化C3后導(dǎo)致的其他補體系統(tǒng)成分活化。C3激活為最重要一步。

TheEarlyStepsofComplementActivationTheclassicalpathwayistriggeredbyfixationofC1toantibody(IgMorIgG)thathascombinedwithantigen,andproteolysisofC2andC4,andsubsequentformationofaC4b2bcomplexthatfunctionsasaC3convertase.Thealternativepathwaycanbetriggeredbymicrobialsurfacemolecules(e.g.,endotoxin,orLPS),complexpolysaccharides,andcobravenom.Itinvolvesadistinctsetofplasmacomponents(properdin,andfactorsBandD).Inthispathway,thespontaneouscleavageofC3thatoccursnormallyisenhancedandstabilizedbyacomplexofC3bandabreakdownproductofFactorBcalledBb;theC3bBbcomplexisaC3convertase.Inthelectinpathway,mannose-bindinglectin,aplasmacollectin,bindstocarbohydrate-containingproteinsonbacteriaandvirusesanddirectlyactivatesC1;theremainingstepsareasintheclassicalpathway.TheC3convertasesbreakdownC3intoC3b,whichremainsattachedtothesurfacewherecomplementisactivated,andasmallerC3afragmentthatdiffusesaway.經(jīng)典激活途徑替代激活途徑MBL途徑激活物質(zhì)抗原抗體復(fù)合物肽聚糖、酵母多糖、脂多糖MBL相關(guān)的絲氨酸蛋白酶起始分子C1qC3C2、C4參與補體成分C1、C4、C2、C3、C5-C9C3、C5-C9、B因子、D因子C2-C9、MASP所需離子Ca2+、Mg2+Mg2+Ca2+C3轉(zhuǎn)化酶C4b2bC3bBbC4b2bC5轉(zhuǎn)化酶C4b2b3bC3bnBbC4b2b3b生物學(xué)作用參與特異性免疫的效應(yīng)階段,感染后期發(fā)揮作用參與非特異性免疫的效應(yīng)階段,感染早期發(fā)揮作用參與非特異性免疫的效應(yīng)階段,感染早期發(fā)揮作用三種途徑比較TheLateStepsofComplementActivationTheC3bthatisgeneratedbyanyofthepathwaysbindstotheC3convertaseandproducesaC5convertase,whichcleavesC5.C5bremainsattachedtothecomplexandformsasubstrateforthesubsequentbindingoftheC6-C9components.PolymerizedC9formsachannelinlipidmembranes,calledthemembraneattackcomplex,whichallowsfluidandionstoenterandcausescelllysis.補體含量和活性相關(guān)的疾病1．免疫相關(guān)性疾?。喝缱陨砻庖咝约膊r，C1、C2、C3、C4和Hf等缺陷；超敏反應(yīng)時（III型超敏反應(yīng)），C3a、C5a等過敏毒素的產(chǎn)生。2．與補體有關(guān)的遺傳性疾病：

①C2、C3缺陷導(dǎo)致的嚴(yán)重感染；

②與C1抑制物缺陷相關(guān)的遺傳性血管神經(jīng)性水腫

③SLE患者出現(xiàn)的細胞表面CR1缺陷與C1C清除障礙

④涉及I因子、H因子缺陷的腎小球腎炎；

⑤DAF缺陷引起的陣發(fā)性血紅蛋白尿；

⑥C1q缺陷表現(xiàn)的嚴(yán)重頑固性皮膚損害，以及C1q、C1r、C4、C2缺陷造成的免疫復(fù)合物性血管炎（包括腎炎）等。(圖)血管神經(jīng)性水腫凝血系統(tǒng)和纖溶系統(tǒng)中心因子為XII因子促使白細胞粘著和成纖維細胞增生血管通透性增高白細胞的趨化因子促進白細胞滲出PlasmaProtein-DerivedComplementPlasma(producedinliver)Leukocytechemotaxisandactivation,opsonization,vasodilation(mastcellstimulation)KininsPlasma(producedinliver)Increasedvascularpermeability,smoothmusclecontraction,vasodilation,painProteasesactivatedduringcoagulationPlasma(producedinliver)Endothelialactivation,leukocyterecruitment炎癥介質(zhì)的相互作用不同介質(zhì)系統(tǒng)相互之間有著密切的聯(lián)系幾乎所有介質(zhì)均處于靈敏的調(diào)控和平衡體系中InterrelationshipsbetweenthefourplasmamediatorsystemstriggeredbyactivationoffactorXII(Hagemanfactor).Notethatthrombininducesinflammationbybindingtoprotease-activatedreceptors(principallyPAR-1)onplatelets,endothelium,smoothmusclecells,andothercells.VasodilationProstaglandins

Histamine，NOIncreasedvascularpermeabilityHistamineandserotonin

C3aandC5a(byliberatingvasoactiveaminesfrommastcells,othercells)

Bradykinin

LeukotrienesC4,D4,E4

PAF

SubstancePLeukocyterecruitmentandactivationTNF,IL-1

Chemokines

C3a,C5a

LeukotrieneB4

(Bacterialproducts,e.g.,N-formylmethylpeptides)FeverIL-1,TNF

ProstaglandinsPainProstaglandins

Bradykinin

NeuropeptidesTissuedamageLysosomalenzymesofleukocytes

Reactiveoxygenspecies,NO急性炎癥的類型漿液性炎纖維素性炎化膿性炎出血性炎漿液性炎漿液滲出，以血漿成分為主，常發(fā)生于粘膜、漿膜和疏松結(jié)締組織。漿液滲出為主

(滲出的蛋白以小分子白蛋白為主)

伴少量纖維蛋白，和炎癥細胞血管壁損傷輕少量滲出可完全吸收，不留痕跡大量滲出，引起壓迫和水腫（喉頭水腫，胸膜和心包積液）卡他(catarrh)：滲出物或分泌物沿粘膜表面順勢下流Hereisanexampleoffluidcollectionintoabodycavity,oraneffusion.Thisisarightpleuraleffusion(inababy).Notetheclear,paleyellowappearanceofthefluid.Thisisaserouseffusion.Serousinflammation.Low-powerviewofacross-sectionofaskinblistershowingtheepidermisseparatedfromthedermisbyafocalcollectionofserouseffusion.纖維素性炎以纖維蛋白滲出為主，繼而形成纖維素。血管壁損傷較重易發(fā)生于粘膜、漿膜和肺組織。（1）發(fā)生在粘膜面的纖維蛋白性炎癥

假膜性炎假膜：纖維蛋白、中性粒細胞、壞死粘膜上皮、病原微生物

白喉-咽部偽膜不易脫落-固膜性炎 -氣管偽膜容易脫落-浮膜性炎

（2）發(fā)生在漿膜面的纖維蛋白性炎癥絨毛心：發(fā)生于心外膜的纖維蛋白性炎

大葉性肺炎

滲出的纖維素被纖維蛋白溶解酶水解，吞噬細胞清除。機化引起纖維素性粘連纖維素滲出過多中性粒細胞滲出過少組織內(nèi)抗胰蛋白酶過多Thisyellow-greenexudateonthesurfaceofaninflamed,hyperemicbowelmucosaconsistsofmanyneutrophilsalongwithfibrinandamorphousdebrisfromdyingcells.Membraneofdiphtherialyingwithinatransversebronchus(A)andformingaperfectcast(removedfromthelung)ofthebranchingrespiratorytree(B).Fibrinouspericarditis.-Depositsoffibrinonthepericardium.Fibrinouspericarditis：pinkmeshworkoffibrinexudate(F)overliesthepericardialsurface(P).Exudationofaprotein-richfluidintoacavityleadstoatransudate.Thefibrininthisfluidcanformafibrinousexudateonthesurfaces.Here,thepericardialcavityhasbeenopenedtorevealafibrinouspericarditiswithstrandsofstringypalefibrinbetweenvisceralandparietalpericardium.Microscopically,thefibrinousexudateisseentoconsistofpinkstrandsoffibrinjuttingfromthepericardialsurfaceattheupperleft.Belowthis,thereareafewscatteredinflammatorycells.化膿性炎以嗜中性粒細胞滲出為主，有不同程度的組織壞死和膿液形成。壞死的中性粒細胞稱為膿細胞。表面化膿和積膿(empyema)蜂窩織炎(phlegmonousinflammation)膿腫（abscess）表面化膿和積膿(empyema)表面化膿是指粘膜組織的化膿性炎僅累及粘膜層膿性滲出物不能排出，聚集在輸卵管或膽囊內(nèi)或胸腹腔內(nèi)，稱積膿。Hereisapurulentexudateinwhichtheexudedfluidalsocontainsalargenumberofacuteinflammatorycells.Thus,theyellowishfluidinthisopenedpericardialcavityisapurulentexudate.ApurulentexudateisseenbeneaththemeningesinthebrainofthispatientwithacutemeningitisfromStreptococcuspneumoniaeinfection.Theexudateobscuresthesulci.Suppurativemeningitis

(subarachnoidempyema)Theabdominalcavityisopenedatautopsyheretorevealanextensivepurulentperitonitisthatresultedfromruptureofthecolon.Athickyellowexudatecoatstheperitonealsurfaces.Aparacentesisyieldedfluidwiththepropertiesofanexudate:highproteincontentwithmanycells(mostlyPMN's).蜂窩織炎(phlegmonousinflammation)

彌漫性化膿性炎主要由溶血性鏈球菌引起透明質(zhì)酸酶、鏈激酶大量中性粒細胞彌漫浸潤與正常組織分界不清，壞死不明顯常見于疏松組織:皮下、肌肉、闌尾AcutephlegmonousappendicitisAcutephlegmonousappendicitis膿腫(abscess):局限性化膿伴膿腔形成病灶局限主要由金葡菌引起

血漿凝固酶-局限病變

層粘連蛋白受體-遷徙性膿腫膿腔內(nèi)有膿液早期壁薄不規(guī)則，后期壁厚為大量肉芽組織AbscessofSkinFuruncle：thelocalizedsuppurativeinflammationofhaircyst,sebaceousgland&surroundingtissues.Carbuncle：Fusionofquiteafewfuruncles.CausedbyStaphylococciSuppurativeinflammation.A,Asubcutaneousbacterialabscesswithcollectionsofpus.B,Theabscesscontainsneutrophils,edemafluid,andcellulardebris.Purulentinflammation.A,Multiplebacterialabscessesinthelung(arrows)inacaseofbronchopneumonia.B,Theabscesscontainsneutrophilsandcellulardebris,andissurroundedbycongestedbloodvessels.Extensiveacuteinflammationmayleadtoabscessformation,asseenherewithroundedabscesses(thepurulentmaterialhasdrainedoutaftersectioningtoleaveacavity)inupperlobeandlowerlobe.Thewhitearrowsmarkareasofabscessformationintheupperlobeofthislung.Theliquefactivenecrosisofanabscessisapparent,becausethepurulentcontentsaredrainingouttoleaveacavity.Onachestradiograph,theliquefiedcentralcontentsofanabscesscanappearasan"air-fluidlevel".Abscessofliver

AbscessofcerebrumAnabscessisalocalizedcollectionofPMN's.Hereisamicroabscessinthemyocardium.Theirregulardarkpurplecenterisacollectionofbacteriathatarethecauseforthisabscess.theabscesshasamixtureofinflammatorycells,butthewalloftheabscessis"organizing"withingrowthofcapillariesandfibroblasts.潰瘍皮膚或黏膜的炎癥，伴有表面組織的壞死脫落。中性粒細胞浸潤急慢性炎癥均可發(fā)生。Themorphologyofanulcer.A,Achronicduodenalulcer.B,Low-powercross-sectionofaduodenalulcercraterwithanacuteinflammatoryexudateinthebase.出血性炎血管損傷嚴(yán)重，滲出物以大量紅細胞為主。常見于流行性出血熱、鉤端螺旋體病和鼠疫等急性傳