病理学课件：第四章 炎症

第四章炎症概述炎症的概念具有血管系统的活体组织对各种损伤因子所发生的一种防御性反应。变质、渗出和增生血管反应是炎症过程的中心环节。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.

炎症的原因致炎因子：引起组织和细胞损伤，诱发炎症反应的因素。物理性因子化学性因子生物性因子-感染坏死组织变态反应或异常免疫反应炎症的基本病理变化变质、渗出和增生早期以变质和渗出为主，后期以增生为主。三者相互联系变质（alteration）炎症局部组织或细胞发生变性和坏死。是致炎因子引起的损伤过程常见的变质性变化：细胞水肿、脂肪变性、细胞凝固性坏死或液化性坏死-实质细胞粘液变性和纤维素样变性或坏死-间质细胞渗出（exudation）炎症局部组织血管内的液体和细胞成分，通过血管壁进入组织间质、体腔、体表和粘膜表面的过程。是炎症最具特征性的变化渗出液和漏出液的区别在炎症早期或急性炎症时表现特别明显ExudateandtransudateCauseinflammationnon-inflammationGrosscloudyclearGravity>1.018<1.018Protein>30g/L<30g/LCellno.>100/mm3<100/mm3Coagulation+-Mucoprotein+-渗出液与漏出液

蛋白含量>30g/L<30g/L

白细胞数0.5×109/L0.1×109/L

比重>1.018<1.018Rivalta试验阳性阴性(浆液粘蛋白定性实验)

凝固性自凝不自凝透明度混浊澄清渗出的作用稀释中和毒素白细胞吞噬搬运坏死组织，清除致病因子带来营养物质带走代谢产物抗体补体消灭病原体纤维素交织成网，限制病原微生物扩散，有利白细胞吞噬，后期成为修复支架，促进成纤维细胞产生胶原纤维渗出物中病原微生物和毒素随淋巴液到达淋巴结，刺激细胞免疫和体液免疫。压迫、阻塞和粘连、硬化增生（proliferation）炎症局部组织内的细胞增生或再生，使细胞数目增多。实质细胞的增生（上皮、腺体等）间质细胞的增生（巨噬细胞、成纤维细胞、血管内皮细胞）炎症的临床局部表现和全身反应局部临床特征：红、肿、热、痛和功能障碍。全身反应：细胞因子（IL-1,IL-6,TNF)发热末梢血白细胞计数的变化（类白血病反应，核左移）急性期反应蛋白（CRP,纤维蛋白原，血清淀粉样蛋白）合成增多慢波睡眠增加厌食，肌肉蛋白降解加速炎症分类根据致炎因子性质和机体对损伤刺激的反应，分为急性炎症和慢性炎症。急性炎症：反应迅速，持续时间短，以渗出性病变为主，浸润炎症细胞以中性粒细胞为主慢性炎症：持续时间长，以增殖性病变为主，浸润炎症细胞以淋巴和单核细胞为主。亚急性炎症急性炎症血管反应白细胞反应炎症介质Themajorlocalmanifestationsofacuteinflammation:(1)vasculardilation;(2)extravasationofplasmafluidandprotein;(3)leukocyteemigrationandaccumulationinthesiteofinjury血管反应-血流动力学变化血流量和血管口径的改变首先是细动脉短暂收缩；继而发生血管扩张、血流加快、此时局部代谢增强、发红、发热。血流速度减慢，血液粘稠度增加。炎症早期的血管形态学改变血管反应-血管通透性增加血管内流体静力压增高血浆胶体渗透压下降间质胶体渗透压增加内皮细胞的病理变化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.内皮的完整性1.内皮细胞收缩-毛细血管后静脉2.内皮细胞穿胞作用

细静脉3.内皮细胞损伤脱落

累及所有微循环血管，包括毛细血管、细动脉和细静脉炎症早期白细胞黏附4.新生毛细血管壁的高通透性血管反应-血管通透性增加血管通透性增加的作用稀释毒素带来营养物质，带走有害物质带来大量抗体、补体用以消灭病原体纤维素有利于吞噬和修复有利于产生体液和细胞免疫压迫、阻塞和粘连、硬化淋巴管炎症环境中淋巴回流增加炎症刺激因子扩散淋巴管炎，引流至淋巴结-反应性淋巴结炎临床皮肤创口的硬性条索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.急性炎症中的白细胞反应Themajorlocalmanifestationsofacuteinflammation,comparedtonormal.(1)Vasculardilationandincreasedbloodflow(causingerythemaandwarmth),(2)extravasationanddepositionofplasmafluidandproteins(edema),and(3)leukocyteemigrationandaccumulationinthesiteofinjury.HereisanexampleofthefibrinmeshinfluidwithPMN'sthathasformedintheareaofacuteinflammation.Itisthisfluidcollectionthatproducesthe"tumor"orswellingaspectofacuteinflammation.Thisanimationdemonstratestheactionsofneutrophilsintheacuteinflammatoryprocess.白细胞游出的过程白细胞边集离开血管中心的轴流，到达血管的边缘，沿着内皮细胞表面滚动、附壁。白细胞粘着依靠细胞表面的黏附分子的作用来完成。Themultistepprocessofleukocytemigrationthroughbloodvessels,shownhereforneutrophils.Theleukocytesfirstroll,thenbecomeactivatedandadheretoendothelium,thentransmigrateacrosstheendothelium,piercethebasementmembrane,andmigratetowardchemoattractantsemanatingfromthesourceofinjury.Differentmoleculesplaypredominantrolesindifferentstepsofthisprocess-selectinsinrolling;chemokinesinactivatingtheneutrophilstoincreaseavidityofintegrins(ingreen);integrinsinfirmadhesion;andCD31(PECAM-1)intransmigration.白细胞游出阿米巴运动的形式早期以中性粒细胞为主，此后是单核细胞。根据致炎因子的不同，分别以中性粒细胞、淋巴细胞和嗜酸性粒细胞为主。Regulationofendothelialandleukocyteadhesionmolecules内皮的活化白细胞在内皮细胞上的滚动Increasedbindingavidityofintegrins整合素（Integrins）为跨膜异二聚体糖蛋白，由α与β亚单位组成，表达于多种细胞表面，与配体结合介导白细胞与内皮细胞，白细胞之间，以及白细胞与基质之间粘附。白细胞与内皮的粘附是由整合素与免疫球蛋白超家族分子（ICAM-1、VCAM-1)介导的。β2integrinsLFA-1、Mac-1(CD11a/CD18、CD11b/CD18)结合ICAM-1,β1integrins(VLA-4)结合VCAM-1.白细胞附壁白细胞游出白细胞游出是炎症反应最重要的指征Schematicandhistologicsequenceofeventsfollowingacuteinjury.Forsakeofsimplicity,edemaisshownasanacutetransientresponse,althoughsecondarywavesofdelayededemaandneutrophilinfiltrationcanalsooccur.趋化作用和趋化因子白细胞游出是炎症反应最重要的指征趋化作用和趋化因子趋化作用（chemotaxis）是指白细胞向化学刺激物作定向移动。这些化学刺激物称为趋化因子。趋化因子外源性可溶性细菌产物，特别是含有N-甲酰基蛋氨酸末端氨基酸的多肽内源性(1)补体成分尤其是C5a(2)白细胞三烯B4(LTB4)(3)细胞因子(如IL-8)趋化因子的作用吸附具有特异性，和细胞受体结合引起生化反应，细胞内微丝、微管收缩，细胞移动Seenhereisvasodilationwithexudationthathasledtoanoutpouringoffluidwithfibrinintothealveolarspaces,alongwithPMN's.Asintheprecedingdiagram,herePMN'sthataremarginatedalongthedilatedvenulewall(arrow)aresqueezingthroughthebasementmembrane(theprocessofdiapedesis)andspillingoutintoextravascularspace.白细胞活化白细胞活化相关的表面受体Toll样受体(TLRs),10种哺乳类TLRs，识别细菌脂多糖，蛋白多糖，脂类，病毒双链RNA。G蛋白耦连受体，识别含有N-甲酰甲硫氨酸的细菌短肽。细胞因子受体，感染后产生，通过与白细胞表面受体结合激活白细胞。最为重要的是IFN-γ，激活巨噬细胞。

调理素受体，包裹微生物，增强吞噬细胞吞噬功能的蛋白质，抗体IgGFc段，补体C3b,凝集素。白细胞活化通过磷脂酶A2和钙离子浓度升高促进花生四烯酸代谢产物产生。脱颗粒和释放溶酶体酶，活性氧产生。释放细胞因子，主要从活化的巨噬细胞产生，促进炎症反应。调节粘附分子。白细胞在局部的作用吞噬和免疫吞噬作用是指白细胞游出到炎症灶，吞噬病原体以及组织碎片的过程。主要由嗜中性粒细胞和巨噬细胞完成吞噬过程识别与附着吞入，形成吞噬溶酶体杀伤或降解依赖氧杀菌机制不依赖氧杀菌机制A,Phagocytosisofaparticle(e.g.,bacterium)involvesattachmentandbindingofFcandC3btoreceptorsontheleukocytemembrane,engulfment,andfusionoflysosomeswithphagocyticvacuoles,followedbydestructionofingestedparticleswithinthephagolysosomes.Notethatduringphagocytosis,granulecontentsmaybereleasedintoextracellulartissues.Productionofmicrobicidalreactiveoxygenintermediateswithinphagocyticvesicles.非氧依赖途径溶酶体内细菌通透性增加蛋白-激活磷脂酶降解细胞膜磷脂溶菌酶水解细菌糖肽外衣白细胞特异性颗粒中乳铁蛋白，吞噬酸性粒细胞主要碱性蛋白-寄生虫防御素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细胞、淋巴细胞和浆细胞。呈递抗原产生淋巴因子和抗体抗感染组织损伤作用白细胞活化过程中将产物释放到细胞外间质释放溶酶体酶、活性氧自由基、前列腺素和白细胞三烯，NETs(neutrophilextracellulartraps)等。引起内皮细胞和组织损伤造成组织溶解和破坏NETs组织损伤作用-白细胞释放机制溶酶体酶释放：吞噬溶酶体完全封闭前与外界相通不能被吞噬的物质引起白细胞胞膜运动表面吞噬作用吞噬的物质本身溶解溶酶体膜中性粒细胞脱颗粒白细胞功能缺陷粘附缺陷吞噬溶酶体形成缺陷杀菌活性障碍骨髓白细胞生成障碍白细胞激活障碍导致严重反复的感染各种炎症细胞的作用中性粒细胞：急性炎症早期和化脓性炎单核细胞巨噬细胞：急性炎症后期、慢性炎症尤其是肉芽肿性炎症，某些特殊微生物感染淋巴细胞：T淋巴细胞识别巨噬细胞传递的抗原，释放淋巴因子，产生细胞免疫。B淋巴细胞转化成浆细胞产生多种抗体，参与体液免疫。嗜酸性粒细胞：变态反应、寄生虫感染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炎症介质在炎症过程中的作用炎症介质（inflammatorymediator)的概念一系列介导炎症反应的化学因子来自血浆(主要在肝脏合成，前体形式存在，蛋白酶水解激活）和细胞（胞内颗粒储存，需要时释放或刺激下即刻合成）通过靶细胞表面特异性抗体发挥作用，或本身具有酶活性或氧化损伤可刺激产生次级炎症介质可作用于一种或多种靶细胞，产生不同作用半衰期短，很快降解灭活或被拮抗因子抑制，清除大多数对正常组织具有潜在危害Chemicalmediatorsofinflammation.EC,endothelialcells.细胞释放的炎症介质血管活性胺包括组胺和5－羟色胺，又称血清素。组胺主要存在于肥大细胞中，使细动脉扩张和细静脉通透性增加。5－HT主要存在于血小板和肠嗜铬细胞，作用与组胺类似。Aflatspreadofomentumshowingmastcellsaroundbloodvesselsandintheinterstitialtissue.Stainedwithmetachromaticstaintoidentifythemastcellgranules(darkblueorpurple).Theredstructuresarefatglobulesstainedwithfatstain.花生四烯酸代谢产物，包括前列腺素（PG）、白细胞三烯（LT）和脂质素(lipoxins)使炎症时血管扩张、水肿加剧，引起发热和疼痛；血管收缩、支气管痉挛以及血管通透性增加。脂质素炎症抑制因子临床上的对症治疗的靶点细胞释放的炎症介质Generationofarachidonicacidmetabolitesandtheirrolesininflammation.Themoleculartargetsofactionofsomeanti-inflammatorydrugsareindicatedbyaredX.COX,cyclooxygenase;HETE,hydroxyeicosatetraenoicacid;HPETE,hydroperoxyeicosatetraenoicacid.Biosynthesisofleukotrienesandlipoxinsbycell-cellinteraction.ActivatedneutrophilsgenerateLTB4fromarachidonicacid-derivedLTA4bytheactionof5-lipoxygenase,buttheydonotpossessLTC4-synthaseactivityandconsequentlydonotproduceLTC4.Incontrast,plateletscannotformLTC4fromendogenoussubstrates,buttheycangenerateLTC4andlipoxinsfromneutrophil-derivedLTA4.TheNobelPrizeinPhysiologyorMedicine1982"fortheirdiscoveriesconcerningprostaglandinsandrelatedbiologicallyactivesubstances".SuneK.BergströmBengtI.SamuelssonJohnR.Vane主要来自嗜中性粒细胞和单核细胞。活性氧代谢产物，与NO结合，影响炎症反应，损伤组织。溶酶体成分，促发炎症，组织破坏，直接降解C3和C5。细胞释放的炎症介质-白细胞产物主要由激活的淋巴细胞和单核巨噬细胞产生。调节淋巴细胞调节自然免疫激活巨噬细胞对不同炎症细胞有趋化作用刺激造血，调节白细胞生长、分化细胞释放的炎症介质-细胞因子和化学趋化因子Majoreffectsofinterleukin-1(IL-1)andtumornecrosisfactor(TNF)ininflammation.细胞因子引起巨噬细胞的活化IL-1/TNF在炎症中的作用血小板激活因子(PAF)来源于多种细胞，参与多方面炎症过程。影响血流动力学改变增加血管通透性促使白细胞与内皮细胞粘着影响趋化作用促使白细胞脱颗粒一氧化氮(NO)由内皮细胞、巨噬细胞和一些特定神经细胞产生。作用于血管平滑肌，使血管扩张抑制血小板粘着和聚集抑制肥大细胞引起的炎症反应调节、控制白细胞向炎症灶的集中减少微生物复制、导致组织的损伤神经肽：P物质，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体液中的炎症介质激肽系统（kininsystem）补体系统（complementsystem)凝血和纤溶系统（coagulationandfibrinolyticsystem)激肽系统（kininsystem）最终产物是缓激肽，增加血管的通透性皮下注射可引起血管扩张、平滑肌收缩、引起疼痛作用时间短暂，易被激肽酶灭活Vascularleakageinducedbychemicalmediators.A,Thisisafixedandclearedpreparationofaratcremastermuscleexaminedunstainedbytransillumination.Onehourbeforesacrifice,bradykininwasinjectedoverthismuscle,andcolloidalcarbonwasgivenintravenously.Plasma,loadedwithcarbon,escaped,butmostofthecarbonparticleswereretainedbythebasementmembraneoftheleakingvessels,withtheresultthatthesebecame"labeled"black.Notethatnotallthevesselsleak-onlythevenules.InB,ahigherpower,thecapillarynetworkisfaintlyvisibleinthebackground.补体系统由20种蛋白质组成是机体抵抗病原微生物的重要因子增加血管通透性、促使化学趋化作用和调理素化作用C3a和C5a具有引起血管扩张、增加血管通透性的影响C3b调理素化作用Theactivationandfunctionsofthecomplementsystem.ActivationofcomplementbydifferentpathwaysleadstocleavageofC3.ThefunctionsofthecomplementsystemaremediatedbybreakdownproductsofC3andothercomplementproteins,andbythemembraneattackcomplex(MAC).补体系统的活化可分为早期和晚期两个阶段。早期阶段由经典、替代，凝集素途径三条通路导致C3蛋白水解。

晚期阶段为活化C3后导致的其他补体系统成分活化。C3激活为最重要一步。

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.经典激活途径替代激活途径MBL途径激活物质抗原抗体复合物肽聚糖、酵母多糖、脂多糖MBL相关的丝氨酸蛋白酶起始分子C1qC3C2、C4参与补体成分C1、C4、C2、C3、C5-C9C3、C5-C9、B因子、D因子C2-C9、MASP所需离子Ca2+、Mg2+Mg2+Ca2+C3转化酶C4b2bC3bBbC4b2bC5转化酶C4b2b3bC3bnBbC4b2b3b生物学作用参与特异性免疫的效应阶段,感染后期发挥作用参与非特异性免疫的效应阶段,感染早期发挥作用参与非特异性免疫的效应阶段,感染早期发挥作用三种途径比较TheLateStepsofComplementActivationTheC3bthatisgeneratedbyanyofthepathwaysbindstotheC3convertaseandproducesaC5convertase,whichcleavesC5.C5bremainsattachedtothecomplexandformsasubstrateforthesubsequentbindingoftheC6-C9components.PolymerizedC9formsachannelinlipidmembranes,calledthemembraneattackcomplex,whichallowsfluidandionstoenterandcausescelllysis.补体含量和活性相关的疾病1．免疫相关性疾病：如自身免疫性疾病时，C1、C2、C3、C4和Hf等缺陷；超敏反应时（III型超敏反应），C3a、C5a等过敏毒素的产生。2．与补体有关的遗传性疾病：

①C2、C3缺陷导致的严重感染；

②与C1抑制物缺陷相关的遗传性血管神经性水肿

③SLE患者出现的细胞表面CR1缺陷与C1C清除障碍

④涉及I因子、H因子缺陷的肾小球肾炎；

⑤DAF缺陷引起的阵发性血红蛋白尿；

⑥C1q缺陷表现的严重顽固性皮肤损害，以及C1q、C1r、C4、C2缺陷造成的免疫复合物性血管炎（包括肾炎）等。(图)血管神经性水肿凝血系统和纤溶系统中心因子为XII因子促使白细胞粘着和成纤维细胞增生血管通透性增高白细胞的趋化因子促进白细胞渗出PlasmaProtein-DerivedComplementPlasma(producedinliver)Leukocytechemotaxisandactivation,opsonization,vasodilation(mastcellstimulation)KininsPlasma(producedinliver)Increasedvascularpermeability,smoothmusclecontraction,vasodilation,painProteasesactivatedduringcoagulationPlasma(producedinliver)Endothelialactivation,leukocyterecruitment炎症介质的相互作用不同介质系统相互之间有着密切的联系几乎所有介质均处于灵敏的调控和平衡体系中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急性炎症的类型浆液性炎纤维素性炎化脓性炎出血性炎浆液性炎浆液渗出，以血浆成分为主，常发生于粘膜、浆膜和疏松结缔组织。浆液渗出为主

(渗出的蛋白以小分子白蛋白为主)

伴少量纤维蛋白，和炎症细胞血管壁损伤轻少量渗出可完全吸收，不留痕迹大量渗出，引起压迫和水肿（喉头水肿，胸膜和心包积液）卡他(catarrh)：渗出物或分泌物沿粘膜表面顺势下流Hereisanexampleoffluidcollectionintoabodycavity,oraneffusion.Thisisarightpleuraleffusion(inababy).Notetheclear,paleyellowappearanceofthefluid.Thisisaserouseffusion.Serousinflammation.Low-powerviewofacross-sectionofaskinblistershowingtheepidermisseparatedfromthedermisbyafocalcollectionofserouseffusion.纤维素性炎以纤维蛋白渗出为主，继而形成纤维素。血管壁损伤较重易发生于粘膜、浆膜和肺组织。（1）发生在粘膜面的纤维蛋白性炎症

假膜性炎假膜：纤维蛋白、中性粒细胞、坏死粘膜上皮、病原微生物

白喉-咽部伪膜不易脱落-固膜性炎 -气管伪膜容易脱落-浮膜性炎

（2）发生在浆膜面的纤维蛋白性炎症绒毛心：发生于心外膜的纤维蛋白性炎

大叶性肺炎

渗出的纤维素被纤维蛋白溶解酶水解，吞噬细胞清除。机化引起纤维素性粘连纤维素渗出过多中性粒细胞渗出过少组织内抗胰蛋白酶过多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.化脓性炎以嗜中性粒细胞渗出为主，有不同程度的组织坏死和脓液形成。坏死的中性粒细胞称为脓细胞。表面化脓和积脓(empyema)蜂窝织炎(phlegmonousinflammation)脓肿（abscess）表面化脓和积脓(empyema)表面化脓是指粘膜组织的化脓性炎仅累及粘膜层脓性渗出物不能排出，聚集在输卵管或胆囊内或胸腹腔内，称积脓。Hereisapurulentexudateinwhichtheexudedfluidalsocontainsalargenumberofacuteinflammatorycells.Thus,theyellowishfluidinthisopenedpericardialcavityisapurulentexudate.ApurulentexudateisseenbeneaththemeningesinthebrainofthispatientwithacutemeningitisfromStreptococcuspneumoniaeinfection.Theexudateobscuresthesulci.Suppurativemeningitis

(subarachnoidempyema)Theabdominalcavityisopenedatautopsyheretorevealanextensivepurulentperitonitisthatresultedfromruptureofthecolon.Athickyellowexudatecoatstheperitonealsurfaces.Aparacentesisyieldedfluidwiththepropertiesofanexudate:highproteincontentwithmanycells(mostlyPMN's).蜂窝织炎(phlegmonousinflammation)

弥漫性化脓性炎主要由溶血性链球菌引起透明质酸酶、链激酶大量中性粒细胞弥漫浸润与正常组织分界不清，坏死不明显常见于疏松组织:皮下、肌肉、阑尾AcutephlegmonousappendicitisAcutephlegmonousappendicitis脓肿(abscess):局限性化脓伴脓腔形成病灶局限主要由金葡菌引起

血浆凝固酶-局限病变

层粘连蛋白受体-迁徙性脓肿脓腔内有脓液早期壁薄不规则，后期壁厚为大量肉芽组织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.溃疡皮肤或黏膜的炎症，伴有表面组织的坏死脱落。中性粒细胞浸润急慢性炎症均可发生。Themorphologyofanulcer.A,Achronicduodenalulcer.B,Low-powercross-sectionofaduodenalulcercraterwithanacuteinflammatoryexudateinthebase.出血性炎血管损伤严重，渗出物以大量红细胞为主。常见于流行性出血热、钩端螺旋体病和鼠疫等急性传