课件-12级4章、细菌感染与免疫

Chapter4BacterialInfectionandImmunityInfection

Bacteriabreakthroughdefencemechanismofhost,growinvivo,andproducevarioustoxicsubstances.Atlast,Itcancausevaryingdegreespathologicalchanges.

Basedonthisconcept,bacteriacanbeclassifiedinto3majorgroups:truepathogens,opportunisticpathogensandnon-pathogens.

Normalfloraandopportunisticpathogens

BacterialpathogenesisOccuranddevelopmentofinfectionAnti-bacteriaimmunityHospitalacquiredinfectionNormalfloralandopportunisticpathogen1.Concept:--resideontheskinandmucousmembranesofhealthynormalpersons--canplayadefiniteroleinmaintaininghealthandnormalfunctionwhenimmunityofthehostisnormalI.NormalfloraNormalfloraOfIntestinaltract2.Classification:

ResidentfloraTransientflora3.Distribution:SkinRespiratorytractIntestinaltractGenitourinarytractNormalfloraofbody乳杆菌、大肠杆菌、类白喉杆菌、白念珠菌等阴道白色葡萄球菌、类白喉杆菌、非致病性分枝杆菌等尿道大肠杆菌产气杆菌、变形杆菌、绿脓杆菌、葡萄球菌、粪链球菌、类杆菌、产气荚膜梭菌、破伤风梭菌、双歧杆菌、真细菌、乳杆菌、白念珠菌等肠道一般无菌胃白色葡萄球菌、干燥杆菌等外耳道葡萄球菌、类自喉杆菌、绿脓杆菌、非致病性分枝杆菌等眼结膜葡萄球菌、甲型和丙型链球菌、肺炎球菌、奈瑟菌、乳杆菌等鼻咽表皮葡萄球菌、甲型和丙型链球菌、肺炎球菌、奈瑟菌、类杆菌、梭杆菌等口腔葡萄球菌、类自喉杆菌、绿脓杆菌、非致病性分枝杆菌、丙酸杆菌、白念珠菌等皮肤主要菌类部位

眼结膜白色葡萄球菌、干燥杆菌人体内正常菌群的分布

阴道

大肠杆菌、乳杆菌白念珠菌、类白喉杆菌、非致病性分枝等

外耳道葡萄球菌、类白喉杆菌绿脓杆菌、非致病性分枝杆菌

鼻咽腔葡萄球菌、甲，丙型链球菌肺炎球菌、奈氏菌、类杆菌等表皮葡萄球菌口腔甲，丙型链球菌类白喉杆菌、肺炎球菌奈氏菌、乳杆菌、梭杆菌螺旋体、放线菌、白念珠菌

皮肤葡萄球菌、绿脓杆菌、白念珠菌丙酸杆菌、类白喉杆菌、非致病性分枝杆菌

尿道白色葡萄球菌、类白喉杆菌、非致病性分枝杆菌

肠道大肠杆菌、产气杆菌、变形杆菌绿脓杆菌、葡萄球菌、厌氧性细菌真菌、乳杆菌，双歧杆菌等4.Physiologicfunctions

:1)BiologicAntagonismFunctionBiologicbarriersChemicalbarriersCompetitionfornutrients

2)NutritionalFunctionSynthesizevitaminKandvitaminBAidintheadsorptionofnutrients

3)ImmuneFunctionPromotedevelopmentofimmuneorganEnhancethehost’simmuneresponseActivatemacrophageandincreasethereleasingofcytokines4)ExpellingoftoxinFunctionLowerG-bacteriainintestinaltractandreducereleaseofendotoxinProduceacidicmaterialandmakeforexpellingoftoxin.ProduceSOD5)Anti-agingFunction6)Anti-tumorFunctionDegradepro-carcinogensinIntestinaltractEnhancephagocyticactivityofphagocyte1.Concept:II.OpportunisticpathogenNormalbacteriaandlatent潜在的pathogenfrombody;Non-pathogenandlatentpathogenfromenvironmentInfectioncausedbyopportunisticpathogenisopportunisticinfection2.Infectionconditions:1)Immunityofhostgettingweak2)Translocation3)DysbacteriosisandsuperinfectionMicroeubiosisMicrodysbiosis生态失调MicroecologicaladjustmentIII.Microecology微生态学BacterialpathogenesisPathogenicity

Pathogenicityistheabilityofamicro-organismtocauseinfectionanddiseaseinaHost.BacteriaHostpathogenicityimmunityVirulenceInvasivenessToxinLD50orID50NumberofinfectionbacterialPortalentryBacterialvirulencefactors1.Invasiveness

ordinarypili

capsule,microcapsuleorLTAVirulence1-1Adhesionand定植Colonization

Adhesin

VariousmechanismPossessaltitudinalspecificityAdhesinistobeligand;Proteinandglycoproteinincellsurfaceistobereceptor.

Adhesionmechanism

Microcolony小菌落；小集落Biofilm生物膜Adhesion

ResultsFirstdayThirddayDaysix

BiofilmP.aeruginosaC.albicans

生物医学材料相关感染：人工心脏瓣膜、人工关节、动静脉导管、气管插管等。

慢性顽固性感染疾病：慢性泛细支气管炎、囊性纤维化、SBE、慢性骨髓炎、褥疮等。InfectionwithBiofilmrecurrentIntractablepersistenceCharacteristicofBiofilminfection

1-2Invasionofhostcells&tissuesInvasinInvasiveenzymesuchasHyaluronidase

1-3ImmuneescapeAnti-phagocytosisanddigestioncapsule,microcapsuleorCoagulasepletephagocytosisProduceIgAproteaseAntigenvariationInterferenceactivityofcomplement2.Toxin2-1ExotoxinOrigin

--ProducedmainlybyG+(includeafewG-)--Liberatedfromlivingbacterialcell

Nature

--virulentProteinCharacter

HighlytoxigenicityHighlyselectivityHighlyantigenicity

and

canproduceantitoxinDetoxificationtoxoidType

Onebacterialstraincanproducevariousexotoxin,butonlyoneorsomeexotoxinaremaininoneinfection.

Basedonitsmodeofactionandaffinitytotissue,exotoxincanbeclassifiedinto3majorgroups:Neurotoxin,CytotoxinandEnterotoxin

Neurotoxin

Actonnervoustissueandcauseabnormalofneurotransmission

Cytotoxin

Includesuppresssynthesisofproteinanddamagecellmembrane.

Enterotoxin

Actonenterocyteandcauseabnormalofbowelfunction.Moleculestructure

TypeA-BtoxinActiveBindingACellsurfaceB

single-chaintoxinVirulencegene

PlasmidTransposonTemperatebacteriophageChromosomeDNAPathogenicityisland2-1EndotoxinOriginNature--ProducedbyG---Liberatedfromcellwallofdeadbacteria--LPS(Lipopolysaccharide)StructureofLPSlipidACorepolysaccharidespecificpolysaccharideWeaktoxigenicityNoselectivityPoorantigenCannotetotoxoid

CharacterMechanismofactionFormofLPS-LBP-CD14complexInteractionbetweenLPS-LBP-CD14andTLR4,MD-2TriggercascadereactionofsignaltransductionReleaseofTNF-α,

IL-1,IL-6,IL-8etc.Produceofinflammatoryfactor

,bioactivemedium,acutephaseproteinetc.FeverleukocytosisorLeukopeniaEndotoxemiaandshockDisseminatedintravascularcoagulation(DIC)Immunregular

BiologicalactivitiesNumberofbacterialentry

NumberofbacteriaandvirulencepresentInverseproportionPortalentrySimplepathwayMulti-pathwayOccurandDevelopmentofinfection1.SourceofInfectionExogenousinfection:patient,carrier,diseasedanimaloranimalcarrier.Endogenousinfection

:mostarenormalflora,causeinfectionunderabnormalcondition.2.Transmission

ofInfection

VerticaltransmissionHorizontaltransmissionSkinRespiratorytractDigestivetractUrogenitaltractMorethanoneroute3.TypeofInfectionAccordingtoresultInapparentor亚临床的subclinicalinfectionApparentinfection:causeapparentclinicsyndromeCarrierstate:carrierAcuteinfectionChronicinfectionSubacuteinfectionAccordingtodegreeofurgencyAccordingtopositionandnatureLocalinfectionGeneralizedorsystemicinfectionToxemia--isthepresenceofexotoxinsintheblood.Endotoxemia--isthepresenceofendotoxinsintheblood.Bacteremia--isaninvasionofthebloodstreambybacteria.Septicemia

--illnessthatoccurswhenpoisonoussubstancesproducedbycertainbacteriaenterthebloodstream.Pyemia

--iscausedbypyogenicbacteriaintheblood.GeneralizedorsystemicinfectionAnti-BacteriaImmunityComponentsoftheImmuneSystemHumoralCellularHumoralCellularSpecificNonspecificcomplement,interferon,TNFetc.macrophages,neutrophilsTcells;othereffectorscellsantibodiesBalancebetweenInfectionandImmunityinfectionimmunityBolusofinfectionxvirulenceimmunityDisease=ResponsetoInfectioninfectionxdiseaseInnateimmunitynodiseaserecoveryadaptiveimmunityre-infectionnodiseasexInnateImmunityAdaptiveImmunityComponents

ofInnateandAdaptiveImmunityskin,blood-brain,blood-placentaLysozyme,antibacteroalpeptide,Complement,cellfactor,ectmacrophage,NKcellNeutrophilphysicalbarrierssolublefactorscellsnoneImmunoglobulins(antibody)TandBlymphocytesPhagocytosisMigrationRecognitionPatternrecognitionreceptor(PRR)--TLR,LPS-RPathogen-associatedmolecularpattern(PAMP)IngestionKilling细胞核Chemotacticresponsetoinflammatorystimulus

MacrophageAttackingE.coli(SEMx8,800)BactericidalMechanismOxygen-dependentbactericidalsystem--O2-,H2O2sterilizedirectly--1O2,OH-damageDNA,lipid,protein--MPOandHalogendamageproteinNitrogen-dependentbactericidalsystem--NOOxygen-no-dependentbactericidalsystem--lysozyme,Defensin,Proteolyticenzyme,Nuclease,ectResultofPhagocytosisCompletephagocytosis

pletephagocytosisDemagetissueandcell内毒素被解毒醋酶血清内毒素解毒因子多种细菌肽蛋白质血清正常调理素革兰阳性菌蛋白质乳汁乳素革兰阳性菌碱性多肽膜、肾、前列腺精素、精胶碱需铁细菌假球蛋白血清转铁蛋白革兰阳性菌含铁叶琳红细胞正铁血红素革兰阳性菌碱性多肽血小板血小板素革兰阳性菌碱性多肽中性粒细胞白细胞素革兰阴性菌碱性多淋巴系统组蛋白多种细菌碱性多肽中性粒细胞吞噬细胞杀菌素革兰阳性菌血清乙型溶素革兰阳性菌碱性多肽吞噬细胞榕酶体、唾液、泪液、乳汁等溶菌酶正常球蛋白血清补体作用对象化学性质主要来源抗菌物质正常体液与组织中的抗菌物质AdaptiveImmunityMucosalimmunity

--Tonsil,Payer’spatches,Epityphlon--MicrofoldcellHumoral体液immunityCellularimmunityInnateImmunityAdaptiveImmunityCharacteristics

ofInnateandAdaptiveImmunityNoImmunologicmemoryAntigenindependentNotimelagNotantigenspecificAntigendependentAlagperiodAntigenspecificDevelopmentofmemory

Typeofinfection

Typeofimmunity

Extracellularbacteria

Antibody-mediatedPhagocyte;Complement

Exotoxins

Antitoxins;SIgA

Intracellularbacteria

T

cell-mediatedimmunity

CharacteristicsofAnti-

bacteriaImmunityHospitalacquiredinfectionIt(ial医院内infection)referstoinfectionamonggroupsofpeoplewhentheyaccepteddiagnose,treatment,andnursingwi