1、InnateImmunityLabDaysAgainPassformsalongandthenforwardsInnateImmunitylecture4/5Innate immunesystemreferstodefencesystemspermanentlyinplace.Onlywhentheseareovercomedoesadaptive immuneresponsekickin.Theadaptiveresponse,whileslowtorespondonfirstexposuretoaforeignantigen,hasthecharacteristicofmemory,suc
2、hthatonsubsequentexposurearapidresponseensues.InnateadaptiveSoluble factorsLysozymeComplementAcutephaseproteinsAntibodyCellsPhagocytesNKCellsT-lymphocytesInnatedefences1Differences in susceptibility to certain pathogens2Anatomical defences3 Microbial antagonism4Tissue bactericides,including compleme
3、nt,acute phase proteins and lysozyme5 Inflammation(ability to undergo an inflammatory response)6 PhagocytosisDifferencesinSusceptibilityAbsenceoftissue/cellreceptorsforattachmentTemperatureofhostLackofnutritionalrequirementsLackoftargetsitefortoxinsIndividualresistanceinsamespeciesAgeSexStressDiet,m
4、alnutritionInter-currentdiseaseortraumaTherapyagainstotherdiseasesPhysicalBarriersSkinMucousMembranesRespiratorytractMouth,stomachandintestinaltractUro-genitaltractEyes(conjunctiva)MicrobialantagonismCompetitionwithnon-indigenousspeciesSpecificantagonism-bacteriocinsNon-specificantagonism-metabolite
5、sMims:p47-48TissuebactericidesandcomplementLysozymeComplementBasicproteins/peptidesLactoferrin/transferrinPeroxidaseFibronectinInterferonsInterleukinsComplementInnateandinducibledefenceTriggeredcascadeenzymesystemCentralroleplayedbyC3convertaseAlternativepathwayNormalplasma-C3spontaneousactivationto
6、releaseC3bC3b+BC3bBbC3bBbnormallybrokendownrapidlyInthepresenceofbacterialsurfacesC3bBbstabilisedPositivefeedbackloopComplementMicrobialproductsstabiliseC3convertaseBuildupofC3bactsasopsoninTightregulationComplementsynergiseswithphagocytesinflammmatoryresponseC3bandC3convertaseactonC5C5aandC3atriger
7、VascularpermeabilisationAllowsexudationoffluidandplasmacomponentsChemotacticfactorsAttractleukocytes(granulocytes/neutrophils)MastcelldegranulationArachidonicacidpathwayAcuteinflammatoryresponseCapillarydilation-erythemaExudationofplasmaproteinsandfluid-edemaAccumulationofneutrophilsFocusesphagocyte
8、sonopsonisedinvaderMastcellmediatorsHistamineVasodilation,capillarypermeability,bronchoconstrictionHeparinAnticoagulantChemokinesAttractphagocytesincludingpolymorphsandmonocyte/macropahgesDestructionofinvaderOpsonisationleadstouptakebyphagocyteorDestructionbymembraneattackcomplexMembraneattackC5bmem
9、braneboundBindsC6,7,8ThiscomplexallowsC9partialunfoldingandinsertioninmembranetomakeanAnnularchannelInfluxofNa+leadstolysisE-MofMACinShigella dysentariaeSummaryofcomplementfunctionsGenerationofinflammatoryfactorsAttractionofphagocytesEnhancementofphagocytosisLysisofbacterialorvirusinfectedcellsRead
10、about in Mims 53-57ProfessionalphagocytesMacrophagesandpolymorphonuclearphagocytes(neutrophils/granulocytes)DistributionTypesofmononuclearphagocytesPhagocytesMacrophageslonglivedNeutrophilsshortlived-nomitochondria-ContaingranuleswithpowerfulenzymesPrimary-myeloperoxidase,lysozyme,cationicproteinsSe
11、condary-lactoferrinandlysozymeTertiary-acidhydrolasesPhagocytesMonocytes=3-7%ofcirculatingwhitebloodcells-activelyphagocyticandbactericidalMigrateintotissuesanddifferentiatetomacrophages-inflammatorystimuliPhagocytosisDeliveryofphagocytetositeofinfectionAdherence-lectinlikereceptorsorcomplementInges
12、tion-pseudopodialextensionsPhagolysosome-fusionwithendosomesIntracellularkilling-enzymes,pH,O2,NOIntracellulardigestionhttp:/ntri.tamuk.edu/immunology/mac.movAcutephaseresponseAcutephaseproteins.Whenmacrophagesaretriggeredintoinflammatorystatebyopsonisedmicrobes,C5a,andtoxins,theyreleasepro-inflamma
13、tory cytokines IL-1,IL-6 and TNF.Thesetriggerthereleaseofacutephaseproteins,suchasC-reactiveproteinwhichassistscomplementfixation.Fever/pyrexiaInterferonsandNKcellsInterferonsInvolvedinantiviralresponse,bytriggeringsynthesisofprotectiveenzymessuchaspolyAsynthase.NKCellsPrimarilyinvolvedindestroyingviralinfectedcells.Triggeredbyglycoproteinsonviralinfectedcells,andkillviaperforinandgranzymeB.ReadingforinnateimmunityMims,Chapter4P47-62
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