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InnateImmunityLabDaysAgainPassformsalongandthenforwardsInnateImmunitylecture4/5Innateimmunesystemreferstodefencesystemspermanentlyinplace.Onlywhentheseareovercomedoesadaptiveimmuneresponsekickin.Theadaptiveresponse,whileslowtorespondonfirstexposuretoaforeignantigen,hasthecharacteristicofmemory,suchthatonsubsequentexposurearapidresponseensues.

InnateadaptiveSolublefactorsLysozymeComplementAcutephaseproteinsAntibodyCellsPhagocytesNKCellsT-lymphocytesInnatedefences1Differencesinsusceptibilitytocertainpathogens

2Anatomicaldefences3Microbialantagonism4

Tissuebactericides,includingcomplement,acutephaseproteinsandlysozyme5Inflammation(abilitytoundergoaninflammatoryresponse)6PhagocytosisDifferencesinSusceptibilityAbsenceoftissue/cellreceptorsforattachmentTemperatureofhostLackofnutritionalrequirementsLackoftargetsitefortoxinsIndividualresistanceinsamespeciesAgeSexStressDiet,malnutritionInter-currentdiseaseortraumaTherapyagainstotherdiseasesPhysicalBarriersSkinMucousMembranesRespiratorytractMouth,stomachandintestinaltractUro-genitaltractEyes(conjunctiva)MicrobialantagonismCompetitionwithnon-indigenousspeciesSpecificantagonism-bacteriocinsNon-specificantagonism-metabolitesMims:p47-48

TissuebactericidesandcomplementLysozymeComplementBasicproteins/peptidesLactoferrin/transferrinPeroxidaseFibronectinInterferonsInterleukinsComplementInnateandinducibledefenceTriggeredcascadeenzymesystemCentralroleplayedbyC3convertaseAlternativepathwayNormalplasma-C3spontaneousactivationtoreleaseC3bC3b+B>>>>>>C3bBbC3bBbnormallybrokendownrapidlyInthepresenceofbacterialsurfacesC3bBbstabilisedPositivefeedbackloopComplementMicrobialproductsstabiliseC3convertaseBuildupofC3bactsasopsoninTightregulationComplementsynergiseswithphagocytes>inflammmatoryresponseC3bandC3convertaseactonC5C5aandC3atrigerVascularpermeabilisation

AllowsexudationoffluidandplasmacomponentsChemotacticfactors

Attractleukocytes(granulocytes/neutrophils)MastcelldegranulationArachidonicacidpathwayAcuteinflammatoryresponseCapillarydilation-erythemaExudationofplasmaproteinsandfluid-edemaAccumulationofneutrophilsFocusesphagocytesonopsonisedinvaderMastcellmediatorsHistamine

Vasodilation,capillarypermeability,bronchoconstrictionHeparin

Anticoagulant

Chemokines

Attractphagocytesincludingpolymorphsandmonocyte/macropahgesDestructionofinvaderOpsonisationleadstouptakebyphagocyte

or

DestructionbymembraneattackcomplexMembraneattackC5bmembraneboundBindsC6,7,8ThiscomplexallowsC9partialunfoldingandinsertioninmembranetomakeanAnnularchannelInfluxofNa+leadstolysisE-MofMACinShigelladysentariaeSummaryofcomplementfunctionsGenerationofinflammatoryfactorsAttractionofphagocytesEnhancementofphagocytosisLysisofbacterialorvirusinfectedcellsReadaboutinMims53-57ProfessionalphagocytesMacrophagesandpolymorphonuclearphagocytes(neutrophils/granulocytes)DistributionTypesofmononuclearphagocytesPhagocytesMacrophageslonglivedNeutrophilsshortlived-nomitochondria-ContaingranuleswithpowerfulenzymesPrimary-myeloperoxidase,lysozyme,cationicproteinsSecondary-lactoferrinandlysozymeTertiary-acidhydrolasesPhagocytesMonocytes=3-7%ofcirculatingwhitebloodcells-activelyphagocyticandbactericidalMigrateintotissuesanddifferentiatetomacrophages-inflammatorystimuliPhagocytosisDeliveryofphagocytetositeofinfectionAdherence-lectinlikereceptorsorcomplementIngestion-pseudopodialextensionsPhagolysosome-fusionwithendosomesIntracellularkilling-enzymes,pH,O2,NOIntracellulardigestion/immunology/mac.movAcutephaseresponseAcutephaseproteins.Whenmacrophagesaretriggeredintoinflammatorystatebyopsonisedmicrobes,C5a,andtoxins,theyreleasepro-inflammatorycytokinesIL-1,IL-6andTNF.Thesetriggerthereleaseofacutephaseproteins,suchasC-reactiveproteinwhichassistscomplementfixation.Fever/pyrexiaInterferonsandNKcellsInterferonsInvolvedinantiviralresponse,bytriggeringsynthesisofprotectiveenzymes

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