InnateimmunityCells of innate immunityMacrophagesDendritic cellsNeutrophilsEosinophilsBasophil Mast cellsNatural Killer cellsPolymorphonuclearleukocytesPhagocytic cells of innate immunityMacrophagesDendritic cellsNeutrophilsEosinophilsBasophil Mast cellsNatural Killer cellsMonocyte/Macrophage/DCPolymorphonuclear phagocytesMonocyteNeutrophilsEosinophilPhagocytemigrationfrombloodcirculationintotissuesTissuemacrophagesPhagocytosisandkillingofabacteriumMicrobicalmechanismsofphagocyticcells-1MPO: MyeloperoxidaseMicrobicalmechanismsofphagocyticcells-2L-NMMA: Arginine analogueRSH: Thiols Microbicalmechanismsofphagocyticcells-3AntibodyandcomplementhelpphagocytosisCells of innate immunityMacrophagesDendritic cellsNeutrophilsEosinophilsBasophil Mast cellsNatural Killer cellsPolymorphonuclearleukocytesDendriticcellsDendriticcellsTwo entirely different types:Interdigitating dendritic cells(dendritic cells)Follicular dendritic cellsDendritic cells provide a link between the innate and adaptive responseDendritic cellThAgMHC IITCRCD4Follicular dendritic cellAgCRFcRCBCR (Ab)BComparisonofDCandFDCCells of innate immunityMacrophagesDendritic cellsNeutrophilsEosinophilsBasophil Mast cellsNatural Killer cellsErythrocytes transport immune complexesPlatelets- release cytokinesPolymorphonuclearleukocytesInflammatorymediatorsreleasedfromtissuemastcellsandbloodbasophilsLeukotrienesProstaglandinse.g. histamineMast cell/BasophilIgECells of innate immunityMacrophagesDendritic cellsNeutrophilsEosinophilsBasophil Mast cellsNatural Killer cellsPolymorphonuclearleukocytesNKcellsMHCClassIInfectedorcancercellActivatorInfectedorcancercellKillKillNKcellNormalcellMHCClassIActivatorActivatingreceptorInhibitoryreceptor Molecules of innate immunity Pattern recognition receptors (PRR) Complement Acute phase proteins Defensins Cytokines (to be covered under adaptive immunity) Molecules of innate immunity Pattern recognition receptors (PRR) Complement Acute phase proteins Defensins Immune system must distinguish pathogenic infectious agents from commensals, self antigens & environmental antigens Intracellular, cell surface and secreted (soluble) patternrecognitionreceptors (PRRs) PRR recognize pathogen-associatedmolecularpatterns (PAMPs) and hostdanger-associatedmolecularpatterns(DAMPs) A major group of PRRs are the Toll-likereceptors (TLRs) When recognise PAMPs they trigger a biochemical cascade Activation of transcription factors Synthesis of inflammatorycytokines ExamplesofcellsurfaceandendosomalTLRsIRF = Interferon response factor Molecules of innate immunity Pattern recognition receptors (PRR) Complement Acute phase proteins DefensinsComplement:AkeycomponentofinflammationA set of 20 or more different proteins which act in an enzymicamplificationcascade system to generate a number of active complement components involved in several aspects of the immune responseThreewaystoactivatecomplement:ClassicalpathwayLectinpathwayAlternativepathwayActivitiesofcomplementcomponents Molecules of innate immunity Pattern recognition receptors (PRR) Complement Acute phase proteins DefensinsCertain cytokines released in response to activation of the PRRsact on the liver to increase secretionof acutephaseproteins(APPs)Plasma concentration of APPs may increase 1000-fold during infectionACUTEPHASERESPONSEManyacutephaseproteinsaremadebytheliverIL-1 IL-6 TNFC3Complement componentC-reactive proteinActivates complementFibrinogenCoagulation Acutephaseresponse Enhances host resistance to infection Minimizes tissue injury Promotes resolution and repair of . inflammatory lesion Molecules of innate immunity Pattern recognition receptors (PRR) Complement Acute phase proteins Defensins DefensinsNaturesantibioticsSmallcationicantimicrobialpeptidesWidelyexpressed,esp.byleukocytesandepithelialcellsIntracellular(e.g.inneutrophilgranules)andsecretedKillbacteriaandfungiTwomainstructuralfamilies: a a-Defensins:Constitutivelyexpressed.-Defensins:Someconstitutivelyexpresssed,othersinduced,e.g.bybacterialendotoxin(LPS)MechanismofactionofdefensinsDefensinPathogenSummaryTheimmunesystemneedstorecognisetheinvaderTheinnateresponsedoesthisinaverybroadwayusing.PRRNKcellscankillinfectedandcancercellsDendriticcellsshowantigentolymphocytesTheacutephaseresponsehelpsinhostresistanceto.infectionDefensinsaresmallcationicpeptideswithantimicrobial.properties