Inflammationisaprotectiveresponsetoinfectionbytheimmunesystemthatrequirescommunicationbetweendifferentclassesofimmunecellstocoordinatetheiractions.Acuteinflammationisanimportantpartoftheimmuneresponse,butchronicinappropriateinflammationcanleadtodestructionoftissuesinautoimmunedisordersandperhapsneurodegenerativeorcardiovasculardisease.Secretedcytokineproteinsprovidesignalsbetweenimmunecellstocoordinatetheinflammatoryresponse.SomecytokinessuchasIL-1,IL-6(seeIL-6pathway)andTNF(seeTNFR1andTNFR2pathways)acttobroadlyprovoketheinflammatoryresponsewhileothersactonspecifictypesofimmunecells.Macrophagesandotherphagocytoticcellsprovideafront-linedefenseagainstbacterialinfection.Macrophagesstimulatetheinflammatoryresponsesofneutrophils,fibroblasts,andendothelialcellsinresponseinfectionbysecretingIL-1andTNF.IL-1andTNFcausefeverthroughalterationofthebodytemperatureset-pointinthehypothalamus.FibroblastsandendothelialcellsrespondtoIL-1andTNFbyrecruitingmoreimmunecellstothesiteofinflammation.SecretedIL-8isachemokinethatattractsneutrophilstositesofinfection.MacrophagesalsopresentantigentoThelpercellsthatplayacentralroleincoordinatingimmuneresponses.ThelpercellsinduceclonalexpansionofTcellsthatrespondtoantigen,withIL-2asakeymediatorofTcellproliferationandactivation(seeIL-2pathway).TGF-betaisanegativeregulatorofproliferationinmanycells,haveanti-inflammatoryactionsinsomesettings(seeTGF-betapathway).ThecytotoxicactivityofNaturalKillercells(NKcells)andlymphokineactivatedkillercells(LAKcells)towardviralinfectedortumorcellsisstimulatedbyIL-2andothercytokines.ThelperssecreteIL-3andIL-5tostimulateeosinophilproliferationandactivation(seeIL-5pathway).Eosinophilsareinvolvedintheimmuneresponsetoparasiticinfection.ThelpercellsarerequiredtostimulateBcellresponsesaswell,withthecytokinesIL-10,IL-4andothercytokinesregulatingtheclonalselectionanddifferentiationofantigen-specificBcellstoformantibody-secretingplasmaBcellsandmemorycells.Inadditiontoinducingactivationandproliferationofspecificdifferentiatedimmunecells,cytokinesactonhematopoeiticstemcells,causingtheirproliferationanddifferentiationintothefullrangeofimmunecells.

Contributor:GlennCroston,PhD

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