16.8Complement

Explaintheroleofcomplementininnateimmunity.a)  Whatarethethreeeffectsonmicrobesby

complement?b)  Whatisthecommonpathway/cascadeofcomplement?c)  WhatarethethreepathwaysofacAvaAng

complement?d)  WhatisananAgen?e)  WhatisananAbody?f)  WhatisalecAn?g)  Whatare2waysbacteriamightevadecomplement?

RoleofComplementSysteminImmunity

•  Complementsystemismadeupofover30proteinssynthesizedbytheliver,circulateintheblood

•  ManycomplementproteinsareinacAveandmustbeacAvated.

•  AcAvatedcomplementactsinacascadethatcauses1.  inflammaAon:dilaAonofarterioles,releaseof

histamine&increasedpermeabilityofcapillaries2.  opsonizaAon:proteinbindstomicrobemakingit

easiertophagocyAze3.  cytolysis:acomplexofseveralproteinscanform

holesinmicrobemembranescausingleakinessandcellrupture

TheCommonPathway

•  Step1–acAvateC3,promotesopsonizaAonandphagocytosis

•  Step2–acAvateC5,promotesinflammaAon

•  Step3–formMAC,promotescytolysis

Step1:Ac*vateC3

•  C3issplitintoC3aandC3b,catalyzedbyC3

convertase

•  C3bbindstosurfacetoenhancephagocytosis(opsonizaAon)

•  C3bisalsoanenzymethatcatalyzesthenextstep

•  C3apromotesinflammaAonbysAmulaAngmastcellstoreleasehistamine

Step2:Ac*vateC5

•  C3bactsastheC5convertase,spliWngC5intoC5aandC5b

•  C5apromotesinflammaAonby

sAmulaAngmastcellstoreleasehistamine(alongwithC3a)

•  C5bisbeginsthechainreacAonofproteinsbindingtothesurfaceofamicrobe

Step3:Forma*onoftheMembraneA:ack

Complex•  C5bbindstothesurface

ofthebacterialcell

•  C6,thenC7andC8bindinsequence

•  These4proteinsa[ractorrecruitC9tobind

•  SeveralC9proteinsbindinapa[erntoformahugeporepuncturingtheplasmamembraneandallowingbacterialcytoplasmtoleakout‐cytolysis

3WaystoAcAvateComplement

•  Classicalpathway–anAbodies(partofacquiredimmunity)

•  AlternaAvepathway–a[racAonofcomplementproteinstomicrobialcellwalls

•  LecAnpathway–proteinsthatbindtobacterialcarbohydrates

TheClassicalPathway:adapAveimmunity

•  AspecificanAbodyrecognizesandbindstoabacterialcell

•  C1bindstotheanAbodies–  TheinteracAonacAvatesenzymaAcfuncAonofC1

•  AcAveC1a[ractsandclipsC2andC4intoC2a,C2b,C4a&C4b

•  C2acombineswithC4btoformanacAveC3convertase

AnAbodies&AnAgens

•  AnAbodiesareproteinsproducedbyBcells•  Partofouracquiredimmunity•  AnAbodiesbindtosmallpiecesofmicrobes,calledanAgens,toiniAateavarietyofimmuneresponses

•  AnAgensaresubstancesthatsAmulatetheproducAonofanAbodies…anAbodygenerators

•  TheclassicalpathwayisiniAatedwhenananAbodybindstoitsanAgen

TheAlternaAvePathway:innateimmunity

•  ComplementproteinsB,D&Fcirculatethroughoutthebody

•  Bindtomicrobialcellwallcomponents(glycolipids)

•  B,D&Fa[ractC3andactasaC3convertase

TheLecAnPathway:innateimmunity

•  LecAnisaproteinthatrecognizesandbindstobacterialcarbohydrates

•  LecAna[ractsC2&C4andcatalyzesthespliWngofbothproteinsintoC2a,C2b,C4a&C4b

•  C2acombineswithC4btoformanacAveC3convertase

EvadingComplement

•  Capsule–  ThecapsuleisacoaAngsurroundingthecellwall– OnecomponentofthecapsuleissialicacidwhichcanpreventopsonizaAon(tooslipperyforC3b)

– AnothercomponentpresentforsomebacteriaisOpolysaccharidewhichblocksbindingoftheMACcomplex(C5b,C6,C7,C8,C9)

•  Secretedenzymes–  SomebacteriasecreteC5apepAdase,whichdestroysC5a–impairinflammaAonandrecruitmentofphagocytes