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Peter Parham

The Immune System


Third Edition
Chapter 9
Immunity Mediated by
B Cells and Antibodies

Copyright Garland Science 2009

Figure9.2

CrosslinkingofBCR
isnecessarybutnot
sufficienttoactivate
aBcell.Needsignals
fromBcellco
receptor(which
consistsofCR2,CD19
&CD81)

Figure9.2

Figure9.3

Section93.AbresponsetocertainAgs
doesnotrequireTcellhelp
NotedthisinathymicpatientswhohadnoT
cellsbuttheyhadnormal#ofBcells.Many
oftheirIRslackedAbproductionbutnotall.
TheseantigensthatdonotrequireTcellhelp
arecalledTindependentantigens
(TIAg)(Twotypes(TI1andTI2))
(ThistermisconfusingsinceitistheBcells
thatareTindependent..nottheantigens

TI1Ag
TorespondtoTI1Ag,aBcellneedsmorethanjust
ligationofBCR&coreceptor.Italsoneedssignaling
fromreceptorsoftheinnateIR(e.g.TLRs).E.g.isLPS
whichisrecognizedbyCD14&TLR4
LigationofthebacterialLPSviaBCR,coreceptor&
TLR4(CD14)proliferation&differentiationofBcell
onlyIgMtoLPS
Anothere.g.isTLR9whichisinhighconc.inside
endocyticvesiclesinBcells.TLR9detectsbacterial
DNA(3rdpaneloffig9.6)

LPSis
TItype1Ag

TI2Ag(Fig.9.7fromoldbook)
Repetitivecarbohydrateorproteinepitopes
ofhighdensityonmicrobes
ActivateBcellbyextensivecrosslinkingof
BCRs&coreceptors
E.g.polysaccharidesofStreptococcus
pneumoniaeactivateB1cells(seetable)
earlyAbIgMoflimitedability.No
isotypeswitchingorsomatichypermutation

Figure9.4

Figure76

Figure412

Section94(seefigures95&96)
(RememberroleofFDCsinsurvivalofBcells(Ch6)in
primarylymphoidfollicles)

FDCsalsoserveasadepositoryofAgs(not
degraded)makingthemavailableforinteraction
withBCRsofBcells
FDCsareperfectforthistasksince
FDCshaveextensivedendritestodisplayAgs&
havereceptorsthattakeupAgs
FDCslackphagocyticactivity
NotesubcapsularmacrophagesassistFDCswiththis
task

Figure9.5

Folliculardendriticcelldecoratedwith
antigens(viruses)(Figure9.5&fig.fromoldtext)

Section95AgactivatedBcellsmoveneartoT
cellareatofindTFH

BcellsenterlymphnodesviaHEVs
PassthroughTcellareaBcellfollicle
IFBCRisspecificforAgdisplayedonFDC
orsubcapsularmacrophage.Agsignaling
impactsBcellexpressionofCD69which
keepstheseBcellsinLN
AgactivatedBcellsendocytoseAg,
processAgandpresentAgonMHCclass
IImolecules

Section95continued

AgactivatedBcellsaredrawnto
interfacebetweenBandTcellzones
ThisallowsinteractionwitheffectorT FH
cells(Thesewerealreadyactivatedbymyeloid

DCthatpresentedAgspecificforTCRofTcell)

TCRofTcellspecificforAgonBcell
interactswithAg:MHCclassIIofBcell
cognateinteractions&formconjugate
pairs.(Fig.9.7&9.8)

Figure9.7

Figure9.8

Figure9.9(Re:section96)

Refertosection97
Figure9.10

Figure9.11(Re:section97)

Figure9.12
Re:section98

Section99&figure9.13.Thetypeofcytokinesreleased
fromaThelpercellontoaBcellinfluencestheclassof
antibodyaBcellproduces.(e.gbelowformice.Specifics
aredifferentforhumansbuttheprincipleisthesame.

InductionofisotypeswitchingbyThelpersalso
requiresligationofCD40onBcellbyCD40ligandon
Tcell
Figure9.14
PeoplewithhyperIgM
syndrome,lackCD40ligand
andcantmakeantibodyto
Tdependentantigens
TheirLNshavenogerminal
centers

Section910
InteractionofThcells&centrocytes
exchangeofsignalshelpsproliferatebothB
andTcells
expandsthepopulationofhighaffinity,
isotypeswitchedBcells
cytokinesfromThcellsdeterminewhether
anantigenactivatedBcellbecomesaplasma
celloramemorycell.

Figure9.16.Notedifferencesinthese2
celltypes

Figure9.15.Duringresolutionofinfectiontowards
theendoftheIR,seeincreaseddevelopmentof
memoryBcellsduetoIL4influence.

Part2ofCh9
Effectorfunctionsofantibodies
AsIRprogresses
increasedisotypeswitchingchangesin
#ofAgbindingsites
flexibility
abilitytoactivatecomplement
abilitytodeliverpathogensto
phagocytes

Section911
InitiallyduringIR,IgMisfirstclassofAbreleased

Advantageofearly,lowaffinity
IgM

Itscarriedthroughthe
blood&lymphtositesof
infection,inflammation,
tissuedamage
Ithas10bindingsites
strongbondingevenifeach
interactionislowaffinity
Itsastrongactivatorof
classicalcomplement
pathwayC3bdeposition
pathogendestruction

DisadvantageofearlyIgM
Itslargesizelimitsits
passiveentryintoinfected
tissues..Eventually,see
isotypeswitchingtoclass
IgGandIgAwhichalso
havehighaffinityFab
regions

Advantageoflater,highaffinityIgGor
monomericIgA

Theirtwobindingsitesare
aseffectiveasthe10ofIgM
Smallsizeallowsbetter
entryintoinfectedtissue
ActiveTpofIgGinto
extracellularspacesdueto
FcRn(Brambellreceptor)

Disadvantageoflaterhigh
affinityIgGormonomericIgA

ItslaterbutbecauseofIgM
thisusuallyisOK.

Figure9.17

NotethatFcRnisalsousedtoallowIgGto
crossintotheplacenta(exclusively)
(seemiddlepaneloffig9.21)

Figure9.18.KnowthefunctionofpolyIgreceptor,
abouttrancytosisofIgA,secretorycomponent

Fig.9.21.IgAisbroughtontomucus
membranesbypolyIgreceptor&this
receptorcanalsobind&TpIgMthereaswell

Fig.9.22.NotethetypesofpassivelytransferredmaternalAb
toaninfant.NotewhenaninfantcanmakeitsownIg&
whichtypeisfirst

IgAisanimportantneutralizerof
viralinfections(fig.9.23)

IgAcanneutralizebacteriaon
mucusmembranes(fig.9.24)

Fig.9.25)

IgAandIgGcanneutralize
microbialtoxins(fig.9.26)

Antibodiescanbemadeinlarge
animalsagainstanimalvenoms
Thesespecificantitoxicantibodycanbe
giventopeoplebittenbyasnakeorinsect
andPXserioustissuedamageorevendeath

Fig.9.27.Antibodiescanactivate
complementviatheclassicalpathwayas
alreadydiscussed.Notethedifferingabilities
ofdifferentclasses&subclassesofAbtobind
complement

Fig.9.28

Fig.4.32

Fig.4.33

Fig.4.34

Fig.4.35

Fig.9.33.FcRIbindsIgG1&IgG3withhighaffinityeven
whentheyhavenotboundtheirAgtrapsAgat
phagocytessurface&targetsthemforuptake

FcRI
Thisisfoundonmacrophages,monocytes
&dendriticcells
Itisinducibleonneutrophils&eosinophils
duetoinflammationorinfection
BindsIgG3>IgG1>IgG4>>>>IgG2

Fig.9.34.OnceFcRI:IgG:pathogenthis
enhancesengulfment

Fig.9.35.FcRIIA,FcRIIIa&FcRIIIbbindonlyIgG
boundtoitsAg.FcRIIB2&FcB1areinhibitory(turn
downtheIR)

Figure9.36

FcRI
(section913&section924)
BindsIgE(notboundtopathogen)withsuchhigh
affinitythatthereisnotmuchcirculatingIgE
Thisreceptorisfoundonmastcellsinconnective
tissue,basophilsinblood,activatedeosinophilsin
mucosaltissue
OncetheIgEsonthesesensitizedcellsarebridged
bytheirspecificAgdegranulationofpreformed
mediatorsofinflammation(histamineetc.)
expulsionofparasiteORallergicS/SX

Read&knowaboutsection913&924asthisis
describingtypeIhypersensitivity(fig.9.19)

Fig.9.20

NotethatthereisalsoaFcRIthatbindsIgAbound
toitspathogen(Figure9.46)

Figure9.37

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