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¢rocytes
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§ion924)
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