From Innate Immunity to Immunological Memory

189 Pages·2006·2.81 MB·English

by  S. Akira (auth.)

311
Current Topics
in Microbiology
and Immunology
Editors
R.W.Compans,Atlanta/Georgia
M.D.Cooper,Birmingham/Alabama
T.Honjo,Kyoto·H.Koprowski,Philadelphia/Pennsylvania
F.Melchers,Basel·M.B.A.Oldstone,LaJolla/California
S.Olsnes,Oslo·C.Svanborg,Lund
P.K.Vogt,LaJolla/California·H.Wagner,Munich
B. Pulendran and R. Ahmed (Eds.)
From Innate Immunity
to Immunological
Memory
With13Figuresand6Tables
123
BaliPulendran,Ph.D.
RafiAhmed,Ph.D.
EmoryVaccineCenter
954GatewoodRoad
Atlante,GA30329
USA
e-mail:[email protected]
[email protected]
CoverIllustration:
Thetwointravitalmulti-photonmicrographsshowAg-presentingdendriticcells(DCs)interacting
withTCRtransgenicTcellsinapopliteallymphnode(LN)ofananesthetizedmouse.Inthe
backgroundimagetheDCs(whichwereinjectedintheanimal’sfootpadonedayearlier)are
showninredandCD4andCD8Tcellsarelabeledinblueandgreen,respectively.Inthesmaller
foregroundimage,ameshworkofLN-residentendogenousDCsareshown,whichexpresschimeric
MHCclassIIlinkedtoGFP(green).CD4Tcellswerelabeledinredandinterstitialcollagenfibers
areblue.BothimagesweregeneratedinDr.UlrichH.vonAndrian’slabbyDr.ThorstenMempel.
LibraryofCongressCatalogNumber72-152360
ISSN 0070-217X
ISBN-10 3-540-32635-9 SpringerBerlinHeidelbergNewYork
ISBN-13 978-3-540-32635-7 SpringerBerlinHeidelbergNewYork
Thisworkissubjecttocopyright.Allrightsreserved,whetherthewholeorpartofthematerial
isconcerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,
broadcasting,reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Dupli-
cationofthispublicationorpartsthereofispermittedonlyundertheprovisionsoftheGerman
CopyrightLawofSeptember,9,1965,initscurrentversion,andpermissionforusemustal-
waysbeobtainedfromSpringer-Verlag.ViolationsareliableforprosecutionundertheGerman
CopyrightLaw.
SpringerisapartofSpringerScience+BusinessMedia
springeronline.com
©Springer-VerlagBerlinHeidelberg2006
Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoes
notimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromthe
relevantprotectivelawsandregulationsandthereforefreeforgeneraluse.
Productliability:Thepublishercannotguaranteetheaccuracyofanyinformationaboutdosage
and application contained in this book. In every individual case the user must check such
informationbyconsultingtherelevantliterature.
Editor:SimonRallison,Heidelberg
Deskeditor:AnneClauss,Heidelberg
Productioneditor:NadjaKroke,Leipzig
Coverdesign:WMXDesign,Heidelberg
Typesetting:LE-TEXJelonek,Schmidt&VöcklerGbR,Leipzig
Printedonacid-freepaper SPIN11679127 27/3150/YL – 5 4 3 2 1 0
FromInnateImmunitytoImmunologicalMemory
The ability to remember an antigenic encounter for several decades, even
foralifetime,isoneofthefundamentalpropertiesoftheimmunesystem.
This phenomenon known as “immunological memory,” is the foundation
upon which the concept of vaccination rests. Therefore, understanding the
mechanismsbywhichimmunologicalmemoryisregulatedisofparamount
importance.Recentadvancesinimmunology,particularlyinthefieldofinnate
immunity, suggest that the innate immune system plays fundamental roles
in influencing the generation and maintenance of immunological memory.
Indeed,emergingevidencesuggeststhateventsthatoccurearly,withinhours
ifnot minutesofpathogen orvaccine entry profoundly shapethequantity,
qualityanddurationofimmunologicalmemory.Thepresentvolumeassem-
blesacollectionofessaysfromleadingexpertsthatspantheentirespectrum
researchfromunderstandingthemolecularmechanismsofinnateimmune
recognition,todendriticcellfunction,tothegenerationandmaintenanceof
antigen-specificBandT-cellresponses,andmemory.
The first two reviews focus on aspects of innate immunity, specifically
on how the innate immune system ‘senses’ pathogens and modulates the
adaptive immunity against them. The article by ShizuoAkira [1] discusses
pathogenrecognitionbyToll-likereceptors[TLRs].Intheeightyearssince
the demonstration of the critical roles they play in microbe sensing in the
mammalianimmunesystem,ithasbecomeclearthateachTLRsensesadif-
ferentsetofmicrobialstimuli,andthatindividualTLRsactivatedistinctbut
overlappingsignalingpathwaysandtranscriptionfactorsthatdrivespecific
biologicalresponsesagainstthepathogens.Followingonthistheme,thearti-
clebySteinmanandHemmireviewstheimportantrolesplayedbydendritic
cells (DCs) in sensing microbes or vaccines, and in modulating the quality
andquantityofadaptiveimmuneresponses.DCsappeartoplayauniquerole
inintegratingsignalsfromvarioussources,includingmicrobialstimulithat
signal directly via TLRs and other pathogen recognition receptors (PRRs),
butalsofromothercellsoftheinnateimmunesystem,includingNKcellsand
NKTcells.
VI FromInnateImmunitytoImmunologicalMemory
The next three chapters focus on aspects of adaptive immunity and im-
munological memory. McHeyzer-Williams and McHeyzer-Williams discuss
the generation and maintenance of antigen-specific T-helper and B cell re-
sponses. Recent studies provide insights into the dynamics of interaction
between antigen-bearing DCs and antigen-specific T-helper cells, and how
thisprogramsthequalityofT-helperandBcellresponses.Followingalong
thistheme,TanandSurhdiscussthedevelopmentofantigen-specificmem-
ory T cells, guided by a progressive set of environmental and cell intrinsic
cues,whichincludethetypeofantigen-bearingDCs,aswellasinflammatory
mediators.Aninterestingaspectofthisisthatinflammatorymediatorsplay
importantroles,notonlyinthegenesisofantigen-specificTcellresponses,
butalsointhemaintenanceandhomeostasisofsuchcells.Finally,thechapter
byWelshandcolleaguesdiscusseshowtheT-cellreceptorrepertoireofcells
inthememoryTcellpoolisgeneratedandmodulatedbytheinnateimmune
cytokines,andhowthisismodulatedinresponsetootherinfections.
TheemergingevidencethatTLRsignalingcontrolscriticalaspectsofin-
nateandadaptiveimmunityoffersnovelstrategiesforenhancingtheefficacy
ofvaccinesagainstinfectiousdiseases.Inthiscontext,thefinalarticlebyMc-
CluskieandKriegdiscusshowCpGDNA,whichsignalsthroughTLR9induce
potentstimulationofplasmacytoidDCs,andBcellsandpromotestrongTh1
responses.TheadditionofCpGDNAtomostvaccinesappeartoinducefaster
seroconversion,withfewervaccinations,whichmightfacilitatereducedanti-
gendoses.Thus,intheshortperiodsincethediscoveryofTLRs,theyhave
alreadybeguntoenterseveralclinicaltrials.Thehopeisspecifictriggeringof
particularcombinationsofTLRsorPRRs,wouldyieldimmuneresponsesand
immunologicalmemory,whichareasgood,orevenbetter,thatthatinduced
bythebestofourempiricallyderivedvaccines.
Atlanta,June2006 BaliPulendran,RafiAhmed
ListofContents
TLRSignaling ............................................... 1
S.Akira
DendriticCells:TranslatingInnatetoAdaptiveImmunity ................ 17
R.M.SteinmanandH.Hemmi
HelperTCell-RegulatedBCellImmunity ............................ 59
L.J.McHeyzer-Williams,L.P.Malherbe,andM.G.McHeyzer-Williams
TCellMemory............................................... 85
J.T.TanandC.D.Surh
ThePrivacyofTCellMemorytoViruses ............................117
R.M.Welsh,S.K.Kim,M.Cornberg,S.C.Clute,L.K.Selin,andY.N.Naumov
EnhancementofInfectiousDiseaseVaccines
ThroughTLR9-DependentRecognitionofCpGDNA ....................155
M.J.McCluskieandA.M.Krieg
SubjectIndex................................................179
ListofContributors
(Addressesstatedatthebeginningofrespectivechapters)
Akira,S. 1 McHeyzer-Williams,L.J. 59
McHeyzer-Williams,M.G. 59
Clute,S.C. 117
Cornberg,M. 117 Naumov,Y.N. 117
Hemmi,H. 17 Selin,L.K. 117
Steinman,R.M. 17
Kim,S.K. 117 Surh,C.D. 85
Krieg,A.M. 155
Tan,J.T. 85
Malherbe,L.P. 59
McCluskie,M.J. 155 Welsh,R.M. 117
CTMI(2006)311:1–16
(cid:1)c Springer-VerlagBerlinHeidelberg2006
TLRSignaling
S.Akira((cid:1))
DepartmentofHostDefense,ResearchInstituteforMicrobialDiseases,
OsakaUniversityandERATO,JST,3-1Yamadaoka,Suita,565-00Osaka,Japan
[email protected]
1 Introduction ........................................... 2
2 TLRSignalingPathways ................................... 3
2.1 MyD88-DependentandIndependentPathways ................... 3
2.2 RolesofAdaptorsinTLRSignaling ........................... 5
2.2.1 TIRAP/Mal ............................................ 5
2.2.2 TRIF ................................................. 6
2.2.3 TRAM................................................ 7
2.3 MechanismsofType1InterferonInduction
byTRIF-DependentPathway ................................ 7
2.3.1 IRF3Kinases,TBK1andIKK-i............................... 7
2.3.2 SignalingPathwaysDownstreamofTRIF ....................... 8
2.4 Type1IFNInductioninPDC................................ 8
3 IntracytoplasmicDetectionofPathogens ....................... 9
3.1 DetectionofPeptidoglycanbyNODFamily...................... 9
3.2 DetectionofIntracellularDouble-StrandedRNAbyRIG-1andMDA-5 .. 11
4 Conclusion ............................................ 12
References.................................................. 13
Abstract Mammalian Toll-like receptors (TLRs) play a critical role in detection of
invadingpathogensas well astriggering of subsequentinflammatory andimmune
responses.EachTLRrecognizesdistinctmicrobialcomponentsandactivatesdiffer-
ent signaling pathways by selective utilization of adaptor molecules. The signaling
viaTLRsisdeliveredfromthecellsurfaceand/ortheendosome.Recently,theintra-
cytoplasmicdetectionsystemofmicrobeshasbeenidentifiedinmammalsaswell.
Peptidoglycan breakdown products and double-stranded RNA are sensed by NOD
familyandRNAhelicasedomaincontainingproteins,respectively.Thus,mammals
make use of both receptor-type and intracellular proteins as detectors of invading
pathogens.
2 S.Akira
1
Introduction
Toll-like receptors (TLRs) play a critical role in innate immunity as well as
acquiredimmunity(Beutler2004;Medzhitov2001;Takedaetal.2003).TLRs
arevertebratecounterpartsofTollinDrosophila.DrosophilaToll,originally
identifiedasareceptorcriticalfordorsoventralaxisformationinflyembry-
onic development, has been shown to be essential to antifungal responses
in flies (Lemaitre et al. 1996). This finding led to identification of TLRs in
mammals (Medzhitov et al. 1997). The TLR family is now composed of 11
members, but only these members may be enough to detect all pathogens
frombacteriatoviruses(Table1).OnereasonisthatTLRtargetsthecom-
Table1 Toll-likereceptorligands
Receptor Ligands Syntheticanalogues
TLR1 Bacteriallipoproteins Triacyllipopeptides
TLR2 Lipoproteins/lipopeptides Diacylandtriacyllipopeptides
Peptidoglycan
Lipoteichoicacid
Zymosan
(Heat-shockprotein70)?
TLR3 Viraldouble-strandedRNA PolyI:C
TLR4 Lipopolysaccharide SyntheticlipidA
Taxol
RSvirusFprotein
(Heat-shockproteins)?
Tamm-Horsfallglycoprotein
TLR5 Bacterialflagellin
TLR6 Mycoplasmalipopeptides Diacyllipopeptides
Zymosan
TLR7 Single-strandedRNA ImidazoquinolinessiRNA
ViralRNA
TLR8 Single-strandedRNA Imidazoquinolines
ViralRNA
TLR9 BacterialDNA CpG-containingoligonucleotides
Hemozoin(malariapigment)
ViralDNA
TLR10 ND ND
TLR11 ND Uropathogenicbacteria
ND,notdetermined