Table Of ContentResults and Problems in Cell Diff erentiation 57
Ellen Hsu
Louis Du Pasquier Editors
Pathogen-Host
Interactions:
Antigenic Variation v.
Somatic Adaptations
Results and Problems in Cell Differentiation
Volume 57
Serieseditors
DietmarRichter
HenriTiedge
More information about this series at http://www.springer.com/series/400
Ellen Hsu (cid:129) Louis Du Pasquier
Editors
Pathogen-Host Interactions:
Antigenic Variation
v. Somatic Adaptations
Editors
EllenHsu LouisDuPasquier
DepartmentofPhysiologyand InstituteofZoologyandEvolutionaryBiology
Pharmacology UniversityofBasel
SUNYDownstateMedicalCenter Basel,Switzerland
Brooklyn,NewYork
USA
SeriesEditors
DietmarRichter HenriTiedge
CenterforMolecularNeurobiology TheRobertF.FurchgottCenterforNeural
UniversityMedicalCenter andBehavioralScience
Hamburg-Eppendorf(UKE) DepartmentofPhysiologyandPharmacology
UniversityofHamburg DepartmentofNeurology
Hamburg SUNYHealthScienceCenteratBrooklyn
Germany Brooklyn,NewYork
USA
ISSN0080-1844 ISSN1861-0412 (electronic)
ResultsandProblemsinCellDifferentiation
ISBN978-3-319-20818-3 ISBN978-3-319-20819-0 (eBook)
DOI10.1007/978-3-319-20819-0
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Preface
Cre´er,c’estrecombiner.—Franc¸oisJacob
Aschangesovertime—evolution—maybecalledadaptationatthespecieslevel,
we refer tosomatic adaptations asthose genetic changesoccurringinan animal’s
cells during its lifetime. The latter phenomenon, with which this volume is
concerned,dealswiththegeneticdiversitygeneratedinvegetativecellsofindivid-
uals,whetherparasiteorhost,enablingindividualizedresponsesforsurvival.This
strategy allows members of the population to survive, procreate, or infect. And
because the survival phenotypic constellation was somatically based, subsequent
generations continue to take individual risks. Thus, it is notso much the resultant
geneticdiversityinitselfbutratherthemechanismgeneratingthisdiversitythathas
beenevolutionarilyselectedfor.
The model systems here exemplify diversification pathways involving DNA,
RNA, or posttranslational modifications and range from protozoan to mollusk to
fishes to humans. In most cases, the diversifying mechanism, be it in host or in
parasite, enables competing responses that escalate in scissors-rock-cloth fashion.
Theadvantageofgeneticdiversificationisrapidadjustmenttonovel(read:poten-
tiallyadverse)circumstances,asintheswitchingofthevariantsurfaceglycoprotein
coating a trypanosome during the host’s mounting immune response, or as in the
proliferation and expansion of vertebrate lymphocytes bearing immunoglobulin,
T-cell receptor, or variable lymphocyte receptor (VLR) when activated in the
courseofaninfection.
As respiration andnourishment have tobe acquired fromthe externalenviron-
ment, complex interactions have originated at these interfaces; the epithelium of
respiratoryorfiltering-feedingorgansandthegutmustbealsobeimmunocompe-
tent.Theimmuneaspectofthevertebrategut,withitsassociatedlymphoidtissues
and molecules, is represented here in bony fishes and in mammals, which have
independently evolved specialized secretory immunoglobulins. Whereas V(D)J
recombinationprovidesfishlymphocyteswithavariableregionthatdirectlysplices
to the IgT C region exons, in mammals it is additional somatic signaling that
v
vi Preface
inducesclassswitchrecombinationtoIgA,diversifyingtheimmunoglobulineffec-
torfunction.Junctionsofcontactwiththeenvironmentmayhavebeentheprimary
siteswheredecisiveselectiveadvantageswereexerted.
Justasthehostsystemsevolvedtorecognizeinvaders,theinvadersevolvedto
become evaders. However, there is yet another important facet: the host needs to
distinguishbeneficentmicroorganisms.Negotiationwithgutmicrobiotaisthusnot
unilaterallydefensivebutcomplexinwaysweareonlybeginningtoexplore.The
protochordate VCBP molecules constitute the only germline-based system
presentedinthisvolume.Thesehighlydiversemoleculeshaveundergoneselection
throughevolution,andtheirroleinthegutinvolvesnotonlyimmunefunctionbut
alsoregulatingmicrobiotahomeostasis.And,intriguingly,stimulationoflympho-
cytesbythegutfloraisnotalwaysahostprotectiveresponse.Asdemonstratedin
rabbit appendix, emerging B lymphocytes interact with gut commensals, and
antibodyrepertoireexpansionthroughgeneconversionandsomatichypermutation
isdrivenbythelocalsuperantigen-likemolecules.Thedevelopingimmunesystem
within an individual is subjected to selection for tolerance versus immunity, self
versus nonself, but the interaction between its immune system and microbiome is
emergingasmultilayeredand,toagreatbutunknownextent,symbiotic.
IftheCRISPRsysteminbacteriaandarchaeaisincluded,theninmostbranches
ofthetreeoflifeorganismshaveevolvedsomaticmechanismsinthis“armsrace”
betweenhostandparasite.Asshowninmodelsreviewedinthisvolume,whenthe
diversification pathway involves combinatorial associations of elements, the gene
organizationtendstowardminimalism.Thatis,instarkcontrasttotheirdiversified
output,therearefarfewergermlineelements.Fewercomponentsfacilitateregula-
tionofthe system.Fewer buildingblocksalsopermitmorestringentselection for
efficacy;mutationsinagermlinecomponentwillhaveamplifiedeffects.Whatwe
discoveringenesystemstobesimplicityandperceiveaselegance,itisinNature
merefunctionality.
Basel,Switzerland,2015 EllenHsu
LouisDuPasquier
Contents
EvolutionofImmunityandPathogens. . . . . . . . . . . . . . . . . . . . . . . . . 1
RobertS.Jack
PartI Pathogens:AntigenRepertoiresandVariations
AHost–PathogenInteractionReducedtoFirstPrinciples:Antigenic
VariationinT.brucei. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
GaladrielHovel-Miner,MonicaMugnier,F.NinaPapavasiliou,
JasonPinger,andDanaeSchulz
AntigenicVariationinPlasmodiumfalciparum. . . . . . . . . . . . . . . . . . 47
MichaelaPetterandMichaelF.Duffy
PolymorphicMucin-LikeProteinsinSchistosomamansoni,aVariable
AntigenandaKeyComponentoftheCompatibilityBetween
theSchistosomeandItsSnailHost. . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
BenjaminGourbal,Andre´ The´ron,ChristophGrunau,
DavidDuval,andGuillaumeMitta
PartII Hosts:AnticipatoryandAdaptingMechanisms
Fibrinogen-RelatedProteins(FREPs)inMollusks. . . . . . . . . . . . . . . . 111
CoenM.Adema
SomaticandGermlineDiversificationofaPutativeImmunoreceptor
withinOnePhylum:DscaminArthropods. . . . . . . . . . . . . . . . . . . . . 131
DanielaBritesandLouisDuPasquier
AnImmuneEffectorSystemintheProtochordateGutShedsLight
onFundamentalAspectsofVertebrateImmunity. . . . . . . . . . . . . . . . 159
AssuntaLiberti,BrittanyLeigh,RosariaDeSantis,MariaRosariaPinto,
JohnP.Cannon,LarryJ.Dishaw,andGaryW.Litman
vii
viii Contents
VariableLymphocyteReceptors:ACurrentOverview. . . . . . . . . . . . 175
MasanoriKasahara
AntibodyRepertoiresinFish. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
EvaBengte´nandMelanieWilson
UniqueFeaturesofFishImmuneRepertoires:Particularitiesof
AdaptiveImmunityWithintheLargestGroupofVertebrates. . . . . . 235
SusanaMagadan,OriolJ.Sunyer,andPierreBoudinot
TheEvolutionandStructureofAtypicalTCellReceptors. . . . . . . . . 265
VictoriaL.HansenandRobertD.Miller
DiversificationofthePrimaryAntibodyRepertoirebyAID-Mediated
GeneConversion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
DennisK.LanningandKatherineL.Knight
AntibodyIsotypeSwitchinginVertebrates. . . . . . . . . . . . . . . . . . . . . 295
KateSenger,JasonHackney,JianPayandeh,andAliA.Zarrin
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Evolution of Immunity and Pathogens
RobertS.Jack
Abstract Hostandpathogenengageinaconstantevolutionarystruggleknownas
a “Red Queen Paradigm”. In this struggle, natural selection favours the pathogen
which evolves effective virulence mechanisms and the host which is able to field
adequate resistance strategies. A number of factors limit what each side can
do. These include the fact that the elaboration of virulence or resistance mecha-
nisms results in costs in genetic fitness and requires the use of ever more of the
limited number of genes available in the genome. In addition, since the pathogen
usually has a very much shorter generation time than the host, it can fix new
virulence mutations much more quickly than the host can evolve matching resis-
tance mechanisms. Finally, the host must ensure that its defence system does not
result in unacceptable levels of collateral damage to its own tissues. This chapter
brieflyoutlineshowtheseconsiderationsshapehost–pathogeninteractions.
1 The Red Queen
Alicestepped throughthe lookingglassandemerged ontheothersideina strange
country.Nosoonerwasshetherethananenergeticladyinalongreddressgrabbed
herbythehandandstartedtorunasfastasshecould.AfterawhileAlicewasoutof
breathandaskedwhytheyhadtorunsofast—especiallyastheydidn’tseemtobe
gettinganywhere.TheRedQueenlookedatherinsurpriseandtoldherthatitwould
take all the running she could do, to keep in the same place. If she wanted to get
somewhereelse,she’dhavetorunatleasttwiceasfast(Carroll1871).Theideathat
resources must beinvested, not toget ahead but simply tomaintainthestatusquo,
wastakenupbythoseinterestedinevolutiontodescribeasituationverycommonin
biology—TheRedQueenParadigm(RQP).Host–pathogeninteractionsareclassical
RQPs—arms races in which the pathogens are forever evolving new virulence
strategieswhile the host responds with ever more effective resistance mechanisms.
R.S.Jack(*)
UniversityofGreifswald,DepartmentofImmunology,SauerbruchstrasseDZ7,Greifswald
D-17487,Germany
e-mail:[email protected]
©SpringerInternationalPublishingSwitzerland2015 1
E.Hsu,L.DuPasquier(eds.),Pathogen-HostInteractions:AntigenicVariation
v.SomaticAdaptations,ResultsandProblemsinCellDifferentiation57,
DOI10.1007/978-3-319-20819-0_1
