Medical Microbiology

Celladhesionmoleculesoftenplayanessentialroleincell-to-cellinterac-

tions.Twolympho-hematopoieticcellscanonlyestablishcontactifoneof

themexpressessurfacemoleculesthatinteractwithligandsexpressedon

thesurfaceoftheothercell.AsforAPCandTcellinteractions,theresult

ofsuchcontactmaybethatasignalcapableofinducingdifferentiation

andfunctionalchangeswillbeinduced.Adhesionproteinsareusuallycom-

prisedofseveralchainswhichcaninducedifferenteffectswhenpresentin

variouscombinations.Interactionofseveralcascadesisoftenrequiredfor

thefinaldifferentiationofacell.Celladhesionmoleculesnormallyform

partoftheIgsuperfamily(e.g.,ICAM,VCAM,CD2),integrinfamily(lympho-

cytefunctionantigen,LFA-1),selectinfamily,cadherinfamily,orvarious

otherfamilies.Selectinsandintegrinsalsoplayanimportantroleininter-

actionsbetweenleukocytesandthevascularwall,andthusmediatethemi-

grationofleukocytesfromthebloodstreamintoinflamedtissues,ortheentry

ofrecirculatinglymphocytesintothelymphnodeparenchymathroughhigh

endothelialvenules(HEV).

Chemokines(chemoattractantcytokines)compriseafamilyofover 30 small

(8– 12 kDa)secretedproteins.Thesecontributetotherecruitmentof“inflam-

matorycells”(e.g.,monocytes)intoinflamedtissues,andinfluencetherecir-

culationofallclassesofleukocytes(Table2. 6 ).Somechemokinesresultinthe

activationoftheirtargetcellinadditiontoexertingchemotaticproperties.

ChemokinescanbeclassifiedintothreefamiliesbasedontheirNterminus

structure:CCchemokinesfeaturetwocontiguouscysteineresiduesattheter-

minus;CXCchemokineshaveanaminoacidbetweenthetworesidues;and

CX3CandCchemokinesthusfarcompriseonlyonemembereach(fractalkine

andlymphotactin,respectively).AlthoughtheNterminuscarriesbioactive

determinants,usingachemokinesaminoacidsequencetopredictitsbiolo-

gicalfunctionisnotreliable.Thechemokinesystemformsaredundantnet-

work,orinotherwords,asinglechemokinecanoftenactuponanumberof

receptors,andthesamereceptormayrecognizeanumberofdifferentche-

mokines.Manyofthechemokinesalsooverlapintermsofbiologicalfunction.

Chemokinescanbegroupedintwofunctionalclasses:inflammatoryche-

mokineswhicharesecretedbyinflamedorinfectedtissuesasmediatorsof

thenonspecificimmuneresponse;andconstitutivechemokineswhichare

producedinprimaryorsecondarylymphoidorgans.Togetherwithendothe-

lialadhesionmolecules,inflammatorychemokinesdeterminethecellular

compositionoftheimmigratinginfiltrate.Incontrast,thefunctionofconsti-

tutivechemokinesistodirectlymphocytestopreciselocationswithinlym-

phoidcompartments.Thus,chemokinesplayamajorroleintheestablish-

mentofinflammatoryandlymphoidmicroenvironments.Chemokinerecep-

torsareGprotein-coupledmembranereceptorswithseventransmembrane

sequences.Inkeepingwiththeabovenomenclature,theyaredesignatedas

CCR,CXCR,orCX3CRplusconsecutivenumbering.Someviruses,forinstance

84 2 BasicPrinciplesofImmunology

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Kayser, Medical Microbiology © 2005 Thieme

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