Medical Microbiology

regionsencodingtheHchainsegmentsCl,Cd,Cc,Ca,andCe,inconsecutive

order.ThusallimmunoglobulinproductionbeginswiththesynthesisofIgM

andIgD(resultingfromtranscriptionoftheVDJandtheClorCdgeneseg-

ments).Thisoccurswithoutpriorantigenstimulusandistransitionalinnat-

ure.Antigenstimulationresultsinasecondgenerearrangement—during

whichtheVDJgeneisrelocatedtothevicinityofCc,Ca,orCebyaprocess

ofrecombinationinvolvingdeletionoftheinterveningregions.Followingthis

event,theBcellnolongerproducesHchainsoftheIgMorIgDclasses,butis

insteadcommittedtotheproductionofIgG,IgA,orIgE—thusallowingsecre-

tionoftheentirerangeofimmunoglobulintypes(Table2. 2 ).Thisprocessis

knownasclassswitching,andresultsinachangeoftheIgclassofanantibody

whilstallowingitsantigenspecificitytoberetained.

Variabilitytypes.Theuseofdifferentheavyorlightchainconstantregions

resultsinnewimmunoglobulinclassesknownasisotypes.IndividualIg

classescanalsodiffer,withsuchgeneticallydeterminedvariationsinthecon-

stantelementsoftheimmunoglobulins(whicharetransmittedaccordingto

theMendelianlaws)areknownasallotypes.Variationwithinthevariable

regionresultsintheformationofdeterminants,knownasidiotypes.The

idiotypedeterminesanimmunoglobulinsantigenicspecificity,andisunique

foreachindividualB-cellclone.

Functions.Eachdifferentclassofantibodyhasaspecificsetoffunctions.IgM

andIgDactasB-cellreceptorsintheirearliertransmembraneforms,although

thefunctionofIgDisnotentirelyclear.Thefirstantibodiesproducedinthe

primaryimmuneresponseareIgMpentamers,theactionofwhichisdirected

largelyagainstmicro-organisms.IgMpentamersareincapableofcrossingthe

placentalbarrier.Theimmunoglobulinclasswhichismostabundantinthe

serumisIgG,withparticularlyhightitersofthisisotypebeingfoundfollowing

secondarystimulation.IgGantibodiespassthroughtheplacentaandsopro-

videthenewbornwithapassiveformofprotectionagainstthosepathogens

forwhichthemotherexhibitsimmunity.Incertainrarecircumstancessuch

antibodiesmayalsoharmthechild,forinstancewhentheyaredirected

againstepitopesexpressedbythechild’sowntissueswhichthemother

hasreactedagainstimmunologically(themostimportantclinicalexample

ofthisisrhesusfactorincompatibility).HighconcentrationsofIgAantibodies

arefoundintheintestinaltractandcontents,saliva,bronchialandnasalse-

cretions,andmilk—wheretheyarestrategicallypositionedtointerceptinfec-

tiouspathogens(particularlycommensals)(Fig.2. 5 ).IgEantibodiesbindto

high-affinityFcereceptorspresentonbasophilicgranulocytesandmastcells.

Cross-linkingofmastcellboundIgEantibodiesbyantigenresultsincellular

degranulationandcausesthereleaseofhighlyactivebiogenicamines(his-

tamine,kinines).IgEantibodiesareproducedinlargequantitiesfollowing

parasiticinfestationsoftheintestine,lungorskin,andplayasignificant

roleinthelocalimmuneresponseraisedagainstthesepathogens.

56 2 BasicPrinciplesofImmunology

2

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