Medical Microbiology

tumors).However,ingeneralthedetectionofautoantibodiesdoesnotne-
cessarilycorrelatewithevidenceofpathologicalchangesorprocesses.In
fact,ourdetectionmethodsoftenmeasurelow-avidityautoantibodiesthat
mayhavenodirectdisease-causingeffects.
Exactlyhowautoantibodyresponsesareinducedremainstobeclarified.
Asexplainedearlier(inthediscussionofimmunologicaltolerance)suchIgG
responsescannotbeinducedwithoutThelp.Thus,intensiveresearchis
currentlyfocusedonthosemechanismsbywhichTcellhelpforautoreactive
Bcellsisregulated;Table2. 12 sumsupsomeofthepossiblemechanisms.

Anti-bloodGroupAntibodyReactions................

ABOsystem.TheseB-cellepitopesconsistofsugargroupspresentinthemem-
branesofredbloodcells.Thefourclassicbloodgroupsaredeterminedbyone
genewiththreealleles.Thisgenecontrolsglycosylation.TheOallelecodes
onlyforabasiccellsurfacestructure(Hsubstance)withtheterminalsugars
galactoseandfucose.TheAalleleaddsN-acetylgalactosaminetothisbasic
structure,theBalleleaddsgalactose.Thisresultsinepitopes,whichare
alsoseenfrequentlyinnaturelargelyascomponentsofintestinalbacteria.In-
dividualswhocarrytheAallelearetoleranttotheA-codedepitope,whilst
individualswiththeBallelearetoleranttotheBepitope.Individualswho
carrybothofthesealleles(genotypeAB)aretoleranttobothepitopes,
whereaspersonswhoarehomozygotesfortheOallelearenottolerantto
eitherAorB.Followingbirth,theintestinaltractiscolonizedbybacteriacon-

ThePathologicalImmuneResponse 111

Table2. 12 MechanismsOfAutoantibodyInduction

Possiblemechanisms Autoimmunepathologyorimmunopathology

PolyclonalB-cellactivation Lipopolysaccharides,viruses,chronicparasitic
infection

Molecularmimicry
(overallveryrare)

Anti-tat(HTLV-1),anti-H.pylori,oranti-strepto-

coccuscrossreactingwithself-antigens

Exposureofhiddenautoantigens Cytopathiceffectsofinfectiousagents

Adjuvanteffects Inthepresenceofgranulomaformationand
chronicinflammatoryreactionslymphoidtissue
mayforminperipheralorgans(e.g.,during
Hashimoto’sthyroiditis)

Breakdownoftolerance DuetocouplingofThelperepitopesto
autoantigens,possibleinconnectionwithvirus
infectionsofcells

2

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Kayser, Medical Microbiology © 2005 Thieme

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