Medical Microbiology

264 4 BacteriaasHumanPathogens

TBareobligateanaerobes.Theirreproductionisenhancedbythepresence

of 5 – 10 %CO 2 intheatmosphere.Theyaregrownonculturemediumswitha

highlipidcontent,e.g.,egg-enrichedglycerolmediumsaccordingtoLo ̈wen-

stein-Jensen(Fig.4. 12 b).ThegenerationtimeofTBisapproximately 12 – 18

hours,sothatculturesmustbeincubatedforthreetosixoreightweeks

at 378 Cuntilproliferationbecomesmacroscopicallyvisible.

Cellwall.ManyofthespecialcharacteristicsofTBareascribedtothechem-

istryoftheircellwall,whichfeaturesamureinlayeraswellasnumerous

lipids,themostimportantbeingtheglycolipids(e.g.,lipoarabinogalactan),

themycolicacids,mycosides,andwaxD.

GlycolipidsandwaxD.

— Responsibleforresistancetochemicalandphysicalnoxae.

— Adjuvanteffect(waxD),i.e.,enhancementofantigenimmunogenicity.

— Intracellularpersistenceinnonactivatedmacrophagesbymeansofin-

hibitionofphagosome-lysosomefusion.

— Complementresistance.

— Virulence.Cordfactor(trehalose6,6-dimycolate).

Tuberculoproteins.

— Immunogens.Themostimportantoftheseisthe 65 kDaprotein.

— Tuberculin.Partiallypurifiedtuberculincontainsamixtureofsmallpro-

teins(1 0 kDa).TuberculinisusedtotestforTBexposure.Delayedallergic

reaction.

Polysaccharides.Ofunknownbiologicalsignificance.

Pathogenesisandclinicalpicture.Itisnecessarytodifferentiatebetween

primaryandsecondarytuberculosis(reactivationorpostprimarytuberculo-

sis)(Fig.4. 13 ).Theclinicalsymptomsarebasedonreactionsofthecellular

immunesystemwithTBantigens.

&Primarytuberculosis.Inthemajorityofcases,thepathogensenterthe

lungindroplets,wheretheyarephagocytosedbyalveolarmacrophages.TB

bacteriaareabletoreproduceinthesemacrophagesduetotheirabilityto

inhibitformationofthephagolysosome.Within 10 – 14 daysareactiveinflam-

matoryfocusdevelops,theso-calledprimaryfocusfromwhichtheTBbac-

teriamoveintotheregionalhilarlymphnodes,wheretheyreproduceand

stimulateacellularimmuneresponse,whichinturnresultsinclonalexpan-

sionofspecificTlymphocytesandattendantlymphnodeswelling.The

Ghon’scomplex(primarycomplex,PC)developsbetweensixand 14 weeks

afterinfection.Atthesametime,granulomasformattheprimaryinfection

siteandintheaffectedlymphnodes,andmacrophagesareactivatedby

thecytokineMAF(macrophageactivatingfactor).Atuberculinallergyalso

developsinthemacroorganism.

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Kayser, Medical Microbiology © 2005 Thieme