大二下学习-微生物课件10.tbdiph

Chapter11

Mycobacteria

p.153结核分枝杆菌

形态、染色、培养特性和抵抗力结核分枝杆菌感染的免疫特点

结核菌素实验的原理、结果判断和应用微生物学检查和防治原则麻风分枝杆菌

形态、染色和致病性结核分枝杆菌感染的免疫特点重点重点与难点难点Rod-shaped,aerobicbacteria,Acid-fastbacilli.Nospore,noflagellum,noexotoxinandnoendotoxin.>100speciesMainlypathogentohuman:

M.tuberclosis,and

M.bovis

---

tuberclosis

M.leprae---leprosy

M.aviumintracellulare---opportunisticinfectionofAIDSBranchedandcappedportionofLAM:LAM末端的分支帽状结构部分(甘露聚糖)；LAM：lipoarabinomannans(脂阿拉伯甘露聚糖);Mycolicacids(分枝菌酸)；Pentaarabinosylmotifs:五阿糖基基序；LM：lipomannans(脂甘露聚糖);Arabinan:(阿拉伯聚糖);Galactan:半乳聚糖；Peptidoglycan:肽聚糖；PIMs：phosphatidylinositolmannosides(磷脂酰肌醇甘露糖苷)；polyprenylsugars:聚异戊稀糖CellwallstructureandchemicalcomponentsofM.TbMilestonesofthehistoryKochfoundM.tuberculosisin1882(Germany)Kochdiscoveredtuberculinin1890(Germany)Calmettle&GuerinmadeBCGin1921(France)chemo-therapybeganin1940BCG:0-7-12Re-emergingafter80’sof20centurypopulationoflatentinfectiondrugresistance,especiallyMDRepidemicofAIDSslackoffprevention&treatment,environmentpollutionWHOdeclared“emergingstate”in4-23,1993WHOdeclaredin1995:3-24as“Dayfortuberculosistreatmentandprevention”CutaneoustuberculosisBonetuberculosisLymphnodetuberculosisRenaltuberculosisPulmonarytuberculosisepidermiology:

intheworld：

infection:

1/3popular，70%inAsiapatients:20million(about1%ofinfection)newpatientsinoneyear:8-9milliondeath:1.5-3million/year

inChina：

infection:0.55billionpatients:1.3million(2ndintheworld)death:250000(1stininfectiondiseases)

Mycobacteriumtuberclosis

I.Biologicalproperties

1.Morphologyandstain:slenderrod-shaped,Acid-faststain(Red,seenextslide).

MuchparticleAcid-faststaining(Ziehl-Neelsenmethod)

thicksmear5%carbol-fuchsion(heat,5min)95%alcoholcontaining3%HCl(decolor)methylblue(1min,counterstaining)M.Tuberculosis

acid-faststainingResultofacid-faststaining:redbacilliinbluebackground2.Culture:(Lazy、greedyandstubborn)1)richnutrients:egg,yolk,potato,glycerol,andcomplexorganicsubstances(malachitegreen),called“Lowensteinmedia”

2).obligateaerobes3).growthrateismuchslower:doublingtime-18h,colony-2~4weeks4).growinclumpsormassesCauliflower-like,Off-white3.Resistancesacids,alkalis,dehydration,drugsensitivityto:heat,ultra-violet,ethanol4.Variation

virulence---BCGdrugresistance,evenMDRII.PathogenesisIngeneral:

withoutproductionofendotoxinorexotoxin;typeⅣhypersensitivity---importantrole1.ConstituentsofTuberclebacilli:Lipid,fattyacidandwaxareresponsiblefordelayedhypersensitivity2.Pathogenicity

A.Toxicfactorcapsule(polysaccharides)

:CR3,TLR1)

2)---AbfordiagnosistuberculinsensitivityⅣhypersensitivitycordfactorphosphatidessulfatideswaxDlipidsproteins

Cordformationinliquidmedia(cordfactor)3)Polysaccharide4)Nucleicacid,especiallyrRNA

B.Pathogenesis&Pathology

a.TwoPrincipalLesions(pathology)1).exudativelesions:bacilli,PMN,monocytes2).

productivetype:centralarea,epithelioidcells,fibroblasts,lymphocytes

b.Spreadoforganisminthehost

directextension,lymphaticchannel,andbloodstream,bronchiandgastrointestinaltract

Tubercle：CaseousnecrosisEpithelioidcellLanghan’scleeLymphocyteFibroblastc.Primary&post-primary(secondary)infections1)primaryinfection:usuallyinchildhood,

a.exudativelesion;b.caseationandcalcifyinglymphnode;c.OTtest---+2)post-primaryinfection(reactivation):

usuallyinadults(bacillisurvivedinprimarylesions)

a.chronictissuelesionsb.formationoftuberclesc.caseationandfibrosis原发感染原发后感染进入肺泡在肺泡巨噬细胞中繁殖释放出的菌体在肺泡内引起炎症-原发灶肺门淋巴结（肿大）原发综合征5%发展成为活动性肺结核>90%经纤维化和钙化自愈淋巴管（炎）原发灶中潜伏的分枝杆菌外界的结核菌再次侵入人体抵抗力下降时繁殖干酪样坏死和空洞抗原呈递细胞免疫干酪样坏死病灶局限病灶中发生剧烈组织反应干酪样结节破溃导致空洞形成

PrimaryInfectionSyndromePrimaryfocus

lymphangitisTBoflymphonodeatportaoflungPrimaryInfectionSyndromeIII.Immunityandhypersensitivity1.MainlyinCellularimmunity:TcandMφ

2.Ab:usefulindiagnosis?hypersensitivity?3.RelationshipofImmunity&Hypersensitivity:infectionsimmunity;

hypersensitivity.

4.*TuberculinTest:

1)material:OT(oldtuberculin),orPPD-CandPPD-BCG2)dose:5TU/0.1ml(1~250TU)3)reaction:time---48~72h.induration<5mm->5mm+>15mm++4)interpretation:-:neverbeeninfectedorImmunity+:infected++:activedisease,especiallyinchildrenTuberculintestPPDinjectedunderskinIV.Laboratorydiagnosis1.Specimen:sputum,gastricwashings,blood,etc.2.SmearAcid-faststain(104~5/ml)3.Culture:(102~3/ml)4.DNAorIS6110detection:<10/ml5.Animaltest:Guineapigs(checklymphnodes)6.Antibodies:?

ChestX-rayofpatientswithfar-advancedtuberculosisV.Preventionandtreatment1.Prevention:BCGinoculation.DNAvaccine?2.Treatment:specificchemotherapy2majordrugsfirst-linedrugs(6)second-linedrugs(7)早期、联合、适量、规律、全程

组别药名（缩写）一线口服抗结核药物异烟肼（H）、利福平（R）、乙胺丁醇（E）、吡嗪酰胺（Z）、利福喷丁（Rft）、利福布丁（Rfb）

注射用抗结核药链霉素（S）、卡那霉素（Km）、阿米卡星（Am）、卷曲霉素（Cm）

氟喹诺酮类药物氧氟沙星（Ofx）、左氧氟沙星（Lfx）、莫西沙星（Mfx）二线口服抑菌抗结核药物乙硫异烟胺（Eto）、丙硫异烟胺（Pto）、环丝氨酸（Cs）、特立齐酮（Trd）、对氨基水杨酸（PAS）、对氨基水杨酸异烟肼（Pa）、氨硫脲（Thz）耐多药结核病治疗中疗效尚不确切的抗结核药物氯法齐明（Cfz）、利奈唑胺（Lzd）、阿莫西林/克拉维酸钾(Amx/Clv)、克拉霉素（Clr）、亚胺培南（Ipm）复习思考题1.结核分枝杆菌的生物学特性？2.结核分枝杆菌致病物质及感染特点？3.结核菌素试验原理、结果判定与用途？中英文关键词结核分枝杆菌Mycobacteriumtuberculosis

卡介苗BCG有菌免疫Infectionimmunity麻风分枝杆菌Mycobacteriuleprae课外阅读资料目录1.马屿,朱莉贞,潘毓萱.《结核病》，人民卫生出版社，20062.唐神结,高文.《临床结核病学》.人民卫生出版社,2011专著文献[1]StephenDLawn,AlimuddinIZumla.Tuberculosis.2011.Lancet378:57–72.[2]PawlowskiA,JanssonM,SköldM,RottenbergME,KälleniusG.TuberculosisandHIVCo-Infection.2012.PLoSPathog8(2):e1002464.

Corynebacteriump.193

C.diphtheriaeI.Biologicalproperties

1.Morphologyandstain:club-shaped,Albertstaining(body---blue,metachromatic

granules---black).

2.Culture:1).Media:Loeffler’sserummedia;blood;

potasiumtellurite---3biotypes

FourbiotypesofC.diphtheriae

GravisintermediusmitisColonysize

big,grayblackincenterblackStarchfermentation+--hemolysis

--+

TelluriteisreducedAlbertstaining

smearAlbert’sstainingsolution(5min)Lugol’siodinesolution(1min)checkundermicroscopeModelfigureofAlbertstainingResultofAlbertstaining:

bodyinblue

metachromaticgranulesinblack

3.Resistances:

notstrongresistancetodehydrationsensitivitytopenicillin,chloromphnic,erythromycinII.PathogenesisIngeneral:

spreadbydropletsorbycontactgrowonmucousmembrane1.Pathogenicmaterial:1)diphtheriatoxin---importantrole2)cordfactor2.Diphtheriatoxin:

producecondition:lysogenicconversionFe+2---0.14~0.5µg/ml

structure:asfollowingfigure

toxicity:verystrong,killonecell/onemoleculeStructureofDiphtheriatoxin

FragmentB:38kD,binding

FragmentA:24kD,toxicityAction:inhibitpolypeptidechainelongationEF-2+NAD+

ADPR-EF-2+NA+H+EF-2:elongationfactor2NAD:nictotinamideadeninedinucleotideADPR:adenosinediphosphate-riboseNA:nicotinamideadenieSusceptibletissue:heartmuscle,adrenalgland,liver,…3.Disease:

1)

diphtheria---isanacuterespiratoryinfectousdisease2)illedage3)thebacilligrowonmucousmembrane

pseudomembrane

toxinblooddistanttoxicdamage4)earlierstage---prostrationanddyspnea

latestage------heartdamage

patiantshealthcarrierdropletrecoveringcarrier

pharynxnasalisproduce

invasivenesspseudomembranetoxin