大二下學(xué)習(xí)-微生物課件10.tbdiph

Chapter11

Mycobacteria

p.153結(jié)核分枝桿菌

形態(tài)、染色、培養(yǎng)特性和抵抗力結(jié)核分枝桿菌感染的免疫特點(diǎn)

結(jié)核菌素實(shí)驗(yàn)的原理、結(jié)果判斷和應(yīng)用微生物學(xué)檢查和防治原則麻風(fēng)分枝桿菌

形態(tài)、染色和致病性結(jié)核分枝桿菌感染的免疫特點(diǎn)重點(diǎn)重點(diǎn)與難點(diǎn)難點(diǎn)Rod-shaped,aerobicbacteria,Acid-fastbacilli.Nospore,noflagellum,noexotoxinandnoendotoxin.>100speciesMainlypathogentohuman:

M.tuberclosis,and

M.bovis

---

tuberclosis

M.leprae---leprosy

M.aviumintracellulare---opportunisticinfectionofAIDSBranchedandcappedportionofLAM:LAM末端的分支帽狀結(jié)構(gòu)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:聚異戊稀糖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原發(fā)感染原發(fā)后感染進(jìn)入肺泡在肺泡巨噬細(xì)胞中繁殖釋放出的菌體在肺泡內(nèi)引起炎癥-原發(fā)灶肺門淋巴結(jié)（腫大）原發(fā)綜合征5%發(fā)展成為活動性肺結(jié)核>90%經(jīng)纖維化和鈣化自愈淋巴管（炎）原發(fā)灶中潛伏的分枝桿菌外界的結(jié)核菌再次侵入人體抵抗力下降時(shí)繁殖干酪樣壞死和空洞抗原呈遞細(xì)胞免疫干酪樣壞死病灶局限病灶中發(fā)生劇烈組織反應(yīng)干酪樣結(jié)節(jié)破潰導(dǎo)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、聯(lián)合、適量、規(guī)律、全程

組別藥名（縮寫）一線口服抗結(jié)核藥物異煙肼（H）、利福平（R）、乙胺丁醇（E）、吡嗪酰胺（Z）、利福噴?。≧ft）、利福布?。≧fb）

注射用抗結(jié)核藥鏈霉素（S）、卡那霉素（Km）、阿米卡星（Am）、卷曲霉素（Cm）

氟喹諾酮類藥物氧氟沙星（Ofx）、左氧氟沙星（Lfx）、莫西沙星（Mfx）二線口服抑菌抗結(jié)核藥物乙硫異煙胺（Eto）、丙硫異煙胺（Pto）、環(huán)絲氨酸（Cs）、特立齊酮（Trd）、對氨基水楊酸（PAS）、對氨基水楊酸異煙肼（Pa）、氨硫脲（Thz）耐多藥結(jié)核病治療中療效尚不確切的抗結(jié)核藥物氯法齊明（Cfz）、利奈唑胺（Lzd）、阿莫西林/克拉維酸鉀(Amx/Clv)、克拉霉素（Clr）、亞胺培南（Ipm）復(fù)習(xí)思考題1.結(jié)核分枝桿菌的生物學(xué)特性？2.結(jié)核分枝桿菌致病物質(zhì)及感染特點(diǎn)？3.結(jié)核菌素試驗(yàn)原理、結(jié)果判定與用途？中英文關(guān)鍵詞結(jié)核分枝桿菌Mycobacteriumtuberculosis

卡介苗BCG有菌免疫Infectionimmunity麻風(fēng)分枝桿菌Mycobacteriuleprae課外閱讀資料目錄1.馬嶼,朱莉貞,潘毓萱.《結(jié)核病》，人民衛(wèi)生出版社，20062.唐神結(jié),高文.《臨床結(jié)核病學(xué)》.人民衛(wèi)生出版社,2011專著文獻(xiàn)[1]StephenDLawn,AlimuddinIZumla.Tuberculosis.2011.Lancet378:57–72.[2]PawlowskiA,JanssonM,Sk?ldM,RottenbergME,K?lleniusG.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