医学微生物学课件：11 分枝白喉

1、Mycobacteria(分枝杆菌属) summaryPrimary characteristicsThin straight , slight curled, filamentous forms, acid-fast (+)obligate aerobeClassification and pathogensM. tuberculosisM. Leprae(麻风分枝杆菌)Other mycobacteria (腐生)-opportunitic pathogensSec. 1 Mycobacterium tuberculosis (tubercle bacilli)结核分枝杆菌cause tu

2、berculosis and is a very important pathogen of human beings. The organism was named Mycobacterium tuberculosis in 1886, presumably because the organism resembles the fungi in its slow growth and colony morphology (Rough form). Primary biologic characteristicsmorphology/structure/stainingAcid-fast(+)

3、, thin straight, bacilliWaxy envelope (胞壁含大量类脂)Culture obligate aerobe, grow slowly （18h/doubling time）Lowenstein-Jensen media(罗氏), pH6.5-6.8,colony: light yellow, cauliflower-like (菜花状)（34w）Lowenstein-Jensen mediaContains defined salts, glycerolcomplex organic substances (eg, fresh eggs or egg yolk

4、s, potato flour, and other ingredients in various combinations)Malachite green ( 孔雀绿，to inhibit other bacteria).EUGONIC GROWTH 14 DAYSDYSGONIC GROWTH 14 DAYSMycobacterium tuberculosisMycobacterium bovis COLONIAL MORPHOLOGY OF THE TUBERCULOSIS COMPLEX MYCOBACTERIAresistance-strongresistance dry、acid

5、& alkaline、dye（malachite green）sensitive wet heat、 ultraviolet、75% ethanol、some drugs (e.g. rifampin and isoniazid)variationL type, multiple drug resistance, virulence -BCG Primary biologic characteristics Pathogenicity & immunityPathogenic factors-mycobacterial cell contentsNo invasiveness & toxinl

6、ipidMycolic acid (分枝菌酸)-acid fastCord factor(索状因子)-damages mitochondria (线粒体), chronic granulomas (慢性肉芽肿) Pathogenicity & immunityPathogenic factors-mycobacterial cell contentslipidPhospholipids(磷脂)-stimulate monocytes, caseous necrosis(干酪样坏死)Waxes D (蜡质D)-delayed hypersensitivitySulfatides(硫酸脑苷酯)-a

7、nti-phagocytosisprotein, polysaccharidesTransmission -tuberculosisM. tuberculosis causes diseasehealthy individuals transmitted man-man airborne dropletsPathogenesis of tuberculosis infects lung distributed within macrophages facultative intracellular pathogen inhibits phagosome-lysosome fusion resi

8、sts lysosomal enzymesClinical findingsTuberculous diseaseMany organs，pulmonary involvement oftenPrimary infection-first contact with TB, rapidly spreads, mild tissue damages , latency carrier(潜伏带菌)Re-infection-local, serious tissue damages 1. Primary infectionexogenous infection （外源性感染）children spec

9、ific immunity not yet pathological changes: easier to spread primary syndrome (原发综合征) primary site (原发灶) lymphangitis(淋巴管炎) 肺门LD炎X ray: dumbbell-like shadow (哑铃形阴影)2. Secondary infection （继发感染, 原发后感染）re-infection(Endogenous infection mostly)Adults oftenSpecific immunity has donePathological changes:

10、local siteproductive type (增殖性病变为主)： tubercle (结核结节等)immunityInfectious immunity cellular immunity cellular immunity and delayed hypersensitivitytuberculin test(结核菌素试验)-OT,PPD tuberculin test(结核菌素试验)Old tuberculin (OT) is a concentrated filtration of broth in which tubercle bacilli have grow for 6 w

11、eeks. This material contains a variety of proteins of tubercle bacilli and of growth medium; therefore physicians should no longer be doing the old TB test due to its poor reliability. PPD (purified protein derivation) is obtained by chemical fractionation of old tuberculin. The PPD test is done by

12、injecting a miniscule amount of PPD under the skin and seeing if there is resulting induration（硬结）, or swelling and firmness, of the skin. A positive tuberculin test with PPD indicates that an individual has been infected in the past and continues to carry viable mycobacteria in some tissue. It does

13、 not imply that active disease or immunity to disease is present.结核菌素试验结果分析阳性强阳性 阴性硬结、红肿直径0.5-1.5cm之间出现超敏反应不表示正患结核病硬结直径超过1.5cm以上表明可能有活动性结核，应进一步检查注射部位有针眼大的红点或稍有红肿，硬结直径小于0.5cm无结核感染，但应考虑：原发感染的早期正患严重结核病正患其他传染病（麻疹）Mycobacterium avium and AIDSThe main cause for death of AIDS.htm M. avium intracellulare (M

14、. avium) non-AIDS infection almost never AIDS major bacterial opportunist multiple drug-resistance Mycobacterium avium-intracellulare infection of lymph node in patient with AIDS Diagnosis lab testsSmears & stainingSputum smear (痰涂片)Acid fast(+), 金胺染色cultureLowenstein-Jensen media (罗氏培养基), 3-4WMolec

15、ular biologic methods-PCR detection金胺-rhodamine（罗丹明） staining Prevention & controlPrevention： BCG （卡介苗）A vaccine containing a strain of live, attenuated M.bovis can be used to induce partial resistance to tuberculosis.treatment：anti-tuberculous drugs extensive time periods (e.g. 9 months)two or more

16、 antibiotics e.g. rifampin and isoniazid （异烟肼）resistance minimized Brief SummaryThin straight bacilli , acid-fast(+), strong resistanceLowenstein-Jensen media , R-type colony, grow rather slowlyNo invasiveness & toxin, lipid cause delayed hypersensitivity and tuberculosis Brief SummaryInfectious imm

17、unity, cellular immunity and delayed hypersensitivity are present at the same timeOT test is useful for diagnosis of tuberculosis and cellular immunityPrevention-BCG two or more antibiotics* M.leprae （麻风分枝杆菌)Morphology & staining：similar to M. tuberculosishas not grown on artificial media.animal ino

18、culation (动物接种: 小白鼠足垫）spread：contact /airborne droplets* M.leprae （麻风分枝杆菌)Tuberculoid (结核样型) few organisms active cell-mediated immunityskin、mucous membrane、superficial nervesPrognosis （预后） is better lepromatous (瘤型麻风)Tuberculoid + organs of whole body immunosuppression strong infectivityprognosis i

19、s badMycobacterium lepraeulcers, resorption of bone worsened from careless use of hands (nerve damage)麻风leprosy感动中国2006候选人李恒英 麻风病防治专家 Mycobacteriaare slightly curved or straight rod-shaped, sometimes branching, aerobic bacteria that do not form spores and responsible for tuberculosis（结核）, leprosy（麻疯

20、病） and a number of saprophytic species, occasionally cause opportunist disease. Although they do not stain readily, once stained they resist decolorization by acid or alcohol and are therefore called acid-fast bacilli. There are more than 50 mycobacterium species, including many that are saprophytes

21、.白喉棒状杆菌Corynebacterium diphtheriaeCorynebacterium(棒状杆菌属) Primary biologic characteristicsMorphology & structureG+, club-shaped(棒状), lie parallel or at acute angle to one another(排列如字母 / 栅栏状)Irregularly distributed within the rod are granules staining deeply with aniline(苯胺) dyes (异染颗粒) 白喉棒状杆菌异染颗粒 Pr

22、imary biologic characteristicscultureLoeffler slant (吕氏血清斜面) tellurite plate (亚碲酸钾平板)Tellurite blood agar plate and blood agar plate （18-24h) Primary biologic characteristicsresistanceStrong in naturespread diseaseSensitive to heat ,disinfectants and penicillin PathogenicityPathogenic factorsdiphthe

23、ria toxin （白喉毒素)cord factor ，K Agdiseasediphtheria pseudomenbrane toxemia (毒血症)coded by bacteriophage tox gene not synthesized if iron present iron-repressor complex forms inhibits expression of tox genediphtheria toxin(白喉毒素)diphtheria toxin(白喉毒素)Lysogenic C. diphtheriae ( reproduce on local site) t

24、oxin(enter blood)B: binds to host cellsA: inhibits polypeptide chain elongation EF-2+NAD+ADPR-EF+烟酰胺+H+Inactive EF-2,inhibit protein synthesis辅酶I腺苷二磷酸核糖Pathogenic changes C. diphtheriae Mucous membrane Skin abrasions Superficial inflammation-Pseudomembrane suffocation (窒息), death diphtheria toxin（to

25、xemia） Necrosis in heart muscles liver kidneys adrenalsParalysis in soft palate eye muscles extremities (手足) This child has diphtheria resulting in a thick gray coating over back of throat. This coating can eventually expand down through airway and, if not treated, the child could die from suffocati

26、on CDC Diagnosis Lab testsdiphtheria toxin virulence testAnimal testElek testsmearscultureToxin identificationElek test Immunity & prevention & treatment Humoral immunity-anti-toxin (IgG/sIgA）Schick test(锡克试验)- neutralization testAnti-toxin？+ toxin (injection)-virulence reaction？detection of immunity for diphtheriaToxin-RBC