医学微生物学英文教学课件：11 mycobacterium

1、Chapter 11Mycobacterium 1. mycobacteria are thin and slightly curved rods. 2. acid-fast bacilli 3. cell wall contains large amount of lipid, which is highly related to staining property, resistance and pathogenicity. M. tuberculosis*M. tuberculosis bacillus M. bovis complex BCG M. africanum M. micro

2、ti*nontuberculosis mycobacteria *M.lepraeTypes of MycobacteriumSection 1. Mycobacterium tuberculosis(tubercle bacillus) Discovery of M.tuberculosisGerman bacteriologist Robert Kochfound & testified on march 24th, 1882Robert KochMortality g Highg Moderateg None or lowGlobal hygiene problemMDR strains

3、 multidrug resistantprimary fatal complication of AIDS鲁迅先生（1881-1936）林徽因（1904-1955）2007 TB anywhere is TB everywhere “结核流行广泛，控制从我做起” I am stopping TB，You can stop TB join us “控制结核，人人有责”World Tuberculosis DayMarch 24th1.morphology & staining*thin,straight or slightly curved rods *acid-fast stain-red

4、(contain large amount of mycolic acid)*thick, complex, lipid-rich cell wall*non-motile, non-spore, non-capsuleI biological properties2.culture*obligate aerobe*special nutrient requirement yolk, glycerol, malachite green, potato*slow growth primary isolation 34 weeks*colony - “cauliflower”*pellicle o

5、n surface of liquid media3.resistance*resistant to dry (in dried sputum, 6-8 months) acid - 3% HCl, 6% H2SO4 alkali - 4% NaOH dyes*sensitive to moist heat disinfectant - alcohol drug - rifampin, isoniazid, etc UV4.Variation 1). virulent variation - BCG (Bacillus Calmette-Guerin)The vaccine contains

6、a strain of live, attenuated M.bovis. BCG vaccine is effective in preventing the appearance of tuberculosis, especially in children. 2). drug resistance variationStrains of M.tuberculosis resist to the main antimycobacterial drug as well as to multiple antibiotics. (multidrug resistant TB, MDR TB )

7、a worldwide problemII Pathogenicity & Immunity M.tuberculosis produces no capsule, no invasive enzymes, no exotoxin and does not contain endotoxin in its cell wall. The pathogenicity is likely related to 1. bacteria reproduction within tissue cells resulting in inflammation2. toxicity of bacterial c

8、omponents and metabolic products3. immunopathological effects 1.Pathogenic factor (1)Lipid (closely related to virulence) cord factor phosphatide wax D sulfatides cord factor1). binds to mitochondrial membrane, cause functional damage to respiration and oxidative phosphorylation 2). inhibits migrati

9、on of leukocyte 3). causes chronic granulomatosis phosphatide 1) stimulates monocytes proliferation - form tubercle 2) Inhibit proteinase - form caseous necrosiswax D acts as an adjuvant resulting in delayed type hypersensitivity (DTH)sulfatides inhibits the fusion of phagosome and lysosome in the p

10、hagocytes(2) Protein tuberculin combined with wax D delayed type hypersensitivity (DTH) 2. pathogenesis usually infect host through respiratory tract, digestive tract or damaged skin cause infection - lung, lymph node, bone, joint, kidney, brain primary infection1) lung infection post-primary infect

11、ion 2) Out lung infection Pulmonary tuberculosis （1）primary tuberculosis organism respiratory tract pulmonary alveolar inflammation hilar lymph nodes fibrosis natural cure （2）post-primary tuberculosis organism infection again inflammation (limited & severe) tubercle fibrosis / caseation necrosisWho

12、is at riskprimary tuberculosis: children post-primary tuberculosis: adultsites of involvement primary tuberculosis: lung disseminated sites 1. gastrointestinal 2. lymph nodes 3. bones 4. kidneys 5. central nervous system-brain, spine (well-oxygenated) 1.the main anti-infectious immunity - CMI (intra

13、cellular parasites) defective cellular immunity predisposes to severe tuberculosis. the antibody is not protective2.infection immunityImmunityCMI and DTH of host greatly influence the development of the disease.3. CMI and DTH (T cells mediated)CMI - lead to protective immunity and resolution of the

14、diseaseDTH - cell necrosis and caseation lesions tissue damage and cavity organisms multiplication and spreadingIt is a skin test for DTH reaction using tuberculin. Reddening and thickening at the site of tuberculin injection after 2-3 days, indicates cellular immunity to tubercle bacilli.Tuberculin

15、 Test PPD injection 48-72h induration, erthyema 1.principle: delayed type hypersensitivity 2.procedure, result and interpretation*OT (old tuberculin) *PPD (tuberculin purified protein derivative) “-” - 5mm: # no TB infection; # early stage of infection; # severe patient suffered with TB; # the level

16、 of cellular immunity is low: tumor, AIDS, use immunosuppressive agent “+” - 5mm 15mm: # infected by TB; # BCG inoculation succeed; hypersensitive to M. tuberculosis, specific immunity “+”- 15mm: # active TB;3. application* detect immunity effect of BCG inoculation * epidemiological investigation of

17、 TB infection* help to diagnosis TBThe steps to diagnose TB infection and disease include A medical evaluation that includes history and risk assessment The tuberculin skin test A chest x-ray A bacteriological examination 1. specimen: sputum * treatment with NaOH and concentration by centrifugation-

18、 acid-fast stain III microbiologic examination 2. culture 3. animal test 4. PCR IV Prevention & Treatment1. specific prevention: BCG2. primary drugs: streptomycin, isoniazid, para-aminosalicyclic acid secondary drugs: ethambutol, pyrazinamide tertiary drugs: capreomycin new drug: rifampin M.tuberculosis enter alveolus phagocytosed by macrophage forming phagosome preve