1、呼吸道感染的細(xì)菌,結(jié)核分枝桿菌 白喉?xiàng)U菌 軍團(tuán)菌 乙型鏈球菌 肺炎鏈球菌 腦膜炎球菌 百日咳鮑特菌 流感嗜血桿菌,分枝桿菌屬M(fèi)ycobacterium,分枝生長(zhǎng) 細(xì)胞壁含大量脂質(zhì)分枝菌酸 抵抗鹽酸酒精脫色（抗酸染色陽性） 致病菌生長(zhǎng)緩慢 引起慢性疾病，伴肉芽腫,分類 人型結(jié)核分枝桿菌 牛型結(jié)核分枝桿菌 結(jié)核分枝桿菌復(fù)合群 非洲分枝桿菌 田鼠分枝桿菌 麻風(fēng)分枝桿菌 非結(jié)核分枝桿菌,Mycobacteria tuberculosis, Discovered tuberculosis bacillus and method of growing it in pure culture in 1882.

2、 Awarded by Nobel Prize for medicine in 1905,Dr. Robert Koch (1843-1910),Tuberculosis結(jié)核病(TB),It is primarily a slowly progressing infectious disease of the lungs caused by the bacterium Mycobacterium tuberculosis . Mycobacterium bovis is also a causative agent.,Bacillus Calmette-Gurin (BCG ),a vacci

3、ne against tuberculosis that is prepared from a strain of the attenuated (weakened) live bovine tuberculosis bacillus,Camille Gurin,Albert Calmette,1943,Selman A. Waksman purified streptomycin ,showed inhibition of M. tuberculosis in animal test. In 1952 he was awarded the Nobel Prize streptomycin t

4、he first antibiotic active against tuberculosis,Selman A. Waksman,結(jié)核分枝桿菌的流行現(xiàn)狀,80年代以前結(jié)核病死亡率,80年代以后結(jié)核病死亡率,中國(guó)： 2006年新發(fā)結(jié)核病例460萬 死亡13萬 每年3月24日 世界結(jié)核日(World TB day),(Mycobacterium tuberculosis),1. 生物學(xué)性狀 細(xì)胞壁中含大量分枝菌酸 抗酸染色陽性 染色后不易被鹽酸酒精脫色,致病菌: 人型及牛型結(jié)核桿菌,結(jié)核分枝桿菌,結(jié)核桿菌（抗酸染色）, 需氧菌，3042生長(zhǎng), 緩慢 可誘導(dǎo)致L型 非抗酸性G+顆粒Much顆粒,結(jié)

5、核桿菌L型, 常用Lowenstein-Jensen培養(yǎng)基或土路豆Trudeau培養(yǎng)基 蛋黃 脂質(zhì)生長(zhǎng)因子 孔雀綠 抑制雜菌生長(zhǎng) 菌落特點(diǎn): 干燥、顆粒狀、結(jié)節(jié)樣、菜花樣米黃色菌落 液體培養(yǎng)基中形成菌膜,不發(fā)酵糖類 熱觸酶試驗(yàn) 可鑒別結(jié)核桿菌和非結(jié)核桿菌, 抵抗力 耐干燥:干燥痰中6-8個(gè)月 烈日曝曬2小時(shí) 耐酸、堿:Acid: 3%HCl or 6% H2SO4 Alkalis:4%NaOH 蛋白質(zhì) 保護(hù) 對(duì)濕熱、紫外線 、乙醇敏感 鏈霉素、異煙肼、利福平 敏感 但易產(chǎn)生耐藥,變異多見 形態(tài)變異 毒力變異 BCG(卡介苗) 耐藥性變異 對(duì)異煙肼（INH）耐藥 編碼過氧化氫-過氧化物酶的基因（

6、katG)中心部位突變或katG基因缺失以及inhA（enoyl-ACP還原酶基因）的調(diào)節(jié)基因發(fā)生突變。,對(duì)利福平耐藥 編碼細(xì)菌RNA聚合酶亞單位的rpoB基因突變，使該酶不再與利福平結(jié)合而耐藥。 在rpoB基因中央附近69bp的高變區(qū)域內(nèi)，存在35種以上的錯(cuò)義突變，其中以Ser531Leu和His526 Tyr最常見，約占總突變65%以上。 對(duì)鏈霉素耐藥 編碼細(xì)菌16SrRNA的rrs基因和編碼S12蛋白的rpsL基因發(fā)生突變，使16SrRNA與鏈霉素?zé)o法結(jié)合。,致病物質(zhì),脂質(zhì): 索狀因子(6,6-雙分枝菌酸海藻糖)：破壞線粒體膜，抑制白細(xì)胞游走，引起慢性肉芽腫 磷脂：促使單核細(xì)胞增生，抑制

7、蛋白酶的分解作用,使巨噬細(xì)胞轉(zhuǎn)變?yōu)轭惿掀ぜ?xì)胞，形成結(jié)核結(jié)節(jié)和干酪樣壞死 蠟質(zhì)D：分枝菌酸和糖肽脂復(fù)合物，具佐劑作用,引起遲發(fā)性超敏反應(yīng) 硫酸腦苷脂：抑制吞噬細(xì)胞的吞噬體與溶酶體結(jié)合 蛋白質(zhì): 結(jié)核菌素(無毒) 蠟質(zhì)D 超敏反應(yīng),Fluorescent stained microcolonies of M.tuberculosis showing serpentine cord formation,原發(fā)感染,結(jié)核桿菌 吸入 肺泡, 巨噬細(xì)胞吞噬 脂質(zhì)抗吞噬 繁殖后破壞巨噬細(xì)胞 釋放 炎癥原發(fā)灶 肺門淋巴結(jié)腫大 原發(fā)綜合征 磷脂 朗罕巨細(xì)胞 干酪樣壞死 結(jié)核桿菌潛伏 結(jié)核結(jié)節(jié) 其他系統(tǒng)結(jié)核 愈合,

8、絕大部分,約15%,The granuloma of primary tuberculosis,Tuberculous nodules in the lung of a patient with tuberculosis.shows the caseous necrosis.,Primary pulmonary tuberculosis,X-RAY shows the lung of the patient suffering miliary tuberculosis,原發(fā)后感染 內(nèi)源性 原發(fā)病灶內(nèi) 外源性 重新感染 病灶多局限 干酪樣壞死灶 鈣化，痊愈 形成空洞,The clinical s

9、igns of pulmonary tuberculosis Low-grade fever weight loss, cough, night sweats, malaise chest pain Blood stained sputum血痰 (phlegm粘痰) hemoptysis(咯血).,肺外結(jié)核,細(xì)胞免疫為主 單核巨噬細(xì)胞在IL-2、 IL- 6及IFN- 等作用下, 吞噬功能 細(xì)胞免疫和超敏反應(yīng)并存 （郭霍現(xiàn)象）,3. 免疫性,結(jié)核菌素試驗(yàn) 舊結(jié)核菌素(OT) 純蛋白衍生物(PPD)：PPD-C和BCG-PPD 目的： 檢測(cè)機(jī)體是否感染過結(jié)核桿菌,機(jī)體對(duì)結(jié)核桿菌是否有超敏反應(yīng)及檢

10、測(cè)機(jī)體的細(xì)胞免疫功能. 方法： PPD-C和BCG-PPD各5單位分別注射兩 前臂皮內(nèi) 結(jié)果：陽性(5mm) 已感染過結(jié)核桿菌或 接種過卡介苗 強(qiáng)陽性（ 15mm) 活動(dòng)性結(jié)核病 陰性 一般表示未感染過結(jié)核桿菌,意義： 確定BCG接種對(duì)象和測(cè)定接種效果 臨床診斷意義，強(qiáng)陽性(15mm) 測(cè)定機(jī)體的細(xì)胞免疫功能 未接種人群TB感染的流行病學(xué)調(diào)查,4. 微生物學(xué)檢查,標(biāo)本 ：痰、支氣管灌洗液、尿、腦脊液等 涂片鏡檢 抗酸染色初步診斷 金胺染色提高檢出率 集菌 離心、4%NaOH 、3%HCl 分離培養(yǎng) Lowenstein-Jensen培養(yǎng)基或土路豆培養(yǎng)基,顆粒、結(jié)節(jié)、菜花樣菌落 快速診斷 PCR

11、, 有假陽性,More sensitive than an acid fast stain, this auramine stain requires fluorescence microscopy. Note the yellow-orange rod-like mycobacteria. Of course, the most sensitive method for detection of mycobacteria is microbiologic culture,5. 防治, 新生兒接種卡介苗：注意復(fù)查 世界范圍內(nèi)有效率0-80% 監(jiān)測(cè)流行情況 發(fā)現(xiàn)和治療痰菌陽性者：我國(guó)免費(fèi)治療 治

12、療原則: 利福平、異煙肼聯(lián)合用藥,防止產(chǎn) 生耐藥,Treatment,prevention,and control,Regimens recommended for treatment include isoniazid(INH)異煙肼and rifampin for 9 months ,with pyrazinamide吡嗪酰胺and ethambutol乙胺丁醇o(jì)r streptomycin added for drug-resistant strains. 全程、足量,DOTS is a abbreviation of Directly Observed,二. 麻風(fēng)桿菌Mycobacte

13、rium leprae, Cause Leprosy(麻風(fēng)病) positive acid-fast stain . cant culture with artificial medium. Can multiply and passage within the paws of mouse and armadillo犰狳,armadillo犰狳,Acording the clinical manifestation ,leprosy has been divided into: tuberculoid(TT) leprosy結(jié)核樣型麻風(fēng) lepromatous(LL) leprosy瘤型麻風(fēng)

14、Intermediate forms,Borderline tuberculoid(BT) mid-borderline (BB) borderline lepromatous(BL ),中間型麻風(fēng),tuberculoid(TT) leprosy結(jié)核樣型麻風(fēng), Is associated with cellular immnity directed hyper-reactive damage of skin and peripheral nerves trunks. The resulting nerve damage is responsible for the main clinical

15、features of leprosy: anaesthesia(感覺消失) and muscle paralysis. Repeated injuries to,and infections of ,the anaesthetic extremities leads to their gradual destruction,result in deformation eventually.,tuberculoid(TT) leprosy結(jié)核樣型麻風(fēng),lepromatous(LL) leprosy瘤型麻風(fēng), mainly infected skin and mucous membrane. W

16、ith dysfunction of cellular immunity,the pathological damage is related to Ag-Ab complex the skin lesions are numerous or confluent and contain huge numbers of bacilli,usually seen as clusters or globi within monocytes. Cooler parts of the body ,such as the ear lobes,are particularly heavily infiltr

17、ated by bacilli.,Biopsy stained with acid-fast stain,shows that in the clinical material from lepromatous patients,the bacilli are typically found within macrophages in dense clumps(called leprotic globi).,麻風(fēng)球,Destruction of the nasal bones may lead to collapse of the nose,白喉棒狀桿菌Corynebacterium diph

18、theriae, G+ rods with tapered end Neisser染色不均勻，有異染顆粒 Cells often contain metachromatic granules異染顆粒(成分:polymetaphosphate) 作用: 儲(chǔ)存養(yǎng)料 有鑒定價(jià)值,C. diphtheriae Cells often contain metachromatic granules(polymetaphosphate) which stain bluish purple with methylene blue,Culture medium, Loeffler medium Pais med

19、ium（白氏培養(yǎng)基) diagnostic and selective medium： On blood agar medium containing tellurite亞碲酸鉀血平板 ,colonies of C. diphtheriae are characteristically black or grey after 24-48h.,白施恩教授,On blood agar medium containing tellurite ,colonies of C. diphtheriae are characteristically black or grey,Pathogenesis, I

20、s the causative agent of diphtheria, diphtheria is an acute upper respiratory tract disease.,respiratory droplets Contact or inhalation Bacteria muitiply intonsils,and Throat,covered with pseudomembrane diphtheria toxin (DT) Blood,heart Peripheral nerves adrenal glands,myocarditis,neuritis,Pathogene

21、sis,diphtheria toxin (DT) is the main virulent factor.,B,A,Binding receptor,ADPR transmissionase activity,Inhibit the protein synthesis of host cells, The gene of DT is located in the genome of -phage ,so Corynebacterium diphtheriae only produces diphtheria toxin when lysogenized by - phage.,白喉毒素的作用機(jī)制：抑制蛋白質(zhì)合成,所致疾病,白喉 急性呼吸道傳染病 傳染源: 病人 傳播途徑: 呼吸道、飛沫 致病過程 鼻粘膜繁殖產(chǎn)毒 炎性細(xì)胞 假膜 壞死組織 白喉?xiàng)U菌 脫落 堵塞呼吸道 窒息,3. 免疫性,抗毒素為主,4. 微生物學(xué)檢