人卫版微生物chapter细菌感染与免疫

1、人卫版微生物chapter细菌感染与免疫Chapter 7 Bacterial Infection and immunity人卫版微生物chapter细菌感染与免疫Basic terms Bacterial infection（细菌的感染） Pathogen（病原菌） Nonpathogen （非病原菌） Opportunistic pathogen（机会致病菌）人卫版微生物chapter细菌感染与免疫Bacterial Infection 细菌的感染 The process of bacteria invading in the body, growing in the tissues, p

2、roducing toxins and causing diseases is called bacterial infection.人卫版微生物chapter细菌感染与免疫 Pathogen（病原菌）（病原菌）Pathogenic bacterium （致病菌）The bacterium which can cause a disease is called pathogen. Nonpathogen（非病原菌）（非病原菌）Nonpathogenic bacterium（非致病菌）A bacterium that does not cause disease is called nonpat

3、hogen.人卫版微生物chapter细菌感染与免疫 Opportunistic pathogen（机会致病菌）（机会致病菌）Conditioned pathogen（条件致病菌）Some bacteria are capable of causing diseases only under certain conditions.These organisms can cause disease only if one or more of the usual defence mechanisms humans have evolved to restrict microorganisms f

4、rom their usually sterile internal organs and tissue are breached by accident, by intent (e.g. surgery), or by an underlying metabolic or an infectious disorder (e.g. AIDS).人卫版微生物chapter细菌感染与免疫OutlineNormal flora and opportunistic pathogenBacterial pathogenesisThe host immune defence systemThe initi

5、ation and course of infectionHospital infection人卫版微生物chapter细菌感染与免疫Section 1 Normal flora and opportunistic pathogen人卫版微生物chapter细菌感染与免疫 Normal flora（正常菌群） Normal microbial flora（正常微生物群） The population of microorganisms that inhabit the skin and mucous membranes of healthy persons. They are usually

6、harmless, some even beneficial, to humans health.人卫版微生物chapter细菌感染与免疫Locations Surface tissues of skin Oral cavity Respiratory tract Gastrointestinal tract Genitourinary tract人卫版微生物chapter细菌感染与免疫Normal flora on intestinal mucosa人卫版微生物chapter细菌感染与免疫肠道的正常菌群肠道的正常菌群Prime of lifeSenium人卫版微生物chapter细菌感染与免

7、疫人卫版微生物chapter细菌感染与免疫 Beneficial effects of the normal floraBiological antagonism （生物拮抗）（生物拮抗）Production of essential nutrients（营养作用）（营养作用）Priming of immune system（免疫作用）（免疫作用）Anti-aging（抗衰老作用）（抗衰老作用）Anti-tumor （抗肿瘤作用）（抗肿瘤作用）人卫版微生物chapter细菌感染与免疫Biological antagonism (生物拮抗)Biological barriers（生物屏障）Rec

8、eptor competition（受体竞争）Harmful metabolites（有害代谢产物）1.Nutrient competition（营养竞争）人卫版微生物chapter细菌感染与免疫 Conditioned pathogen（条件致病菌） Some bacteria are capable of causing diseases only under certain conditions. These bacteria are called opportunistic (conditioned) pathogens and this kind of infection is ca

9、lled opportunistic infection（机会性感染）. Opportunistic pathogen（机会致病菌）（机会致病菌）人卫版微生物chapter细菌感染与免疫 Conditions of opportunistic infectionChange of inhabiting places（寄居部位改变）（寄居部位改变）Immune system compromise（宿主免疫功能低下）宿主免疫功能低下）Dysbacteriosis（菌群失调）（菌群失调）人卫版微生物chapter细菌感染与免疫Dysbacteriosis（菌群失调）（菌群失调）If flora di

10、sequilibrium occurs, for example, when the resident flora is disturbed, some little significant microorganisms may colonize, proliferate, and produce disease, which is called dysbacteriosis. Dysbacteriosis mainly resulted from long term and large dose antibiotics taken.人卫版微生物chapter细菌感染与免疫Superinfec

11、tion（重叠感染）（重叠感染） A frequent complication of drug therapy for microbial infection. It may result from opportunistic colonization following immunosuppression by the primary pathogen and can be influenced by the time interval between infections, microbial physiology, or host resistance. 人卫版微生物chapter细菌

12、感染与免疫Dysbacteriosis and superinfection人卫版微生物chapter细菌感染与免疫肠道的正常菌群肠道的正常菌群健康青壮年健康青壮年粪便涂片粪便涂片健康老年粪便涂片健康老年粪便涂片（双歧杆菌）（双歧杆菌）人卫版微生物chapter细菌感染与免疫Probiotics（益生菌）（益生菌）人卫版微生物chapter细菌感染与免疫Probiotics（益生菌）（益生菌）& Prebiotics（益生元）（益生元）人卫版微生物chapter细菌感染与免疫Section 2 Bacterial PathogenesisBasic termBacterial Pathogen

13、icity Bacterial virulenceNumber of invading organisms1.Portal of entry 人卫版微生物chapter细菌感染与免疫 Pathogenicity（致病性）（致病性） is used to describe the capacity of bacteria to initiate diseases. The term of virulence（毒力）（毒力） is used as a comparison of pathogenicity in the quantitative sense. ID50（median infecti

14、ous dose, 半数感染量）:, Infectious dose of bacteria for 50% of the test population. LD50 （median lethal dose, 半数致死量） : Lethal dose of bacteria for 50% of the test population.Basic Term人卫版微生物chapter细菌感染与免疫ExotoxinPili (Fimbrial)CapsuleVirulent EnzymeAdhesinsFlagellaIron bindingproteinVirulence surface pro

15、tein人卫版微生物chapter细菌感染与免疫Bacterial virulence（细菌的毒力）（细菌的毒力）Virulence（毒力）（毒力）Invasiveness（侵袭力）（侵袭力）Toxin（毒素）（毒素）Adherence & permanent planting（黏附与定植）（黏附与定植）Multiplication &diffusion （增殖与扩散）（增殖与扩散）Anti-defense functionof host （免疫逃逸）（免疫逃逸）Endotoxin（内毒素）（内毒素）Exotoxin（外毒素）（外毒素）人卫版微生物chapter细菌感染与免疫Adhesion

16、and field planting（黏附与定植）（黏附与定植）Invasion（侵入）（侵入）Multiplication and diffusion（繁殖与扩散）（繁殖与扩散）Local diffusion（局部扩散）（局部扩散）Systemic diffusion（全身性（全身性扩散）扩散） Invasiveness（侵袭力）（侵袭力） Definition: Bacterial capability that can break through the physiologic barriers (skin, mucosa), settle down, multiply, and spr

17、ead in the host.Adhesive factors: adhesin and capsuleInvasive substancesBacterial biofilm人卫版微生物chapter细菌感染与免疫1. Adhesin（粘附素）（粘附素） Protiens on bacterial surface associated with adhesion. Adhesins bind to adhesin receptors on host cells. Classification:Pili (fimbriae) adhesin (菌毛黏附素)Non-fimbriae adhes

18、in (非菌毛黏附素)人卫版微生物chapter细菌感染与免疫Adhesion人卫版微生物chapter细菌感染与免疫人卫版微生物chapter细菌感染与免疫 Protect the cell wall against attack by drugs Inhibit ingestion and killing by phagocytes Play a role in the adherence of human tissue Antigenicity2. Capsule（荚膜）（荚膜）人卫版微生物chapter细菌感染与免疫3. Invasive substances（侵袭性物质）（侵袭性物质

19、） Invasin（侵袭素）（侵袭素）Encoded by invasive genes（侵袭基因）Mediate invading adjacent epithelial cellsInvasive enzyme（侵袭性酶）（侵袭性酶）Some bacteria may generate invasive enzymes, which can damage body tissues and promote the invasion and diffusion of the bacteria.人卫版微生物chapter细菌感染与免疫4. Bacterial biofilm（细菌生物被膜）（细菌

20、生物被膜） Definition： The membraneous bacterial community composed of bacteria and the extracellular polymers secreted by bacteria after they adhere to the surface of living or nonliving materials.人卫版微生物chapter细菌感染与免疫Bacterial biofilm FunctionsFacilitates bacterial adhesionBaffles the penetration of ant

21、ibiotic and the rejection of immune systemProfits signal communication among bacteria.人卫版微生物chapter细菌感染与免疫Bacterial biofilm人卫版微生物chapter细菌感染与免疫人卫版微生物chapter细菌感染与免疫 Biofilm in the endoscope（内窥镜）（内窥镜）人卫版微生物chapter细菌感染与免疫Staphylococcus epidermidis（表皮葡萄球菌）biofilm in the surface of venous catheter（静脉导管）人

22、卫版微生物chapter细菌感染与免疫ExotoxinsEndotoxinsExcreted by living cells; high concentrations in liquid medium.Integral part of the cell wall of G- bacteria. Released on bacterial death and in part during growth. May not need to be released to have biologic activity.Produced by both G+ and G- bacteria.Found o

23、nly in G- bacteria.PolypeptidesLPS (lipid A portion probably responsible for toxicity.)Relatively unstable; toxicity often destroyed rapidly by heating at temperatures above 60.Relatively stable; withstand heating at temperatures above 60 for hours without loss of toxicity.人卫版微生物chapter细菌感染与免疫Exotox

24、insEndotoxinsHighly antigenic; stimulate formation of high-titer antitoxin (抗毒素). Antitoxin neutralizes toxin.Weakly immunogenic; antibodies are antitoxic and protective. Relationship between antibody titers and protection from disease is less clear than with exotoxins.Converted to antigenic, nontox

25、ic toxoids (类毒素) by formalin, acid, heat, etc. Toxoids are used to immunize.Not converted to toxoids.Highly toxic; fatal to animals in microgram quantities or less.Moderately toxic; fatal for animals in tens to hundreds of micrograms.人卫版微生物chapter细菌感染与免疫ExotoxinsEndotoxinsUsually bind to specific re

26、ceptors on cells.Specific receptors not found on cells.Usually do not produce fever in the host. Selective toxicity and specific clinical syndromes. Neurotoxins (神经毒素) Cytotoxins (细胞毒素) Enterotoxins (肠毒素)Usually produce fever in the host by release of IL-1 and other mediators.Frequently controlled b

27、y extrachromosomal genes (e.g. plasmids).Synthesis directed by chromosomal genes.人卫版微生物chapter细菌感染与免疫区别要点区别要点外毒素外毒素内毒素内毒素来源来源革兰阳性菌与部分革兰阴性菌革兰阳性菌与部分革兰阴性菌革兰阴性菌革兰阴性菌编码基因编码基因质粒、前噬菌体或染色体基因质粒、前噬菌体或染色体基因 染色体基因染色体基因存在部分存在部分从活菌分泌出，少数菌崩解后从活菌分泌出，少数菌崩解后释出释出细胞壁组分，菌裂解后细胞壁组分，菌裂解后释出释出化学成分化学成分蛋白质蛋白质脂多糖脂多糖稳定性稳定性6080，3

28、0分钟破坏分钟破坏160，24小时破坏小时破坏毒性作用毒性作用强，对组织器官有选择性毒害强，对组织器官有选择性毒害效应，引起特殊的临床表现效应，引起特殊的临床表现较弱，各菌的毒性效应较弱，各菌的毒性效应大致相同，引起发热、大致相同，引起发热、白细胞增多、微循环障白细胞增多、微循环障碍、休克、碍、休克、DIC等等抗原性抗原性强，刺激机体产生抗毒素；甲强，刺激机体产生抗毒素；甲醛液处理脱毒形成类毒素醛液处理脱毒形成类毒素弱，刺激机体产生的中弱，刺激机体产生的中和抗体作用弱；甲醛液和抗体作用弱；甲醛液不能脱毒形成类毒素不能脱毒形成类毒素人卫版微生物chapter细菌感染与免疫Specific pol

29、ysaccharideLPS人卫版微生物chapter细菌感染与免疫Procedure Procedure 人卫版微生物chapter细菌感染与免疫Cytotoxins（细胞毒素） Diphtheria toxin（白喉毒素）（白喉毒素）inhibits protein synthesis in mammalian cells and causes necrosis of cells人卫版微生物chapter细菌感染与免疫Neurotoxin（神经毒素） Tetanus toxin（破伤风毒素）人卫版微生物chapter细菌感染与免疫Enterotoxin（肠毒素） Cholera enter

30、otoxin 人卫版微生物chapter细菌感染与免疫Biological roles of endotoxinFever（发热）Leukopenia and leukocytosis（白细胞反应 ）Endotoxemia and shock（内毒素血症与休克）人卫版微生物chapter细菌感染与免疫人卫版微生物chapter细菌感染与免疫EndotoxinActivatesmacrophagesActivatescomplementActivatesHageman factorIL-1 ,TNF, Nitric oxideFever and hypotensionC3a, C5a Hypot

31、ension EdemaCoagulation cascadeDIC人卫版微生物chapter细菌感染与免疫Section 4 the initiation and process of infectionSources of infectionPathway of bacterial entranceTypes of bacterial infection人卫版微生物chapter细菌感染与免疫 Exogenous infection（外源性感染）PatientsCarriers（带菌者）（带菌者）Animals Endogenous infection（内源性感染）Opportunisti

32、c pathogens Sources of infection人卫版微生物chapter细菌感染与免疫Pathway of pathogen entrance Respiratory Gastrointestinal Genital Skin and mucosa Animal bites Blood Sexual transmission人卫版微生物chapter细菌感染与免疫Types of bacterial infectionInapparent infection（隐性感染）（隐性感染）Apparent infection（显性感染）（显性感染）Carrier state（带菌状态

33、）（带菌状态）人卫版微生物chapter细菌感染与免疫Inapparent infection（隐性感染）（隐性感染） Subclinical infection（亚临床型感染） An infection that has no observable symptoms. It occurs when the host immunity is potent or the pathogenicity of the pathogen is weak. 人卫版微生物chapter细菌感染与免疫The tip of the iceberg 人卫版微生物chapter细菌感染与免疫Apparent inf

34、ection（显性感染） Acute infection Chronic infectionLocal infectionGeneralized infection Toxemia (毒血症)Endotoxemia (内毒素血症)Bacteremia (菌血症)Septicemia (败血症)1.Pyemia (脓毒血症)人卫版微生物chapter细菌感染与免疫Toxemia（毒血症）Bacteria mutiply at invading location and do not enter blood stream, but the exotoxins（外毒素）enter blood and

35、 cause corresponding toxic symptoms.Endotoxemia（内毒素血症）Gram-negative bacteria multiply at location or in blood stream, release a lot of amount endotoxin（内毒素） released from bacterial cell rupture.人卫版微生物chapter细菌感染与免疫Bacteremia（菌血症）After entering blood, bacteria circulate but not multiply in the blood.

36、Septicemia（败血症）Bacteria circulate and multiply in the blood, in which bacteria produce toxic products and cause high swinging type of fever and other toxic symptoms.人卫版微生物chapter细菌感染与免疫Pyemia（脓毒血症）Pyogenic（化脓性） bacteria produce septicemia with multiple abscess（脓肿） in internal organs such as spleen , liver and kidneys.人卫版微生物chapter细菌感染与免疫 Carrier state（带菌状态）（带菌状态） After