醫(yī)學(xué)微生物學(xué)課件：4 細(xì)菌的感染與致病機制

1、Bacterial Infection and PathogenesisPathogenicMicroorgranismHost bodyinfectionWhat means about infection?Multiplication of an infectious agent within the body.Why do people get infectious diseases?Pathogens Chain of transmissionHost defense declineSection 1 Normal floraNormal microbial flora or norm

2、al floraThe populations of microorganisms that inhabit the skin and mucous membranes of healthy normal personsSkin and tractsBacteria in mouthBacteria in noseRoles of the resident floraPrevent colonization of pathogens“bacterial interference”NutritionImmunityAnti-tumorAnti-senescence(衰老)conditional

3、pathogensConditions defense mechanisms are impaired translocation:removed from the restrictions of that environment dysbacteriosisOpportunistic infectionOpportunistic pathogen (conditional pathogen)Section 2 Hospital infectionHospital infection Nosocomial infectionHospital acquired infectionNosocomi

4、al comes from the Greek word nosokomeion ( ) meaning hospital (nosos = disease, komeo = to take care of). This type of infection is also known as a hospital-acquired infection (or more generically healthcare-associated infection).In the United States, the Centers for Disease Control and Prevention e

5、stimates that roughly 1.7 million hospital-associated infections, from all types of bacteria combined, cause or contribute to 99,000 deaths each year.origin of infection ExogenousPatientCarrierReserviorAnimalEndogenousroutes of infection ContactAirbornepreventionDisinfection and sterilizationIsolati

6、on precautionNosocomial infections are infections which are a result of treatment in a hospital or a healthcare service unit.Infections are considered nosocomial if they first appear 48 hours or more after hospital admission or within 30 days after dischargeSection 3 Bacterial Infectionbacterial inf

7、ectionExogenousReservoir patient and carrieranimalmode of transmissionHorizontal TransmissionVertical TransmissionEndogenousNosocomialHorizontal TransmissionVertical TransmissionRoute of Transmissionmucosa skinsexualTypes of Bacterial Infectionstoxemiabacteremiasepticemiapyemiaacute & chroniclocalsy

8、stemicinapparent apparent carrierendotoxemiaAfter inapparent infection or apparent infection the pathogens dont be eliminated in time, and still survive and multiply in host at low speed and can spread into the environment.Section 4 Bacterial PathogenesisBacterial Pathogenicitypathogenpathogenicity

9、Virulencemedian lethal dose （LD50半數(shù)致死量）median infective dose （ID50半數(shù)感染量）Virulence factorsnumberPositionothersThe virulence is a quantitative measure of pathogenicity and is measured by the number of organisms required to cause disease.LD50/ID50Pathogenicity islandPathogenicity island: movable DNA se

10、quence with carries genes encoding virulence factors.Properties of PAIsPAIs carry genes encoding one or more virulence factors: adhesins, toxins, invasins, etc.They are located on bacterial chromosome , plasmid, transposable element, and prophageOne species of bacteria may have more than one PAI.Vir

11、ulence, toxic factorInvasivenessinvasion The process whereby pathogen enters host cells or tissues and spread in the body.toxinsinvasivenessStructuresadhesinpili, fimbriae, colonization factorafimbrial adhesin: LTA, OMP capsule, microcapsulecapsule, K Ag, M protein, Vi Aginvasive materialscoagulase,

12、 invasive enzymesMicrocolonyA colony of bacteria visible only under a low power microscope. growing under suboptimal conditions Biofilman aggregate of microorganisms in which cells adhere to each other and/or to a surface. These adherent cells are frequently embedded within a self-produced matrix of

13、 extracellular polymeric substance (EPS). 粘連蛋白膜磷壁酸 G+菌毛受體（糖類）細(xì)菌G- InvasivenessadhesionadhesionadhesinEpitheliumreceptorBacteriumS. pyogenesFibronectin(纖維連接蛋白)lipoteichoic acidFBP(fibronectin-binding protein)After Adhesiona. on surface or produce toxinsb. invade epitheliac. spread by enter bloodInfla

14、mmationapoptosisBio-filmAnti-phagocytosisCapsule - PneumococcusMicrocapsule, glycocalyxE.coli-K AgS.typhi-Vi Ag Streptcoccus pyogenes-M proteinSPA - S.aureusinvasivenessStructuresadhesinpili, fimbriae, colonization factorafimbrial adhesin: LTA, OMP capsule, microcapsulecapsule, K Ag, M protein, Vi A

15、ginvasive materialscoagulase, invasive enzymesExoenzymes Coagulase-Boil(癤) Hyaluronidase Carbuncle(癰)IgA proteaseIt splits hyaluronic acid, an important component of the ground substance of connective tissue.toxinExotoxinEndotoxinExotoxinSecreted by G+ and G-ProteinNot stableStrong toxicSelectiveStr

16、ong antigensThe exotoxin can be modified by formalin treatment so that it retains its epitopes but loses its toxicity; the resulting toxoid is used as a vaccine.Exotoxin 0.4% formalin toxoid injection antitoxinClassification of ExotoxinNeurotoxinTetanus toxinBotulinum toxinCytotoxinDiphtheria toxin

17、/ exotoxin AEnterotoxinCholera toxin, LT, STmechanism of ExotoxinActive signal pathway Cholera toxin, LT, ST, Pertussis toxin Inhibit protein synthesisDiphtheria toxin Damage membrane CytolyticSuperantigenProteases PhospholipasesDetergent-like actionMembrane damaging exotoxinsPore-Forming CytolysinS

18、taph.aureustoxinStrep.pyogenes streptolysin OClostridium perfringens-toxinTetanospasmin (破傷風(fēng)痙攣毒素)Blocks release of neurotransmitters for inhibitory synapses(神經(jīng)元), causes persistent spasms of the muscles.Botulinum Toxin(肉毒毒素)Blocks peripheral cholinergic synapses (膽堿能神經(jīng)元) by preventing release of ace

19、tylcholine(ACH,乙酰膽堿), works muscle slack paralysis(麻痹).Pyrogenic Exotoxins (Erythrogenic Toxins,紅疹毒素)Produced by lysogenic strains of streptococci , act as superantigens, interacting with both M and Th with the release of IL-1,IL-2,IL-6, TNF,IFN- causing shock, organ failure, rash observed in patien

20、ts with scarlet fever.Bacteria Produced EnterotoxinsEnterotoxigenic E.coli, ETECClostradium perfringens (產(chǎn)氣莢膜梭菌)Staph.aureus (金黃色葡萄球菌)S.typhimurium (鼠傷寒桿菌)Enterotoxins(腸毒素)Cholera Toxin(霍亂毒素)Is a complex A-B toxin that binds to specific receptors in the small intestine, enters the mucosal cells, cau

21、sing hypersecretion of electralytes and water.Cholera toxin and E. coli labile toxinADP-ribosylate adenylate cyclasecyclic AMP active ion and water secretiondiarrheaCharacteristics of S.aureus EnterotoxinMeat food contaminated with the toxin causing food poisoning Stable to heating at 100C, 30minCNS

22、 effect manifested by nausea and vomitingPromote intestinal peristalsis(蠕動) and fluid lossDiphtheria Toxin(白喉毒素) produced by lysogenic strains, inactivate the entire EF-2 content in a cell, completely terminating host cell protein synthesis. LPS lipopolysacharide Split and releasestableNot change to

23、 toxiodWeak Immungen G-菌崩解和內(nèi)毒素釋放過程演示endotoxinEndotoxinFeverWBC reaction: ShockDICEndotoxin - Clinical findings Mediator -Fever M: IL-1Hypotension(shock) TNF, C3a, Nitric oxideInflammation C3a, C5a,TNF Coagulation(DIC) activation of XII ,PAF Bleeding-petechial rashmultiple organ failure -exotoxinsG+/

24、G-excreted by living cells polypeptidesRelatively unstableHighly antigenic Converted to antigenic, nontoxic toxiodsHighly toxic: mg or lessUsually bind to specific receptors on cells Frequently controlled by extrachromosomal genes, (eg. Plasmids)G-Intergral part of the cell wallLPS, Lipid ARelativel

25、y stableWeakly immunogenic Not converted toxoidsModerately toxic 10100mgSpecific receptors not found on cellsSynthesis directed by chromosomal genesendotoxinsExotoxinsExotoxins are produced by several gram-positive and gram-negative bacteria, in contrast to endotoxins, which are present only in gram

26、-negative bacteria. The essential characteristic of exotoxins is that they are secreted by the bacteria, whereas endotoxin is a component of the cell wall. Exotoxins are polypeptides whose genes are frequently located on plasmids or lysogenic bacteriophages.EndotoxinsEndotoxins are integral parts of

27、 the cell walls of both gram-negative rods and cocci, in contrast to exotoxins, which are released from the cell. Endotoxins are lipopolysaccharides (LPS); the enzymes that produce the LPS are encoded by genes on the bacterial chromosome.Regulation of Virulence Pathogenicity island（致病島，毒力島）TransferC

28、hromosome / Plasmid / Transposon / ProphageTwo-component signal-transduction system（G-，雙組分調(diào)控系統(tǒng)）Sensor protein（感應(yīng)蛋白）-Protein KinaseRegulator （調(diào)節(jié)蛋白） -activator or supressorSection 5 Immunityin Bacterial InfectionsAntimicrobial ImmunityComponents of the Immune SystemHumoralCellularHumoralCellularSpecif

29、icNonspecificcomplement, interferon, TNF etc.macrophages, neutrophilsT cells; other effectors cellsantibodiesInnate immunitySkin & mucous membranesIntact skinFatty acidssebaceous glandsMucous membrane of respiratory tract ciliary action traps many microorganisms LysozymeNormal floraInnate immunityIn

30、flammatory response & phagocytosis(early host responses to bacteria infection)Bacteria infection vasoactive factors the increased permeability Chemokines neutrophils and macrophagesInnate immunity 1. Structural barriersSkin and mucous membraneBlood-brain barrier- infantPlacental barrier- within 3 months2.Phagocytes Neutrophil monocytes, macrophagesPhagocytosis and bactericidal activity接觸、吞噬 吞噬體 溶酶體吞噬溶酶體 殺死消化病原菌 invade chemoto