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1、Chapter 4 Bacterial Infection and Immunity Section 1 Normal flora and Opportunistic pathogen normal flora the microorganism that parasitize on the body surface or tracts connecting with external, dont harm the host in ordinary condition.I.Distribution of normal flora skin oral cavity: anaerobes inte

2、stinal tract: anaerobes: aerobes=1000:1 vagina: Lactobacillus. respiratory II. Role of normal flora 1. biological barrier: antagonism 2.nutrient synthesize : amino acid, VB, Vk 3.immunity: enhance and develop and maturation of immune system 4. removal of harmful substances 5. anti-aging 6. anti-tumo

3、rOpportunistic pathogen some bacteria are unable to cause infection in ordinary condition , but can initiate infection under some certain condition.Normal floraOpportunistic pathogenconditionopportunistic pathogen If: (1) host immunity reduce (2) dysbacteriosis balance of normal flora was broken (3)

4、 translocation normal flora leave their ordinary habitant and gain access to other part Section 2 Bacterial Pathogenesis Mechanismvirulence:refers to extent (the degree) of pathogenicity median lethal dose(LD50): The number of pathogens required to cause lethal disease in half of the exposed hosts i

5、s called an LD50. median infective dose(ID50 ): The number of pathogens required to cause disease (or, at least, infection) in half of the exposed hosts is called the ID50.Infection and Disease virulence of bacteriathe amount of invading bacteriathe portal of entry the immunity of host Virulence sur

6、face structureinvasive substanceexotoxinendotoxininvasivenesstoxinimmune escape(I)Invasiveness: The ability of bacteria to resist host defence, colonize, multiply and spread. 1.adherence factors -surface structure bacteria to host cell: pili (/flagella) capsule lipoteichoic acid colonization factor

7、bacteria to bacteria: microcolony biofilm2.Penetration and spread invasin invasive enzyme - exoenzyme coagulase- S. aureus fibrinogenfibrin surround bacteria hyaluronidase (spreading factor) hydrolyze hyaluronic acid tissue loose B. spreads streptokinase. SK -Lyse fibrin B. spreads immune escape cap

8、sule-anti-phagocytosis IgA protease-cleave local IgA(II). toxin 1.exotoxin:excreted by living cells, G+ bacteria (most) polypeptide heat-unstable, 60, 1-2hr destroystrong antigenicity,exotoxin toxoid highly toxichigh selection for tissues structure : A subunit-B subunit neurotoxin cytotoxin enteroto

9、xin exotoxin subunit A:toxicity active subunit B: non-toxicity , bind receptor of sensitive cell exotoxin neurotoxin: tetanospasmin spinal cord cytotoxin: diphtherotoxin inhibit cell protein synthesis enterotoxin: cholera toxin A severe case of tetanus. muscles, back and legs are rigid muscle spasms

10、 can break bones can be fatal (e.g respiratory falure)Clostridium tetani Vibrio choleraBGM1ANa+,Cl-adenylate cyclase ATP cAMPNa+,Cl-,H2OThis 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 chi

11、ld could die from suffocationCorynebacterium Diphtheria2. endotoxin integral part of G bacteria cell wall. release after bacteria disintegration LPS, main toxic part: Lipid A heat-stable: 160 2-4hr cant converted into toxoid weakly toxic non-specificity all endotoxins produce the same symptoms. feve

12、r WBC reaction endotoxemia and shock Shwartzman and DIC 内毒素结构示意图Section 3 Bacterial InfectionOrigin of infection 1.Exogenous infection (1) patient (2) carrier (3) animal 2.Endogenous infection normal flora dysbacteriosisVertical transmissionHorizontal transmissionpersonpersonanimalmotheroffspringpla

13、centa birth canalbreast milk(zoonosis) The mode of infection 1.damaged skin or mucous membranes 2. respiratory tract 3. digestive tract 4. genital and urinary tract. inapparent infectionII . apparent infection The type of infection apparent infection acute infection local infection chronic infection

14、 systemic infection furuncle carbuncle bacteremia toxemia septicemia pyemia whole body infection bacteremia: is an invasion of the bloodstream by bacteria.toxemia: is the presence of exotoxin in the blood.endotoxemia: is the presence of endotoxin in the blood.septicemia: illness that occurs when poi

15、sonous substances (toxins) produced by certain bacteria enter the bloodstream. pyemia: is caused by purulent microorganisms inthe blood. Section 4 Immunity against Bacterial Infections Non-specific immunity Specific immunity Non-specific or innate immunityanatomical barriers humoral factors phagocyt

16、ic cells 1. skin and mucosa barrier : the intact skin and mucous membranes of the body afford a high degree of protection against pathogens. secrete bactericin , fatty acid, lactic acid,antibacterial peptide lysozyme,lactoferrin etc. normal flora 2. blood-brain barrier 3. placental barrier Anatomica

17、l barriersPhagocytic cells small phagocytic cell - neutrophil larger phagocytic cell - MPS (mononuclear phagocyte system) 1. The steps of phagocytosis : chemotaxisrecognition and bindingingestiondigestion(phagolysome)(phagosome)2. bactericidal mechanism:phagosomelysosomephagolysomefusedigestion of t

18、he ingested material Oxygen-dependent mechanism reactive oxygen intermediateROI O - , H O , OH-22 2halogenation of the bacterial cell wallhydrogen peroxide halide ions myeloperoxidaseconverting amino acid into aldehydesNitrogen-dependent mechanism enzyme: NO synthase Oxygen-independent mechanism enz

19、yme: lysozyme; defensins; hydrolase TNF pH: 3.5-4.03. Results of Phagocytosis complete phagocytose: The lysosomes fuse with the phagosomes containing the ingested microbes and the microbes are destroyed. un-complete phagocytose: Some bacteria, such as Legionella pneumophila and Mycobacterium species

20、 , are more resistant to phagocytic destruction once engulfed. tissue damage:hydrolase inflammationhumoral factors 1complement C5b6789;C3b,C4b;C3a,C5a 2cytokines IL-1,IL-6,TNF- 3acute-phase protein C-reaction protein Acquired immunity humoral immunity cell-mediated immunity IgEIgGIgDIgMIgAperforingranzyme IFN-IL-2、TNF- Mucosa immunityCD4+Th1CD 8+ CTLSIgAanti- extracellular bacteria Skin and mucosa barrier phagocytic cells: neutrophil (PMN) ,macrophage , monocytes complement antibody cell mediated immune response CD4+Th2Anti-intracelllular bacteria phag

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