病原生物学英文课件：Bacterial Infection and Immunity

1、Chapter 5 Bacterial Infection and Immunity,教学目标,1041 掌握正常菌群、条件致病菌、菌群失调、菌群失调症、医院感染、菌血症、败血症及脓毒血症的概念。 2042 掌握感染、致病菌、非致病菌、毒血症、毒力、内毒素血症、带菌者和带菌状态的概念。 1043 举例说明正常菌群的生理学功能及条件致病菌的致病条件。 1044 陈述细菌的致病机制，列表比较细菌内、外毒素的主要区别。 1045 熟悉宿主的免疫防御机制包括固有免疫的组成、吞噬细胞吞噬作用的后果以及胞外菌感染、胞内菌感染、外毒素致病的免疫特点。 1046 举例说明感染来源、传播途径以及感染的类型。 1

2、047 熟悉医院感染的来源和控制。,Normal flora:the population of microorganisms that inhabit the skin and mucous membranes of healthy normal people.,Scanning electron micrograph of ileal villus (dog),Scanning electron micrograph of ileal villus (rat),Scanning electron micrograph of the surface of murine stomach,Sca

3、nning electron micrograph of the surface of murine colon, Luckey TD. Am J Clin Nutr.1977 Nov;30(11):1753-61.,35-55,35,55,Function of the resident flora,Members of the resident flora in the intestinal tract synthesize vitamin K and aid in the absorption of nutrients. Members of the resident flora on

4、mucous membranes and skin may prevent colonization by pathogens and possible disease through “bacterial interference”. The normal flora may antagonize other bacteria through the production of substances which inhibit or kill nonindigenous species. The normal flora stimulates the development of certa

5、in tissues, e.g., the caecum and certain lymphatic tissues (Peyers patches) in the GI tract The normal flora stimulates the production of cross-reactive antibodies.,Colonization resistance by normal ora,Opportunistic pathogen,Many species among the normal flora may act as opportunistic pathogens. Ho

6、sts immunity is impaired Dysbacteriosis On the occasion of flora disequilibrium, e.g. when the resident flora is disturbed, some pathogenic microorganisms may colonize, proliferate and lead to diseases In severe cases, dysbacteriosis might lead to microbial selection and substitution. Translocation

7、change of inhabiting places,Pathogen: A microorganism capable of causing disease.,Infection: Multiplication of an infectious agent within the body. Multiplication of the bacteria that are part of the normal flora of the gastrointestinal tract, skin, etc, is generally not considered an infection; on

8、the other hand, multiplication of pathogenic bacteria (eg, salmonella species) even if the person is asymptomatic is deemed an infection. Pathogenicity: The ability of an infectious agent to cause disease. (See also virulence.) Virulence: The quantitative ability of an agent to cause disease. Virule

9、nt agents cause disease when introduced into the host in small numbers. Virulence involves invasion and toxigenicity.,半数致死量（median lethal dose, LD50） 半数感染量（median infective dose, ID50）,Factors affecting pathogenicity of bacteria,Virulence Number of invasive bacteria Pathway of invasion,Virulence,Inv

10、asiveness The ability of bacteria to enter host cells or tissues, colonize, proliferate, spread and Survival throughout the body Toxin The ability of microorganism to produce toxin that contributes to the development of disease.,Adhesion the process by which bacteria adhere to the surfaces of host c

11、ells: via pili, lipoteichoic acid,F protein,adhesin,EPITHELIUM,receptor,BACTERIUM,16,S. pyogenes,fibronectin,F-protein lipoteichoic acid,Penetration and spread,Bacteria are able to penetrate body barriers but remain at the site of invasion. For example, Shigella penetrates by activating epithelial c

12、ells of the intestine to become endocytic; the Shigella do not usually spread to the bloodstream. Bacteria (e.g. Salmonella typhi) pass through epithelial cells into the bloodstream. Bacteria (e.g. Borrelia burgdorferi)are transmitted into the bloodstream through the skin by a tick bite. Certain deg

13、radative exotoxins secreted by some bacteria (e.g. hyaluronidase or collagenase) can loosen the connective tissue matrix and thus making it easier for bacteria to pass through,18,Penetration and spread,Vibrio cholerae,S. enterica serovar Enteritidis,Salmonella enterica serovar Typhi,Epithelium,Gut l

14、umen,Blood stream,Survival in the host,Many bacterial pathogens are able to resist the cytotoxic action of plasma and other body fluids involving antibody and complement(classical pathway) complement alone (alternative pathway) lysozyme Anti-phagocytosis,Survival in the host,Capsules (many pathogens

15、).,Survival in the host,Protein A is a surface constituent of S. aureus as well as a secretory product that binds to the Fc region of immunoglobulins. Protein A is anti-opsonization,Survival in the host,Intracellular pathogens (both obligate and facultative) avoid being killed within phagolysosomes

16、by avoiding being engulfed by phagocytes and entering phagolysosomes preventing fusion of phagosome to lysosome preventing reduction of pH within phagolysosomes,Survival in the host,IgA proteases help bacterial survival on external surfaces H. influenzae S. pneumoniae N. gonorrhoeae N. meningitidis,

17、25,Immunopathology,Overstimulation of cytokine production and complement activation by endotoxins in the absence of immune response can lead to tissue injury. Continuously generated antigens released from persisting viable microbes will subsequently elicit humoral antibodies and cell mediated immuni

18、ty resulting in chronic immunopathology. Certain poorly degradable antigens (e.g pneumococcal polysaccharide and group A streptococcal cell walls) can maintain immunopathology even in the absence of persistent live agents. Other bacterial antigens cross-react with host tissue antigens generating aut

19、oimmunity (e.g. the M protein of S. pyogenes cross-reacts with mammalian myosin). Immunopathology can thus persist even after the elimination of microbial antigens.,Toxin,Exotoxins Endotoxins,Endotoxins:Lipopolysaccharide (LPS),Fever-pyrogen Leukopenia/ leukocytosis Hypoglycemia Hypotension Shock Di

20、sseminated Intravascular Coagulation(DIC). Death from massive organ dysfunction,Endotoxins,A：Toxic activity B：Mediates adherence,Exotoxins,A-B type toxin,Exotoxins,Neurotoxin Tetanospasmin Enterotoxin Cholera toxin Cytolytic toxin,Mechanism of pathogenesis of enterotoxin,TOXINS,不 同 病 原 微 生 物 的 感 染 剂

21、 量,Microbial pathogenesis.,Immunity of host,Physical, chemical, and anatomical barriers to infection,Physiological barriers Skin and mucous membrane barrier Blood-brain barrier Placental barrier,Chemotactic response to inflammatory stimulus,Toll-like receptors Phagocytes have a variety of Toll-like

22、receptors (Pattern Recognition Receptors or PRRs) which recognize broad molecular patterns called PAMPs (pathogen associated molecular patterns) on infectious agents. Fc receptors Bacteria with IgG antibody on their surface have the Fc region exposed and this part of the Ig molecule can bind to the

23、receptor on phagocytes. Complement receptors Phagocytic cells have a receptor for the C3b. Scavenger receptors Scavenger receptors bind a wide variety of polyanions on bacterial surfaces resulting in phagocytosis of bacteria.,吞噬细胞表面受体识别“病原相关分子模式”，引发吞噬和杀灭,Toll样受体识别“病原相关分子模式”,Immunity of extracellular

24、 bacterial infection: antibodies (IgG, IgM, SIgA); phagocytes (neutrophils); complement; humoral immunity mainly. Immunity of intracellular bacterial infection: cell-mediated immunity (delayed-type hypersensitivity, DTH response (DTH) involving TH1and macrophages) mainly.,Original and devolopment of

25、 Bacterial Infection,Source of infection,Exogenous infection外源性感染 patient, carrier, diseased animal or animal carrier Endogenous condition内源性感染 most are normal flora, cause infection under abnormal condition.,Transmission Airborne droplets Food Water Sexual contact,Routes of infection Respiratory Ga

26、strointestinal Genitourinary tract Closely contact Insect bitting Blood transfusion Wounds Mucous membranes,Kinds of infection,Inapparent or Subclinical infection Latent Infection Apparent Infection Carrier state : carrier,Inapparent infection隐性感染,Inapparent infection are termed subclinical, and the

27、 individual is sometimes referred to as a carrier. The host with inapparent infections are without clear clinic symptoms because they have higher immunity defence or there is no sufficient amounts of pathogen to cause clinical symptoms.,The hosts have evident clinic symptoms. Acute infection急性感染 Chr

28、onic infection慢性感染 Local infection局部感染 Generalized infection; systemic infection全身感染,Apparent infection显性感染,Generalized infection全身感染,Toxemia毒血症: Bacteria multiply at invading location and do not enter blood stream, but the exotoxins enter blood and cause corresponding toxic symptoms.,Endotoxemia内毒素血症