微生物学美国IndianaUniversityPurdueUniversity授课08课件.ppt
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- 微生物学 美国 IndianaUniversityPurdueUniversity 授课 08 课件
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1、Lecture 8BIOL 5331Microbial Interference with Host DefensesBIOL 533Lecture 8Medical MicrobiologyLecture 8BIOL 5332Overall Strategies Defense against complement Subversion of phagocytosis Subversion of immune responsesLecture 8BIOL 5333General Aspects Pathogen finds itself in hostile territory Host f
2、ights back and usuallybut not alwayswins Hosts defenses are interrelated and so are organisms countermeasuresLecture 8BIOL 5334General Aspects Given organism sometimes has numerous different virulence factors Does not have to harm tissue to be called virulence factor,although many do Have to determi
3、ne precise role of each factor if a large number are involved Not always sure in vitro situation is same as in disease stateLecture 8BIOL 5335Defense Against Complement Overall strategies Inhibit complement activation Mask activating substances Capsule IgA antibodies Cover up target of complement me
4、mbrane attack complexLecture 8BIOL 5336Defense Against Complement Overall strategies,continued Appropriate inhibitor to activation to surface Inactivate complement chemotaxin C5aLecture 8BIOL 5337Prevent Complement Activation Masking surface components that activate by the alternative pathway Capsul
5、es Murein of S.aureus good activator,but is covered by capsule Capsules rich in sialic acid of Group B streptococci and strains of E.coliLecture 8BIOL 5338Prevent Complement Activation IgA antibodies Meningococci get coated with IgA antibody Does not activate complement Prevents other Ab that can ac
6、tivate from reaching surface of cellLecture 8BIOL 5339Prevent Complement Activation Cost of having capsule antigenic Elicits activation by primary pathway Defend better against immediate defenses than later onesLecture 8BIOL 53310Prevent Complement Activation Cover up target of membrane attack compl
7、ex(outer membrane)Gram,such as Salmonella or E.coli Smooth strains with long 0 antigen polysaccharide chain do not allow access of mac while rough strains(with little or no 0 antigen)do Correlates with pathogenicityLecture 8BIOL 53311Subversion of Phagocytosis Overall strategies Inhibition of phagoc
8、yte recruitment Microbial killing of phagocytes Escape of ingestionLecture 8BIOL 53312Subversion of Phagocytosis Overall strategies,continued Survival inside phagocytes Escape into the cytoplasm Inhibition of lysosome and phagosome fusion Resistance to lysosomal enzymes Inhibition of phagocyte oxida
9、tive pathway Antibody effects(host counters)Lecture 8BIOL 53313Subversion of Phagocytosis General aspects Being inside cell is not necessarily bad for an organism Powerful strategy is to grow within nonphagocytic cell Shielded from antibodies and drugsLecture 8BIOL 53314Subversion of Phagocytosis In
10、hibition of phagocyte recruitment Direct inhibition of neutrophil motility and chemotaxisBordetella pertussis produces toxins Adenylate cyclase toxin Increase cyclic AMP in neutrophils Leads to paralysis Pertussis toxin Impairs migration of monocytesLecture 8BIOL 53315Subversion of Phagocytosis Micr
11、obial killing of phagocytes Leukocidins(exotoxins)kill neutrophils and macrophages Can work at distance or after ingestion Typical producers are highly invasive bacteriaPseudomonas,staphylococci,group A streptococci,gas gangrene clostridiaLecture 8BIOL 53316Subversion of Phagocytosis Escaping ingest
12、ion Naked capsule is effective(pneumococci)Opsonized bacteria not as effective Countering opsonization by complement components or Ab Any mechanism inhibits Activation of complement Synthesis or activity of AbLecture 8BIOL 53317Subversion of Phagocytosis Escaping ingestion,continued Countering opson
13、ization when antibodies are present Staphylococci and streptococci Make surface component(protein A)Binds to IgG molecules by the wrong end(Fc region)Cannot act as opsonins because Fc region not free to bind to Fc receptors on phagocytic cells Not known if antiphagocytic defense is relevant to disea
14、se processLecture 8BIOL 53318Subversion of Phagocytosis Survival inside phagocytes Escape into cytoplasm Rickettsia(Rocky Mountain Spotted Fever)or trypanosomes of Chagas disease cross membrane of phagosome to enter cytoplasm Since lysosomes do not secrete contents into cytoplasm,organism is safe Ho
15、w they enter cytoplasm is not known for certain Possess surface-bound phospholipase,which may weaken membraneLecture 8BIOL 53319Subversion of Phagocytosis Survival inside phagocytes,continued Inhibition of lysosome and phagosome fusion Examplesbacteria that cause:Tuberculosis Psittacosis Legionnaire
16、s diseaseLecture 8BIOL 53320Subversion of Phagocytosis Mechanism of tuberculosis Induced by complex glycolipids(sulfatides)not certain Facts:Inhibition must be due to modification of phagosome membrane Microorganism might contribute by compounds secreted or present on the surfaceLecture 8BIOL 53321S
17、ubversion of Phagocytosis Survival inside phagocytes,continued Resistance to lysosomal enzymessurvive in phagolysosome(pH as low as 4)Leishmania(protozoa)resistance may be due to:Resistant cell surfaces Excretion of enzyme inhibitorsLecture 8BIOL 53322Subversion of Phagocytosis Survival inside phago
18、cytes,continued Inhibition of phagocytes oxidative pathway Bacillus of Legionnaires disease Inhibits hexose-monophosphate shunt and oxygen consumption in neutrophils Reduces respiratory burst for killing microbes Staphylococciproduces catalase that degrades hydrogen peroxide necessary for oxidative
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