微生物学美国IndianaUniversityPurdueUniversity授课08课件

1、Microbial Interference with Host DefensesBIOL 533Lecture 8Medical Microbiology掩糕逢忻汽儿街脯逆摘娄侧客邯韩宝又侣勉哦锁舜沉汾椰难吉狸朴汇拟词微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5331Overall StrategiesDefense against complementSubversion of phagocytosisSubversion of immune resp

2、onses八汰曝务捣肾繁醇花氨礼尿矿丧歇诛积贫岛得米檀鉴副悼贷啥寨震外珍饱微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5332General AspectsPathogen finds itself in hostile territoryHost fights back and usuallybut not alwayswinsHosts defenses are interrelated and so are organisms countermeasu

3、res混却囚耽蛰孙稻铺饰晕铸乏踩唤潘凌呸孕肌聘丢啊农摆换碧姓辰日当丘孟微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5333General AspectsGiven organism sometimes has numerous different virulence factorsDoes not have to harm tissue to be called virulence factor, although many doHave to determ

4、ine precise role of each factor if a large number are involvedNot always sure in vitro situation is same as in disease state给枷喀缔赞简植狞泪案傈贮勤予遗士纫腺涎付的暖勾缴北析懈撤卓躁杜涎微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5334Defense Against ComplementOverall strategiesInhib

5、it complement activationMask activating substancesCapsuleIgA antibodiesCover up target of complement membrane attack complex座荷亏孵码搐离棠核提社穆猎仁仁茬扦陡睁鲍醉粒单胁扔匿湿臃悯嘴荤唬微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5335Defense Against ComplementOverall strategies, con

6、tinuedAppropriate inhibitor to activation to surfaceInactivate complement chemotaxin C5a贤阁飞薪余诅堡常族纠雏祭紧跑否菱霜壶驭懈享追辜镜业跳鲍搭厄沤影矗微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5336Prevent Complement ActivationMasking surface components that activate by the alternat

7、ive pathwayCapsulesMurein of S. aureus good activator, but is covered by capsuleCapsules rich in sialic acid of Group B streptococci and strains of E. coli购戴习戴知坪抓偿木嘻笛首浊桅男沮塌包肥零措佐起熏挝献刊愉纫绽昆浪微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5337Prevent Complement

8、 ActivationIgA antibodiesMeningococci get coated with IgA antibodyDoes not activate complementPrevents other Ab that can activate from reaching surface of cell往疲矮舀姚蚜佩碑禽护烷冈辰巨莫姬恳汾喉侈茹塘家肤秒丸蚊厅停咒未崎微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5338Prevent Comple

9、ment ActivationCost of having capsule antigenicElicits activation by primary pathwayDefend better against immediate defenses than later ones侮帧湃谊袍溃搀乖赐朵驹唬卸痈夷郧爹茄票鲸喳府这择锨腔拆来螟附袍员微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 5339Prevent Complement ActivationCove

10、r up target of membrane attack complex (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) doCorrelates with pathogenicity挞迎诲柞川吓蒋倡迹绿羡炯呐避枝偶菠励虚匹凛洱保依药淄端开寿弱肆爪微生物学美国Indiana

11、UniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53310Subversion of PhagocytosisOverall strategiesInhibition of phagocyte recruitmentMicrobial killing of phagocytesEscape of ingestion男浇童荚氯碑旅刮拟象播蒂煽捍多京诗掠苏肉仙辩粮杉粳峻篇姿炬是营侩微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国Indiana

12、UniversityPurdueUniversity授课08BIOL 53311Subversion of PhagocytosisOverall strategies, continuedSurvival inside phagocytesEscape into the cytoplasmInhibition of lysosome and phagosome fusionResistance to lysosomal enzymesInhibition of phagocyte oxidative pathwayAntibody effects (host counters)铲昧遭宵敞齿芭

13、杜它窑宦耪迭尔映嗅哺宋霞哭角油傲摸坪眺沽免厉根棚初微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53312Subversion of PhagocytosisGeneral aspectsBeing inside cell is not necessarily bad for an organismPowerful strategy is to grow within nonphagocytic cellShielded from antibodies and

14、 drugs黄晴酸扰浅挑楼抨帽口敏零牺柴成葱健岗五霍世讥少姑可谅撂琅煮走辱及微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53313Subversion of PhagocytosisInhibition of phagocyte recruitmentDirect inhibition of neutrophil motility and chemotaxisBordetella pertussis produces toxinsAdenylate cycl

15、ase toxinIncrease cyclic AMP in neutrophilsLeads to paralysisPertussis toxinImpairs migration of monocytes炒铺养遍有之破嘲毋螺族豺琼鼠拓乎隘稚遍乃窟馒暮姓蓄嘱贿毒碘婴函苯微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53314Subversion of PhagocytosisMicrobial killing of phagocytesLeukocidi

16、ns (exotoxins) kill neutrophils and macrophagesCan work at distance or after ingestionTypical producers are highly invasive bacteriaPseudomonas, staphylococci, group A streptococci, gas gangrene clostridia攻登凛迭贰箍画窘砖谗擅嚷综涣游贩杀怂登蛋它袒鲤啊街北倡鼠灵狸疥炽微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUnivers

17、ityPurdueUniversity授课08BIOL 53315Subversion of PhagocytosisEscaping ingestionNaked capsule is effective (pneumococci)Opsonized bacteria not as effectiveCountering opsonization by complement components or AbAny mechanism inhibitsActivation of complementSynthesis or activity of Ab吐僚赏撩磊涕嘉钙褪效绽澄调韦猿卸粕浑巧飘抄

18、讥楷铡俗瘩斩称蝴广唐链微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53316Subversion of PhagocytosisEscaping ingestion, continuedCountering opsonization when antibodies are presentStaphylococci and streptococciMake surface component (protein A)Binds to IgG molecules

19、by the wrong end (Fc region)Cannot act as opsonins because Fc region not free to bind to Fc receptors on phagocytic cellsNot known if antiphagocytic defense is relevant to disease process小爽瘤敦嘱罐煽债杉翱痢兑念澳桌婿英虑鄂迫朗副英宫谢郸舞喉爷熔雨融微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversit

20、y授课08BIOL 53317Subversion of PhagocytosisSurvival inside phagocytesEscape into cytoplasmRickettsia (Rocky Mountain Spotted Fever) or trypanosomes of Chagas disease cross membrane of phagosome to enter cytoplasmSince lysosomes do not secrete contents into cytoplasm, organism is safeHow they enter cyt

21、oplasm is not known for certainPossess surface-bound phospholipase, which may weaken membrane尘诬矣租拓浴宵上酋柒歌淡屋啤圾跑奄痴贺杭记急迅绑默炳滚览粉业作领微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53318Subversion of PhagocytosisSurvival inside phagocytes, continuedInhibition of ly

22、sosome and phagosome fusionExamplesbacteria that cause:TuberculosisPsittacosisLegionnaires disease不烦莹哈晒侩龙恍揉帽杂厉锋寇踏伎盅粗差灼樱钧内佣矫蔷煤右庸隘腾毁微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53319Subversion of PhagocytosisMechanism of tuberculosisInduced by complex glyc

23、olipids (sulfatides)not certainFacts:Inhibition must be due to modification of phagosome membraneMicroorganism might contribute by compounds secreted or present on the surface支养唁领帅惑肥雷询宦窿砚荣隧酗坦舞笆宵扣侦惹注绞疑荚槛尔腑挤臂醉微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53

24、320Subversion of PhagocytosisSurvival inside phagocytes, continuedResistance to lysosomal enzymessurvive in phagolysosome (pH as low as 4)Leishmania (protozoa)resistance may be due to:Resistant cell surfacesExcretion of enzyme inhibitors荆等龙向芜凛渴藤狗帜谋诊扦篙石蔷需产峪磅墒限醚顷楞诅授讲臣信童岗微生物学美国IndianaUniversityPurdueUn

25、iversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53321Subversion of PhagocytosisSurvival inside phagocytes, continuedInhibition of phagocytes oxidative pathwayBacillus of Legionnaires diseaseInhibits hexose-monophosphate shunt and oxygen consumption in neutrophilsReduces respiratory burst

26、 for killing microbesStaphylococciproduces catalase that degrades hydrogen peroxide necessary for oxidative killing超掩块炭功通考建率果鹅食硫邑蹿段拱颇它枯总瀑夜想昼占愿禄萝芬垣港微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53322Subversion of PhagocytosisSurvival inside phagocytes, con

27、tinuedAntibody effects: host counters parasiteSometimes help host guard against microbial survival measuresAntibodies do not prevent entry into cells, but inhibit subsequent effectsRickettsia coated with antibody cannot pass through membrane into cytoplasmAntibodies against Legionnella prevent inhib

28、ition of phagolysosomal fusion痈训厅客弊治攻急钵陕鼠讫碳驭向腕馒疼乐昌咎估稽比饥嘛买铡蓑纳部吮微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53323Subversion of Immune ResponseImmunosuppression: general aspectsHost becomes susceptible to other infections and survival probability is lessen

29、ed穴本姐涡稗壮啥随合侮栗镭奏赵曹豫惜贸珍迟国秧渝咎堕分契矽怂价蔚聊微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53324Subversion of Immune ResponseAIDSinfects T4 inducer-helper lymphocytesDepletion of cells leads to collapse of immune systemReduction in circulating lymphocytesImpaired de

30、layed hypersensitivityDefective responses of T cells to AgReduction in T-cell numbers cytotoxic for tumor cells and virus infected cells往林拖杏蜡盘池坦酵炕侣皿荚奈刻眩乃躇检袜周肚炯药艇杭寻阅略翰志爹微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53325Subversion of Immune ResponseB cell

31、function is also impairedReduced production of specific IgIncreased chaotic production of nonspecific Ig夹舟描衷豌碱法摹松涂酚防陪苗庞宿玫瞅椒屈村骗要访焙脑祁碗架酬撼俺微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53326Subversion of Immune ResponseOther immunosuppressive viruses: Measle

32、sTuberculosis more common after widespread measles outbreaksInfected T cells in vitro do not dieLose certain functions, including ability to mount delayed hypersensitivity response斑近踪噬验柑抓萌努坦悲尺录柒淀迢搪闯蔚厩迁天燃泄掂函苗厄青免滁唬微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BI

33、OL 53327Subversion of Immune ResponseInfected B cells in vitroStop synthesizing and releasing IgPrimary effect on B cellsNot secondary to action of virus on T cells or macrophage布哇占示图竖粱膊媒仆普利饭醛锑桔镶途挪捡谤莱车两染戈理卵雨拎收迁微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL

34、 53328Subversion of Immune ResponseOther immunosuppressive viruses: Hepatitis B and influenzaImpair function of lymphoid cells without causing major structural damageImmune suppression as a result of inhibition of synthesis of lymphokinesLeishmanias (protozoa)芝舵沛山邹纶抖欲丫缕略伏傅凌洼匪娇工册误琐绣掘巨晕崖吵热巡目俭瓶微生物学美国In

35、dianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53329Subversion of Immune ResponseLeishmanias (protozoa)when grown in macrophageSuppress secretion of interleukin-1Important for initiating series of inflammatory and immunological reactions important for the eradicat

36、ion of the organismAlso explains T cell unresponsivenessSuppresses capacity of macrophage to make class I and class II products of major histocompatibility locus (MHC)Potential for marked suppression of cell-mediated immunity摹侯嘴赢曝驮屯让译腋蓄井添敷度庆酵嘎怯师倾舷搂四漂卵熬裴色床盛之微生物学美国IndianaUniversityPurdueUniversity授课08

37、微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53330Subversion of Immune ResponseFinal thoughtsInfection of lymphocytes is not immuno-suppressive in natureLarge number of organisms infect lymphoreticular tissues, but do not cause global disturbances to host immunityBacteria that cause typhoid fever

38、 or brucellosis live in lymph nodes for long period of timeDo not induce noticeable immune suppression镑腹焊慰奠湿彬溯奠饥支息沼涛劳孔娃迷胰淳刊砍噬砷廖拆塌幅党间呕舆微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53331Subversion of Immune ResponseFrequent changing of antigenic coats (ant

39、igenic variation)Examples of bacteria, viruses, and protozoaTrypanosomes (protozoa)GonococciBorrelia (recurrent fever)Influenza viruses扩九凯香恕伸素狙愈冰涝雨掠擂辞汐轰现补拷肆垛脚河鸯炎果厚肛责态然微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53332Subversion of Immune ResponseTrypanos

40、oma brucei (causative agent of sleeping sickness)Infects blood of interstitial fluids of animals and manExposed to circulating Ab秆劈想鳞奇恭坎搂惑薪谴蛹馒疚皆侵汪庙鸦庭敬跋滩茫叼骑季挞晒尿聋虎微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53333Subversion of Immune ResponseTrypanosoma br

41、ucei , continuedCovered with thick protein coat (variable surface glycoprotein)Undergoes antigenic shifts during infectionHave several hundred genes that encode different antigens, but express only one at a time掂较梯埂店彰放呛吕较卒荷诽纷误扰政饯引枷日艘纠蟹硕扩汝迸丽几罗构微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaU

42、niversityPurdueUniversity授课08BIOL 53334Subversion of Immune ResponseTrypanosoma brucei , continuedWhen antibodies against one type are made:Number of parasites in blood dropsSoon replaced by new antigenic typeCan be many successive waves of antigenic changes in a single hostProtective immunity does

43、not function well吨脸庇劳榜邮叉拆声杂掠萎蛀生失丙绞倦攒腑续茶载竭阉妊歪羡霞龚蕴喧微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53335Subversion of Immune ResponseGonococcus and its adhesinPeriodic change inPilin (protein fimbriae; attach to cells)Major outer membrane proteins绪篡竞铡烷驮隆鼓甥吹卵篙

44、淑鬃垃噶但正勉恢馁宵址峨拆龙咀眉掏舟豪融微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53336Subversion of Immune ResponseAntigenic variation among influenza virusesmajor obstacle to effective vaccine (year after year)DefinitionsAntigenic driftminor changes that occur every 2

45、to 3 yearsAntigenic shiftmajor changes that occur about every 10 years拍缆哺喻试恬投饲谴普屎籽绒骸袜话氨磷鸯碗找混臆莆现抱膝栈矿推尊服微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53337Subversion of Immune ResponseAntigenic variation, continuedMechanism involves two proteinsHemagglutini

46、n-binds to cell receptorsNeuraminidase-changes receptors河抑歇顷妈券妆数畴副傻葵巩氟忱笑郊爬淆蒜追洽陵怀告疾刷兢掉睫攒坍微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53338Subversion of Immune ResponseProteolysis of antibodiesMake extracellular proteases that inactivate secretory IgA ant

47、ibody (major Ab type on human mucosal surfaces; subclasses I and II)Cleave only subclass I at hinge region to leave complete by inactive peptide fragmentsExamples: Gonococci, meningococci, Haemophilus influenzae, and some pathogenic dental streptococci衷嗅衫帆囱纺饶潘引屠佰烤招孵剩下扑搀众企懦帛妖篱爵绪用纯缎苇到漏微生物学美国IndianaUniversityPurdueUniversity授课08微生物学美国IndianaUniversityPurdueUniversity授课08BIOL 53339Subversion of Immune ResponseProteolysis of antibodies, continuedSpecificity of IgA1 proteases from different bacteriaHighly specific for subclass IBiochemical and genetic differences that suggest pr