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1、Lecture One微生物学美国IndianaUniversityPurdueUniversity授课01Stillwatersrundeep.流静水深流静水深,人静心深人静心深Wherethereislife,thereishope。有生命必有希望。有生命必有希望Lecture OneDefinitionsMicrobial pathogenesisprocess of causing diseaseColonizationpresence of microbes at site of bodyDoes not imply tissue damage or disease symptoms
2、Does imply invasion of site and multiplication BIOL 5332Lecture OneCharacteristics of ParasitismEncounter: agent meets hostEntry: agent enters hostSpread: agent spreadsMultiplication: agent multipliesDamage: agent, host response, or both cause damageOutcome: agent or host wins, or coexistBIOL 5333Le
3、cture OneEncounterIn uteroDo not normally come in contact with organismsProtection of fetal membranesDo not normally come in contact with organisms from motherNormally only present sporadicallyExceptions: sexual diseases, virus causes, rubellaBIOL 5334Lecture OneEncounterAt moment of birthCome in co
4、ntact with organisms present in vaginal canal and on skinPreviously, antibodies passed from mother to fetusDefenses are good for a period of time, then they waneBIOL 5335Lecture OneEncounterChallenge between man and microbe wages many times during lifetimeMost disappear rapidlySome become part of no
5、rmal floraOnly a few cause diseaseBIOL 5336Lecture OneLater EncountersExogenous: encountered in environmentEndogenous: encountered in or on bodyOrganisms present on skin can cause disease when they go into deeper tissuesBIOL 5337Lecture OneLater EncountersExample:Staphylococcus aureus enters cut and
6、 forms boilIn this case, encounter took place long before disease (at time skin was colonized)Encounter is not always sharply demarcatedBIOL 5338Lecture OneNormal FloraWhat constitutes normal flora?Some people possess Streptococcus pyogenes in their throat for long periods, but rarely contract disea
7、seOpportunistic pathogen existence (carrier state)95% of people never have this bacterium, and when they do, they get sickBIOL 5339Lecture OneNormal Flora DefinedConstitutes normal flora if definition is “any organism present that is not causing disease”Not normal flora if used to mean organisms pre
8、sent in majority of populationBIOL 53310Lecture OneHost-Parasite InteractionExposure to virulent agents does not always lead to diseaseTyphus and Black Plague epidemics: only half of population became sick, even though most likely exposedBIOL 53311Lecture OneHost-Parasite InteractionResponse of part
9、icular microbe to particular hostDepends on factors unique to each interactionWithin a single individualChanges with:AgeNutritional stateOther factorsBIOL 53312Lecture OneEntryMuch of inside of body is connected to the outside; for example:Lumen of intestineAlveoli of lungTubules of kidneyAlmost all
10、 organs within thorax and abdomen are topologically connected to the outsideBIOL 53313Lecture OneEntryMechanisms to keep out invadersSphincters and valvesWith exception of digestive and genitourinary systems, these sites are normally sterileOrganism that resides on lumen side of intestine or lung al
11、veoli has not penetrated bodyBIOL 53314Lecture OneEntry DefinedIngress of microbes into body cavities contiguous with outsideBIOL 53315Lecture OneDigestive SystemEnter through eatingNumbers of organisms are reduced one million or more in stomachBacillary dysentery can result from only a few hundred
12、organismsNot many survive in intestine because of digestive enzymes and strong force of peristalsisBIOL 53316Lecture OneDigestive SystemMore survive in ileum, but need mechanisms to prevent expulsionSurface components serve as adhesins to allow adherence to epithelial cellsPili and surface polysacch
13、aridesDiseases such as cholera and “travelers diarrhea” are caused without penetrating epitheliumToxins that affect epithelial cellsBIOL 53317Lecture OneRespiratory SystemEnter through being inhaledAir containing microbes goes through air passages (nasal turbinates, oropharynx, larynx)Microbes reach
14、ing lower respiratory system face powerful epithelium sweeping actionColonization requires adhesion mechanismsBIOL 53318Lecture OneOtherNo term for urinary or genital entryBy bypassing epithelial tissue, microbes can cause disease without penetrating deep into tissuesCholera, whooping cough, infecti
15、on of urinary bladderBIOL 53319Lecture OnePenetration into Deeper TissuesVery few organisms can penetrate unbroken skin (worms are an exception)Some organisms can penetrate epithelial tissue; for example:S. pneumoniae, Treponema pallidumNormally after some injury to tissue (many times caused by a vi
16、rus)Viruses, by receptorsBIOL 53320Lecture OneCarried in by MacrophageAlveolar macrophage trap organisms in lungNormally carry upward on ciliary epitheliumSome cases, can carry deeper into tissuesSome organisms can live, grow in macrophage:LegionellaBordetella pertussisHIV (via virus-laden macrophag
17、e from semen)BIOL 53321Lecture OnePenetration by Other MeansInsect bites: numerous viral and protozoan diseasesCuts and wounds: dont normally lead to diseaseBrushing teeth or defecating vigorously causes minute abrasions of epitheliumOrganisms quickly cleared from blood by reticuloendothelial system
18、BIOL 53322Lecture OnePenetration by Other MeansInjury to internal tissue disrupts defense mechanisms and serious disease can result; for exampleSubacute bacterial endocarditisDevastating before antibioticsCaused by oral streptococci that became implanted on heart valves damaged by rheumatic feverBIO
19、L 53323Lecture OnePenetration by Other MeansOrgan transplants or blood transfusionsJakob-Cruetzfeldt disease from transplanted corneasCytomegalovirus from kidneys, probably in donor kidneyBecause immunosuppressive drugs are used, virus may be endogenousHepatitis B, HIV transmitted by bloodBIOL 53324
20、Lecture OneDisease CausationWhy are organisms adapted to various locations?Temperature optima; athletes foot yeast cannot grow at 37COxygen requirementsSpecialized factors important for causing disease (i.e., virulence factors)Virulence: degree of pathogenicityBIOL 53325Lecture OneVirulence Factor E
21、xamplesExotoxinsEndotoxinsCapsulesIgA proteasesAdhesins (pili)MotilityInvasive propertiesAbility to acquire ironSerum resistanceAbility to survive inside phagocytesBIOL 53326Lecture OneInoculum SizeInoculum size can determine whether organisms cause diseaseNormally, high number needed to cause disea
22、se/overcome defenses; e.g.Baths in contaminated hot tubs (veritable culture of bacteriaover one hundred million organisms per ml)BIOL 53327Lecture OneInoculum SizeNormally harmless organisms can overcome defenses; e.g.,People get boils all over bodyIf large number of organisms deposited in deeper ti
23、ssues, infection usually resultsSurgeon preps area to reduce numbersBIOL 53328Lecture OneSpread of DiseaseGeneral: spread only if overcome host defensesSometimes precedes, sometimes follows microbial multiplicationPrecede: parasite causes malaria disseminated before multiplicationFollow: S. aureus m
24、ultiplies locally before being disseminatedBIOL 53329Lecture OneSpread of DiseaseTypes:Direct lateral propagation to contiguous tissuesDissemination to distant sitesCharacteristics:Anatomical factors (e.g., ear infections)Active participation by pathogens enzymesBIOL 53330Lecture OneMultiplicationFa
25、ctors that affectMicrobial nutrition: body is very nutritious, but it also has antimicrobial substancesBody contains very little free ironPhysical factors: temperature, etc.Narrow temperature optimaprudence of lowering fever by “take two aspirin and call me in the morning”BIOL 53331Lecture OneDamage
26、General: type and intensity depend on specific organism and tissueTypes:Mechanical: mostly result of inflammationCell death: depends on:Which cellsHow many infectedHow fast infection proceedsBIOL 53332Lecture OneDamageTypes, continued:Pharmacological: toxins alter metabolismDamage due to host responsesInflammation can lead to destruction of neighboring cellsImmune responseBIOL 53333Lecture OneLecture OneQuestions?Comments?Assignments.BIOL 53334
