1 Microbial Pathogenesis Medical Microbiology. 2 Definitions Microbial pathogenesis—process of...
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Transcript of 1 Microbial Pathogenesis Medical Microbiology. 2 Definitions Microbial pathogenesis—process of...
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Microbial Pathogenesis
Medical Microbiology
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Definitions
Microbial pathogenesis—process of causing disease
Colonization—presence of microbes at site of body– Does not imply tissue damage or disease
symptoms– Does imply invasion of site and multiplication
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Characteristics of Parasitism
Encounter: agent meets host Entry: agent enters host Spread: agent spreads Multiplication: agent multiplies Damage: agent, host response, or both
cause damage Outcome: agent or host wins, or coexist
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Encounter
In utero– Do not normally come in contact with organisms
Protection of fetal membranes Do not normally come in contact with organisms from
mother– Normally only present sporadically– Exceptions: sexual diseases, virus causes, rubella
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Encounter
At moment of birth– Come in contact with organisms present in
vaginal canal and on skin Previously, antibodies passed from mother to fetus Defenses are good for a period of time, then they wane
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Encounter
Challenge between man and microbe wages many times during lifetime– Most disappear rapidly– Some become part of normal flora– Only a few cause disease
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Later Encounters
Exogenous: encountered in environment Endogenous: encountered in or on body
– Organisms present on skin can cause disease when they go into deeper tissues
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Later Encounters
Example:– Staphylococcus aureus enters cut and forms boil– In this case, encounter took place long before
disease (at time skin was colonized)
Encounter is not always sharply demarcated
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Normal Flora
What constitutes normal flora?– Some people possess Streptococcus pyogenes in
their throat for long periods, but rarely contract disease
Opportunistic pathogen existence (carrier state)
– 95% of people never have this bacterium, and when they do, they get sick
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Normal Flora Defined
Constitutes normal flora if definition is “any organism present that is not causing disease”
Not normal flora if used to mean organisms present in majority of population
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Host-Parasite Interaction
Exposure to virulent agents does not always lead to disease– Typhus and Black Plague epidemics: only half
of population became sick, even though most likely exposed
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Host-Parasite Interaction
Response of particular microbe to particular host– Depends on factors unique to each interaction– Within a single individual– Changes with:
Age Nutritional state Other factors
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Entry
Much of inside of body is connected to the outside; for example:– Lumen of intestine– Alveoli of lung– Tubules of kidney
Almost all organs within thorax and abdomen are topologically connected to the outside
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Entry
Mechanisms to keep out invaders– Sphincters and valves– With exception of digestive and genitourinary
systems, these sites are normally sterile– Organism that resides on lumen side of intestine
or lung alveoli has not penetrated body
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Entry Defined
Ingress of microbes into body cavities contiguous with outside
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Digestive System
Enter through eating– Numbers of organisms are reduced one million or
more in stomach Bacillary dysentery can result from only a few hundred
organisms
– Not many survive in intestine because of digestive enzymes and strong force of peristalsis
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Digestive System
More survive in ileum, but need mechanisms to prevent expulsion– Surface components serve as adhesins to allow
adherence to epithelial cells Pili and surface polysaccharides
– Diseases such as cholera and “traveler’s diarrhea” are caused without penetrating epithelium
Toxins that affect epithelial cells
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Respiratory System
Enter through being inhaled– Air containing microbes goes through air
passages (nasal turbinates, oropharynx, larynx)– Microbes reaching lower respiratory system face
powerful epithelium sweeping action– Colonization requires adhesion mechanisms
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Other
No term for urinary or genital entry
By bypassing epithelial tissue, microbes can cause disease without penetrating deep into tissues– Cholera, whooping cough, infection of urinary
bladder
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Penetration into Deeper Tissues
Very few organisms can penetrate unbroken skin (worms are an exception)
Some organisms can penetrate epithelial tissue; for example:– S. pneumoniae, Treponema pallidum
Normally after some injury to tissue (many times caused by a virus)
– Viruses, by receptors
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Carried in by Macrophage
Alveolar macrophage trap organisms in lung– Normally carry upward on ciliary epithelium– Some cases, can carry deeper into tissues
Some organisms can live, grow in macrophage:– Legionella– Bordetella pertussis– HIV (via virus-laden macrophage from semen)
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Penetration by Other Means
Insect bites: numerous viral and protozoan diseases
Cuts and wounds: don’t normally lead to disease– Brushing teeth or defecating vigorously causes
minute abrasions of epithelium Organisms quickly cleared from blood by
reticuloendothelial system
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Penetration by Other Means
– Injury to internal tissue disrupts defense mechanisms and serious disease can result; for example
Subacute bacterial endocarditis– Devastating before antibiotics– Caused by oral streptococci that became implanted on
heart valves damaged by rheumatic fever
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Penetration by Other Means
Organ transplants or blood transfusions– Jakob-Cruetzfeldt disease from transplanted
corneas– Cytomegalovirus from kidneys, probably in donor
kidney
Because immunosuppressive drugs are used, virus may be endogenous
Hepatitis B, HIV transmitted by blood
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Disease Causation
Why are organisms adapted to various locations?– Temperature optima; athletes foot yeast cannot
grow at 37°C– Oxygen requirements– Specialized factors important for causing disease
(i.e., virulence factors)– Virulence: degree of pathogenicity
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Virulence Factor Examples
Exotoxins Endotoxins Capsules IgA proteases Adhesins (pili) Motility
Invasive properties Ability to acquire iron Serum resistance Ability to survive inside
phagocytes
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Inoculum Size
Inoculum size can determine whether organisms cause disease
Normally, high number needed to cause disease/overcome defenses; e.g.
– Baths in contaminated hot tubs (veritable culture of bacteria—over one hundred million organisms per ml)
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Inoculum Size
Normally harmless organisms can overcome defenses; e.g.,
– People get boils all over body
If large number of organisms deposited in deeper tissues, infection usually results
– Surgeon preps area to reduce numbers
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Spread of Disease
General: spread only if overcome host defenses
Sometimes precedes, sometimes follows microbial multiplication– Precede: parasite causes malaria disseminated before
multiplication
– Follow: S. aureus multiplies locally before being disseminated
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Spread of Disease
Types:– Direct lateral propagation to contiguous tissues– Dissemination to distant sites
Characteristics:– Anatomical factors (e.g., ear infections)– Active participation by pathogens— enzymes
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Multiplication
Factors that affect– Microbial nutrition: body is very nutritious, but it
also has antimicrobial substances– Body contains very little free iron
Physical factors: temperature, etc.– Narrow temperature optima—prudence of lowering fever
by “take two aspirin and call me in the morning”
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Damage
General: type and intensity depend on specific organism and tissue
Types:– Mechanical: mostly result of inflammation– Cell death: depends on:
Which cells How many infected How fast infection proceeds
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Damage
Types, continued:– Pharmacological: toxins alter metabolism– Damage due to host responses
Inflammation can lead to destruction of neighboring cells Immune response