Lecture OneBIOL 533 1
Host-Parasite Relationships
Medical Microbiology
Lecture One
Agents That Cause Disease.
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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
Lecture One
Agents That Cause Disease.
Lecture One
• Outcome: agent or host wins, or coexist
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