Transcript Host-parasite

Medical Microbiology
Host-Parasite Relationships
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Lecture One
Agents That Cause Disease.
Pathogens
Viruses
Bacteria
Parasites
Fungi
Lecture One
Characteristics of Parasitism
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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
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Exotoxins
Endotoxins
Capsules
IgA proteases
Adhesins (pili)
Motility
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• 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
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Lecture One
Agents That Cause Disease.
Pathogens
Viruses
Bacteria
Parasites
Fungi
Lecture One
• Outcome: agent or host wins, or coexist
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Lecture One