Lecture One BIOL 533 1
Microbial Pathogenesis
and Host-Parasite Relationships
BIOL 533
Lecture 1
Medical Microbiology
Lecture One BIOL 533 2
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
Lecture One BIOL 533 3
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
Lecture One BIOL 533 4
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
Lecture One BIOL 533 5
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
Lecture One BIOL 533 6
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
Lecture One BIOL 533 7
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
Lecture One BIOL 533 8
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
Lecture One BIOL 533 9
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
Lecture One BIOL 533 10
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
Lecture One BIOL 533 11
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
Lecture One BIOL 533 12
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
Lecture One BIOL 533 13
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
Lecture One BIOL 533 14
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
Lecture One BIOL 533 15
Entry Defined
? Ingress of microbes into body cavities
contiguous with outside
Lecture One BIOL 533 16
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
Lecture One BIOL 533 17
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
Lecture One BIOL 533 18
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
Lecture One BIOL 533 19
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
Lecture One BIOL 533 20
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
Lecture One BIOL 533 21
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)
Lecture One BIOL 533 22
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
Lecture One BIOL 533 23
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
Lecture One BIOL 533 24
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
Lecture One BIOL 533 25
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
Lecture One BIOL 533 26
Virulence Factor Examples
? Exotoxins
? Endotoxins
? Capsules
? IgA proteases
? Adhesins (pili)
? Motility
? Invasive properties
? Ability to acquire
iron
? Serum resistance
? Ability to survive
inside phagocytes
Lecture One BIOL 533 27
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)
Lecture One BIOL 533 28
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
Lecture One BIOL 533 29
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
Lecture One BIOL 533 30
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
Lecture One BIOL 533 31
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‖
Lecture One BIOL 533 32
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
Lecture One BIOL 533 33
Damage
? Types,continued,
– Pharmacological,toxins alter metabolism
– Damage due to host responses
? Inflammation can lead to destruction of
neighboring cells
? Immune response
Lecture One BIOL 533 34
Lecture One
? Questions?
? Comments?
? Assignments..,
Microbial Pathogenesis
and Host-Parasite Relationships
BIOL 533
Lecture 1
Medical Microbiology
Lecture One BIOL 533 2
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
Lecture One BIOL 533 3
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
Lecture One BIOL 533 4
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
Lecture One BIOL 533 5
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
Lecture One BIOL 533 6
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
Lecture One BIOL 533 7
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
Lecture One BIOL 533 8
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
Lecture One BIOL 533 9
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
Lecture One BIOL 533 10
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
Lecture One BIOL 533 11
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
Lecture One BIOL 533 12
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
Lecture One BIOL 533 13
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
Lecture One BIOL 533 14
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
Lecture One BIOL 533 15
Entry Defined
? Ingress of microbes into body cavities
contiguous with outside
Lecture One BIOL 533 16
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
Lecture One BIOL 533 17
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
Lecture One BIOL 533 18
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
Lecture One BIOL 533 19
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
Lecture One BIOL 533 20
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
Lecture One BIOL 533 21
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)
Lecture One BIOL 533 22
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
Lecture One BIOL 533 23
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
Lecture One BIOL 533 24
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
Lecture One BIOL 533 25
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
Lecture One BIOL 533 26
Virulence Factor Examples
? Exotoxins
? Endotoxins
? Capsules
? IgA proteases
? Adhesins (pili)
? Motility
? Invasive properties
? Ability to acquire
iron
? Serum resistance
? Ability to survive
inside phagocytes
Lecture One BIOL 533 27
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)
Lecture One BIOL 533 28
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
Lecture One BIOL 533 29
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
Lecture One BIOL 533 30
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
Lecture One BIOL 533 31
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‖
Lecture One BIOL 533 32
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
Lecture One BIOL 533 33
Damage
? Types,continued,
– Pharmacological,toxins alter metabolism
– Damage due to host responses
? Inflammation can lead to destruction of
neighboring cells
? Immune response
Lecture One BIOL 533 34
Lecture One
? Questions?
? Comments?
? Assignments..,
