Microbial Pathogenesis and HostParasite Relationships

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Microbial Pathogenesis and Host-Parasite
Relationships
Medical Microbiology

• BIOL 533
• Lecture 1

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Definitions

• Microbial pathogenesisprocess of causing disease
• Colonizationpresence 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 travelers
  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 dont 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 37C
• 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 bacteriaover 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 optimaprudence 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

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