Pathogenic%20Mechanisms

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Pathogenic Mechanisms

• Hugh B. Fackrell
• Filename PathMech.ppt

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Outline

• Infection vs Disease
• Pathogenicity
• Virulence
• Pathogenic factors
• Latency Dormancy
• Communicability

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Saprophyte

• nutrient source is non-living
• can become parasite

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Parasitism

• host/microorganism interaction
• Mutualism - both host and parasite benefit.
• Commensalism - the parasite does no damage to the
  host.
• Pathogen - the parasite damages the host.
• Opportunism - the parasite takes advantage of the
  weakened condition of the host.

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Microbial Infection vs Disease

• Infection colonization of the body with microbe
• usually non pathogenic
• indigenous or commensal
• beneficial
• Disease breach of host defenses
• microbes infect tissues not normally exposed

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Infection Benefits

• Metabolites
• E. coli makes vitamin K
• Bacterial antagonism
• E.coli blocks colonization of gut by S. aureus
• evidence antibiotic sterilization before
  abdominal surgery
• subsequent Staphylococcal infections
• enteritis
• Encourage immune system
• axenic animals have poor immunity

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Infection Adverse Effects

• Staphylococcal infection
• Produces penicillinase
• Concurrent infection of Neisseria gonorrhaeae
• Becomes disease gonorrhea

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Microbial Disease

• Microbial disease is the exception
• imbalance favours the microbe
• 3 of all microbes pathogenic
• majority of known microbes
• gt95 do not cause disease
• virtually unknown

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Location of Microbe in Host

• Location often decides outcome of Infection vs
  disease
• Streptococcus
• Infection nasopharynx
• Disease heart
• bacterimiae after tooth extraction
• E. coli
• Infection gut
• Disease cystitis in urinary tract

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Contagious Transmission

• can be transmitted from one host to another
  (communicable)
• some infections acquired from indigenous flora
  are categorized as communicable.

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Communicability

• Communicable spread directly or indirectly from
  one host to another
• chickenpox, measles, tuberculosis, typhoid fever
• Contagious easily communicable
• eg chickenpox,measles, sore throat
• Non communicable Not spread from host to host
• tetanus

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Dormancy

• Latency Dormancy causative microbe remains
  inactive in the host for some time but later
  becomes active to produce the signs and symptoms
  of the disease

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Carrier State

• Individual infected
• results from a previous disease state (may be
  temporary)
• the host is a true carrier
• microbe in balance with that individual
• No overt signs or symptoms
• reservoir for infection of others
• Typhoid Mary

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Kochs Postulates

• The organism should be found in all cases of the
  disease and its distribution in the body should
  be in accordance with the lesions observed.
• The organism should be cultivated outside the
  body of the host, in pure culture, for several
  generations of the pathogen.
• The disease should be reproduced in susceptible
  animals.

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Etiology

• Science of the causes of disease
• the nature of the host - species
• the condition of the host
• the nature of the disease agent
• the transmission of the agent

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Etiology of Disease (1/2)

• Specimen from patient containing infectious agent
  cultured.
• Pure culture obtained and described identified
  if possible.
• Inoculation and observation of test animal.
• Many organs removed and cultured.

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Etiology of Disease (2/2)

• Isolation and identification of the test
  organism.
• Inoculation of a second test animal.
• Culture of second test animal.
• Antibodies in blood of human or animal.
• Immunity developed to the infecting agent in
  recently recovered animal.
• Animal protected by vaccine or toxoid.

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Pathogenicity

• Ability or potential to cause disease attributed
  to a genus or species
• Dependent on ability to
• enter the host
• adapt and multiply in the host
• exit from the host
• transmit to new host

Keppie Smith
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Portal of Entry

• May multiply at entry sitegt lesion
• Often enters multiplies elsewhere
• 2/3 Respiratory
• 1/3 intestine, urethra, conjunctiva and skin

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Multiplication in Host

• Rate of multiplication different in vivo and in
  vitro
• time to overt symptoms
• Carrier state
• reservoir gall bladder
• Temperature
• viruses
• aspirin

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Exit from Host

• Usually by same route a entry

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Bacterial transmission

• Droplets
• Fomites
• Direct contact
• sexual
• non sexual
• Bites
• insects
• animals

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Types of Pathogens

• pathogens characterized as frank - Salmonella
• opportunistic pathogens - E. coli in urinary
  tract
• non-pathogens - such as Serratia marcescens may
  become infectious agents

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Virulence

• DEGREE of pathogenicity shown by a specific
  strain of an organism
• C. diptheriae gt diptheria
• variables include
• number of infecting bacteria
• route of entry into body
• specific host defense mechanisms
• non-specific host defense mechanisms
• virulence factors of the bacterium

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Virulence Measurement

• Measures the pathogenicity of a isolate
• variable among strains
• Measure of Virulence
• Median Dose
• Minimum Effective Dose

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Median Dose
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Cause of Virulence Variation

• Dose of pathogen
• Virulence/Pathogenic factors

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Dose of Pathogen

• Typhoid Fever
• S. typhosa contaminated water
• 1-100 bacteria no effect
• Boils
• Staphylococcus aureus
• just on surface 7 x 10 6cells
• on suture or scratch 1000 cells
• stictch abcesses

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Pathogenic Factors

• Gene mutation
• S. pneumoniae- capsule
• Shigella gt dysentery
• Lysogeny
• scarlet fever
• diptheria
• Capsules
• Klebsiella gt polysaccharide
• Anthrax gt protein capsule

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Pathogenic Factors

• Inhibit host metabolism
• M. tuberculosis gt tuberculosis
• mycolic acid blocks lysosomal enzymes
• Resist host metabolism
• stomach acids
• bile salts
• enzymes
• salt

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Invasion Factors

• usually surface components
• also enzymes - proteases
• tissue lysins
• Adherence factors
• pili (fimbriae)
• fibronectin receptors
• Capsules
• prevent phagocytosis
• opsonization

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Adhesion to Host

• Allows Microbe more stable foothold at the
  portal of entry
• bind to host cells
• penetrate the epithelial boundary
• become established in the tissues

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Adhesion Mechanisms

• Fimbriae on bacterial cells
• Adherent capsules, slime layers or other sticky
  substances
• Viral envelope spikes
• Pathogen hooks on filaments of target cells

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Adhesins

• Afimbrial adhesins are proteins that assist in
  binding bacteria to the host cell.
• F ProteinStreptococcus pyogenes
• assists binding to fibronectin,a protein on host
  cell surface.
• M Protein
• Lipoteichoic acid

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Biofilm

• - multilayer bacterial populations embedded in a
  polysaccharide matrix that is attached to same
  surface.

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Siderophores

• Iron acquisition Fe low in human and is bound
  to
• lactoferrin
• transferrin
• ferritin
• hemin
• Bacteria compete for Fe using Siderophores
• Low molecular weight compounds that
• chelate iron
• Ex. Enterochelin Fe

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Siderophore Competes for Fe3
Sideriophore
Siderophore Receceptor
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Toxigenicity

• Production and release of an extracellular
  microbial product that disrupts the hosts normal
  physiology
• Proteins gt exotoxins
• Function away from bacterium
• Potent poisons
• diptheria toxin
• tetanus toxin
• botulism toxin

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Exotoxins vs Endotoxins

• Exotoxins
• usually Gram ve
• extracellular
• released from live cell
• protein
• MW 15,000 -100,000
• Heat labile
• toxoid
• Antigenic gt vaccine
• extremely potent

• Endotoxins
• from Gram -ve
• part of cell wall
• released from dead cell
• lipopolysaccharide
• MW millions
• heat stable
• no toxoid
• poorly antigenic
• less potent

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Toxins Biological Functions

• Exotoxins
• Cytotoxic
• Neurotoxic
• Enterotoxic
• enteron gut

• Endotoxins
• cause fever
• changes in blood pressure
• inflammation
• lethal shock

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Infection Process

• an infection develops into disease when the
  balance between microbial pathogenicity and host
  resistance is tipped toward the agent.

Infectious Agent
Host (human, animal, plant)
Infection Rejected no disease
Host Physiology Protects
Infection Established
Infection Moderate subclinical disease
Infectious Agent Successful
Infection Established disease
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Host Susceptibility

• Humoral Defense Mechanisms
• Cellular Defense Mechanisms
• Inflammation - a combination of humoral and
  cellular

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Resistance to Bacterial Infections

• Phagocytosis
• Immune response
• Non-specific mechanisms
• 2. Bacteria
• multiply
• objective not to destroy the host
• 3. Host - Mediated Pathogenesis
• for example, tuberculosis - tissue damage results
  from toxic mediators released by lymphoid cells.

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Non-Specific Physiological Host Defense Mechanisms

• Innate or Natural Immunity
• an individual is born with certain mechanisms of
  resistance to infectious agents
• also called racial or inherent immunity.

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Mechanisms of Microbial Antagonism

• attachment site occupied with indigenous flora
  (commensals) usually bacteria
• bacteriocins - proteins secreted by the
  indigenous flora that inhibit the growth of other
  bacteria
• competitive deletion of essential nutrients
• production of toxic by-products
• genitourinary tract - at menarche, tissues of
  vagina and cervix become populated with
  Lactobacilli which lower the pH to 4.4-4.6
  inhibitory to gram negative enterics.

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Physical Barriers Chemical Agents

• Intact Skin
• acid pH
• epithelial surface
• Staphylococcus aureus (pathogen) also carried as
  indigenous flora
• Mucous membranes
• vagina
• bowel
• respiratory tract
• more easily penetrated than the intact skin

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Mucous

• motion of cilia
• coughing/sneezing

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Physical Barriers Chemical Agents

• Eyes
• flushing action
• lysozyme
• Outer ear canal
• wax

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Alimentary canal

• saliva (antibodies)
• some protection from stomach acid (over rated)
• indigenous flora
• diarrhea

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Genitourinary

• urine flushes out pathogens
• vaginal pH prevents some bacteria from growing

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Physical Barriers

• Phagocytic cells
• Ingests and destroys pathogens
• Ciliated cells
• sweep pathogens away from other cells

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Chemical Agents

• Lysozyme
• dissolves peptidoglycan
• Fatty acids
• prevents bacterial growth
• sebaceous glands
• Complement
• Mediates phagocytosis
• Perspiration
• lactic acid lowers pH

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Mucosal Surfaces - Chemical Agents

• Lysozyme
• breaks the N-acetylmuraminic acid and N-acetyl
  glucosamine link in gram positive bacteria (i.e.
  tears)
• Lactoferrin
• iron binding protein competes with microbes for
  iron
• Lactoperoxidase
• milk and saliva
• Secretory IgA
• inferfers with the attachment and microbial
  mobility, agglutinate the microorganisms
• neutralize exotoxins

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Mucosal Surfaces - Chemical Agents

• pH and Peristalsis in Gastrointestinal System
• pH of the stomach during digestion drops to 2-4
• Peristalsis - intestine
• Respiratory Mucosa
• particles greater than 5 µm are moved by cilia
• particles smaller than 5 µm are phagocytized by
  alveolar macrophages
• Urinary Tract
• acidic pH has a flushing action

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Bacteria as Disease Agents

• Depend on
• the structure and function of the organism i.e.
  How metabolism and growth characteristics relate
  to the disease state and diagnosis
• host defense mechanisms and host/ parasite
  interactions
• mechanism of pathogenicity
• toxins
• invasive factors

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Diagnosis of Bacterial Disease

• Clinical - signs and symptoms, history, exposure,
  epidemiology
• Laboratory - specimens sent to laboratory
• Both not always necessary but preferable

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Bacterial Defense Mechanisms

• Cell Envelope
• Capsule
• Peptidoglycan
• Cytoplasmic membrane

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Capsules

• usually seen only in direct smear of clinical
  material
• prevents phagocytosis

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Peptidoglycan

• simulates endogenous pyrogen
• osmotic regulation
• leucocyte chemoattractant
• anticomplementary

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Cytoplasmic Membrane

• osmotic barrier
• regulates transport

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Growth Patterns of Bacterial Pathogens

• Obligate intracellular pathogens
• Faculative intracelular pathogens
• extracellular pathogens

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Obligate IntracellularBacterial Pathogens

• Rickettsia spp
• Coxiella burnetii
• Chlamydia spp

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Facultative Intracellular Bacterial Pathogens

• Salmonella spp
• Shigella spp
• Legionella pneumophila
• Invasive Escherichia coli
• Neisseria spp
• Mycobacterium spp
• Bordetella pertussis

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Predominantly Extracellular Bacterial Pathogens

• Mycoplasma spp Pseudomonas aeruginosa Enterot
  oxigenic Escherichia coli Vibrio
  cholerae Staphylococcus aureus Streptococcus
  pyogenes Haemophilus influenzae Bacillus
  anthracis