Download Pathogenic Mechanisms

Pathogenic Mechanisms
• Hugh B. Fackrell
• Filename: PathMech.ppt
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Outline
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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
• >95% 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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Koch’s 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
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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
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Keppie Smith
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Portal of Entry
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May multiply at entry site> 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 > diptheria
• variables include:
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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
Amount that
affects half the
population
Pathogen
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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
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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 > dysentery
• Lysogeny
– scarlet fever
– diptheria
• Capsules
– Klebsiella > polysaccharide
– Anthrax > protein capsule
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“Pathogenic Factors”
• Inhibit host metabolism
– M. tuberculosis > tuberculosis
– mycolic acid blocks lysosomal enzymes
• Resist host metabolism
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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 Protein:Streptococcus 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
Lactorferrin
Fe3+
Siderophore
Receceptor
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Transferrin
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Toxigenicity
• Production and release of an extracellular
microbial product that disrupts the host’s
normal physiology
• Proteins > exotoxins
• Function away from bacterium
• Potent poisons
– diptheria toxin
– tetanus toxin
– botulism toxin
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Exotoxins vs Endotoxins
Exotoxins
Endotoxins
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usually Gram +ve
extracellular
released from live cell
protein
MW 15,000 -100,000
Heat labile
toxoid
Antigenic > vaccine
extremely potent
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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
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Exotoxins
Cytotoxic
Neurotoxic
Enterotoxic
– enteron = gut
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• 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 Established
Infection Rejected = no disease
Host Physiology Protects
Infection Moderate = subclinical disease
Infectious Agent Successful
41 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
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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 4/30/201
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Mucous:
• motion of cilia
• coughing/sneezing
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Physical Barriers & Chemical
Agents
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Eyes:
flushing action
lysozyme
Outer ear canal:
wax
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Alimentary canal
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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 Nacetyl glucosamine link in gram positive
bacteria (i.e. tears)
• Lactoferrin
• iron binding protein competes with
microbes for iron
• Lactoperoxidase
• milk and saliva
•53Secretory IgA
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Mucosal Surfaces - Chemical Agents
• pH and Peristalsis in Gastrointestinal System
• pH of the stomach during digestion drops to
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• 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
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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 Intracellular
Bacterial 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
Enterotoxigenic Escherichia coli
Vibrio cholerae
Staphylococcus aureus
Streptococcus pyogenes
Haemophilus influenzae
Bacillus anthracis
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