Establishment of Infection
• In order to cause disease pathogen must
follow a series of steps
– Gain entrance to host
– Adherence
– Colonization
– Avoid Host Defenses
– Cause host damage
Portals of entry
1. Mucus membranes
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Respiratory tract
Gastrointestinal tract
Genitourinary tract
Placenta
2. Skin
3. Parenteral route
• Bite, puncture,
injection, wound
• Most microbes have a preferred portal of entry
– Streptococci when inhaled may cause pneumonia;
when ingested they do not
• A few microbes cause illness no matter how they enter
– May cause different illness based on portal
– Plague has 2 forms; bubonic and pneumonic
– Anthrax has 3 forms
• Adherence (adhesion)
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Critical Step
Bacteria use adhesins (ligands)
Viruses has surface attachment proteins
Binding to host cells receptors is highly specific
• Colonization
– Organism must multiply in order to colonize
– New organisms must compete with
established organisms for nutrients and
space
– May form biofilms
• Virulence factors
– Structural or physiological characteristics
that aid in penetrating or avoiding host
defenses
• Capsules
– Avoid phagocytosis; Prevents dessication; aids
attachment
• Incomplete phagocytosis
– Escape the phagosome
– Prevent fusion with lysozome
– Survive inside phagolysozome
• Fimbrae
– Attachment
• Components of cell wall
– M proteins of Streptococcus
– Mycolic acid of Mycobacteria and Norcardia
– Outer membrane of Gram- bacteria
• Extra-cellular enzymes (exoenzymes)
– Coagulases
– Kinases
– Hyaluronidase
• Dissolves hyaluronic acid
– Collagenase
– IgA proteases
– Leukocidins
• Antigenic variation
– Avoid antibodies by altering surface antigens
– Neisseria varies pili type
• Penetration into host cytoskeleton
– Manipulate actin to penetrate cells and to move
between cells
– Some pathogens induce non-phagocytic cells into
endocytosis
– Disruption of cytoskeleton may cause membrane
ruffling
Damage to the Host
• In order to cause disease pathogen must
cause damage
– Damage facilitates dispersal of organisms
• Vibrio cholerae causes diarrhea
• Bordetella pertussis causes coughing
– Damage can be direct result of pathogen
such as toxin production or indirect via
immune response
Bacterial Damage to Host Cells
• Use host cell’s nutrients
• Binding to and invading host cells
• Induce hypersensitivity reactions
(allergies)
• Production of toxins (Toxigenicity)
– May be exotoxins or endotoxins
– Exotoxins
– Produced by G+ bacteria
• Produced as part of their metabolism
• Secreted externally or released following
cell lysis
• Proteins
– Enzymatic nature
– Highly soluble
– Heat Liable
– Among most lethal substances
– Toxoids
• Inactivated exotoxins
• Induce antitoxins that provide immunity
– Antibodies against a specific toxin
• Passive immunity in form of antitoxin
can be given as treatment
– Grouped into functional categories
• Neurotoxins
• Enterotoxins
• Cytotoxins
• Staphylococcus aureus
– enterotoxin – may be heat stable
– exofoliatin toxin
• Scalded skin syndrome
– Toxic Shock Syndrome (cytotoxin)
• Vibrio cholera
– cholera enterotoxin
• Clostridium botulinum
– botulinum neurotoxin
• Clostridium perfringens
– Gas gangrene
• Clostridium tetani
– tetanus neurotoxin
• Endotoxins
– part of the outer portion of the G- cell wall
– lipopolysaccharides (LPS)
• lipid portion (lipid A)
– Released when cells die and cell walls lyse
– Antibiotics used to treat diseases can lyse cells
• May cause an immediate worsening of symptoms
– All endotoxins produce the same symptoms
• Chills, fever, weakness, aches
• May activate blood clotting proteins
• May cause septic shock that can be fatal
– Heat stable; not suitable for use as toxoids
• Do not cause formation of antitoxins
– Antibodies may enhance action of toxins
– Salmonella typhi, Proteus spp. and Neisseria
meningitidis
Mechanisms of Viral Pathogenesis
• Cytopathic effects
• Avoiding immune responses
• Antibodies interact with extracellular viruses only
• Viruses can remain intracellular by forcing
neighboring cells to fuse in the formation of
syncytium
• Viruses can outpace body’s capacity to produce
antibody
• Some virus-infected cells release interferons
to warn neighbor cells
– Anti-viral proteins
– Helps limit viral replication
– Some viruses encode specific proteins to
interrupt activity of interferons
Mechanisms of
Eukaryotic Pathogenesis
• Fungi
– Generally opportunistic
– Most serious fungal infections caused by
dimorphic fungi
– Some produce mycotoxins
• Claviceps; Ergot toxin
• Aspergillus; Aflatoxin
• Amanita; Neurotoxins
• Parasites
– Most live within intestinal tract or enter
body via bite of an arthropod
– Use host nutrients
– Presence of parasite interferes with host
function
– Parasite's metabolic waste can cause
symptoms
• Algae
– A few species produce neurotoxins
• Alexandrium produces toxin that causes
paralytic shellfish poisoning
• Produces symptoms similar to botulism
Portals of Exit
• Respiratory and
gastrointestinal tracts
– Most common
• Genitourinary tract
• Skin/wounds
• Biting insects
• Contaminated needles and
syringes