establishment of infection in order to cause disease pathogen must follow a series of steps –gain...
TRANSCRIPT
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• 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)– 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
• 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
Mechanisms of Viral Pathogenesis
• 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