Faculty: Dr. Alvin Fox
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Key Words
Pathogen
Transmission
Outbreak, Epidemic, Pandemic
Adhesion
Normal flora
Penetration
Infection
Invasiveness/spread
Infectious diseases
Extra/intra cellular pathogen
Compromised host
Exotoxin
Opportunistic infection
Endotoxin - non-specific immunity
Nosocomial
Specific immunity
Koch’s postulates
Autoimmunity
Bioterrorism
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Pathogenicity
• virulence factors
• number of initial organisms
• immune status
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Pathogens
• The “usual” rate
• Oubreak - local
• Epidemic - regional/national
• Pandemic – widespread (international)
– infections “beyond the norm”
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Koch's postulates
• isolated
– diseased not healthy people
• growth
– pure culture
• induce disease
– susceptible animals
• re-isolated
– susceptible animals
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Opportunistic infections
– normal flora
– environment
– often compromised individuals
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Opportunists - normal flora
• Skin
– Staphylococcus aureus
– Staphylococcus epidermidis
– Propionibacterium acnes
• Intestine
– Bacteroides
* high numbers
– Enterobacteriaceae
* low number
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Opportunists - environment
•
•
•
•
air
water
soil
food
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Opportunists
• Community-acquired
• Nosocomial - hospital
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Transmission
• airborne droplets
• food
• water
• sexual contact
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Host defenses
• Gut
– peristalsis
– defecation
• respiratory tract
– ciliary action
– coughing
– sneezing
• urogenital tract
– urination
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Adhesion
BACTERIUM
adhesin
receptor
EPITHELIUM
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S. pyogenes
F-protein
lipoteichoic acid
fibronectin
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E. coli
Fimbriae
Flagella
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E. coli fimbriae
Type 1
mannose
P
galactose
– glycolipids
– glycoproteins
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Penetration and spread
Epithelium
Blood stream
Salmonella typhi
Salmonella enteritidis
Vibrio cholerae
Gut lumen
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Connective tissue destrction
• Helps bacterial dissemination
– collagenase
– hyaluronidase
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Extracellular pathogens
• resistant to extra-cellular killing
• killed on phagocytosis
• resist killing
–by avoiding internalization
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Protein A inhibits phagocytosis
Fc receptor
immunoglobulin
PHAGOCYTE
Protein A
BACTERIUM
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M protein inhibits phagocytosis
Complement
fibrinogen
M protein
r
peptidoglycan
r
r
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Intracellular parasite
Lysozome
Bacteria
Macrophage or neutrophil
Phagosome
No fusion
Fusion
Enter cytoplasm
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Killing of intracellular parasite
• Cell mediated immunity
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Tissue Injury
• exotoxins
• endotoxins and non-specific immunity
- no antigen
• specific immunity
- antigen
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Exotoxins
• proteins
• usually enzymes
• destroy cellular structures
• destroy extracellular matrix
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A-B toxins
Cell surface
Active
Binding
A
B
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• Diphtheria toxin and Pseudomonas exotoxin A
– ADP-ribosylates elongation factor (EF2)
– inhibits protein synthesis
– kills cells, destroys tissues
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Cholera toxin and E. coli labile toxin
• ADP-ribosylation of regulator
• adenylate cyclase activation
• cyclic AMP
• active ion and water secretion
• diarrhea
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Shiga toxin - shigellosis
Shiga-like toxin – enterohemorrhagic E. coli
• lyses 28S rRNA in ribosome
• death of epithelial cells
• poor water absorption
• diarrhea
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• Botulinum toxin
– inhibits acetylcholine release
– inhibits nerve impulses
– muscles inactive
–flacid paralysis
• Tetanus toxin
– inhibits glycine release
– inactivates inhibitory neurons
– muscles over-active
– rigid paralysis
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Exotoxins - extracellular matrix of
connective tissue
• Clostridium perfringens
- collagenase
• Staphylococcus aureus
- hyaluronidase
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Membrane damaging exotoxins
• Proteases
• Phospholipases
• Detergent-like action
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C. perfringens phospholipase
• destroys blood vessels
• stops influx inflammatory cells
• creates anaerobic environment
• allows growth of this strict anaerobe.
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Exotoxins
• Antibodies (anti-toxins) neutralize
– vaccination
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Endotoxin
• Lipopolysaccharide - endotoxin
• peptidoglycan -endotoxin-like action
• cell envelope components
• not proteins/enzymes
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Septic shock
• hypotension (tissue pooling of fluids)
• disseminated intravascular coagulation
• fever
• lack of effective oxygenation
• overall system failure
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Endotoxins
•
•
•
•
•
•
non-specific inflammation
cytokine release
complement activation
B cell mitogens
polyclonal B cell activators
adjuvants
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Specific immunity and
immunopathology
• chronic infection
• tuberculosis
• leprosy
• syphilis
• persisting bacterial remnants
• autoimmunity
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IgA proteases
• help survival on external surfaces
– H. influenzae
– S. pneumoniae
– N. gonorrhoeae
– N. meningitidis
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Bioterrorism
• air
– most common
• no previous exposure
– zoonoses
• manifest initially
– colds/flu-like
– death or debilitation
• recognition
– clinically (e.g. common source clusters)
– clinical microbiology
– biodetection (environment)
• future
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