Pathogenesis41
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Pathogenesis41

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Pathogenesis41 Pathogenesis41 Presentation Transcript

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