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Pathogenesis41
 

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