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GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture 33

GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture 33. Faculty: Dr. Alvin Fox. Key Words. Pathogen Transmission Outbreak, Epidemic, Pandemic Adhesion Normal flora Penetration Infection Invasiveness/spread

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GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture 33

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  1. GENERAL ASPECTS OF BACTERIAL PATHOGENESIS Lecture 33 Faculty: Dr. Alvin Fox

  2. 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

  3. Pathogenicity • virulence factors • number of initial organisms • immune status

  4. Pathogens • The “usual” rate • Oubreak - local • Epidemic - regional/national • Pandemic – widespread (international) • infections “beyond the norm”

  5. Koch's postulates • isolated • diseased not healthy people • growth • pure culture • induce disease • susceptible animals • re-isolated • susceptible animals

  6. Opportunistic infections • normal flora • environment • often compromised individuals

  7. Opportunists - normal flora • Skin • Staphylococcus aureus • Staphylococcus epidermidis • Propionibacterium acnes • Intestine • Bacteroides • high numbers • Enterobacteriaceae • low number

  8. Opportunists - environment • air • water • soil • food

  9. Opportunists • Community-acquired • Nosocomial - hospital

  10. Transmission • airborne droplets • food • water • sexual contact

  11. Host defenses • Gut • peristalsis • defecation • respiratory tract • ciliary action • coughing • sneezing • urogenital tract • urination

  12. Adhesion BACTERIUM adhesin receptor EPITHELIUM

  13. S. pyogenes F-protein lipoteichoic acid fibronectin

  14. E. coli Fimbriae Flagella

  15. E. coli fimbriae Type 1 mannose P • galactose • glycolipids • glycoproteins

  16. Penetration and spread Epithelium Blood stream Salmonella typhi Salmonella enteritidis Vibrio cholerae Gut lumen

  17. Connective tissue destrction • Helps bacterial dissemination • collagenase • hyaluronidase

  18. Extracellular pathogens • resistant to extra-cellular killing • killed on phagocytosis • resist killing • by avoiding internalization

  19. Protein A inhibits phagocytosis PHAGOCYTE Fc receptor Protein A immunoglobulin BACTERIUM

  20. r r r M protein inhibits phagocytosis Complement fibrinogen M protein peptidoglycan

  21. Intracellular parasite Bacteria Macrophage or neutrophil Lysozome Phagosome Enter cytoplasm Fusion No fusion

  22. Killing of intracellular parasite • Cell mediated immunity

  23. Tissue Injury • exotoxins • endotoxins and non-specific immunity • - no antigen • specific immunity • - antigen

  24. Exotoxins • proteins • usually enzymes • destroy cellular structures • destroy extracellular matrix

  25. A-B toxins Cell surface Active Binding A B

  26. Diphtheria toxin and Pseudomonas exotoxin A • ADP-ribosylates elongation factor (EF2) • inhibits protein synthesis • kills cells, destroys tissues

  27. Cholera toxin and E. coli labile toxin • ADP-ribosylation of regulator • adenylate cyclase activation • cyclic AMP • active ion and water secretion • diarrhea

  28. Shiga toxin - shigellosis • Shiga-like toxin – enterohemorrhagicE. coli • lyses 28S rRNA in ribosome • death of epithelial cells • poor water absorption • diarrhea

  29. 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

  30. Exotoxins - extracellular matrix of connective tissue • Clostridium perfringens • collagenase • Staphylococcus aureus • - hyaluronidase

  31. Membrane damaging exotoxins • Proteases • Phospholipases • Detergent-like action

  32. C. perfringens phospholipase • destroys blood vessels • stops influx inflammatory cells • creates anaerobic environment • allows growth of this strict anaerobe.

  33. Exotoxins • Antibodies (anti-toxins) neutralize • vaccination

  34. Endotoxin • Lipopolysaccharide - endotoxin • peptidoglycan -endotoxin-like action • cell envelope components • not proteins/enzymes

  35. Septic shock • hypotension (tissue pooling of fluids) • disseminated intravascular coagulation • fever • lack of effective oxygenation • overall system failure

  36. Endotoxins • non-specific inflammation • cytokine release • complement activation • B cell mitogens • polyclonal B cell activators • adjuvants

  37. Specific immunity and immunopathology • chronic infection • tuberculosis • leprosy • syphilis • persisting bacterial remnants • autoimmunity

  38. IgA proteases • help survival on external surfaces • H. influenzae • S. pneumoniae • N. gonorrhoeae • N. meningitidis

  39. 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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