Lecture 20

• bacterial intracellular pathogens

  Chlamydia

  Rickettsia

  Mycobacterium

  Salmonella

  Listeria monocytogens
• Listeria monocytogenes

  gram positive, food borne pathogen

  produces raw milk, cheese, deli meat

  psychrophile (0-20)

  can cross placenta

  polymerizes host actin to move inside and between host cells

  A) listeria

  B) actin tail

  
• bacteria can evade innate and adaptive immunity by forming biofilms

  Streptococcus pneumoniae

  Pseudomonas

  Staphylococcus / Enterococcus

  Streptococcus mutans
• Streptococcus pneumoniae - biofilm

  otitis media (infection of ear)
• pseudomonas - biofilm

  in cystic fibrosis lung
• staphylococcus / enterococcus - biofilm

  on heart valves - endocarditis
• streptococcus mutans - biofilms

  dental plaque
• bacteria can evade innate and adaptive immunity by forming biofilms

  bacteria in biofilms often not actively growing, antibiotics not effective
• substances that damage host

  exotoxins: protein, made and released extracellularly

  endotoxins
• exotoxin types


  membrane disrupting

  superantigens

  AB
• membrane disrupting endotoxin

  function by forming pores

  ex: hemolysis

  
• superantigens

  cause T cells (>30%) to overexpress, release cytokines

  failure of multiple host organs

  Toxic shock syndrome: caused by S. aureus superantigen

  A) superantigen

  B) MHC Class 2

  C) antigen

  D) macrophage

  E) T helper cell

  F) TCR

  G) CD

  
• AB exotoxins


  two subunits

  • A - toxic effect
  • B - binds target cell receptor

  many are ADP ribosyl transferases

  remove ADP ribose group from NAD, attach it to host cell protein - protein inactivated or functions abnormally

  ex: diphtheria, cholera, botulinum toxins
• diphtheria toxin 


  Corynebacterium diphtheriae

  binds growth factor receptor

  enters by endocytosis

  ADP ribosyl transferase

  EF 2: attaches ADP ribose from NAD onto EF2 (host protein)

  
• cholera toxin


  AB exotoxin

  enterotoxin produced by Vibrio cholerae

  ADP ribosyl transferase

  ADP ribosylates host G protein controlling cAMP production

  high cAMP causes water secretion from cells, leading to diarrhea
• botulinum toxin


  AB toxin

  neurotoxin produced by Clostridium botulinum

  blocks release of acetylcholine at neuromuscular junctions

  muscles cant contract, flaccid paralysis
• exotoxins are proteins that are often antigenic


  antibody (antitoxin) can neutralize toxicity

  exotoxins are generally unstable, lose toxicity but remain antigenic

  toxoid vaccines
• toxoid


  inactivated toxin that can still elicit an immune response

  basis of toxoid vaccines (ex: DTaP - diphtheria)