6

• microbial latency 


  when a microbes persistence in a host doesn't upset homeostasis enough to cause disease
• how microbial latency is achieves

  microbes slows or stops replication due to a genetic or functional change (change gene expression due to environment)
• why latency is important

  latent microbes can be transmitted to other hosts, risk of growth, increase risk of other disease
• how bacteria and viruses evade innate and adaptive immune systems

  1. apoptosis - programmed cell death
  2. altered inflammatory response resulting in cytokine production
  3. inhibition of Ag presentation
  4. hide from immune surveillance by being latent
  5. inhibition of phagocytosis - effect macrophages ability to engulf bacteria
  6. interfere with TLR signalling
  7. change surface structure to avoid recognition
• PAMPS


  molecular signatures from bacteria and viruses that are recognised by TLRs on host innate immune cells
• what does recognition of PAMP by TLR do

  trigger inflammatory and immune cascade (TLD on host innate immune cells)
• different TLRs triggered by different patterns (PAMPS) on bacteria and viral cells
• PAMPs in bacteria


  lipopeptides (cell surface TLRs recognise)
• PAMPs in viruses 


  dsDNA and ssDNA (intracellular TLRs recognise)
• CpG DNA


  sequences of unmethylated CG repeats that are highly prevalent in bacterial DNA
• what does TLR9 recognise

  CpG DNA
• CpG sequences in mammalian cells

  less common, the cytosine is normally methylated
• key concepts biomedical ethics

  studies must be conducted with informed consent of patients, must be given choice to quit, must have access to best standard of care treatment options and cannot be given inferior treatment
• example of a zoonoses

  Rickettsial disease
• zoonosis def


  disease or infection that is naturally transmissible from vertebrate animals to humans usually acquired through a vector (animals maintain them in nature)
• vector 


  organism, usually biting insect that transmits a disease or parasite from an animal to another (gives zoonosis to humans)
• reasons for emergence of zoonotic diseases

  environmental disruption by humans results in spillover of infections into humans, modification of the environment
• examples of how zoonotic disease re emergence

  changes in land use (move in suburban areas), less preferred animals host shifts vectors to humans, animal production systems, antimicrobial use
• spirochaetes 


  gram negative flexible helical cells
• spirochaetes examples


  Treponema pallidum (syphilis) and borrella burgdorferi (lyme disease)
• examples of obligately intracellular gram negative


  clamydia and rickettsia
• infection of syphilis 


  growth of organism at site of infection, disseminated to various tissues including CNS
• primary syphilis 


  chancre (sore on mount with raised edges), regional lymph nodes swell
• secondary syphilis 


  all lymph nodes swollen, disseminated rash
• latent syphilis 


  75% no complications, rest can re emerge as territory syphilis (gum lesions, and neurological complications)
• what causes lyme disease

  borrelia burgdorferi
• lyme disease transmission


  transmitted by ticks
• acute lyme disease


  fever, bulls eye rash
• chronic lyme disease 


  weeks to years later recurrent arthritis and chronic involvement of CNS
• genome reduction


  loss of genes for biosynthetic pathways that are not required in a host cell (parasites)
• rickettsiae and mitochondria share a common ancestor
• rickettsiae australis


  queensland tick typhus
• rickettsiae


  gram negative, small rods or cocci that are obligate intracellular parasites of humans, animals
• actin role 


  create cytoskeleton needed for cell replication and motility
• actin remodelling


  intracellular bacteria hijack host action cytoskeleton to facilitate cellular invasion, replication and dissemination helps them move around human cells
• 3 mechanisms of actin remodelling

  1 - action tails to facilitate mobility 2 - vacuoles pinched off extruded 3 - connect neighbouring cells by protrusions
• how lyme disease (borrelia burgdorferi) evades host immune response

  antigenic variation
• how borrelia burgdorferi antigenic variation occurs

  new variants of surface protein vlseE (protein on cell wall) are generated by recombination from 15 silent vls gene cassettes into vlsE locus