innate immunity

innate immunity

1. definition

   • non specific: first line of defence
   • adaptive works by enhancing this

2. examples of an innate mediator

   • defensins
     • small cistern rich cationic(positive charge) proteins
     • found in both invertebrates and vertebrates
     • produced by innate cells: i.e. epithelial cells
     • act in lungs against bacteria fungi and viruses
       • cystic fibrosis
         • Patients with cystic fibrosis who have fewer copies numbers of defensin genes are more susceptible to Pseudomonas aeruginosa.
     • integrate into microbial cell membrane and disrupt it
   • the complement system
     • a biochemical cascade in all vertebrates which clears pathogens
     • many plasma protein enzymes
     • inactive in blood
     • active at bacterial surface
     • initiating a sequential enzyme amplification cascade
     • enzyme products work together to
       • lyze pathogen cell membranes
         • put holes in bacterial cell membrane: loses integrity
           • membrane attack complex
       • regulate inflammation
         • chemotaxis
         • microbial opsonisation
     • deficiencies associated with recurrent infections

3. how innate cells recognise pathogens

   • pathogens have molecular structures distinguishable from self
     • pathogen-associated-molecular-patterns: PAMPs
       • innate immune cells have receptors to recognise these
         • pattern recognition receptors:PRRs
           • these are present on cell surface and within cell for viruses
         • TLR3 intracellular for viruses TLR4 cell surface for bacteria

4. during infection

   • PAMPs on microbes are recognised by PRRs on innate cells
     • Cells respond by activation and release mediators causing inflammation

5. highly conserved

   • present in drosophila
   • in fungi
     • Toll-Like Receptors (TLRs)

6. TLR in plants: aribadopsis

   • A 22-amino acid sequence (flg22) of bacterial flagellin protein is recognised by A. thaliana by the receptor FLS2 (flagellin-sensitive-2).
     • when bound, more than 900 genes are activated
     • Synthetic flg22-peptide enhances resistance against bacteria.