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Evolu-on  of  the  immune  system  

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Three  main  lines  of  defense  

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Innate  Immunity:  the  immediate  response  to  infec-on    

•  Complement  System:  Lecture  by  Piet  Gros,  12th  of  June.  

•  Plasma  proteins:  limit  the  spread  of  the  infec-on  

•  Defensins:  kill  pathogens  via  perturbing  their  membranes  

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Plasma  proteins  •  Coagula-on  system:  A  cascade  of  plasma  enzymes  that  forms  blood  clots.  

•  Pentraxins:  bridging  molecules  to  bind  pathogens  and  e.g.,  pahagocytes  

•  Protease  inhibitors  

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Defensins  

•  Pep-des  of  35-­‐40  amino  acids  long  

•  Mainly  produced  by  neutrophils  and  Paneth  cells    

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Defensins  vary  from  one  individual  to  another  

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Three  main  lines  of  defense  

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Immune  cells  

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More  in  detail  at  the  lecture  of  Leila  Perie,  Monday,  17th  of  June.  

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Innate  immune  cells  have  receptors  that  discriminate  self  from  non-­‐self  

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Following  recogni-on  

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Toll-­‐like  receptors  sense  the  presence  of  infec-on  

Chapter 3 Innate Immunity

 TLR  are  transmembrane  proteins  with  a  Toll-­‐interleukin  receptor  (TIR)  signalling  domain  on  the  cytoplamic  side  of  the  membrane  and  a  horse  shoe  shaped  sensor  domain  on  the  other  side  

   

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Sensing  via  TLR4  starts  synthesis  of  inflammatory  cytokines  

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Ac-va-on  of  resident  macrophages  induces    inflamma-on  at  sites  of  infec-on

 

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Protec-on  and  danger  induced  by  Macrophages  

TNF-­‐α  released  by  macrophages  induces  protec-on  at  the  local  level  but  can  lead  to  a  catastrophe    when  released  systemically   15  

Neutrophils  are  dedicated  phagocytes  that  are  summoned  to  sites  of  infec-on  

40-­‐75%  of  leukocytes    are  neutrophils  

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Neutrophil  chasing  a  bacteria  

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A  small  wound  made  in  the  ventral  tail  fin  of  a  4-­‐day-­‐old  zebrafish  larva  results  in  recruitment  of  fluorescently  tagged  neutrophils  (red)  to  the  wound  site  within  minutes,  where  they  persist  for  several  hours,  providing  a  miniature  model  of  the  human  wound  inflammatory  response.  Hydrogen  peroxide  is  implicated  as  the  earliest  signal  recrui-ng  neutrophils  to  the  wound.  Mar-n  &  Feng,  Nature  2009.  

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Neutrophils  express  

receptors  for  many  bacterial  and  fungal  cons-tuents  

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Neutrophils  die  young!  Macrophages  live  longer….  

Chapter 3 Innate Immunity

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Movie  

Movie  Janeway  1.1  Innate  recogni-on  of  the  pathogens    

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Immunology  in  News  

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Immunology  in  News  

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 Significance    Although  we  know  much  about  the  molecular  mechanisms  of  cross-­‐presenta-on,  its  actual  contribu-on  to  cytotoxic  T  cell  (CTL)  immunity  under  physiological  condi-ons  in  vivo  is  s-ll  unclear.  Cross-­‐presenta-on  is  based  on  the  idea  that  dendri-c  cells  (DCs)  are  the  only  professional  an-gen-­‐presen-ng  cells  able  to  prime  naïve  T  cells.  If  DCs  are  not  directly  infected,  they  must  take  up  an-gen  and  present  it  indirectly.  However,  recent  evidence  suggests  that  other  cells  also  may  be  involved  in  T  cell  priming,  which  probably  makes  cross-­‐presenta-on  less  central.  This  study  shows  that  cross-­‐priming  DCs  generate  highly  restricted  CTL  repertoires,  biased  to  strong  MHC  I  binding  epitopes  only.  Furthermore,  the  presence  of  an-gen  in  CD169+  macrophages  is  sufficient  for  genera-on  of  CTLs  with  broader  repertoires.  

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Other  components  of  the  innate  immune  system  

• NK  Cells:  Lecture  by  Paola  Carrillo-­‐Bustamante,    29th  of  April.    

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