Part I

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Apr 22, 2013 ... Web Page: theory.bio.uu.nl/immbio. (check regularly for updates). • Book: The Immune System by Peter Parham. • Teachers: Bontrop, de Boer, ...
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ImmunoBiology  2013  

Form  of  the  course  

•  Coordinator:  Can  Keşmir  ([email protected])     Kruyt,  Z509     •  Web  Page:  theory.bio.uu.nl/immbio    (check  regularly  for  updates)  

•  Book:  The  Immune  System  by  Peter  Parham     •  Teachers:  Bontrop,  de  Boer,  de  Haard,  Klarenbeek,  

Borghans  and  Kesmir,  together  with  a  number  of  TAs  and   quest  lecturers.  

•  Overlaps  with:    Cancer  and  AIDS   •  ComputaUonal  part:  

•  Lectures   •  Werkcolleges/Computer  Exercises     (in  groups  of  2  or  3)   •  Experimental  work  (PracUca,  further   seperaUon  in  groups  A  and  B)   •  ArUcle  discussions  

–  TheoreUcal  Ecology/ComputaUonal  Biology/Genome   Biology   1  

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Volunteers  for  student  lecture? (Bonus)  

Assessment   •  Exam:  40%   •  Two  wri\en  reports    

•  You  can  choose  one  of  the  chapters  3-­‐14  (or   part  of  it)   •  You  will  prepare  a  lecture  of  20  minutes     •  Slides/Figures  of  the  corresponding  chapter   will  be  available     •  Please  email  me  at  least  two  days  beforehand      

–  25%:  About  one  of  the  computer  exercise/ werkcollege  (there  are  8  all  together)     –  20%:  Experimental  work  and  follow-­‐up  data   analysis  

•  ArUcle  presentaUons  and  discussions  (15%)    

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Chapter 1

Chapter 1 & 2:

Elements of the Immune System and their Roles in Defense

•  Immunology  is  the  study  of  physiological   mechanisms  that  h
 umans  and  other   animals  use  to  defend  their  bodies  from   invasion  by  other  organisms  

Elements of the Immune System and their Roles in Defense The innate immune system

•  The  hosts  invests  heavily  in  cells  dedicated   to  defense,  which  collecUvely  form  the   Immune  system  

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Greatest  triumph  of  Immunology:   VaccinaUon  or  ImmunizaUon  

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Immune  cells  

•  In  Asia  people  were  immunized  with  small   amounts  of  virus  to  induce  protecUve   immunity   •  Method  was  introduced  in  Western   Europe  in  1721  by  Lady  Montagu   •  Edward  Jenner  introduced  in  1796  a  safer   method  by  inoculaUon  with  cowpox  virus   •  Jenner  called  this  method  vaccinaUon   ager  the  mild  disease  (vaccinia)  produced   by  cowpox   7  

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Innate  and  adapUve  immunity  are   complimentary  

EvoluUon  of  the  immune  system  

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Chapter 1

Elements of the Immune System and their Roles in Defense



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         Creepies  and  Crawlies   a)  b)  c)  d)  e)  f)  g)  h)  i)  j)  k)  l) 

Chapter 1

HIV-­‐1   Influenza  virus   Staphylococcus  aureus   Streptococcus  pyogenes   Salmonella  enteri5dis   Mycobacterium  tuberculosis     Listeria  monocytogenes     Pneumocys5s  carinii   Epidermophyton  floccosum   Candida  albicans   Trypanosoma  brucei   Schistosoma  mansoni  

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Elements of the Immune System and their Roles in Defense

Skin  and  mucosal  surfaces  form  barriers  against  infecUon  

 



Strong  barriers  to  infecUon  provided  by  the  skin,  hair  and  nails  are   colored  blue.  More  vulnerable  mucosal  membranes  are  colored  red  

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Chapter 1

Elements of the Immune System and their Roles in Defense

Immune  defense  involves  recogniUon  of  pathogens  followed  by  their                                                                                      destrucUon  

Not  all  microorganisms  are  pathogens.  Numerous   commensal  ones  inhabit  healthy  human  bodies  



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Immune  cells  

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What  do  we  learn  from  this   exercise?  

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Chapter 2

Chapter 2

Innate Immunity

Innate  immune  receptors   disUnguish  features  of   microbial  structure  

Innate Immunity

Toll-­‐like  receptors  sense  the  presence  of  infecUon  




                 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  

•  LecUns:  recognizes  carbohydrates     that  are  not  found  in  human  body     (mannose,  glucan)     •  Scavenger:  Ligands  that  are  posiUvely     charged  (ogen  Gram-­‐posiUve  bacteria)   •  CR3  and  CR4:  LPS  

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AcUvaUon  of  resident  macrophages  induces     inflammaUon  at  sites  of  infecUon

ProtecUon  and   danger:   Macrophages  

 

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TNF-­‐α  released  by  macrophages  induces  protecUon  at  the  local  level  but  can  lead  to  a  catastrophe    when  released  systemically   26  

Neutrophils  are  dedicated  phagocytes  that  are   summoned  to  sites  of  infecUon  

40-­‐75%  of  leukocytes     are  neutrophils  

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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  recruiUng  neutrophils  to  the  wound.   28   MarUn  &  Feng,  Nature  2009.  

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Neutrophils  express  receptors  for   many  bacterial  and  fungal  consUtuents  

Chapter 2

Innate Immunity

Neutrophils  die  young!  Macrophages  live  longer….  

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Chapter 2

Innate Immunity

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Chapter 1

Elements of the Immune System and their Roles in Defense

The  adapUve  immune  response  adds  to  an  ongoing   innate  immune   response   


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Chapter 1

Elements of the Immune System and their Roles in Defense

Most  lymphocytes  are  present  in  specialized   lymphoid  Ussues  



CirculaUng  lymphocytes     meet  lymph-­‐borne  pathogens    in  draining  lymph  nodes  

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Architecture  of  the  lymp  node,  the  place  where  blood-­‐borne  lymphocytes  respond  to   lymph-­‐borne  pathogens  

Clonal  selecUon  of  lymphocytes  by  a  pathogen  (adapUve  response)  

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Chapter 1

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Chapter 1

Elements of the Immune System and their Roles in Defense

AdapUve  immune  responses  generally  give  rise  to  long-­‐lived   immunological  memory  and  protecUve  immunity  



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Elements of the Immune System and their Roles in Defense

Spleen  provides  adapUve  immunity  to  blood  infecUons

 



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Chapter 1

Other  components  of  the  innate   immune  system  

Elements of the Immune System and their Roles in Defense

Most  lymphoid  Ussue  is  associated  with  the  gut  



•  NK  Cells     •  Complement  

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Chapter 2

Chapter 2

Innate Immunity NK  cells  provide  an  early  defense  against  intracellular   infecUons  

Innate Immunity NK-­‐cell  receptors  differ  in  the  ligands  they  bind  and  the   signals  they  generate

 



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NK  cell  receptors  disUnguish  unhealthy  cells    from  healthy  cells  

NK  cells  regulate  other  immune   responses  

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Modeling  NK  cell  regula5on  within  hosts  and    host-­‐pathogen  co-­‐evolu5on  in  popula5ons  

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Complement  System   •  Ancient  defence  mechanism  (>1.000  Myears)   •  Involves  30  large  mulU-­‐domain  plasma  proteins   and  cell-­‐surface  receptors   •  Two-­‐edged  sword:   –  Clearance  of  pathogens     –  Host  Ussue  damage  

•  When  pathological:  therapies  needed  to  control   (down-­‐regulate  or  acUvate)  complement   responses   •  Interested?  Check  out  Piet  Gros’  group   h\p://www.crystal.chem.uu.nl/~gros/ complement.html    

Paola  Carillo-­‐Bustamante     Lecture:  3rd  of  May   47  

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Most  important:  C3  

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Beginning  of  the  cascade:   alternaUve  pathway  

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C3b  bound  pathogens  are  taken  in  and   removed  faster  from  the  system  

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Protec5on  of  host  cells  from   Complement  responses  

Other  complement  proteins  in  acUon  

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CD59  prevents  membrane  a\ack   complex  formaUon  on  human  cells  

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