Dendritic Cell Seminar

1
Dendritic Cell Seminar

• ?????????

2
CONTENTS

• Part One Brief Introduction
• Part Two Genesis and Distribution
• Part Three Life Cycle
• Part Four Function
• Part Five Application in Clinical
• Immunology
• Part Six In vitro culture

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Part One Brief Introduction

• ????????

4
Pictures of DCs
5
History

• The word "dendritic"
• means branched like a
• tree." It comesfrom the
• Greek "dendron (tree) ".
• Dendritic cells were first
• described by Paul Langerhans (Langerhans
  cells) in the late nineteenth century. It wasn't
  until 1973, however, that the term "dendritic
  cells" was coined by Ralph M. Steinman. In 2007
  Steinman was awarded the Albert Lasker Medical
  Research Award for his discovery.

6
Brief Introduction

• Dendritic cells (DCs) are potent antigen
  presenting cells (APCs) that possess the ability
  to stimulate naïve T cells. They comprise a
  system of leukocytes widely distributed in all
  tissues, especially in those that provide an
  environmental interface.
• DCs are receiving increasing scientific and
  clinical interest due to their key role in
  anti-cancer host responses and potential use as
  biological adjuvants in tumour vaccines, as well
  as their involvement in the immunobiology of
  tolerance and autoimmunity.

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Part Two Genesis and Distribution

• ???????????

8
????????

• ????,??DC ???????DC(myeloid DC)???????DC(lymphoid
  DC)???,??????DC ??????????????,???????????????????
  ????,?????????DC ??(??????????????)??????????,????
  DC ??(?T?NK ?????????)????????????DC?????,????????
  ,??????????

9
??????????

• DC ??????????????,???????????????1
  ??,??????0.2-0.5 ?
• ?????????,??DC ????
• ????????DC,????
• ???DC(interdigitating cell,
• IDC)
• ???DC
• ???DC(follicular DC, FDC)
• ?????????DC,??
• ???DC
• ??????(Langerhans cell,
• LC)?
• ?????DC,??
• ????(veiled cell)
• ??DC

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• LC ?????????????????DC,???FcR??????MHC I?II
  ???,???????Birbeck ?????????,???LC ???LC
  ?????????????????,???????????
• FDC ???MHC II ???,????FcR ?C3bR,????-????????-??-?
  ??????????????,?B ????,????????????????
• IDC ??????T ???,?LC ????????,???MHC I ????II
  ???,???FcR ?????,???????????

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????APC?????????

• ?????????????????????????????
• ???? ???? MHC-II FcR C3R Birbeck??
  
• -----------------------------
• DC??
• ??DC ???? /- -
  
• ????? ??,???? - - -
  
• ?????
• ??DC ?? ?
  
• ???? ???????
  
• ?????
• ???DC ??????? ? ?
  
• ???????
• ???? ?????? ? ? -
  
• ??/???? ????,?? /- -
• B?? ???,??? -
  
• CTL???? ?????? MHC-I??
• ?????????????????????????????

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Part Three Life Cycle

• ??????????

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• ?????????DC ????DC,?T ???????????????????????DC
  ????????????????DC ????????????????
• ???????????DC ???????(immature),?????????????????,
  ????MLR ????,??????????????????
• ????????????(????????LPS?IL-1ß?TNF-a)?,??????(matu
  re),?MHC ?????????????????????,????MLR
  ????,???????????????
• DC ????????????(migration),?????(??????)??????/???
  ?????????,????T ?????
• ??DC ????????????????????????????,???DC
  ?????????

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1? ????DC

• ????????????????????????????????????????,?????????
  ??DC????,??????????????????DC ??????????
• ???????(PBMC)????Mf?DC ?????,?????????????????????
  ?DC,?????????????????,???????????????????,????DC
  ?Mf?
• ????????,DC ???????????????

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2? ????DC

• ??DC ???????????????????DC ????,??????????,???DC
  ????????????????
• ???DC ????????????????????(???DC
  ??LC),?????????FC?R???????(?DC)?DEC205
  ??(?DC),???????DC ???????DC ???????????????????DC
  ????????????????M?C?????,???MHC ???????,???DC
  ???????????????????????????,?LC
  ???TNF-a?IL-1?IL-6?IL-15????,???DC
  ??????????????,??????T ??????????????????,????????
  ???????????????

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3? ???DC

• DC ??????MHC ????????????,??????,??????????????,??
  ??,?????????????????,????????,DC ??????????
• ??DC ????????????????????????,?????????,??????????
  ?????????????????????,????T ?????????

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4? ???DC

• ???DC ????????????????????????????????????T
  ???,????????????????,?????T ??????
• ??DC ?????????????????,????MHC I ????MHC II
  ????CD80?CD86?CD40?CD54 ????????(intercellular
  adhesion molecule-1, ICAM-1)??????(heat shock
  protein,HSP)????????
• ????DC????????-MHC ???????????????CD80?CD86 ?CD40
  ?,????IL-12,????CD40 ?????????Th1
  ?????,????????????????T ??,?????,??T ?????????????

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(No Transcript)
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Part Four Function

• ????????

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??????DC????

• ??????DC
• - ????????
• - ???????
• - ????MHC
• - ???????
• - ???????
• ???????DC
• - ???????
• - ??????? (B7-1,
• B7-2)
• - ???MHC?????
• - ???????

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DC????

• 1.????????????,?????????,???????????????????
• (1)????(pinocytosis ) ???????????????????????
  ??
• (2)?????????(receptor-mediated
  endocytosis)?????????????????????????,???????????
  ?????????
• (3)????(phagocytosis)????????????????????????
  (?????????)????

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DC????

• 2.DC???????????
• ?,??????????
• ????????????
• ???
• (1) ??IL-12??T?????Th1??,????????
• (2) ????IFN,????????????
• (3) ??IL-10,TGF-ß,??B????Ig????,??IgA????
• (4) ??IL-1ß,??T?B?????

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DC???????
CD1??????
??????
?????
24
??TAP???????????????????
??????????,??????
????????????TAP????MHC-I????
???????????????????
25
????????????????,???????
?????????,??????
????????,????MHC-II??
MHC-II?????????????,??????????
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CD1???CD1A?B?C?D?E, ?b2m??????MHCI/II????30???,
?????????APC??,???????/??????,?????????,?????????
????????,???????????? ???CD4T?CD8T?CD4-CD8-T?NK
T???
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Toll????DC?????????

• ??????(pattern recognition receptor,PRR)????????
  ???????????????????????????????????????TLRs???????
  PRR?
• MyD88???????????????,??????TIR???,??????????,??,?
  ???????????,(death domain,DD)????????????,??????
• MyD88???????TLR???????????,???????DC??????????????
  ??????MyD88???????DC?????????????DC???????????????
  ??

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Toll????DC?????????

• DC???Toll???????????????????????????????
• TLRs??????????????????????88(MyD88)?????MyD88????
  ????????????????????????,?????????????,???????????
  ????

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Part Five Application in Clinical Immunology

• ??????

30
????

• ??????MHC-??MHC-????,???????????
  DC??????????????????
• MHC-??MHC-???????????,??????????????CD8 ?CD4
  T????
• CD54/ICAM-????????????l(LFA-1)???,??????
• CD58(LFA-3)?T??????CD2?????,????????????
• ??????????(CD45RO)????????
• CD44??T???????
• CD40-CD40L??B?????????????,????DC??B7?????,??????T
  ????(Th??)??IL-4?IL-5????(IFN-?)????,???IL-12??T??
  ????IFN-? ?
• ????DC???FcR?CRl???????????????????
• DC????I?????????(HIV-1)?? DC-SIGN,???????C??????
  ??,???T???????ICAM-3??,??DC???T?????????,??HIV-l??
  CD4 T?????
• ?LC????????,???????????????,???DC????????????
• CDwl50(1PO-3)??????,???????

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?????????

• ????,DC ??T?B ???????????????
• DC ???????????,????T ??????DC ?????T ??,???DC
  ?????????-MHC I ??????????-MHC II
  ??????,????CD8?CD4T ?????????????
• DC ???T ???????-MHC ???????????(????)?,????CD80?CD
  86?CD40 ???????,?T ?????????????DC ???ICAM-1
  ?????,?????T ?????????
• ??,DC ????IL-12 ????T ?????Th1 ???????????DC
  ??????Ig????????????????????B ?????????
• DC ?????????????DC ?????????T ???????????????,????
  ?????T ????,???????????????????,?????????,??????,?
  ??DC ???DC ???????????????

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??????

• DC??????????????????,?????????????,???????????????
  ?????
• ?GM-CSF?IL-4??????,DC????????DC,??????MHC-I?MHC-II
  ???,??????????,???T???TCR?????,??DC???????B7-1?B7-
  2?CD40??,???DC??????????????DCT IL-12
  Th1????,?????????DC????????,???????T??,??T????,???
  T??????

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??????

• ??DC ?????????????????,??DC ?????????,????????????
  DC,???????????????,????????????????????DC
  ????????????????,??????DC ?????????,???DC
  ????????????,?????????DC ?????DC
  ????????,??????????????DC ???????????????????????
  ??????,?????DC ?APC ??,?????DC ???????????,???????
  ???????

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DC????

• ??????????????????????,???????????????????,???????
  ??????,????????????????????,??????????????????????
  ????????????????????????????,???????????,?
  ???DC????????????DC,??????????????,????DC?????????
  
• DC?????????
• DC????????
• DC????mRNA??
• DC??????
• DC?????????
• DC???????????????????? ? Fong???,?????????DC??Th1?
  ????????????????,??????????????????????
• ??????
• ????????????????????????????????????????????
  ??????????

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Part Six In vitro culture

• ??????????

36
????????????????

• ????
• ??GM-CSF ?IL-4 ????????????????,??IFN-a???????????
  
• ?????
• ?????(??)????
• ???????????HanKs(CMF-HanKs)?
• ?????GM-CSF(hrGM-CSF)?hrIL-4 hr IFN-a?
• ???
• (1) RPMI1640 ???RPMI1640 10 ????( FCS????)
  2mmol/LL-???? 100IU/ml ??? 100µg/ml ??? 1g/L
  ?????? 1 mmol/L ???? 5105 mol/L 2 ?????
• (2) RPMI1640/IL-4/GM-CSF?RPMI ??? IL-4(40ng/ml)
  GM-CSF(50ng/ml)
• (3) RPMI1640/IFN-a?RPMI ??? IFN-a(1 10ng/ml)?
• ?????
• ???(25ml 75 ml)CO2 ?????????????????????????????

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????????????????

• ????
• 1???????
• 2???????????GM-CSF ?IL-4 ?RPMI1640
  ????,?????1106 /ml,?5CO2???, 37???3??
• 3????3 ???,????????,??????IL-4 ?GM-CSF ???1640
  ???,???CO2 ???
• 4???????????????IL-4 ?GM-CSF ?????,7
  ?????????????,??????????????IL-4 ?GM-CSF ?1640
  ???,???????IFN-a?RPMI1640 ???,???5CO2
  ???,37???,??9 ??????????????

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DC????????

• ????????DC ????????,?????????????????????????????(
  MLR)??????T ????????????????
• ??,????DC ?????????????????,??33D1 ?NLDC145 ???DC
  ?????????DC ?????????CD1a?CD11c ?CD83?
• CDla??????????DC,???????????DC?????,???DC????????R
  ouard???CD83?DC?????,???T?????????Birbeck?????????
  ??Birbeck??,??LC???????????,?LC??????Fascin???????
  ?DCs????
• DC ???????????????????FcR,?????????????DC ???MHC
  II ??????????CD80 ?CD86?????CD40?CD54 ??ß1?ß2
  ???????,??????????,DC ????IL-1?IL-6?IL-12?TNF-a?IF
  N-a/ß???????????????,??????????

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Thank you !

• ????
• ??? ??? ??? ??