????????? ( Non-specific or innate immunity

1

• ??? ???????
• ?????????

2
???? ????????? ( Non-specific or innate
immunity ) ????????? ( Specific or adaptive
immunity )
The differences between the two types of immunity
????
?????
??????( antigen-independent)
?????( antigen-dependent)
??( immediate)??????
?????????? (lag time )
??????
?????
?????????(pattern)
??????(Macromolecules)
?????
??????
3

• ????????????????
• ?????????????NK?????????????????????????????
  NKT???B1????dT????
• (1)????? (neutrophils)????
• (2)???? (macrophages)??????
• ?????????????????
• T???B??????????

4
??????
???? ???? ???? ?????? ?????
???? NK?? ????? ???? ?????
5
??? ????

• ????????
• ?? ????(monocyte)
• ????(macrophage, MF)

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? ? ? ? ? ?
????????,???(?,????)??????????????????????
?????(?)????????????????????(?)?
7

• ????
• ??????????????
• ??????????????
• ?(??)?????(??)?

8
????????????????
? ?
? ?
? ?
?????
???? ???????? ???????
????? ?????????????? ???????????
????????? ????? ????A???
????
?????
?????
?????
????
9

• ???????
• ????????????????
• (?)?????????????????
• 1.?????????????????
• ??????(pattern recognition receptor,PRR)?????????
  ?????????????????????????????????
• ????????(pathogen associated molecular pattern,
  PAMP)???????????????????????????????

10

• ?????????????(scavenger receptor,SR)??????(?????
  ??)?Toll?????

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?????(mannose receptor,MR)????180
kDa,??????8???????????????,????????????????? ?????
????????????????????
?????
NH2
CRD
F2
CL
CL
CL
CL
CL
CL
CL
CL
COOH
12
????
?????(scavenger receptor,SR)
COOH
HOOC
S
COOH
S
S
??????????????????????? ?????,??C?????????????????
????? ????????????????? ?
2HN
NH2
NH2
?????(scavenger receptor),???????????????????????
13
Toll???

• LBP (???????)
• sCD14(Soluble CD14)LPS??

14

• 2.????????????????
• ????(complement receptor, CR)
• Fc?R?

IgG C3b
???
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?????????
??
??
CD11b/CD18
CD16 (Fc?R III)
? ? ? ? ? ? ? ?
IL-2
????
CD25
CD71
B7-2
CD28
CD64 (Fc ? R I)
CD35 (CR1)
CD32 (Fc ? R II)
??
??
??
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Adherence of bacteria via receptors
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• (?)??????????????????????
• ??????????????????
• A ???? --- H2O2?O2-?NO
  
• B ?????--- ?????????
• C ??--- ???

18
??????
? ? ? ? ? ? ? ? ?
??????????????(??pattern)??????,
????????????,???????????
??????????????,?????,
19
??????? ???? ??????????????????,??????????
?????????????????????? II (NADPH) ??????????????
b558???
??
NADPH H
????b558
????
e- O2
O2-
H
H2O2
20
? ? ? ? ?
? ?????? O2 NADPH
O2- NADP H ? ??????
2O2 2H2
H2O2 O2 ? ????
H2O2 Cl H
HOCl H2O ? ??????
HOCl R-NH RNCl H2O
? ??????? H2O2 OCl-
1 O2 H2O Cl- ?
??????? H2O2 O2-
O2 OH- .OH
NADPH ???
???????
21
NO ? ?
? ??NO L-??? 1/2O2
??? NO ? ?????????
NO O2 -
ONOO-
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Oxygen-independent mechanisms of intracellular
killing
????
? ?
???????? ??????? ?????????? ????????
Cationic ?? (?? ?????) ??? ?????? ?????
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Macrophage Phagocytosis
24

• ???????????

?????????????
25

• ?? ??????????????????????ADCC???????

26

• ?????????,?????????
• ???????,????????
• ??Th1???????????????

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• ???????? --- ??????
• (IL-1?IL-6?IL-8?IL-12?TNF-a?)?
• -????IL-1/12,TNF-a
• -???????TGF-ß

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??????????? ????(resting state) ????(primed
state) -- IFN-? ????(activated state) --
C3bLPSIFN- ?
32
????? ????? ????CR1?CR3 ? CR4
Fc??lgG Fc??(Fc?R?/?/?),
IgA Fc?? ????? LFA-1?IL-8R??
33

• ???????
• ????????????,???????????
• A.???????????
• B.???????????????????
• IgG-Ag ? Fc?R ? ?????
• ???? ? ?? ? IgM?? ? ???
• ? ? CR ? ???

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??? ????? (Dentritic Cells, DC)

• ??????????????,??????(naïve)
  T????,??DC?T????????????????????????????
• ??????????????
• ????????CD1a?CD11c?CD83
• ?????????????????MLR??????T???????????????

36
??
37
DC????? ?????????,??PBMC?1???
???????DC(???DC)
????????DC(LC) ????DC ??DC
???DC
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DC????????????

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

39

• ????????????????????

????????????
????
????????????????,??T????IR?
???????????
? ?????????T??
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• ???DC
• a.?????????????????
• b.??Fc?R????????
• c.?????????????????
• d.????????
• e.??B7??
• f. ??DEC205???
• ??????????,?????????????????????????????

41

• ??DC
• a.????????????MHC -I??II???
• b.??????DC-CK ????
• ?T??
• c.????????????
• d.?????????
• ??T??????????

42
??????????????

• ????
• ????T??
• ??B??Ig???????B?????
• ????
• ???????????

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• ??? NK??(natural killer cell,??????)
• ?????????(large granular lymphocyte,
  LGL)??????????
• ??T???B?????--
• ?TCR???Ig????????
• TCR-?mIg-?CD56?CD16?????? --- NK??
• ?????(?CTL),
• ??????(?Th ??IFN???)
• ???????????????510
• ???12
• ?????????NK?????

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Human NK cell
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NK??
N
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• NK????????
• 1.??????????
• 2.???????T?? --- ??
• A.???NK?? --- CD3,??NK?? --- CD3-?
• B.????NK???T????????????
• a.????? --- ????CD16??
• CD16CD4-CD8-??? ? ?????? ?T??
• CD16CD4-CD8-??? ? ???????? ? NK
• b.?????? --- NK??????CD56??
• CD3-CD4-CD8-??,??CD56 ? NK ??
• ??CD56- ? T??
  
• 3.????????
• ????(CD34CD7)?NK??(CD2CD16CD56)
  

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??NK????????????????????

• (?)NK??????HLA???????????
• 1.????????????(KIR)
• ???????????Ig???????,???KIR2D?KIR3D?????
• ??????????,???????????
• ?(ITIM),?KIR2DL?KIR3DL,????????
• ?,???????
• ??????????,????????,?
• KIR2DS?KIR3DS?????????????,??
• ?????????????????????????
• ????(ITAM)DAP-12???????????
• ?,???????????,???????

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• 2.??????????(KLR)
• CD94/NKG2A??????
• CD94/NKG2C??????
• 3.KIR?KLR???????

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NK???????????(KIR),???????????????????????????
?MHC I ?????,????MHC I ???????????NK?????
? ? NKCR ? ? ? ? ?
(A)
(B)
MHC-I ??
MHC-I- ??
???
MHC-I
??
KIR
KAR
NK
NK
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• NK??????????
• 1.??????
• (1)??????
• A.???/?????
• B.Fas/FasL????
• C.TNF-a?TNFR-?????

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• (2)???????????????(ADCC)
• Fc?R?(NK??) IgG??(??
• ?) ? ??????

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• 2.??????
• ??????(?IFN-??TNF-a?GM-CSF?IL-3?M-CSF?)?
• A.??T?B?APC???
• B.????????????

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Antibody Dependent Cell-Medicated
CytotoxicityADCC???????????????

• ADCC??IgG???V?????????????????,?Fc??????(?NK?????
  ??)??Fc?R??,?????????IgG???????????????????

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NKCR
???? NKCR
Ig?NKCR( KIR)
HOOC COOH
NH2
-S-S-
ITIM
ITIM
H2N NH2
COOH
ITIM immunoreceptor tyrosine-based inhibitory
motifs ???????????
57
NK?????????
Target cell
CD69
CD16 Fc?RIII
CD2
ADCC (antibody-dependent cell-mediated
cytotoxicity) ???????????????
58
 NK cells and their activation
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Electron micrograph of an NK cell


High power view of an NK cell granule containing
perforin, granzymes, and other mediators
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Phase contrast micrograph of NK cell attacking a
target cell projection.
An "NK" cell (N) attached to a "target" cell
"T".. The NK cell will kill the now helpless
target cell quickly, by the injection of deadly
perforin
63
??? NKT??

• ????
• ???NK1.1???TCR-CD3??????T???????CD4-CD8-???T??,?
  ??CD4???T??,TCR???,????TCRaß,???TCR?d?
• ??????
• ?????????????CD1?????????????????MHC???

64

• ?????
• (1)?????---????FasL???????
• ??????????????????
• (2)??????---NK1.1T?? DC Mf??
• ??????
• a.????????DCMf?IL-12???NK1.1T???IFN-?IL-12?
  Th0?Th1??????
• b.??????NK1.1T???IL-4?Th0?Th2?
• ??IgE?IgG1?

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(No Transcript)
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• ??? ????????
• ?.??????
• ????
• 1.????FceR?
• 2.???????IL-5?CC????
• (chemokines, ?MCP-3)???

67

• ?????????
• A.????????,???????(major basic protein)
• B.?????????????
• C.????,?IL-3?IL-5??
• ?????
• 1.?????????
• 2.????????????,?????????????????????,???????

68
??????
69

• ?? ????(mast cell)???????(basophils)
• ????? ???????
• ???????---??,0.2
• ????---??????????????
• ?????????????,??????
• ???1.FceR?(IgE?Fc??)
• 2.C3aR ? C5aR?

70

• ??????????????
• 1.IgE-Ag ? ?FceR?????
• 2.?????C3a?C5a???

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(No Transcript)
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(No Transcript)
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??????????????????
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(No Transcript)
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• ??????
• A.????????
• ??(histamine)???C4(leukotriene C4)
  ????D2(prostaglandine D2)?
• B.??????
• ??????(TNF)
• IL-8????????(PAF)??

77

• ?????
• A.?????????????????(??? ??)
• B.?IgE?????????????,?????????????
• C.???????

78
??????

• ?????????????????????,??????????????????????????
• ???????????????????,??????,??????????????????????
  ???????????

79
?????????????????

• ?? ????????
• (?)???????????????
• 1.????
• 2.????
• 3.?????
• (?)????
• (?)?-???

80

• ????????????
• ????
• NK??
• ?dT??
• NKT??
• B1??

81

• ????????????????
• ????
• ????
• 1.??????????????
• 2.??????????????
• 3.???????????????
• ???
• ???
• ????

82
???????????
??
?? ????
?????????? ?????????? ???????????
0-4h ??,?????
??
4-96h ?????NK? ?????????

gt96h APC
83
???????????? (0-4h)
????
M??
????
??
?????
84
???????????? (4-96h)
TNF,IL-12
?-IFN
????
????
LTB4 (???B4)
IL-1
PAF (???????)
IL-6
MCP-1 (????????-1)
PGE (????E)
IL-8
85
????????????? (96h??)
APC (?????? antigen-presenting cell)
86
???(???????????)
87
??????????????????????

• ???????????
• (?)???????????
• 1.??????(pattern recognition receptor,
  PRR)?????????(pathogen associated pattern,PAMP)
• 2.??????(Toll???)?????????
• (?)???????????

88
???????????????????

• (?)???????????????
• (?)??????????????????
• (?)?????????????????????

89
(No Transcript)
90
???????????????????
?? ?????? ???????
??????? ??????? ???? ???? ???? ???? ???? ??????????????????NK???NKT????dT???B1?? ????????????????? ??96?? ??????,????????,????? ????????????????????,????????? ?????????,????????,???????? ?????? aßT???Th1?Th2?CTL?B2????????? ????? 96????? ?????????,??????????,??????? T????APC??????-MHC?????B??????????,??????? ????????,???????????,???????? ??????
91
?????????
?? (inflammation ) ???????????????????(??
??)??????????????
?? ??
???? (acute inflammation)
??-1? ??,?????
???? (chronic inflammation)
??-?? ??,????,????
92
? ? ? ? ? ? ? ? ?
93
???? ????? ?????? ????
????
????
???? ??????
???????
??
??????????
94
??????????
?????????????P?E???,
??????????????????????
??????????????????????ICAM??,??????????????,
????????????
95
????????
????????????????????????????
?????????????????????????????
96
???????
????????????
????
??????
N-???
?????
????5-???
PAF,C5a,LTB4,PAF?
?????
C3a ,C5a


PGD2 LTC4,LTD4, TXE,PAF
????(IL-8)
?????
????? ??????
??????
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(No Transcript)
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• ????
• ?????????????????????
• ????????????????????????????????????????????????
  ????????????????????????
• ??-????????????????,?????????????????,??????????
  ???????????????????????????????

99
NK??????????,??????????????????????????????ADC
C??? ????????????????????IgE?Fc??,?IgE???????
??????,????????????????????????????
100

• ????
• ??????????????(ADCC)
• NK??????????IgGFc??(CDl6?FcrR?),?IgG??????????????
  ????,????Fc??NK????FcrR???,??NK?????IgG???????????
  ?????????,??????????????????????NK???,??????????AD
  CC???

101
???

• 1.???????????????????????????
• ??????????????????????,??????To11???2?4(TLR2?TLR
  4)?
• ?????????????????????????????????????????????????
  ??????G-?????G?????????????????????????TLR2?????
  ??G?????????,???????????????,????????????????????
  ?TLR4?????G???????????

102

• 2.?????????????
• ??????????????
• ?????????
• ?????????????????
• ???????,?????????
• ?????? --- ??????