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

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Title: ????????? ( 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)

6
? ? ? ? ? ?
????????,???(?,????)??????????????????????
?????(?)????????????????????(?)?
7
  • ????
  • ??????????????
  • ??????????????
  • ?(??)?????(??)?

8
????????????????
? ?
? ?
? ?
?????
???? ???????? ???????
????? ?????????????? ???????????
????????? ????? ????A???
????
?????
?????
?????
????
9
  • ???????
  • ????????????????
  • (?)?????????????????
  • 1.?????????????????
  • ??????(pattern recognition receptor,PRR)?????????
    ?????????????????????????????????
  • ????????(pathogen associated molecular pattern,
    PAMP)???????????????????????????????

10
  • ?????????????(scavenger receptor,SR)??????(?????
    ??)?Toll?????

11
?????(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
???
15
?????????
??
??
CD11b/CD18
CD16 (Fc?R III)
? ? ? ? ? ? ? ?
IL-2
????
CD25
CD71
B7-2
CD28
CD64 (Fc ? R I)
CD35 (CR1)
CD32 (Fc ? R II)
??
??
??
16
Adherence of bacteria via receptors
17
  • (?)??????????????????????
  • ??????????????????
  • 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-
22
Oxygen-independent mechanisms of intracellular
killing
????
? ?
???????? ??????? ?????????? ????????
Cationic ?? (?? ?????) ??? ?????? ?????
23
Macrophage Phagocytosis
24
  • ???????????

?????????????
25
  • ?? ??????????????????????ADCC???????

26
  • ?????????,?????????
  • ???????,????????
  • ??Th1???????????????

27
  • ???????? --- ??????
  • (IL-1?IL-6?IL-8?IL-12?TNF-a?)?
  • -????IL-1/12,TNF-a
  • -???????TGF-ß

28
(No Transcript)
29
(No Transcript)
30
(No Transcript)
31
??????????? ????(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 ? ???

34
(No Transcript)
35
??? ????? (Dentritic Cells, DC)
  • ??????????????,??????(naïve)
    T????,??DC?T????????????????????????????
  • ??????????????
  • ????????CD1a?CD11c?CD83
  • ?????????????????MLR??????T???????????????

36
??
37
DC????? ?????????,??PBMC?1???
???????DC(???DC)
????????DC(LC) ????DC ??DC
???DC
38
DC????????????
  • ?????,???DC?????????????????????????????
    ,?????
  • ?????,??????,??????????????????????

39
  • ????????????????????

????????????
????
????????????????,??T????IR?
???????????
? ?????????T??
40
  • ???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?????
  • ????
  • ???????????

43
  • ??? NK??(natural killer cell,??????)
  • ?????????(large granular lymphocyte,
    LGL)??????????
  • ??T???B?????--
  • ?TCR???Ig????????
  • TCR-?mIg-?CD56?CD16?????? --- NK??
  • ?????(?CTL),
  • ??????(?Th ??IFN???)
  • ???????????????510
  • ???12
  • ?????????NK?????

44
Human NK cell
45
NK??
N
46
  • 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)

47
??NK????????????????????
  • (?)NK??????HLA???????????
  • 1.????????????(KIR)
  • ???????????Ig???????,???KIR2D?KIR3D?????
  • ??????????,???????????
  • ?(ITIM),?KIR2DL?KIR3DL,????????
  • ?,???????
  • ??????????,????????,?
  • KIR2DS?KIR3DS?????????????,??
  • ?????????????????????????
  • ????(ITAM)DAP-12???????????
  • ?,???????????,???????

48
  • 2.??????????(KLR)
  • CD94/NKG2A??????
  • CD94/NKG2C??????
  • 3.KIR?KLR???????

49
NK???????????(KIR),???????????????????????????
?MHC I ?????,????MHC I ???????????NK?????
? ? NKCR ? ? ? ? ?
(A)
(B)
MHC-I ??
MHC-I- ??
???
MHC-I
??
KIR
KAR
NK
NK
50
(No Transcript)
51
  • NK??????????
  • 1.??????
  • (1)??????
  • A.???/?????
  • B.Fas/FasL????
  • C.TNF-a?TNFR-?????

52
  • (2)???????????????(ADCC)
  • Fc?R?(NK??) IgG??(??
  • ?) ? ??????

53
  • 2.??????
  • ??????(?IFN-??TNF-a?GM-CSF?IL-3?M-CSF?)?
  • A.??T?B?APC???
  • B.????????????

54
Antibody Dependent Cell-Medicated
CytotoxicityADCC???????????????
  • ADCC??IgG???V?????????????????,?Fc??????(?NK?????
    ??)??Fc?R??,?????????IgG???????????????????

55
(No Transcript)
56
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
59
Electron micrograph of an NK cell


High power view of an NK cell granule containing
perforin, granzymes, and other mediators
60
(No Transcript)
61
(No Transcript)
62
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?

65
(No Transcript)
66
  • ??? ????????
  • ?.??????
  • ????
  • 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???

71
(No Transcript)
72
(No Transcript)
73
(No Transcript)
74
??????????????????
75
(No Transcript)
76
  • ??????
  • 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)
?????
????? ??????
??????
97
(No Transcript)
98
  • ????
  • ?????????????????????
  • ????????????????????????????????????????????????
    ????????????????????????
  • ??-????????????????,?????????????????,??????????
    ???????????????????????????????

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