Зачем в действительности нужна толерантность?

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(http://vk.com/physimmun).
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- 2014/2015
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22
2014
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4.
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5.
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7.
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9.
10.
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MHC II
MHC I
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CD8,
MHCI
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CD4,
MHCII
IgG
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IgM
IgA
IgE
IgD
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,
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,
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YF-17D
YF-17D ,
7
15
4-6
18
30-40
. YF-17D
(TLR2, 7, 8, 9, RIG-I, MDA5),
.
, IgM
IgM
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B.
IgG
,
CD8+ TCD4+ T-
IgG
,
.
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.
1
12-20
.
,
.
IgM
,
IgG -
,
-
,
,
)-
.
.
IL-17
Th17
Th1
ROR t
T-bet
IFN
STAT3
TGF , IL-6
,
STAT4
IFN , IL-12
IL-21
IL-4
,
Th0
IL-6
STAT3
Tfh
Ascl2
TGF
STAT5
TGF
IL-10
IL-35
IL-4
STAT6
Treg
Th2
FoxP3
GATA3
IL-4
IL-10
IL-13
anti-TGF R
anti-STAT3
anti-ROR t
anti-IL-17
IL-17
ROR t
STAT3
TGF R
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• Aire • Fas / FasL • TGF , IL-10 • CTLA-4, PD-1 • FoxP3 •
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(
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Th2
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IL-4, IL-10,
- Th1
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0
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III(B)
IV( B)
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B
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IV( B)
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MHCI,
NK-
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CD47.
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CD47
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B
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N-
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H
II ( )
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III ( )
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IV (AB)
A, B
-A,
»
0
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»
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H-2b
H-2k
x
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MHC?
MHCI (6
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TCR
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MHCI,
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TCR
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MHCI,
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MHC -
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MHC
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MHC
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NFAT.
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MDSC = myeloid-derived suppressor cells.
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Vesely et al, Annu Rev Immunol 2011, 29:235-271.
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(
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•
(
(MSI-H).
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,
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).
•
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CTL /
CD8+/FoxP3+
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Treg)
•
(
).
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-
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•
(
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TAA.
•
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:
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16
2.6
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,
15
1909
1910
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(
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(1894—1966)
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–
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–
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17.01.1945 . -
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25%
,
80%
80%
10%
HPV = Human papillomavirus (
HBV, HCV = Human hepatitis B, C virus (
EBV = Epstein-Barr virus (
)
)
10%
)
30%
2
20%
005.
)
,
Harald zur Hausen
HPV
HPV 100
HPV18,
.
,
, HPV16
70%
.
HPV
.
,
.
2011: anti-CTLA-4
Ipilimumab /
MDX-010/101 /
Yervoy (Bristol-Myers)
2014: anti-PD-1
James P. Allison, Ph.D
Pembrolizumab /
MK-3475 / Keytruda
(Merck)
Sipuleucel-T (Provenge)
Prostatic specific acid
phosphatase (PSAP)
+
Keyhole limpet
hemocyanin (KLH)
:
:
TLR
.
:
"
-"
"
:
1.
.
2.
(
).
3.
,
,
,
):
,
,
:
5%
.
:
10
.
10%,
.
:
60
3
.
-
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