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11 ().

IN VIVO VERITAS ()
/


18 2015 .

In vivo veritas

,
:
1.


.
2. .

!

.
,




(IRAK).
.

.
Jak3 (combined severe
immunodeficiency, SCID ).




B, D

3(2)

3(H2O)Bb

C3

C3b

C3bBb

.D

C5

C4b2a3b

MBP
C4b2a
4

C4b

C5b

C5b6

C6

C5b67

C7

C678

C8

C6789

C9

3/5-
C3

C2
C1q, r, s

C3bnBb(P)

C1qrs
3/5-
-



C1q, C1r, C2, C4

()

C3

C5, C6, C7, C8

I, H

C1inh

CD4+ T-

TCR

MHC-II

BCR
CD154
ZAP-70

CD4

BLNK

ZAP-70
Lck

Btk

SH2D1A

IL-2R

MHC-I
Jak3

TAP
NF-B

WASP

ATM

RFX5
RFXAP

CIITA

RFXANK


( )
Hematopoietins
I

II

III

IV

VI

VII

VIII

IX

XI

XII

TIR
domain

IFN/IL-10
family

TNF superfamily

Common
chain

Common
chain

Common
gp130

Common
IL12R

Epo family

PDGF
family

TGF-
family

IL-17
family

7 TM

IL-1

IFN-

TNF

CD27L

IL-2

IL-3

IL-6

IL-12

Epo

PDGFs

TGF-
(1,2,3)

IL-17A-F

LTN

IL-1

IFN-
IFN-

LT

CD30L

IL-4

IL-5

IL-11

IL-23

Tpo

VEGFs

BMPs

CC

LT

CD40L

IL-7

GM-CSF

LIF

IL-27

EGF

Act

CXC

IL-10

FasL

APRIL

IL-9

Inh

Fractalkine

IL-18
IL-33

CT-1
M-CSF

IL-15
IL-1Ra

TRAIL

TALL-1

OSM

Flt-3L

(G-CSF)

SCF

IL-21
TRANCE

4-1BBL

LIGHT

OX40L

TWEAK

GITRL

Chemokines

IFN family

CC

IFN-

IFN-1

IFN-2

IFN-4

IFN-11

MIP-1

MIP-1

MIP-1

MPIF-1

HCC-1

HCC-4

SCYA26

IFN-13
IFN-F

IFN-A
IFN-I

IFN-B2
IFN-J1

IFN-C
IFN-K

IFN-D
IFN-WA

PARC

Eot1,2

I-309

MCP-2

MCP-4

TARC

RANTES
MIP-3

MCP-1

MCP-3

6Ckine
MIP-3

TECK

MDC

IL-10 family
IL-19
IL-24

CXC
IL-20
IL-26

IL-22
(IL28/29/IFN)

IL-8
ENA-78

GCP-2
IP-10

MIG
NAP-2

SDF-1
GRO

I-TAC
BLC

PF4
BRAK

X-
(X-SCID), c

Jak3

-
CD4+

NK

- -IgM-

IPEX=
Immune dysregulation,
polyendocrinopathy,
enteropathy,
X-linked

David, the bubble boy (1971-1984)


.
( .. )



HIV-1 (-1)
CD4.
: CCR5 (
RANTES, MIP1a MIP1b) CXCR4 (
SDF-1 CXCL12).
CD4+
, FDC, ,
(
-).
CCR5,

.

CXCR1 --- IL8 >> GCP2 >> NAP2, ENA78


CXCR2 --- GRO, NAP2, IL8, ENA78, GCP2, .

CXCR4* --- SDF1


CXCR3 --- IP10, MIG, I-TAC

CXCR5 --- BLC


CXCR6 - CXCL16

Tfh

CX3CR1 --- Fractalkine


CCR1 --- MIP1, RANTES, MCP2-4

CCR2 --- MCP1-5


CCR3 --- Eotaxin1-2, RANTES, MCP2-4, MIP1

CCR4 --- TAPC, MDC

CCR5* --- MIP1, MIP1, RANTES

CCR6 --- LARC


CCR7 --- ELC, SLC

CCR8 --I-309, TARC, MIP1


Chemokine
specificity

CD4+ T

-1

CD4+ - 1 3

()


,
..

: Pantaleo, G et al. 1993. New concepts in the immunopathogenesis of human


immunodeficiency virus infection. New England Journal of Medicine 328:327-335.

?
1.


CD4+ .
.

2.

3.

4.


,
.

/
1.

(HAART)

.

2.

( )
(
).

3.


,

. !

4.

,

!


1) 90% - , 10% - .
2) 20 1
.
3) , , . , .
4) Firmicutes (+) Bacteroidetes (-).
5) 1000
!
6)
.
7)
.


1) .
2) , .
3) ,
, ,
. 3-
.
4) ,
.
5) (NOD2,
NLRP, MyD88 .) .
6)
, !

R. Ley and J. Gordon, 2008

1)
(high-fat diet),
(obese (ob/ob)).
2) ,
.


?
1. .
2.
.
3. () ,
.
, .
4.
( : , ,
, .)
5.
.


1. .. (1941-2013).
2. .. , ..
, .. ..
.
3.
.

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