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Pancreatic lymph node. Islet. CD8 +. En- viron- ment. Perforin?. Co-stimu- latory signals. •. •. •. •. DC. •. •. •. •. •. •. •. •. •. •. •. •. . •. •. •. •. DC. •. •. •. •. IL-1 TNF . O 2. NO. •. •. . •. Th 1. •. •. •. •. •. •. •.

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Presentation Transcript
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Pancreatic

lymph node

Islet

CD8+

En-viron-ment

Perforin?

Co-stimu- latory signals

DC

DC

IL-1

TNF

O2

NO

Th1

Fas

FasL

IFN

T- and B-cell

clonal ex- pansion

Th1

Mandrup-Poulson


Slide2 l.jpg

SOD2

NOS2

NFKB

BCL2

INS

T1DM

FASL

FAS

CTLA4

CD4

IL6

IL12B

IL1RN

IL1RI

IFNG

HLA

TNFA

IL1B

Mandrup-Poulson


Slide3 l.jpg

IFNg

IL-1ß

Cytokine-signaling

 Energy

generation

 Defense

 Repair

 NO production

Mitochondria

 Apoptosis

 Insulin production/ß-cell function

ß-cell destruction

Mandrup-Poulson



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Mitogen and stress stimuli

Ras Rho TRAF

MAPKKK

Raf ASK MEKK MLK TAK1 TPL2

ATP

ADP

MEK1/2 MKK3/6 MKK4/7

MAPKK

ATP

ADP

ERK p38 JNK

MAPK

Elk-1 ATF2 c-jun

Mandrup-Poulson


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TNF

IL-1

TNF

IL-1

p60

IL-1R1

IL-1AcP

MyD88

TRADD

TRAF2

IRAK

TRAF6

FADD

NIK

IKK

IkB

NFkB

IkB

NFkB

Gene expression

Cellular response

Mandrup-Poulson


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IFN

IFN

IFN

IFNgR1

IFNgR2

IFNgR2

P

STAT1

JAK1

JAK1

JAK1

JAK1

JAK1

JAK2

JAK2

STAT1

P

STAT1

Translocation to nucleus

Gene expression

Mandrup-Poulson


Slide8 l.jpg

energy generation

 insulin production/ß-cell function

 defense

 NO production

+cytokines

 cytokine-signaling

 apoptosis

 repair

ß-cell survival

ß-cell destruction

Mandrup-Poulson


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