Date post: | 26-Jan-2015 |
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KELVIN G. HUAYLLAZO M.
THE INTERFERONS AND THEIR RECEPTORS
– DISTRIBUTION AND REGULATION
INTRODUCTION
The IFNs are cytokines which participate in several process of the immune system.
Isaacs (1957, INTERFERence influenza virus in its growning)They are 3 types descript:
IFN type I IFN type II Recently IFN type III has been described
JAK/STAT SIGNALING
• JAnus Kinase• Signal Transducers and
Activators of Transcription
• JAK (-1,-2.-3) y Tyk2• STAT (-1.-2.-3.-4.-5a/5b,
-6)• Heterodim, Homodim• SOCS (-1.-2,-3)• PIAS
INTERFERON RECEPTOR SYSTEMS
IFN type
IFNS Receptor
Signaling molecules
I α (13 types), β, δ (pigs), ε, κ, τ (ruminant), ω, ζ, ν
IFNAR1IFNAR2
JAK1, Tyk2 / STAT-1,-2,-3,-4,-5MAPK, PI3K, Akt, NF-κB, p53, PRMT1
II γ IFNGR1IFNGR2
JAK1, JAK2/ STAT-1,-2,-3,-5MAPK, PI3K, Akt, NF-κB
III λ IFNLR1IL10RB
JAK1, Tyk2/ STAT-1,-2,-3,-4,-5MAPK, PI3K, Akt
ESTRUCTURA, SÍNTESIS
VÍAS
IFN-α: pDCs, mono
IFN-β: FibroblastosEstímulos: RNA mc/bc CpG DNA viral Receptores TLR-3,-
7,-9Sensores iC (RIG-
1/MDA-5) IRF
IFN IFNR JAK/STAT IRF-9 ISRE–AN
STAT-1/STAT-1(P) GAS–AN
MAPKPI3K
TYPE I IFN
TYPE I IFN
ACCIONES BIOLÓGICAS Protección vs Inf. Virus
Enzimas PKR16 1’5’ OAS/Rnase L18,19
Señales: Paracrina/Autocrina ↑ MHC-I
CTL CD8+/NK x IL-12R? Th1 favorece expresión IL-12R Favorece secuestro de linfocitos en Gang Linf Inhibición In vitro de muchas células (Apoptosis, alt metabólica
enzimáticaUSOS IFN-α Hepatitis, NM Linfomas, Tricoleucemias IFN-β Esclerosis múltiple ?? ¿IL-10?
ESTRUCTURA, SÍNTESIS
VÍAS
Fuentes: M activo LB LT
IFN-γ MTbet1
Th1(+)/GATA3 Th2(-)
IFN IFNR JAK/STAT GAS
… STAT1/IRF-1
TYPE II IFN
TYPE II IFN
IFN-γ LB PC Switching IgG2aMHC-I, MHC-II, CoestimuladoresEndotelio TNF Potencia acciones (Adh Lt,
extravasación)Favorece las Rx InflamatoriasInhibe reacciones ricas en Eosinófilos IgEAgs tumoralesTranscripción phox-91 (complejo Oxidasa del M)Defensa contra L. donovani, major, Plasmodium
(resistencia contra esporozoitos)
TYPE III IFN
IFN-λ1 IFN-λ2IFN-λ3¿Ancestro IFN?TLR-8,-9JAK/STATHCV >>type I IFNsApoptosis no dep p53
MHC-I, 2’5’OAS, MxA
IFN & TISSUES
PATHWAYS OF IFN SIGNALING