Apararea antivirala

Celulele NK
Apararea antiinfectioasa
Organism Reprez Fag
(II)
CK
(II)
NK
(II)
Complement Ac
neutral
CTL
VIRUSURI

Grip
Oreion
Pojar
Rinovirus
+++
+++
+++
+++


IFN
+++
+++
+++
+++
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+++
+++
+++
+++

+++
+++
+++
+++

BACT
INTRA
CELULARE
Listeria m
Legionella
Mycobact
Ricketsia
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---
+++
+++
+++
+++
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---
+++
+++
+++
+++

+++
+++
+++
+++

BACT
EXTRA
CELULARE
Staph spp
Strep spp
Neisseria
Salmonella
+++
+
+
+++
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+++
+
+
+++
+++
+++
+++
+++

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RI antiviral:
Innascut si Adaptat
Apararea antivirala
innascuta si adaptata
Interferoni
Structura
Stimuli:
Receptori:
Efecte:



Principalele functii ale familiei
IFN

Efectele
anti-virale
ale IFN /
fosforilare
Auto-
Fosforilare
PKR
PKR
eIF2= subunit of eukaryotic initiation factor 2
PKR=protein kinase
(dsRNA-dependent)
Apararea antivirala innascuta si adaptata
RIC: celule
I. Celule efectoare
1. specifice:T CD8+ (LTC)
2. ne-specifice: Natural killer
(NK)
Roluri:
Recunoasterea celulelor-tinta
(mecanisme diferite)
Distrugerea celulelor-tinta
(mecanisme similare)
II. Celule Auxiliare:
procesare Ag MHC I, II
1. APC ( TCD4)
2. TCD4 (TH) TCD8
Rol: activarea completa a LT CD8

APC
1
2
remember:
Hematopoiesis
I. Celulele imunitatii innascute
remember:
Celule NK
NK Cell
Tumor Cell
remember:
Celule NK: caracteristici (I)
Denumirea:
Localizari:

Identificare:


FENOTIP:
remember:
3 Subseturi- fenotip, functie

Celule NK: caracteristici (II)
Receptori*
caracteristici

Recunoaste:

Recunoastere:
Activare:

Actiuni:
Celule NK: caracteristici (III)
Celule NK: importanta
RIC mediat NK n infeciile cu:
Timpul de raspuns:
Vivier, E. et al. Innate or adaptive immunity? The example of natural killer cells. Science. 331, 44-49 (2011).
Receptori
NK
Ce recunosc NK?
Prezenta & absenta Selfului : MHC I: HLA-A, -Bw, -Cw, -G
Self-ul indus/ modificat: proteine care semnalizeaza stresul
celular: HSP, MIC-A, MIC-B, (MHC I chain-related proteins type A, B)




Fam Receptori NK

Natura
Moleculara
Liganzi
Coresp.
soarece
KIR (killer Ig-like R) Superfamilia Ig HLA-A, -Bw, -Cw, -G gp49
ILT/LIR Superfamilia Ig HLA Cls Ia (-G) LRC
CD94/NKG2 (KLR) C-type lectin-like HLA Cls Ib (-E) NKC / Ly49
KAR (NKG2D, KLRK1) C-type lectin-like MIC A,B & MHC I-like NKG2D
NCR Superfamilia Ig Hemaglutinine Virale, NCR
Receptorii Inhibitori ai NK
(KIR*)
ITIM =Immunoreceptor Tyrosine based Inhibitor motif
Dupa Abas at al. 2012 Elsevier/Saunders
Mecanisme de Activare ai
KIR
Receptorii Activatori ai NK
(KAR)
ITAM= Immunoreceptor Tyrosine based activation motif
Dupa Abas at al. 2012 Elsevier/Saunders
Mecanisme de Activare ai
KAR
Recunoasterea
celulelor
infectate
(transformate)
1 2
Asocierile cu Boala
ale Combinatiilor Alelice KIR & HLA


Disease KIR HLA Disease progression Proposed contribution by KIRs
AIDS 3DS1
3DS1 homozygous
HLA-Bw4
Ile80

No HLA-Bw4
Ile80

Decreased
Increased
Less inhibition
More inhibition

HCV infection

2DL3 homozygous

HLA-C1 homozygous

Decreased

Less inhibition

Cervical neoplasia
(HPV-induced)

3DS1

No 3DS1

HLA-C1 homozygous
and no HLA-Bw4
HLA-C2 and/or HLA-Bw4

Increased

Decreased

Less inhibition

More inhibition

Malignant melanoma

2DL2 and/or 2DL3

HLA-C1

Increased

More inhibition

Psoriatic arthritis

2DS1 and/or 2DS2

HLA-C1 homozygous or
HLA-C2 homozygous

Increased

Less inhibition

Type I diabetes

2DS2

HLA-C1 and no HLA-C2,
no HLA-Bw4

Increased

Less inhibition

Preeclampsia

2DL1 with fewer
2DS (mother)

HLA-C2 (fetus)

Increased

More inhibition
Rajagopalan, S., Long, E. Understanding how combinations of HLA and KIR genes influence disease. J. Exp. Med. 201, 1025-1029 (2005).
Mecanismele efectoare ale NK
I. Citotoxicitate
A. Directa:
B. Indirecta:
C. ADCC:*

Mecanismele citotoxice ale NK
Citotoxicitate directa:
Etape:



Mecanismele citotoxice ale NK
Smyth, M. J. et al. Activation of NK cell cytotoxicity. Mol. Immunol. 42, 501510 (2005).
Mecanismele Efectoare ale NK (II)
II. Secretie de citokine:

Dupa Abas at al. 2012 Elsevier/Saunders
Mecanisme virale de evadare
2. Inhibarea procesarii Ag
pe calea MHC I