Académique Documents
Professionnel Documents
Culture Documents
Celulele NK
Apararea antivirala
Apararea antiinfectioasa
Organism
Reprez
Fag
(II)
VIRUSURI Grip
Oreion
Pojar
Rinovirus
+++
+++
+++
+++
BACT
Listeria m
INTRA
Legionella
CELULARE Mycobact
Ricketsia
BACT
Staph spp
EXTRA
Strep spp
CELULARE Neisseria
Salmonella
CK
(II)
NK
(II)
Complement
Ac
neutral
CTL
+++
+++
+++
+++
---------
+++
+++
+++
+++
+++
+++
+++
+++
---------
+++
+++
+++
+++
---------
+++
+++
+++
+++
+++
+++
+++
+++
+++
+
+
+++
---------
+++
+
+
+++
+++
+++
+++
+++
---------
IFN
Apararea anti-virala
RIC: celule
I. Celule efectoare
APC
Roluri:
Recunoasterea celulelor-tinta
(mecanisme diferite)
Distrugerea celulelor-tinta
(mecanisme similare)
Apararea antivirala
innascuta si adaptata
RI antiviral:
Innascut si Adaptat
Interferoni
Structura Prot & Gp familii:
Tip I (, , ,,) -secretati de
Tip II ( ) secretati de
Stimuli:
Infectia virala ( , )
Status inflamator ()
Receptori:
Efecte: Similare
2. activeaza M
3. mobilizeaza NKs
Efectele
anti-virale
ale IFN /
PKR
2. AutoFosforilare
PKR
1.fosforilare
PKR=protein kinase
(dsRNA-dependent)
eIF2= subunit of eukaryotic initiation factor 2
remember:
RIC: celule
I. Celule efectoare
APC
1
Roluri:
Recunoasterea celulelor-tinta
(mecanisme diferite)
Distrugerea celulelor-tinta
(mecanisme similare)
remember:
remember:
Celule NK
I linie de aparare impotriva:
1. Celulelor infectate viral
2. Celulelor tumorale
3. Altor patogeni intracelulari
Implicate in:
4. Respingerea grefei
5. Autoimunitate
6. Avortul Spontan
NK Cell
Tumor Cell
Minoritate: CD3_CD56brightCD16-
Rare: CD3-CD56-CD16+
Recunosc:
Recunoastere:
(Nespecifica)
Activare:
Actiuni:
liza celulelor-tinta
secreta CK implicate in apararea antivirala
Timpul de raspuns:
Rspunsurile maxime celule NK: ore / zile
Rspunsurile maxime celule T & B: > 7zile
Receptori
NK
Vivier, E. et al. Innate or adaptive immunity? The example of natural killer cells. Science. 331, 44-49 (2011).
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
ILT/LIR
Superfamilia Ig
LRC
CD94/NKG2 (KLR)
C-type lectin-like
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*)
I. C-type lectin:
CD94 ( NKG2A)
Ligand: MHC I
Semnal ITIM
Mecanisme de Activare ai
KIR
Celulele nucleate self N (sanatoase)
Receptorii Activatori ai NK
(KAR)
Caracteristic: ITAM
I. C-type lectin:
NKG2D:
Leaga MIC-A,B
Semnal ITAM
Mecanisme de Activare ai
KAR
Recunoastere
celule
infectate
(maligne)
Asocierile cu Boala
ale Combinatiilor Alelice KIR & HLA
Disease
AIDS
KIR
3DS1
3DS1 homozygous
HLA
HLA-Bw4Ile80
No HLA-Bw4Ile80
Disease progression
Decreased
Increased
HCV infection
2DL3 homozygous
HLA-C1 homozygous
Decreased
Less inhibition
3DS1
Increased
Less inhibition
No 3DS1
HLA-C1 homozygous
and no HLA-Bw4
HLA-C2 and/or HLA-Bw4
Decreased
More inhibition
Malignant melanoma
HLA-C1
Increased
More inhibition
Psoriatic arthritis
HLA-C1 homozygous or
HLA-C2 homozygous
Increased
Less inhibition
Type I diabetes
2DS2
Increased
Less inhibition
Preeclampsia
HLA-C2 (fetus)
Increased
More inhibition
Cervical neoplasia
(HPV-induced)
Rajagopalan, S., Long, E. Understanding how combinations of HLA and KIR genes influence disease. J. Exp. Med. 201, 1025-1029 (2005).
I. Citotoxicitate
A.
B.
C.
Directa:
Indirecta:
caspaze)
Stimulata de CK II:
IL-12 (GF)
IL-15 (GF)
IL-18
IFN /
-Degranularea
1. Adeziunea
inter-celulara,
2. polarizarea
citoscheletului
1.Adeziunea ,
2.Polarizarea
citoschelet
3. Liza eficienta a
celulei-tinta
Smyth, M. J. et al. Activation of NK cell cytotoxicity. Mol. Immunol. 42, 501510 (2005).
2. Inhibarea procesarii Ag
pe calea MHC I