January 24, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Lecture : Complement; Natural cytotoxicity Dr. Daniel Scott-Algara
January 24 – February 5, 2005 at the Institut Pasteur in Ho Chi Minh City, Vietnam
with kind support from ANRS & Université Pierre et Marie Curie
Jointly organized by Institut Pasteur in Ho Chi Minh City and Institut Pasteur
Basis of Immunology and Immunophysiopathology of Infectious Diseases
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Killing
KAR KAL
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
No Killing
MHC I KIR
Regulation Regulation of of NK NK Cell Cell Function Function
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
and andabsence absenceof ofCD3 CD3 activated activatedby byIL2 IL2and andIFN-( IFN-(to to become becomeLAK LAKcells cells
are areidentified identifiedby bythe the presence presenceof ofCD56 CD56&&CD16 CD16
kill kill infected infectedand andmalignant malignant cells cells
also alsoknown knownas aslarge largegranular granular lymphocytes lymphocytes(LGL) (LGL)
Natural Natural Killer Killer (NK) (NK) cells cells
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
NK!!
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Mécanismes Moléculaires?
Interaction avec DC, Macrophages?
Cellules NK et contrôle de la maladie?
L’expression des ligands est-elle différente?
Existe-il un répertoire des cellules NK particulier?
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
20
30
40
* * *
50:1
* * *
0
EU C Sbs Sas
* * *
EU
C Sbs Sas
EU C Sbs Sas DAUDI
K-562
25:1
25:1
0
10
20
30
40
50
0
10
20
30
40
50
60
70
EU
C Sbs Sas
EU C Sbs Sas DAUDI
K-562
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
0
10
20
20
10
30
30
50 40
DAUDI
40
50
0
0
EU C Sbs Sas
10
10
20
30
40
50
70
50
50:1
60
K-562
60
70
% OF LYSIS
12:1
12:1
B
% of stained NK cells
C
EU
*
C
*
*
EU
C
Sbs
Sas
0
EU
EU
EU
*
*
C
C
C
Stimulated
*
Sbs
*
Sbs
Sbs
*
Sas
*
Sas
*
Sas
*
CCL5
CCL4
CCL3
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
0
10
20
20
*
30
30
*
40
40
10
50
0
50
Sas 60
Sbs
60
0
10
20
20
10
30
30
40
40
0
50
Sas
50
Sbs 60
EU
60
0
10
20
20
*
30
30
*
40
40
*
50
50
10
60
60
Unstimulated
A
% of stained NK cells
EU
C
Sbs Sas
EU
EU
C
C
*
* Sbs Sas
*
Sbs Sas
*
Stimulated
TNF-α
IFN-γ
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
EU
10
10
0
20
20
0
30
30
*
40
40
*
50
0
50
Sbs Sas 60
C
60
0
10
10
*
20
20
*
30
30
*
40
50
50
40
60
60
Unstimulated
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
The function of natural killer cells is regulated by a balance between signals transmitted by activating receptors, which recognize ligands on tumours and virusinfected cells, and inhibitory receptors specific for major histocompatibility complex class I molecules..
Natural killer cells are innate immune cells that control certain microbial infections and tumours.
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Activating NK cell receptors use transmembrane adaptor proteins such as FcRI, CD3 and DAP12 to stimulate the ZAP70 and Syk tyrosine kinase pathways, and another transmembrane adaptor protein DAP10 to activate the phosphatidylinositol 3kinase pathway.
Natural killer (NK) cell function (cytotoxic activity and cytokine secretion) is regulated by a balance of signals transmitted by opposing activating and inhibitory receptors.
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
The activating NKG2D receptor binds to human major histocompatibility complex (MHC) class-Ichain-related A (MICA) and MICB proteins, encoded by genes within the MHC, and to glycoproteins that represent orthologues of the mouse retinoic acid early inducible (RAE-1) molecules.
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
A role of NK cells in anti-viral immunity has been demonstrated most convincingly in protection against cytomegalovirus and other herpesviruses.
NK cells kill tumours expressing the MIC or RAE-1 ligands of the NKG2D receptor, even when the tumours express MHC class I molecules that are recognized by the inhibitory NK cell receptors.
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Cytomegalovirus encodes several proteins that bind to MHC class I and MIC that might inhibit recognition by T cells and NK cells.
The mouse activating Ly49H receptor has been implicated in host resistance to mouse cytomegalovirus.
Infection with human cytomegalovirus induces expression of MIC proteins, ligands of the activating NKG2D receptor.
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
Basis of Immunology and Immunophysiopathology of Infectious Diseases, Institut Pasteur in Ho Chi Minh City, Vietnam, January 24 – February 5, 2005
