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Printable Handouts
Navigable Slide Index
- Introduction
- Natural Killer (NK) cell cytotoxicity
- Sequential and serial killing by NK cells
- Human activating NK cell receptors
- Integrins and the immunological synapse (1)
- Integrins and the immunological synapse (2)
- The principle of single-cell force spectroscopy (1)
- The principle of single-cell force spectroscopy (2)
- The principle of single-cell force spectroscopy (3)
- 2B4/CD48-mediated adhesion is LFA-1 dependent
- LFA-1 activation: inside-out signaling
- LFA-1 activation and inhibition
- Integrins and the immunological synapse (3)
- Two ways to kill: parallel pathways
- Two ways to kill: granzyme B and caspase-8
- Fluorescence localization reporter
- Measuring granzyme B and caspase-8 activity (1)
- Detecting granzyme B activity
- Measuring granzyme B and caspase-8 activity (2)
- NK cell serial killing: microwells video
- NK cell serial killing: switching methods
- NK cell serial killing: method distribution
- NK cell serial killing: method by target
- Two ways to kill: order of pathways
- Dynamics of perforin, GrzB and FasL content
- Two ways to kill: granules vs. ligands
- Dynamics of killing events (1)
- Dynamics of killing events (2)
- Dynamics of killing events (3)
- Two ways to kill: perforin knockout
- No death receptor-mediated serial killing (1)
- No death receptor-mediated serial killing (2)
- Two ways to kill: FAS ligand knockout
- Serial killing in the absence of Fas (1)
- Serial killing in the absence of Fas (2)
- Serial killing in the absence of Fas and TRAIL
- Summary
- Acknowledgements
Topics Covered
- Natural killer (NK) cells can kill infected or transformed cells
- Cytotoxic activity and target cell adhesion
- Integrin mediation
- Immunological synapse formation
- Cell apoptosis via lytic granule exocytosis
- NK cell expression of FasL or TRAIL
- Death receptor-mediated apoptosis
- Single force cell spectroscopy
- Granzyme B
- Caspase 8
Links
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Talk Citation
Watzl, C. (2023, January 31). Mechanisms of natural killer cell cytotoxicity [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 6, 2024, from https://doi.org/10.69645/MWDT1026.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Carsten Watzl has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Mechanisms of natural killer cell cytotoxicity
Published on January 31, 2023
37 min
A selection of talks on Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is Carsten Watzl
and I'm from the
Leibniz Research Centre
in Dortmund in Germany,
and I work with
natural killer cells.
The subject of this presentation
will be the mechanisms
of natural killer cell (NK)
cytotoxicity -
how NK cells kill other cells.
0:20
The best way to introduce this
subject is to actually
show you a video
that we made in our lab.
Here you see tumor cells
that are labeled
in green and NK cells
that are labelled in red.
When we start the video you see
that the NK cells
attach themselves
to the tumor cells and kill
these tumor cells by
direct cellular contact.
They kill the tumor cells
by inducing classical apoptosis,
so you see the
hallmarks of apoptosis,
so the cell shrinking
and the membrane blebbing.
Over the time course
of these three hours,
the NK cells have killed many
of the tumor cells
in this video.
You can see that the
NK cells cytotoxicity
is a rather potent mechanism,
and it's one of the
major functions
of these innate lymphocytes.
The NK cells cytotoxicity is
actually also being
used therapeutically
when we're talking
about CAR T-cell,
so other cancer immunotherapies.
Therefore, it is
important to understand
how NK cells actually
kill tumor cells.
1:22
NK cells are not just killers,
they're actually serial killers,
so they can kill
multiple targets,
but they can only kill
one target at a time.
This is what you see
in these images
that are also taken
from a video that we made.
Again, the NK cell here
is labelled in red
and the tumor cells
are not labeled,
but they will turn
green when they die.
You see in the upper
left picture that
the NK cell makes contact
to tumor cell number one,
and then this cell turns green,
indicative of this cell dying
and being killed by the NK cell.
Then the NK cell makes contact
with tumor cell number two,
kills this one, and so on.
So over the time course
of 12 hours here,
the NK cell has killed
five individual target cells
in a strictly serial fashion.
I'll get to that in a
minute why the NK cells
can only kill one
target at a time.