Real-Time Observation Sheds New Light On MS
Tick
Real-Time Observation Sheds New Light On Multiple Sclerosis
06 Nov 2009
In diseases such as multiple sclerosis, cells of the immune system
infiltrate the brain tissue, where they cause immense damage. For many
years, it was an enigma as to how these cells can escape from the
bloodstream. This is no trivial feat, given that specialized blood
vessels act as a barrier between the nervous system and the
bloodstream. Until now, tissue sections provided the sole evidence
that the immune cells really do manage to reach the nerve cells. Now,
a team of scientists from the Max Planck Institute of Neurobiology,
the University Medical Center Göttingen, and other institutes, has
witnessed the movements of these cells "live" under the microscope for
the very first time. In the process, they discovered several new
behavioural traits of the immune cells. The consolidated findings mark
a significant step forward in our understanding of this complex
disease. (Nature, 14 October 2009)
The brain and the spinal cord monitor and control the functions of all
body parts and co-ordinate the whole organism's movements, senses and
behaviour. Adequate protection of the brain and spinal cord are
therefore of the utmost importance. Physical influences and injuries
are warded off by the cranial bone and the vertebral column. Dangers
lurking within the body, such as viruses circulating in the
bloodstream, are kept at bay by highly specialized blood vessels. The
vessels' walls form a barrier that cannot be penetrated by the cells
or various other small particles, thus serving to protect the delicate
nerve cells.
There are, however, exceptions to the rule. In diseases such as
multiple sclerosis (MS), aggressive cells in the immune system manage
to break through the blood vessels' barrier. Having invaded the brain
tissue, these cells wreak havoc by triggering off inflammatory
reactions and attacking nerve cells. In Germany alone, the resulting
adverse effects afflict over 120,000 MS-patients.
Tracking down the culprits
Since there is normally a clear division between the blood circulatory
system and the central nervous system (i.e. brain plus spinal cord),
scientists were baffled as to how immune cells manage to cross the
blood-brain-barrier. This knowledge may aid in understanding the
origins of multiple sclerosis. In the 1980s, scientists were able to
prove conclusively that, under certain conditions, so called T-cells
can recognize and attack components of the body's own brain cells.
Thanks to tissue sections performed over the last few decades,
scientists now have much better knowledge of the migration of these
cells from their point of origin to their point of penetration into
the brain and the damage that they cause. However, actual observations
of such movements long remained impossible
Observing aggressive cells in action
Scientists at the Max Planck Institute of Neurobiology, the University
Medical Center Göttingen and their colleagues have now overcome this
impossibility. Using a two-photon microscope, the researchers
succeeded in tracing the movements of aggressive T-cells labelled with
the green fluorescent protein (GFP) in the living tissue of rats. The
systematic observation of these cells during the course of the disease
provided amazing new insights into the cell's behaviour.
The scientists discovered that the aggressive T-cells overcome the
barrier between blood and nerve tissue in a number of steps. Outside
the nervous system, the labelled cells moved just as we would expect
them to; most cells were floating along with the flow of the
bloodstream. Only now and again did a cell attach itself briefly onto
the vascular wall. Here they rolled in the direction of the blood
stream or were being carried off again by the current. Yet, once the
cells reached the blood vessels of the nervous system, they began to
act in a completely different manner. The scientists observed here far
more cells clinging to the vascular walls. "Things got really exciting
when we observed that the cells can actually crawl, a behaviour so far
unheard of for T-cells", Ingo Bartholomäus relates his observations.
Here, "crawling" describes an active cell movement, usually against
the flow of the bloodstream. The scientists watched T-cells as they
took anything between a few minutes and several hours to crawl along
the vessels' walls. At the end of such a search movement, the cells
were either swept away again by the bloodstream or they managed to
squeeze through the vascular wall.
Ominous encounters
Having successfully penetrated the blood-brain-barrier, the cells
continued their search in the vicinity of the blood vessels. It was
thus only a question of time before the T-cells encountered one of the
phagocytic cells abundant on the outer linings of blood vessels and on
the surface of the nerve tissue. When a mobile T-cell came across such
a phagocyte, the two cells formed a closely connected pair. Some of
these pairs remained inseparable for several minutes.
Although the scientists already knew that T-cells must make contact
with phagocytes in order to become immune-activated, they were now
able to observe these interactions right where they happened, i.e. at
the blood-brain-barrier. And indeed, the T-cells did not launch their
attack on the nervous system by releasing their inflammatory
neurotransmitters until they had bonded with the phagocytes. As a
result of the T-cells' activation, more and more T-cells passed
through the vascular walls. "The activation of T-cells at the border
to the nerve tissue appears to be a decisive signal for the invasion
of the immune cells", concludes Alexander Flügel, supervisor of the
study and director of the Department of Experimental and Clinical
Neuroimmunology at the University Medical Center Göttingen and Head of
the MS Hertie-Institute.
Light bulb moments
Thanks to their sophisticated observation methods, the scientists also
established that some of the antibodies already being used in MS-
therapy cause the crawling cells to disappear. As Ingo Bartholomäus
explains "Up to now, it was only known that these antibodies prevented
the T-cells' escaping from the blood vessels, but as our observations
now show, they actually prevent them from crawling".
Thanks to the scientists' observations, we now have a much clearer
picture of how the immune cells move and obtain access to the nervous
system. This knowledge is likely to also increase our knowledge of the
immune system's security system functions in healthy tissue. However,
as is often the case, new insights and information also give rise to
many new questions. How do the immune cells manage to cling to the
lining of the blood vessels and how do they recognize the weak spots,
where they can slip through the barrier between the bloodstream and
the nervous system? What governs the cells once they have surmounted
the blood-brain-barrier? These are some of the questions the
scientists will be addressing next. The long-term goal will be to
develop new forms of therapy and medication for multiple sclerosis and
other diseases.
Original work
Ingo Bartholomäus*, Naoto Kawakami*, Francesca Odoardi, Christian
Schläger, Djordje Miljkovic, Joachim W. Ellwart, Wolfgang EF Klinkert,
Cassandra Flügel-Koch, Thomas B. Issekutz, Hartmut Wekerle, Alexander
Flügel [*equal contribution] Effector T cell interactions with
meningeal vascular structures in nascent autoimmune CNS lesions
Source: Dr. Stefanie Merker
Max-Planck-Gesellschaft
--------------------------------------------------------------------------------
Article URL: http://www.medicalnewstoday.com/articles/170153.php
D_Frum...@ndersnat.ch
> Article URL: http://www.medicalnewstoday.com/articles/170153.php
Very, VERY impressive article. I remember just a couple of weeks ago
on this NG that someone said there was no proof that MS was caused by
T-cells attacking myelin. I responded that no, I had never personally
watched the cells penetrate the blood-brain barrier and attack through a
microscope, but it seemed to be the scientific consensus that they did.
This makes me wonder how trials of fingolimod are coming. It's
supposed to strengthen the BBB.
Bill
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| With enough education and brains the average man would make |
| a good lawyer - and so would the average lawyer. |
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evilzona
duhhhhh
HappyPoet
> duhhhhh
Does evilzona ever offer posts above the junior high school level?
Perhaps I'm being too harsh; after all, MS could have damaged his
brain to this extent.
~HappyPoet
evilzona
> On Sat, 14 Nov 2009 10:14:06 -0800 (PST), HappyPoet
>
> I have him in my twit filter. Never see the buffoon's useless
> responses that way.
>
> I wonder where Tee has gone, I liked her.
lol, but the dumass sees my replies anyway when other dumasses like
poet reply.
like I said, duhhhhhhh..
evilzona
> I wonder where Tee has gone, I liked her.
speaking of duhhhhh!
evilzona
oh, and hey poet.
all these wonderful posts by tickwad,
and who do you reply to?
...nice!
Tee
I'm here. We are in the middle of a major remodel of our kitchen. What a
mess! I've learned all about putting drywall plaster on new drywall and how
to sand it all back down. I've also been schooled in painting 101! I don't
like any of those courses! LOL
I sit a lot and I take a lot of breaks, so it takes me a lot longer to get
stuff done than it would an able bodied person, but I feel good (albeit
tired) in what I've accomplished. We had the new floor laid last week and
new cabinets are due in the week of Nov. 30 with counter tops to follow soon
after. I really hope to have everything done (except of course all the trim
work and new ceiling) by Christmas. The bathroom is done except for putting
the new vanity in.. maybe tonight.. along with getting the new stove and
fridge back into the kitchen.
We had to enlarge the kitchen so I can get around in my wheelchair (when I
have to use it) the old kitchen was a small U-shape and I tore up more
appliances trying to turn around in there in my chair! I'm not in it very
often as of late, (thank goodness) but when I am, this new layout will be so
much easier to get in and do what I love to do... COOK! :)
I hope everyone here is doing well!
Tee :)
"Peter Black" <no...@none.us> wrote in message
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Tee
"HappyPoet" <pal...@gmail.com> wrote in message
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evilzona
> No. Never.
>
> "HappyPoet" <pali...@gmail.com> wrote in message
Tee
Oh and I see you learned a new word.
Finally.
"evilzona" <davei...@gmail.com> wrote in message
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