Subject: Interesting Info on how Beta Interferon works

From: [email-masked] (STramp)
Date: 16 Jan 1997 03:14:48 GMT

Pardon posting this twice, but my first subject looked like I was asking a
question, not answering one...

I found the following passage in a wonderful mass market science book
titled "The Edge of the Unknown: 101 Things you don't know about Science
and no one else does either" by James Trefil. Great book, can't say enough
good things about it. On of the chapters is the question "Why Doesn't Your
Immune System Attack Your Own Cells?" It goes into MS and what it does
with a good description of how the beta interferon drugs (Betaseron and
Avonex) work. There is also some info on forthcoming research. I know when
my wife first started taking Avonex we both wanted to know what it was
doing. We found this information very enlightening and helpful. I hope
everyone else feels the same. Sorry about any copywrite violations, but
I'm sure the people at Houghton Mifflin are cool. If not, well, sorry
guys. (Everyone should buy the book anyway, it is really great) I quote
directly from the book from here on. 

"The Immune System is designed to protect us from all manner of foreign
invaders. To do its job, it produces a wide variety of cells, the most
important being B and T cells (the letters stand for bone marrow and
thymus, respectively, where the cells are made). These cells have
structures called receptors on their outer surfaces that act as keys that
fit locks on molucules of invading organisms. It is this molecular
recognition that is the central event in the immune response.
Under normal circumstances, every cell in the body sports bits of protein
on its surface, carried there by other specialized molecules. These
displayed proteins play the same role in the body as a password does in
the military. Passing T cells sense these proteins and leave the cell
alone. We say the T cell ³recognizes self.² Autoimmune diseases like
multiple sclerosis and rheumatoid arthritis occur when something goes
wrong with the password recognition system and the immune system starts to
attack healthy tissue.
One of the great problems in immunology has been to understand exactly how
the immune system recognizes self -- why it will attack cells in a
transplanted liver, for example, but leave the patient¹s own liver alone.
The immune system generates billions of different receptors, and the
immune response is triggerd when one of them fits an invader molecule.
This diversity of molecular keys is produced by a basically random mixing
of bits of protein, so it is extremely unlikely that your immune system
would produce no T cells that could attack your cells. However, the system
tests the T cells before they are released from the thymus into the body.
Because the thymus is replete with self cells, any T cell that sports a
key for your cell¹s lock will inevitably bind to a nearby cell. If this
happens, the T cell stops growing and eventually dies. Thus the only
mature T cells that emerge from the thymus are those that do not react
with self cells.
We do not know in detail why T and B cells that have been selected for
their ability to ignore self cells suddenly start to attack them. One
popular theory is that viruses trying to gain entry present to the immune
system molecules that mimic those of the host¹s body. This process could
prime the system to attack any cells bearing similar molecules, even self
cells.
As is so often the case in modern medicine, dealing with autoimmune
diseases requires a detailed understanding of what is happening at the
molecular level. In Multiple Sclerosis, for example, B and T cells attack
the sheathing that surrounds nerve cells in the brain and spinal cord.
First one set of molecules on the membranes of T cells sticks to
corresponding molecules in the walls of blood vessels, triggering the
production of proteins that create a small hole in the vessel wall. This
allows the T cells to get through the vessel wall and into the brain.
There they encounter triggering molecules on the surface of nerve cells
and innitiate the immune response. The net effect is that the other cells
from the immune system, as well as the T cells themselves, cooperate to
destroy the sheathing around major nerve cells.
Understanding the basic process involved in MS as the molecular level has
allowed scientists to begin to develope a multipronged attack on the
disease. The basic idea is to take each step in the chain of events
outlined above and find a molecule that will block it. One technique is to
use drugs that block the processes that bring bits of protein to the
surface of the nerve cells. In fact, the first approved therapy for MS (in
1993) involved the use of a drug called beta interferon, which prevents
production of the molecules that carry the proteins. Without the carriers,
there are no proteins for the T cell to recognize on the cell surface, and
the disease is blocked. 
Other strategies, now under development, would block the disease process
at other points. For example, scientists are working to develope decoy
molecules that would lock to the molecules that normally bring proteins to
the cell surface, preventing those molecules from displaying self proteins
that would trigger T cells. Another strategy involves finding molecules
that will prevent T Cells from sticking to the walls of blood vessels by
making molecules that occupy the ³sticky spots² on the T Cells or on the
vessel walls. Think of this strategy as covering up Velcro patches on the
T cell or the blood vessel -- patches that would otherwise stick to each
other. Finally, we can try to develop antibodies that will attack some of
the molecules that actually damage the nerve sheathing.
This long list of possibilities illustrates the way medicine is likely to
proceed in the future. First we will understand the basic molecular
workings of the disease process, then find molecular strategies for
blocking it. I¹ve concentrated on MS here, but I expect to see this
strategy adopted across the board in the future."