Scientists have learned a great deal about MS in
recent years; still, its cause remains elusive. Many
investigators believe MS to be an autoimmune
disease-one in which the body, through its
immune system, launches a defensive attack against
its own tissues. In the case of MS, it is the nerve-insulating
myelin that comes under assault. Such assaults may
be linked to an unknown environmental trigger,
perhaps a virus.
To understand what is happening when a person has
MS, it is first necessary to know a little about how
the healthy immune system works. The immune system -
a complex network of specialized cells and organs -
defends the body against attacks by "foreign"
invaders such as bacteria, viruses, fungi, and
parasites. It does this by seeking out and
destroying the interlopers as they enter the body.
Substances capable of triggering an immune response
are called antigens.
The immune system displays both enormous
diversity and extraordinary specificity. It can
recognize millions of distinctive foreign molecules
and produce its own molecules and cells to match up
with and counteract each of them. In order to have
room for enough cells to match the millions of
possible foreign invaders, the immune system stores
just a few cells for each specific antigen. When an
antigen appears, those few specifically matched
cells are stimulated to multiply into a full-scale
army. Later, to prevent this army from overexpanding,
powerful mechanisms to suppress the immune response
come into play.
T cells, so named because they are
processed in the thymus, appear to play a
particularly important role in MS. They travel
widely and continuously throughout the body
patrolling for foreign invaders. In order to
recognize and respond to each specific antigen, each
T cell's surface carries special receptor
molecules for particular antigens.
T cells contribute to the body's defenses in two
major ways. Regulatory T cells help orchestrate the
elaborate immune system. For instance, they assist
other cells to make antibodies, proteins
programmed to match one specific antigen much as a
key matches a lock. Antibodies typically interact
with circulating antigens, such as bacteria, but are
unable to penetrate living cells. Chief among the
regulatory T cells are those known as helper (or
inducer) cells. Helper T cells are essential for
activating the body's defenses against foreign
substances. Yet another subset of regulatory T cells
acts to turn off, or suppress, various immune system
cells when their job is done.
Killer T cells, on the other hand, directly
attack diseased or damaged body cells by binding to
them and bombarding them with lethal chemicals
called cytokines. Since T cells can attack
cells directly, they must be able to discriminate
between "self" cells (those of the body) and
"nonself" cells (foreign invaders). To enable the
immune system to distinguish the self, each body
cell carries identifying molecules on its surface. T
cells likely to react against the self are usually
eliminated before leaving the thymus; the remaining
T cells recognize the molecular markers and coexist
peaceably with body tissues in a state of
self-tolerance.
In autoimmune diseases such as MS, the detente
between the immune system and the body is disrupted
when the immune system seems to wrongly identify
self as nonself and declares war on the part of the
body (myelin) it no longer recognizes. Through
intensive research efforts, scientists are
unraveling the complex secrets of the malfunctioning
immune system of patients with MS.
Components of myelin such as myelin basic
protein have been the focus of much research
because, when injected into laboratory animals, they
can precipitate experimental allergic
encephalomyelitis (EAE), a chronic relapsing
brain and spinal cord disease that resembles MS. The
injected myelin probably stimulates the immune
system to produce anti-myelin T cells that attack
the animal's own myelin.
Investigators are also looking for abnormalities
or malfunctions in the blood/brain barrier, a
protective membrane that controls the passage of
substances from the blood into the central nervous
system. It is possible that, in MS, components of
the immune system get through the barrier and cause
nervous system damage.
Scientists have studied a number of infectious
agents (such as viruses) that have been suspected of
causing MS, but have been unable to implicate any
one particular agent. Viral infections are usually
accompanied by inflammation and the production of
gamma interferon, a naturally occurring body
chemical that has been shown to worsen the clinical
course of MS. It is possible that the immune
response to viral infections may themselves
precipitate an MS attack. There seems to be little
doubt that something in the environment is involved
in triggering MS.
In addition, increasing scientific evidence suggests
that genetics may play a role in determining a
person's susceptibility to MS. Some populations,
such as Gypsies, Eskimos, and Bantus, never get MS.
Native Indians of North and South America, the
Japanese, and other Asian peoples have very low
incidence rates. It is unclear whether this is due
mostly to genetic or environmental factors.
In the population at large, the chance of
developing MS is less than a tenth of one percent.
However, if one person in a family has MS, that
person's first-degree relatives-parents, children,
and siblings-have a one to three percent chance of
getting the disease.
For identical twins, the likelihood that the
second twin may develop MS if the first twin does is
about 30 percent; for fraternal twins (who do not
inherit identical gene pools), the likelihood is
closer to that for non-twin siblings, or about 4
percent. The fact that the rate for identical twins
both developing MS is significantly less than 100
percent suggests that the disease is not entirely
genetically controlled. Some (but definitely not all)
of this effect may be due to shared exposure to
something in the environment, or to the fact that
some people with MS lesions remain
essentially asymptomatic throughout their lives.
Further indications that more than one gene is
involved in MS susceptibility comes from studies of
families in which more than one member has MS.
Several research teams found that people with MS
inherit certain regions on individual genes more
frequently than people without MS. Of particular
interest is the human leukocyte antigen (HLA)
or major histocompatibility complex region on
chromosome 6. HLAs are genetically determined
proteins that influence the immune system.
The HLA patterns of MS patients tend to be
different from those of people without the disease.
Investigations in northern Europe and America have
detected three HLAs that are more prevalent in
people with MS than in the general population.
Studies of American MS patients have shown that
people with MS also tend to exhibit these HLAs in
combination-that is, they have more than one of the
three HLAs-more frequently than the rest of the
population. Furthermore, there is evidence that
different combinations of the HLAs may correspond to
variations in disease severity and progression.
Studies of families with multiple cases of MS and
research comparing genetic regions of humans to
those of mice with EAE suggest that another area
related to MS susceptibility may be located on
chromosome 5. Other regions on chromosomes 2, 3, 7,
11, 17, 19, and X have also been identified as
possibly containing genes involved in the
development of MS.
These studies strengthen the theory that MS is
the result of a number of factors rather than a
single gene or other agent. Development of MS is
likely to be influenced by the interactions of a
number of genes, each of which (individually) has
only a modest effect. Additional studies are needed
to specifically pinpoint which genes are involved,
determine their function, and learn how each gene's
interactions with other genes and with the
environment make an individual susceptible to MS. In
addition to leading to better ways to diagnose MS,
such studies should yield clues to the underlying
causes of MS and, eventually, to better treatments
or a way to prevent the disease.
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