Dec. 18, 2006 — What causes autoimmune
diseases?
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Response
by Jatin Vyas
Visiting scientist |
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Autoimmunity is when a person’s immune system
attacks the body for no apparent reason. We do not know
why this happens in the first place, but we do have
some hints.
To understand autoimmunity, it is important to review
the components of a typical immune response. The goal
of the immune system is to protect the host from invasive
microorganisms. When a microorganism breaches one of
our natural defenses (i.e., skin, mucosal surfaces,
etc.), these bugs encounter the first wave of the immune
cells such as neutrophils and macrophages. These cells
promote inflammation, alert other cells of the immune
system of the impending danger and promote migration
of other cells.
While the initial responders depend on pattern recognition
to initiate their response, a more specific amplified
response is required to control infection and establish
long-lasting immunity. This task is performed by B cells
and T cells (collectively termed lymphocytes), which
originate in the bone marrow. Both cell types generate
specific receptors to identify these invading microorganisms.
Our ability to ward off the same infection in the future
requires the T and B cells to remember the initial infection.
Before lymphocytes join the fight against infection,
they must first learn the difference between self and
non-self. Many T and B cells fail to meet the body’s
quality standards and are destroyed before being released
into the circulation. Despite this rigorous method,
some auto-reactive lymphocytes do escape into the periphery.
These cells recognize tissue in the host as “foreign,”
leading to eventual destruction of normal tissue.
In addition to genetic factors, many scientists believe
that environmental factors, including some infectious
agents, may trigger auto-reactive lymphocytes to initiate
an autoimmune response. Unfortunately, in many cases,
patients do not come to clinical attention until the
autoimmune destruction is nearly complete, resulting
in the failure of a key organ. An example of this process
is diabetes mellitus type I (or juvenile diabetes).
In this case, autoreactive T lymphocytes destroy the
insulin-producing cells of the pancreas.
Why don't autoimmune diseases occur more often?
Despite the body’s rigorous destruction of auto-reactive
lymphocytes, some of these cells do escape into the
periphery. How are they controlled?
Emerging evidence points to a subset of T cells that
are thought to play a regulatory role in the immune
response. These cells are similar to military police
(MPs), keeping auto-reactive lymphocytes under control
through signals that they send. In this manner, auto-reactive
lymphocytes do not harm the host.
If the T cells are defective, then the auto-reactive
lymphocytes are allowed to destroy the tissues within
the host. If additional research elucidates the precise
role of the T cells, understanding the rules that govern
their function may yield new avenues of therapeutics
in a collection of diseases that share similar mechanisms.
While it remains unclear as to why only certain individuals
develop autoimmune diseases, many scientists favor the
hypothesis that environmental factors in genetically-susceptible
individuals trigger these responses.
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