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An Attack on Self Tissues
hen the immune system mistakes self tissues
for nonself and mounts an inappropriate
attack, the result is an autoimmune disease.
|There are many different autoimmune
diseases. Some examples are Wegener's
granulomatosis, multiple sclerosis, type 1
diabetes mellitus, and rheumatoid arthritis.
Autoimmune diseases can each affect the
body in different ways. For instance, the
autoimmune reaction is directed against the
brain in multiple sclerosis and the gut in
Crohn's disease. In other diseases, such as
systemic lupus erythematosus (lupus),
affected tissues and organs may vary among
individuals with the same disease.
Many autoimmune diseases are rare. As a
group, however, they afflict millions of
Americans. Most autoimmune diseases strike
women more often than men, particularly
affecting women of working age and during
their childbearing years.
FIGURE 1. Cells of
the immune system potentially involved in demyelination. APCs can
take up Antigen or Ag from a foreign source (such as an invading pathogen) or
from self-tissue (myelin or oligodendrocyte proteins)
|(no. 1). Ag is
processed into peptides, which are loaded onto MHCs and presented to
T cells via the TCR
(no. 2). Activated cytolytic T cells (Tc,
activated by MHC class I on APCs) cause damage by direct lysis of
(no. 3). Th cells (activated by MHC class II) release
inflammatory cytokines that are directly damaging to tissue and also
activate monocytes/macrophages (Mϕ)
(no. 4). T cells may be specific
for self-tissue (direct damage), specific for a tissue-resident
pathogen (bystander damage), or cross-reactive with pathogen and
self-epitopes (molecular mimicry). Surface Ag (foreign or self) is
recognized by B cells via the BCR
(no. 5). Upon receiving T cell
help (no. 6), the B cell secretes Abs specific for self or dual
specific for foreign and self-epitopes (molecular mimicry)
The binding of Ab to tissue may interfere with biological function
(no. 8). Abs can also simultaneously bind to and activate Mϕ via its
FcR (Fc), which mediate tissue damage
(no. 9). Damaged tissue
releases self-Ag, including new Ags not involved in the initial
(no. 10), which are taken up by APCs (epitope spread)
(no. 11). This further propagates the self-reactive immune response
and leads to additional tissue damage.
The immune system
is a complex network of specialized cells and organs. When it
malfunctions, it can cause a wide array of problems. Scientists are
making great strides in detecting, treating, and preventing
disorders of the immune system.
Inappropriate Immune Responses
some people, a usually harmless substance
such as a food, pollen or animal dander
provokes the inappropriate immune response
known as allergy.
In 1967 a husband and wife team of NIAID-supported
scientists discovered the IgE antibody that
causes most allergic reactions.
people produce small amounts of this
antibody, but allergy sufferers produce vast
quantities as a reaction to allergens.
IgE antibodies bind to two types of cells,
basophils (circulating in blood) and mast
cells, that are plentiful in the lungs,
skin, tongue, and linings of the nose and
intestinal tract. These cells then release
histamines and other chemicals that cause
When the susceptible person encounters
the same allergen again, it attaches to the
IgE antibodies already bound to basophils
and mast cells, starting the same chain
Anatomy of an allergic reaction
Inner-City Asthma Study
In 1997, a large NIAID-supported
study documented that a combination of
cockroach allergy and exposure to insects is
a major cause of asthma-related illness and
hospitalizations among inner-city children.
|Scientists with NIAID's
National Cooperative Inner-City Asthma Study
looked at 476 children living in the New
York City area. Most were either African
American (78%) or Hispanic (16%). The
researchers measured levels of cockroach,
dust mite, and cat allergens in the
children's homes. They also tested the
children for allergies to these substances
and assessed the severity of the children's
asthma over the previous 12 months.
Their discovery: children who were
both allergic to cockroaches and exposed to
high levels of cockroach allergens were
hospitalized for asthma 3.3 times more often
than children who had only one of these two
risk factors. In contrast, neither dust mite
nor cat allergens was so closely associated
with more severe asthma.
Little boy with "spacer" bag
As part of the Inner City
Asthma Project, this little boy is
using a "spacer," a device that can
be added on to an inhaler.
A spacer allows for greater
dispersion of the aerosol medication
that's expelled from the inhaler.
|The study's findings will
aid efforts to prevent and treat asthma in
high-risk populations. That is an important
public health goal--asthma-related deaths
rose 118% from 1980 to 1993 among Americans
younger than age 25.
message from God.