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A Biomedical Research Institute update for patients and families - who are part of discoveries in the making
Winter 2011
A Breakthrough in Understanding the Immune System
When we think of the relationship between a healthy immune system and the
skin, we often think of white blood cells
whizzing through the bloodstream to fight
off an infection that is trying to penetrate
the body’s surface. This conventional way
of thinking was also widely accepted by
the scientific community, who believed
the bloodstream was the most important
source of T cells, which are white blood
cells capable of fighting infection. However,
thanks to research at BWH, there has been
a dramatic shift in how researchers believe
a healthy immune system protects the skin
– a breakthrough that has the potential to
change the way doctors treat and cure disease.
Research led by Rachael Clark, MD,
PhD, and Thomas Kupper, MD, revealed
that the skin of a healthy person contains
approximately 20 billion T cells – two times
the number found in the entire circulating
blood volume. After this startling discovery, Drs. Clark and Kupper investigated why
there were so many T cells in the skin and
how this knowledge might be useful for
treating skin cancers and other diseases.
The researchers found that T cells do
not simply travel through the bloodstream
to the skin, fight an infection and then go
away. Instead, T cells fight off the infection
and then remain in the skin long term, perhaps even for a lifetime. These T cells then
rapidly and effectively protect the skin
when the same infection is encountered in
the future. In this way, the skin accumulates
a protective, immune memory. In other
words, every time you get an infection, the
researchers state, you vaccinate yourself
against that infection.
This new knowledge is helping researchers to improve vaccines and develop
more effective treatments for cancer. By
immunizing through the skin and tailoring
cancer therapies to generate long lived, resident T cells, we can teach skin how to fight
off infections and cancers. This should result in life-long protection for the skin from
these challenges. Although Dr. Clark’s and
Dr. Kupper’s work focuses on the skin, similar resident T cells are now being discovered in the lung and gastrointestinal tract.
Because the skin is an accessible tissue in
which to study human immune responses,
the work of Drs. Clark and Kupper is leading
the way in understanding and improving
the body’s ability to fight off infections and
cancers.
For more information, see Dr. Clark’s
review of skin resident T cells at: http://
www.ncbi.nlm.nih.gov/pmc/ar ticles/
PMC2922675/.
A blood vessel from normal human skin stained for
the T cell marker CD3 (red) and the immunosuppressive regulatory T cell marker FOXP3 (green). This image demonstrates that normal human skin contains
a large number of T cells that can fight off infections
(red cells without a green center) and a large number of regulatory T cells (red cells with a green center) that prevent autoimmunity.
Researchers Study Chronic Inflammation’s Role in IBD and Colon Cancer
Though not something many of us care to visualize, the human body is covered with
an astonishing number and variety of microorganisms. Some of these bacteria are neither
beneficial nor harmful, while others perform tasks that are useful to the body. The digestive
tract has a particularly large community of bacteria, which communicate with the immune
system to ward off infection and keep us healthy.
Researchers have found, however, that this interaction between bacteria and the immune system is not always peaceful. In some individuals, the immune system’s reaction to
bacteria in the digestive tract results in chronic gut inflammation, manifesting in conditions
such as inflammatory bowel disease (IBD) and colon cancer.
Research led by Wendy Garrett, MD, PhD, is looking into how this gut-to-immune system communication takes place, as well as what causes the communication to break down
and lead to chronic inflammation and disease. Such questions are critical, since IBD affects
(Chronic Inflammation, cont. on back)
www.brighamandwomens.org/research/briefs/
Chronic Inflammation (cont.)
1.4 million people in the US in the form of
Crohn’s disease and ulcerative colitis. In
addition, research shows that having IBD
increases your risk for developing colon cancer.
So far, Dr. Garrett and her lab have
found that there are different communities
of bacteria within the guts of healthy mice
and those sick with IBD. Furthermore, the researchers have determined that two bacte-
ria in particular, which were present only in
the sick mice, appear to instigate the chronic, digestive-tract inflammation associated
with IBD and colon cancer.
Why these bacteria exist only in sick
mice, how they got there and how they
work against the body’s immune system are
all questions Dr. Garrett and her team hope
to answer. Her lab is also focused on understanding how gut bacteria may influence
the development of colon cancer. By studying the communities of bacteria in the gut
and their interactions with the immune system, Dr. Garrett is hopeful that her research
team and others can eventually find ways to
prevent and treat IBD and colon cancer.
For more information about the Garrett
Lab, visit www.hsph.harvard.edu/garrettlab/.
Research Literacy
Acute inflammation: A normal, short-term immune
Inflammation: Occurs normally when the body’s white
Autoimmune disease: A type of inflammatory disorder
Inflammatory Bowel Disease (IBD): A condition in
response that typically appears within a few minutes or hours
after an injury. It is characterized by PRISH: pain, redness, immobility (or loss of function), swelling and heat.
that results from an overactive immune system and is characterized by chronic inflammation. Here, the body’s immune
system triggers an immune response even though no bacteria
or viruses are present, inappropriately attacking the body’s
own tissue and causing damage to this tissue.
Colon: The last part of the digestive system in humans. Al-
though it does not play a major role in the absorption of foods
and nutrients, the colon extracts water and salt from solid
waste and absorbs potassium and some fat soluble vitamins.
Gut: Also known as the bowel, the gut consists of the small
and large intestines. It extends from the stomach to the anus.
blood cells release inflammatory chemicals into the blood (i.e.
when the body elicits an immune response) to protect the
body from infection and foreign substances.
which the large or small intestine becomes irritated and/or
infected.
Immune system: The body’s defense system or protection
against infection and foreign substances (also called antigens)
such as bacteria and viruses. It allows the body to heal from
wounds and infection.
T cells: A type of white blood cell that plays a central role in
cell-mediated immunity. Also known as T lymphocytes, T cells
have special receptors (CD3) on their cell surface. The abbreviation T, in T cell, stands for thymus, since this is the principal
organ responsible for the maturation of T cells.
Be Part of Discoveries in the Making
Predictive, proactive, and preventive. The physicians and scientists at the Biomedical Research Institute (BRI) approach disease
where it starts – at the cellular and molecular level. With a foundation of excellent clinical care, the BRI is discovering new ways to understand and treat illness. For more than a decade, BWH has ranked
second in National Institutes of Health funding for independent hospitals. Our
success is measured by the size and scope of our research portfolio, the dedication of our faculty and staff, and the support of our patients and families.
You can join others and be part of discoveries in the making by supporting BWH research in one of several ways: sign up to receive BRIefs each season
([email protected]), make a gift through the Development Office (https://
giving.brighamandwomens.org/BRI), or volunteer to participate in a clinical trial
(http://clinicaltrials.partners.org).
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