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What is the antigen in heart disease?
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Taka
Aug 19, 2012, 9:02:57 PM8/19/12
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A vaccine for heart disease? La Jolla Institute discovery points up
this possibility
Researcher finds autoimmune response contributes to inflammation in
the artery wall
Most people probably know that heart disease remains the nation's No.
1 killer. But what many may be surprised to learn is that cholesterol
has a major accomplice in causing dangerous arterial plaque buildup
that can trigger a heart attack. The culprit? Inflammatory cells
produced by the immune system.
A number of research studies have demonstrated inflammation's role in
fueling plaque buildup, also known as atherosclerosis, which is the
underlying cause of most heart attacks and strokes, but knowledge of
which immune cells are key to this process has been limited – until
now.
Researchers at the La Jolla Institute for Allergy & Immunology have
identified the specific type of immune cells (CD4 T cells) that
orchestrate the inflammatory attack on the artery wall. Further, the
researchers discovered that these immune cells behave as if they have
previously seen the antigen that causes them to launch the attack.
"The thing that excites me most about this finding is that these
immune cells appear to have 'memory' of the molecule brought forth by
the antigen-presenting cells," said Klaus Ley, M.D., a renowned expert
in vascular immunology, who led the study in mouse models. "Immune
memory is the underlying basis of successful vaccines. This means that
conceptually it becomes possible to consider the development of a
vaccine for heart disease."
Dr. Ley said he believes the antigen involved is actually a normal
protein that the body mistakes as being foreign and therefore launches
an immune attack resulting in inflammation in the arteries.
"Essentially, we're saying that there appears to be a strong
autoimmune component in heart disease," he said, explaining that
autoimmune diseases result from the body's mistaken attack on normal
cells. "Consequently, we could explore creating a "tolerogenic"
vaccine, such as those now being explored in diabetes, which could
induce tolerance by the body of this self-protein to stop the
inflammatory attack."
The study was published online Monday in the Journal of Clinical
Investigation in a paper entitled "Dynamic T cell–APC interactions
sustain chronic inflammation in atherosclerosis."
Dr. Ley cautions that creating a vaccine is a complex process that
could take years to develop. However it offers exciting potential. "If
successful, a tolerogenic vaccine could stop the inflammation
component of heart disease," he said. "This could probably be used in
conjunction with the statins (cholesterol-lowering drugs) that have
already taken a significant chunk out of the numbers of people with
heart disease. Together, they could deliver a nice one-two punch that
could be important in further reducing heart disease."
Dr. Ley said antigen-presenting cells take up infectious organisms,
foreign materials and self-proteins (in the case of autoimmune
diseases) and "chop them into little pieces called epitopes" and then
display the pieces on the surface of the cell. "The T cell comes
along, and if it has the correct receptors, it will recognize the
epitope pieces and make cytokines (a type of immune system soldier
molecule) that attack the material and cause inflammation." Autoimmune
diseases include such illnesses as type 1 diabetes, rheumatoid
arthritis and multiple sclerosis.
In the study, Dr. Ley and his team used live cell imaging techniques
to track immune cells in normal and artherosclerotic mouse aortas. He
said in mice with atherosclerosis, there are a large number of antigen-
experienced T cells that have already seen certain epitope pieces
(from self proteins) that they perceive as foreign. "The T cells talk
to the antigen-presenting cells and, in response, make cytokines that
launch an attack. This is what makes the inflammation in the vessel
wall persistent." Inflammatory cells join fat and cholesterol to form
artery-clogging plaque that can eventually block blood flow, leading
to a heart attack.
"It wasn't previously known that antigen-experienced T cells existed
in the vessel wall," said Dr. Ley. "This experiment makes me now
believe that it may be possible to build a vaccine for heart disease."
SOURCE: http://www.eurekalert.org/pub_releases/2012-08/ljif-avf081412.php
this possibility
Researcher finds autoimmune response contributes to inflammation in
the artery wall
Most people probably know that heart disease remains the nation's No.
1 killer. But what many may be surprised to learn is that cholesterol
has a major accomplice in causing dangerous arterial plaque buildup
that can trigger a heart attack. The culprit? Inflammatory cells
produced by the immune system.
A number of research studies have demonstrated inflammation's role in
fueling plaque buildup, also known as atherosclerosis, which is the
underlying cause of most heart attacks and strokes, but knowledge of
which immune cells are key to this process has been limited – until
now.
Researchers at the La Jolla Institute for Allergy & Immunology have
identified the specific type of immune cells (CD4 T cells) that
orchestrate the inflammatory attack on the artery wall. Further, the
researchers discovered that these immune cells behave as if they have
previously seen the antigen that causes them to launch the attack.
"The thing that excites me most about this finding is that these
immune cells appear to have 'memory' of the molecule brought forth by
the antigen-presenting cells," said Klaus Ley, M.D., a renowned expert
in vascular immunology, who led the study in mouse models. "Immune
memory is the underlying basis of successful vaccines. This means that
conceptually it becomes possible to consider the development of a
vaccine for heart disease."
Dr. Ley said he believes the antigen involved is actually a normal
protein that the body mistakes as being foreign and therefore launches
an immune attack resulting in inflammation in the arteries.
"Essentially, we're saying that there appears to be a strong
autoimmune component in heart disease," he said, explaining that
autoimmune diseases result from the body's mistaken attack on normal
cells. "Consequently, we could explore creating a "tolerogenic"
vaccine, such as those now being explored in diabetes, which could
induce tolerance by the body of this self-protein to stop the
inflammatory attack."
The study was published online Monday in the Journal of Clinical
Investigation in a paper entitled "Dynamic T cell–APC interactions
sustain chronic inflammation in atherosclerosis."
Dr. Ley cautions that creating a vaccine is a complex process that
could take years to develop. However it offers exciting potential. "If
successful, a tolerogenic vaccine could stop the inflammation
component of heart disease," he said. "This could probably be used in
conjunction with the statins (cholesterol-lowering drugs) that have
already taken a significant chunk out of the numbers of people with
heart disease. Together, they could deliver a nice one-two punch that
could be important in further reducing heart disease."
Dr. Ley said antigen-presenting cells take up infectious organisms,
foreign materials and self-proteins (in the case of autoimmune
diseases) and "chop them into little pieces called epitopes" and then
display the pieces on the surface of the cell. "The T cell comes
along, and if it has the correct receptors, it will recognize the
epitope pieces and make cytokines (a type of immune system soldier
molecule) that attack the material and cause inflammation." Autoimmune
diseases include such illnesses as type 1 diabetes, rheumatoid
arthritis and multiple sclerosis.
In the study, Dr. Ley and his team used live cell imaging techniques
to track immune cells in normal and artherosclerotic mouse aortas. He
said in mice with atherosclerosis, there are a large number of antigen-
experienced T cells that have already seen certain epitope pieces
(from self proteins) that they perceive as foreign. "The T cells talk
to the antigen-presenting cells and, in response, make cytokines that
launch an attack. This is what makes the inflammation in the vessel
wall persistent." Inflammatory cells join fat and cholesterol to form
artery-clogging plaque that can eventually block blood flow, leading
to a heart attack.
"It wasn't previously known that antigen-experienced T cells existed
in the vessel wall," said Dr. Ley. "This experiment makes me now
believe that it may be possible to build a vaccine for heart disease."
SOURCE: http://www.eurekalert.org/pub_releases/2012-08/ljif-avf081412.php
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