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1. Understanding How Lymph Nodes Respond To Infection May Redefine

How Immune

System Functions

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Date: Fri, 21 Nov 2003 09:11:29 -0500

From: Irwin Mortman <Irwin@...>

Subject: Understanding How Lymph Nodes Respond To Infection May

Redefine How Immune System Functions

Posting of the following article has been approved by ScienceDaily -

http://www.sciencedaily.com/

Source: Duke University Medical Center

Date: 2003-11-21

URL: http://www.sciencedaily.com/releases/2003/11/031121072013.htm

Understanding How Lymph Nodes Respond To Infection May Redefine How

Immune System Functions

DURHAM, N.C. -- Duke University Medical Center researchers may have

solved the mystery of why lymph nodes swell when the body fights

infection. Their findings may redefine how the immune system

functions, they said.

Their research, published in the December 2003 issue of Nature

Immunology, centered on the role of mast cells. Mast cells are immune

cells that are typically found just under the skin and in the lining

of the intestine and lungs and were previously associated primarily

with the induction of allergic reactions. The Duke researchers report

that allergic reactions are only a side effect of mast cells' much

more important role as a regulator of the body's immune system.

" Mast cells serve as the command post for the immune system during

infections, " said Soman Abraham, Ph.D., professor of pathology,

associate professor of immunology and senior author of the paper.

" White blood cells are sequestered within these nodes and, following

proper activation, they can specifically target infectious agents and

aid the host in clearing unwanted pathogens. "

Abraham said the discovery that mast cells can initiate the

activation and swelling of nodes through release of specific

signaling molecules points to the possible use of mast cell products

for the development of vaccines designed to boost the potency of the

immune response.

" Mast cells have been much maligned because of their contribution to

many diseases including asthma, arthritis, Crohn's disease and

multiple sclerosis, " said Abraham. " Our research shows that mast

cells play an important role in immune surveillance and defense

against infectious agents. "

The human immune system comprises two components that protect it

against invading pathogens. The first line of defense is the innate

immune system, a quick-acting response triggered immediately when a

pathogen enters the body. The innate immune response responds the

same regardless of the pathogen and attacks the pathogen for the

first several days until the adaptive immune response can begin its

attack.

The adaptive immune system is tailored specifically to the pathogen

it is attacking. Once the immune system identifies an invader,

draining lymph nodes recruit infection-fighting T-cells within 24

hours. During the next week or so, the T-cells proliferate and induce

B-cells to produce antibodies specific to the invader. The result is

swollen lymph nodes, which are the first discernable sign that the

adaptive immune system is in effect.

Previous studies by Abraham showed that mast cells trigger the body's

innate immune system by releasing a molecule called tumor necrosis

factor (TNF) and recruiting infection-clearing cells called

neutrophils. However, the role of mast cells in the adaptive immune

system remained unknown.

To examine the role of mast cells in the adaptive immune system, the

Duke researchers studied the lymph nodes of mast cell-deficient mice.

When the scientists introduced bacteria into the animals, their lymph

nodes did not swell. However, when the mice were injected with mast

cells, their nodes did swell. Further, specific activation of mast

cells in the skin induced a rapid increase in TNF in the lymph nodes

and recruitment of T cells.

" We are showing that the mast cells are critically involved in both

the innate and adaptive immune systems, " said Abraham. " Both are

triggered with the release of TNF by the mast cells. The innate

immune system, through TNF and neutrophils, attack the pathogen

first, but within hours, TNF has reached the lymph nodes, triggering

the adaptive immune system. Infection fighting T-cells are recruited

and a specific attack on the pathogen begins. Within days, the body

is producing antibodies and fighting back. "

The involvement of mast cells in the adaptive response is a major

shift in the understanding of the immune system and its function,

said Salvatore Pizzo, M.D., Ph.D., chairman of the department of

pathology and a member of the research team.

" When you pick up a textbook two years from now that shows how the

immune system functions and the way a node responds to an infectious

agent, you are going to see a whole new pathway, " said Pizzo. " Mast

cells are much more than just bad actors making you feel sick when

you are exposed to noxious agents. They are actually major players

helping you deal with these noxious agents. "

" With a clearer understanding of the adaptive immune system and the

role of mast cells, comes the opportunity for new therapeutics that

could improve disease protection, " said Abraham.

" It's been known, particularly with allergy and asthma, that mast

cells are involved in immune dysfunction, " he said. " But their real

physiological role is triggering both the innate and adaptive immune

systems. Future research needs to focus on this role. We need to

continue to dissect the process and adapt some of it to improve

immunity and disease protection. "

The National Institutes of Health and the Sandler Foundation for

Asthma Research funded the research. Co-authors of the paper include

B. McLachlan; P. Hart, Ph.D.; P. Shelburne,

Ph.D.; Herman F. Staats, Ph.D.; and D. Gunn, M.D., all of

Duke University Medical Center.

This story has been adapted from a news release issued by Duke

University Medical Center.

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