NEWS: Chronic infections may create autoimmune response

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Chronic infections may create autoimmune response

By Rice University

Sep 13, 2005, 04:58

New research finds the human immune system has foregone evolutionary

changes that would allow it to produce better antibodies in less time

because the improved antibodies would be far more likely to attack

the body's own tissues. The Rice University study finds the immune

system has evolved a near-perfect balance for producing antibodies

that are both effective against pathogens and unlikely to cause

autoimmune disease.

The findings will be published in the journal Physical Review

Letters. They are based on a new model of the immune system that is

the first to simulate the hierarchical nature of the body's immune

response. The model predicts that chronic infections may lead to

autoimmune diseases, a scenario that has been proposed as a cause of

some rheumatic diseases like arthritis.

" There are as many as a 100 million unique antibodies circulating

through our bodies at any given time, but just three or four of these

might be effective against any particular disease, " said

Deem, the W. Professor in Biochemical and Genetic

Engineering and professor of physics and astronomy. " When we get

sick, the immune system identifies the particular antibodies that are

effective, as it rapidly creates and mass produces mutant white blood

cells called B cells that make only these antibodies. "

Deem said prior research has identified a number of alternate

strategies the immune system could use to reduce the time needed to

create an effective B cell. In addition, these methods also could

produce antibodies that are more apt to bind with disease cells. The

upshot would be an immune system that responds faster and more

effectively against disease.

" This should help us get well faster, so the question becomes, 'Why

didn't we evolve that kind of adaptive response?' " Deem said.

Deem's analysis falls within a branch of physics called statistical

mechanics, which uses a system's physical behavior at the molecular

or atomic scale to build up a picture of the behavior at a larger

level. In this case, Deem and postdoctoral researchers Jun Sun and

J. Earl studied the physical properties of fragments of DNA to

determine the origins, behavior, and generation of antibodies.

Generating antibodies is one of the primary functions of the immune

system. Antibodies are protein molecules that are made by B cells.

Each antibody has a chemical signature that allows it to bind only

with a particular sequence of amino acids.

" In our study, we first sought to understand the evolutionary rules

that govern the way the immune system responds to an infection, " Deem

said. " With that framework in place, we identified a biologically-

plausible strategy that would allow the immune system to react more

quickly and with more effective antibodies. Our analysis revealed

that such a system would be about 1,000 times more likely to produce

antibodies that attack healthy tissues. "

Antibodies that bind with something other than the antigen they

evolved to attack are called cross-reactive, and some researchers

believe cross-reactivity causes some autoimmune diseases.

For example, some scientists have found a correlation between chronic

infection and an increased probability of autoimmune disease, but the

strength and significance of the correlation is controversial. Rice's

model suggests that a correlation does exist, but that the length of

the infection prior to onset of autoimmune disease is highly variable.

" People have been looking for a clear, significant correlation in

time, but a long distribution of onset times would lead to weaker

statistical correlations, particularly in those cases where the

infection persisted the longest, " said Deem. " Searching for this

distribution in health and medical statistics could shed light on

this immunological puzzle and settle the scientific controversy. "

The Rice analysis finds the human immune system evolved to minimize

the risk of cross-reactivity. For example, each cell in our bodies

contains about 100,000 proteins with an average of 500 amino acids

apiece. Consequently, there are about one trillion potential docking

sites, or epitopes, where antibodies could mistakenly attach

themselves to proteins in a healthy cell. The mutation response

method employed by our adaptive immune system seems keyed to this

number, producing antibodies that are statistically likely to

mistakenly bond with healthy proteins slightly less than one in a

trillion times, meaning that on average, they recognize only invading

pathogens.

http://www.rxpgnews.com/research/immunology/autoimmunediseases/

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