Momtezuma Tuatara
01-10-09, 05:18 AM
http://www.rice.edu/sallyport/2003/fall/sallyport/flu.html
Will a Flu Shot This Year Make You More Susceptible Next Year?
Michael Deem was getting a flu shot a few years ago when the nurse warned him that he would be at greater risk for getting the flu the following winter if he failed to get next year’s flu shot.
http://www.rice.edu/sallyport/2003/fall/photos/pg5_needle.jpg
The offhand comment piqued Deem’s curiosity. An expert in molecular and computational biology, he couldn’t reconcile the nurse’s comment with what he knew about the human immune system. He knew that the effects from vaccination last for years. In addition, there were classic studies in immunology that proved that repeated vaccination did not confer greater immunity.
“I asked my doctor about it, and of course, he knew nothing,” Deem says. “So I asked the head of immunology at UCLA, and she told me there was no reason for that to be true.”
http://www.rice.edu/sallyport/2003/fall/photos/pg5_FluShot.jpg
More curious than ever, Deem, who is the John W. Cox Professor of Bioengineering, undertook his own study of the literature and found what he was looking for—a phenomenon known as “original antigenic sin.” Though little-known, the phenomenon turned out to be well-documented, not just in influenza but for a few other viruses, such as dengue fever and AIDS.
The precise reasons why people need regular vaccinations against some viruses, like the flu, and not against others, like polio, are related to two different factors: how fast the viruses mutate and the way the immune system recognizes and targets the invading organisms, known as antigens.
It is the job of antibodies—proteins produced in white blood cells—to recognize antigens and either kill the invaders themselves by binding to them or by recruiting other immune cells to help destroy the antigens. White blood cells don’t know the biochemical signature of each invader ahead of time, so they compensate with volume and diversity. At any given time, there are about 100 million antibodies in the human system, Deem says. A significant portion of these are created using random segments of DNA so that they can recognize different antigens, even those that the immune system has never encountered.
But the immune system pays particular attention to diseases it has fought before and maintains antibodies for those at about 100 times higher concentration than the randomly created varieties. That’s why vaccination works: It prepares the immune system to attack specific antigens by activating this recognition system, allowing the body to maintain a high level of antibodies against a specific disease it’s never actually contracted.
Original antigenic sin occurs when it would be more advantageous for the body to rely on its randomly created antibodies than on the more numerous “remembered” varieties. Take a fast-mutating virus like the flu, for example. It has several distinct areas where antibodies can bind, but each year, those may change.
If a person has four antibodies that worked against one variety of flu, and he or she contracts another variety that has only two similar binding areas, then his or her immune system will be predisposed to make antibodies against only the two sites the varieties have in common. Moreover, immune systems will never learn to recognize the two new binding signatures that are present on the new strain, choosing instead to go with what worked in prior cases. Over time, as the disease mutates more and more and has progressively less in common with the original “remembered” variety, antibodies become ill-prepared to recognize it.
A computational model developed in Deem’s lab to demonstrate exactly how original antigenic sin operates indicates that it is a systemic problem that persists even if the model is adjusted so that the binding regions on the antigen are smaller and even when the body is given more time to recognize the disease. “Because the system tends to go with what worked before, we end up with a localization and a reduction in diversity,” Deem explains. In effect, the system forgoes whole classes of random combinations that might actually work against the new mutant in favor of tried-and-true varieties that will not.
Deem says the findings from the research could prove helpful to vaccine designers and to those studying public health. Also, the methodology used to study the system might also be applicable in other disciplines, such as ecology, where researchers are attempting to study the long-term consequences of reduction in diversity of species.
What it means for those of you who have been getting flu shots in the past is that there is good reason to keep them up.
Will a Flu Shot This Year Make You More Susceptible Next Year?
Michael Deem was getting a flu shot a few years ago when the nurse warned him that he would be at greater risk for getting the flu the following winter if he failed to get next year’s flu shot.
http://www.rice.edu/sallyport/2003/fall/photos/pg5_needle.jpg
The offhand comment piqued Deem’s curiosity. An expert in molecular and computational biology, he couldn’t reconcile the nurse’s comment with what he knew about the human immune system. He knew that the effects from vaccination last for years. In addition, there were classic studies in immunology that proved that repeated vaccination did not confer greater immunity.
“I asked my doctor about it, and of course, he knew nothing,” Deem says. “So I asked the head of immunology at UCLA, and she told me there was no reason for that to be true.”
http://www.rice.edu/sallyport/2003/fall/photos/pg5_FluShot.jpg
More curious than ever, Deem, who is the John W. Cox Professor of Bioengineering, undertook his own study of the literature and found what he was looking for—a phenomenon known as “original antigenic sin.” Though little-known, the phenomenon turned out to be well-documented, not just in influenza but for a few other viruses, such as dengue fever and AIDS.
The precise reasons why people need regular vaccinations against some viruses, like the flu, and not against others, like polio, are related to two different factors: how fast the viruses mutate and the way the immune system recognizes and targets the invading organisms, known as antigens.
It is the job of antibodies—proteins produced in white blood cells—to recognize antigens and either kill the invaders themselves by binding to them or by recruiting other immune cells to help destroy the antigens. White blood cells don’t know the biochemical signature of each invader ahead of time, so they compensate with volume and diversity. At any given time, there are about 100 million antibodies in the human system, Deem says. A significant portion of these are created using random segments of DNA so that they can recognize different antigens, even those that the immune system has never encountered.
But the immune system pays particular attention to diseases it has fought before and maintains antibodies for those at about 100 times higher concentration than the randomly created varieties. That’s why vaccination works: It prepares the immune system to attack specific antigens by activating this recognition system, allowing the body to maintain a high level of antibodies against a specific disease it’s never actually contracted.
Original antigenic sin occurs when it would be more advantageous for the body to rely on its randomly created antibodies than on the more numerous “remembered” varieties. Take a fast-mutating virus like the flu, for example. It has several distinct areas where antibodies can bind, but each year, those may change.
If a person has four antibodies that worked against one variety of flu, and he or she contracts another variety that has only two similar binding areas, then his or her immune system will be predisposed to make antibodies against only the two sites the varieties have in common. Moreover, immune systems will never learn to recognize the two new binding signatures that are present on the new strain, choosing instead to go with what worked in prior cases. Over time, as the disease mutates more and more and has progressively less in common with the original “remembered” variety, antibodies become ill-prepared to recognize it.
A computational model developed in Deem’s lab to demonstrate exactly how original antigenic sin operates indicates that it is a systemic problem that persists even if the model is adjusted so that the binding regions on the antigen are smaller and even when the body is given more time to recognize the disease. “Because the system tends to go with what worked before, we end up with a localization and a reduction in diversity,” Deem explains. In effect, the system forgoes whole classes of random combinations that might actually work against the new mutant in favor of tried-and-true varieties that will not.
Deem says the findings from the research could prove helpful to vaccine designers and to those studying public health. Also, the methodology used to study the system might also be applicable in other disciplines, such as ecology, where researchers are attempting to study the long-term consequences of reduction in diversity of species.
What it means for those of you who have been getting flu shots in the past is that there is good reason to keep them up.