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Maggie Chen
The immunological formula is complicated. And for a smart reason: protecting the human body from external threats (like covid-19) is a full-time job. At its most sensible, a person’s immune formula responds uniquely to an invasive threat. Unravel why it has challenged scientists for years.
It has long been known that biological sex has some influence. “In general, men tend to have more severe infections than women,” says Camila Consiglio, a systemic immunologist at Lund University in Sweden. “On the other hand, we know that women have a greater response to vaccines. “But what wasn’t known before the pandemic is that an infection, such as Covid, can adjust for those gender differences, expanding variation in immune responses within the population.
In a paper recently published in Nature, a team led by John Tsang, a systems immunologist at Yale University, found that Covid can react immune-long after infection, changing the way other people respond to an upcoming vaccine rather than another disease. Specifically, they found that men who had recovered from a mild covid episode responded more vigorously to the upcoming flu shot than women who had recovered from covid, and also more vigorously than healthy controls, reversing the same previous gender difference. Researchers believe those discoveries can help Researchers create better vaccines and understand why pathogens have such a different effect on other people. Knowing whether you are more or less vulnerable to infections can help personalize your health care in the future, making this information potentially vital.
Tsang’s organization had in the past investigated the long-term influence of infections on a person’s immune system, but the arrival of Covid in 2020 suddenly made this study much easier. “having so many other people who had suffered a mild infection and then recovered was a rare event, and he created a wonderful organization from which to sample. By following those relatively healthy patients in another way, Tsang thought they might only reliably check how other people’s immune systems responded to a vaccine after an infection.
The team then took blood samples from 33 patients who had recovered from mild covid, as well as 40 healthy controls of the same age and sex who had not yet contracted the virus. Later, all participants won the seasonal flu vaccine and after that. This blood was taken several times (with some samples taken up to a hundred days after vaccination).
The next step is to pass all those samples through whole blood transcriptomics, a form of genetic sequencing that shows all the genes used (or “expressed”) through blood cells to create the ingredients they need, adding immune molecules. This provided high-level information on possible differences in immune activity between men and women. Although there were some slight fundamental differences before receiving the flu vaccine, scientists discovered clearer ones without delay afterward. “Particularly more potent inflammatory reactions are seen in men recovered through Covid,” says Tsang, indicating that men recovered through Covid created more antibodies and antibody-producing cells in reaction to the vaccine. “It’s a big surprise. Often, you find that this type of reaction is greater in women.
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While total blood transcriptomics was helpful, it only provided a general picture of what was happening. The scientists then turned to a strategy called CITE-seq. This allowed them to notice which cells expressed which genes in men and women, and which proteins they expressed. created. The most productive component was that CITE-seq can be used simply with the same blood samples taken from patients. “There’s only one type of sample, and you just measure it,” Tsang says.
One specific type of mobile appeared to contribute to the flu vaccine reaction: effective memory T mobiles (which are generated after infection and can “remember” the express pathogen they found) with a receptor called GPR56 expressed on their surface. . It turns out that men recovered from Covid had more of those mobiles than women recovered from Covid and healthy controls. But why would those mobiles, connected to Covid, respond to a flu vaccine?
“The canonical assumption is that an infection will generate specific cells of the virus,” Tsang says. But, as he explains, this is not necessarily the case. Other more broadly reactive immune cells may also be activated. Known as “control cells,” those react very temporarily to vaccination, sending alarm bells that lead the immune formula to create antibodies in response.
In fact, when scientists tested the GPR56-positive T cells, they found that they shared similarities with control cells already known to activate acute Covid infection. Therefore, they hypothesized that those GPR56-positive cells probably acted in the same way as the bystander cells. , persisting in the post-Covid framework and triggering immune responses opposed to other invaders, in this case, the flu vaccine.
To develop this theory, scientists needed to see how GPR56-positive T mobiles responded to something resembling infection or vaccination. Producing infection or vaccination, scientists found that T phones secreted high levels of inflammatory proteins found in men recovered from Covid, offering evidence that this type of phone could have triggered the immune reaction that eventually produced more flu antibodies. They had discovered his smoking gun.
Consiglio is curious to see, in the future, what effect those differences have on immune systems between men and women recovered from Covid when a user is actually inflamed with the flu or some other virus. Looking at sex and past infections also raises the question of how other points might influence the immune response. Sabra Klein, a microbiologist at Johns Hopkins University, needs to see how something like age can also be factored into the equation and perhaps create a sliding scale of immune responses. variables like binaries: you’re young or you’re old, you’re a boy or you’re a woguy, and we don’t do enough to interrogate those intersections,” Klein says.
Ultimately, Tsang and his team hope those locations can help scientists design more effective vaccines or find tactics to wait for how a user might respond to an infection. They need to know if those GPR-positive cells may be better prepared to respond to an infection. pathogen. On the other hand, scientists are also curious about how those cells (and others) serve as autoimmunity, where the immune formula is overactive.
Until then, they will continue to appreciate the complexities of the immune formula, especially how it evolves during the pandemic. “We have the idea of looking for the human immune formula as a very varied herbal delight,” says Tsang. Thanks to After the Pandemic, the opportunity to be informed of this experience was even greater, meaning we now know more about why our immune formulas are so different and how they are replaced over time.
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