The Secret Source of Immunity: Why Antibodies Are Unreliable and Where to Look for COVID-19 Protection
'22.09.2020'
Source: Air force
Recent studies have shown that antibodies to Covid-19 can disappear within a few months. However, it is possible that it is not they who form the immunity to this disease, but the mysterious T cells. New findings of scientists are encouraging, writes Air force.
The clues were formed gradually. First, the researchers found patients who had overcome Covid-19, but strangely did not have antibodies to it. Then it turned out that there could be many such people.
Then it became known that many of the antibodies first appeared, but after a few months they disappeared.
In other words, while antibodies help track the spread of a pandemic, they are obviously not as important to immunity as we previously thought.
If we want long-term protection against coronavirus disease, we will have to look elsewhere.
While the whole world was busy with antibodies, researchers began to realize that there is another form of immunity that has been hidden in our bodies for years. These are rather mysterious T-lymphocytes that can play a crucial role in our fight against Covid-19.
These are immune cells, the main task of which is to identify and neutralize pathogens that have entered the cells or to destroy the infected cells themselves. Proteins on the surface of T cells combine with proteins on the surface of intruders in the body, thus breaking them down.
T cells have trillions of possible versions of surface proteins, each of which recognizes a different target. Because T cells remain in the blood for many years after an infection, they also contribute to the formation of a “long-term memory” of the immune system and allow it to respond faster and more efficiently when it encounters an old enemy again.
Several studies have shown that people who recover from Covid-19 are left with T cells that can recognize the virus, whether they experience symptoms or not.
This is clear. However, scientists recently discovered a more mysterious nuance. It turned out that in some people, the test for antibodies to Covid-19 can be negative, and for T cells that can recognize the virus - positive. This suggested that a certain level of immunity against the disease may be twice as prevalent as previously thought.
The biggest mystery, however, was that scientists found Covid-19-specific T cells in blood samples taken years before the pandemic began. It turns out that some people already had a certain degree of immunity to the coronavirus, even before the first person got sick with it.
As it turned out, surprisingly many people, 40-60% of those who have never been in contact with the virus, have such T cells. It seems that T cells are the secret source of immunity to Covid-19.
This discovery also helps to understand some things that have remained a mystery until now. First, the rapid increase in the risk of developing diseases with age, and secondly, the ability of the virus to destroy the spleen, incomprehensible to scientists.
T cell research is not just a matter of scientific curiosity. If scientists know which aspects of the immune system are critical, they can develop effective vaccines and treatments for the disease.
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How immunity is formed
Few people remember about T-cells or T-lymphocytes from biology lessons. However, to understand their importance for immunity, it is worth looking at what happens to the body in the late stage of AIDS.
Fever, ulcers, fatigue, weight loss, and sometimes cancers. The patient develops severe infections that are caused by microorganisms that are absolutely harmless to healthy people, for example, the fungus Candida albicans.
For months or years, HIV sets up a kind of genocide of T-cells, it suppresses them, gets inside and systematically forces them to commit suicide.
“HIV destroys most of them,” explains Adrian Heidy, professor of immunology at King's College London and team leader at the Francis Crick Institute.
"This shows how important these cells are, and that antibodies alone are not enough to fight infections."
With a normal immune response of the body, for example, to the influenza virus, the innate immune system acts as the first line of defense. She begins to sound the alarm with white blood cells and other chemical signals.
This triggers the production of antibodies, which begins after a few weeks.
“In parallel, around the fourth to fifth day after infection, T-lymphocytes, which recognize cells infected with the virus, begin to activate,” Heidi says.
T-lymphocytes quickly and violently destroy infected cells either with their own hands or with the help of other elements of the immune system. Thus, the virus fails to turn healthy cells into factories for the production of their pathogenic copies.
Good news and bad news
So what do we know about T cells and Covid-19?
“Looking at patients with Covid-19, as well as those with mild illness, it's safe to say that T cells are responding to the coronavirus,” Heidi says.
“This is very good news for those developing a vaccine, because we can create T cells that recognize the virus. It's a good news".
In fact, one of the vaccines currently being developed by researchers at the University of Oxford has already shown that, in addition to antibodies, it also stimulates the body to produce T lymphocytes.
It is too early to talk about the effectiveness of this vaccine, but one member of the research team told BBC News that the first results are "extremely encouraging."
However, there is one "but". In many patients hospitalized with severe Covid-19, the T-cell response did not go quite as planned.
“What happens to many T cells in this case is a bit like a wedding party or a bachelor party that is out of control. The activity of T-lymphocytes increases insanely, while some cells simply disappear from the blood. "
One theory is that T cells go where they are needed most, such as the lungs. However, researchers believe that, most likely, most of them die.
“Autopsies on Covid-19 patients show tissue necrosis, which is, in fact, putrefaction,” explains Professor Heidi. This is primarily manifested in the area of the spleen and lymph glands, where T cells live.
The bad news is that spleen necrosis is a symptom of a T cell disease in which immune cells attack themselves.
“We see the same picture in those who died from AIDS,” says the researcher.
"But HIV is a virus that directly infects T cells, they are its main target." However, there is no evidence that the coronavirus can do this as well.
“There may be many reasons for this, but there is no single answer,” Heidi says.
“It turns out that T cells can be your defense for many years. But when a person gets sick, they knock the soil out from under his feet. ”
The decline in T-cell counts with age also explains why older people are much harder to tolerate Covid-19.
“After 30, the thymus, or thymus gland, begins to contract, decreasing the production of T cells in the human body,” says the professor of immunology.
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How does this affect long-term immunity?
The suggestion that coronaviruses cause resistant T cells recently prompted scientists to test old blood samples taken from people between 2015 and 2018.
The fact that the immune systems of some of them learned to recognize Covid-19 long before the start of the pandemic indicates that their bodies have already encountered influenza viruses with similar surface proteins in the past.
Unfortunately, scientists have not yet tested whether T cells appear in the body in response to any of the coronaviruses that cause the common cold.
“It takes a Herculean effort to get funding for such a study,” says Heidi. SARS research went out of fashion in the 1980s, it got stuck in place, and scientists began to move on to other projects, such as HIV research.
Researchers are faced with a problem: the common cold can be caused by any of hundreds of viral strains, many of which are constantly mutating.
Will this help create a vaccine?
If past colds contribute to the milder course of Covid-19, this offers a good chance of developing an effective vaccine. After all, this proves that T cells are able to provide protection for a long time.
But even if that's not the case, the involvement of T cells can still be beneficial - and the more we understand what's going on, the better.
Heidi explains that the way vaccines are developed depends on the type of immune response that scientists hope to get. One of them provokes the production of antibodies - free proteins that can bind to pathogenic microorganisms and neutralize them or transport them to another part of the immune system.
Other types of immune responses can attract T cells or provoke responses from other parts of the immune system.
“There are actually many ways to create a vaccine,” Heidi says. The scientist is first of all pleased that the immune system recognizes the Covid-19 virus very well, even in those patients who are difficult to tolerate the disease.
“So if we can learn to repair the damage the coronavirus does to T cells, we can better control the disease.”
It looks like we'll be hearing a lot more about T cells soon.
