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Infant Immune Systems Are Stronger Than You Think

New study may help explain why infants are less affected by COVID than adults

December 10, 2021

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As any parent knows, infants are prone to getting respiratory infections.

But a new study shows that the infant immune system is stronger than most people think and beats adults at fighting off new pathogens.

The infant immune system has a reputation for being weak and underdeveloped when compared to the adult immune system, but the comparison isn’t quite fair, says Donna Farber, PhD, professor of microbiology & immunology and the George H. Humphreys II Professor of Surgical Sciences at Columbia University Vagelos College of Physicians and Surgeons.

Babies do get a lot of respiratory illnesses from viruses, like influenza and respiratory syncytial virus, compared to adults. But unlike adults, babies are seeing these viruses for the first time. “Adults don’t get sick as often because we’ve recorded memories of these viruse, and the memories protect us,” Farber says, “whereas everything the baby encounters is new to them. ”

In the new study, Farber and colleagues leveled the playing field and only tested the immune system’s ability to respond to a new pathogen, essentially eliminating any contribution from immunological memories.

For the head-to-head comparison, the researchers collected naïve T cells—immune cells that have never encountered a pathogen—from both infant and adult mice. The cells were placed into an adult mouse infected with a virus.

In the competition to eradicate the virus, the infant T cells won handily: Naïve T cells from infant mice detect lower levels of the virus than adult cells and the infant cells proliferated faster and traveled in greater numbers to the site of infection, rapidly building a strong defense against the virus. A laboratory comparison found similar enhancements among human infant compared to adult T cells.

“We were looking at naïve T cells that have never been activated, so it was a surprise that they behaved differently based on age,” Farber says. “What this is saying is that the infant’s immune system is robust, it's efficient, and it can get rid of pathogens in early life. In some ways, it may be even better than the adult immune system, since it’s designed to respond to a multitude of new pathogens.”

That appears to be playing out in the case of COVID. “SARS-CoV-2 is new to absolutely everybody, so we’re now seeing a natural, side-by-side comparison of the adult and infant immune system,” Farber says. “And the kids are doing much better. Adults faced with a novel pathogen are slower to react. That gives the virus a chance to replicate more, and that’s when you get sick.”

The findings also help explain why vaccines are particularly effective in childhood, when T cells are very robust. “That is the time to get vaccines and you shouldn't worry about getting multiple vaccines in that window,” Farber says. “Any child living in the world, particularly before we started wearing masks, is exposed to a huge number of new antigens every day. They’re already handling multiple exposures.”

The study could lead to better vaccine designs for children.

“Most vaccine formulations and doses are the same for all ages, but understanding the distinct immune responses in childhood suggests we can use lower doses for children and could help us design vaccines that are more effective for this age group,” Farber says.

References

More information

The paper, titled "Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling," was published Dec. 10 in Science Immunology.

Donna Farber also is chief of the Division of Surgical Sciences in the Department of Surgery, Columbia University Vagelos College of Physicians and Surgeons, and principal investigator at the Columbia Center for Translational Immunology.

All authors (all from Columbia University unless noted): Puspa Thapa, Rebecca S. Guyer, Alexander Y. Yang, Christopher A. Parks, Todd M. Brusko (University of Florida), Maigan Brusko (University of Florida), Thomas J. Connors, and Donna L. Farber.

This work was supported by the U.S. National Institutes of Health (NIH grants AI100119, AI106697, K23 AI141686, and AI42288) and the Helmsley Charitable Trust. Studies were performed in the Columbia Center for Translational Immunology’s Flow Cytometry Core, supported by NIH grants S10RR027050 and S10OD020056, and the Columbia Stem Cell Initiative’s Flow Core, supported in part by NIH grant S10OD026845.

The authors declared no competing interests.

CHILD IMMUNITY STARTS IN THE Maternity Hospital!

What influences the formation of a child's immunity and what measures should parents take to increase the body's defenses? Andrey Petrovich Prodeus, pediatrician-immunologist, doctor of medical sciences, professor, chief pediatrician of the Children's City Clinical Hospital No. G.N. Speransky, chief freelance pediatric allergist-immunologist of the Ministry of Health of the Moscow Region, head of the Department of Clinical Immunology and Allergology of the Higher Medical School.

What does high immunity in a child depend on?

I would single out four main factors responsible for strong immunity.

The first is a full-term pregnancy. If a child is born on time, it means that his immune system has formed sufficiently to meet the world of viruses and bacteria. The more premature a baby is born, the more immature its protective cells will be and the more difficult it will be for his body to adapt to the characteristics of the environment.

The second factor is the type of delivery. If the birth ends with a caesarean section, then the child will receive a completely different microbiota: he will not pass through the woman's birth canal and will not "pick up" the mother's bacteria, which form the initial interaction between him and the environment.

The third factor is breastfeeding. The longer the baby receives mother's milk, the better will be his immune response to infections from the outside world.

The fourth factor is timely vaccination. Properly done and with a personal approach to the child, it will form the normal development of the immune response.

Babies born by caesarean section are several times more likely to suffer from allergies, be overweight and respond less well to vaccinations.

Do all children need to boost their immunity?

Definitely not for everyone. Children have another interesting feature: they do not always show an active aggressive response to some kind of infection. Imagine that a virus or bacterium enters the nasopharyngeal mucosa and an adult develops nasal congestion, snot, and a red throat. Is this good or bad? In principle, it’s good, because it says that our immunity has begun a war against infection.

On the other hand, this is nothing but a manifestation of a disease. Ideally, the picture looks like this: a virus or bacterium got on the mucous membrane, but the immune system dealt with it so quickly and effectively that we did not notice it. Conclusion: do we want to increase the strength of the immune response indefinitely? Probably not always.

Because if we actively increase the response of, say, a child of the 1st year of life, then instead of calmly reacting to some virus or bacterium that comes to him from outside, he will begin to suck badly, not sleep and put on a little weight, and parents will start to worry a lot. But if, in response to the invasion of a viral agent, nasal congestion appears in a 14-year-old teenager, then nothing terrible will happen: he will blow his nose and still go to play football.

That is, the same problem can be perceived differently and have different consequences for children of different ages. The difference in adaptive immune response is designed in such a way by nature that it limits the strength of the response in the child until he adapts to the environment. And you should not interfere in this process.

Hardening can help in strengthening the immune system?

I wouldn't use that wording. Any kind of hardening, as well as playing sports, is not a little about immunity. Here we are talking about general physical processes. We, pediatricians, only welcome them, because it instills healthy lifestyle skills in a child.

However, to date, there is no direct clinically proven link between these activities and the strengthening of the immune response anywhere in the world. Yes, indeed, sports and hardening can theoretically increase the adaptive abilities of the body, but the question is exclusively individual: it will help someone, but not so much for someone. Therefore, I would recommend that all parents treat these things without fanaticism and do not tyrannize children with sports clubs or cold showers "in the name of immunity."

How can parents strengthen their child's immune system at home?

There are two cornerstones: a daily routine and a balanced diet. The daily routine for a child is absolutely essential for strengthening the immune response. Why? Because all organs and systems of the body, including immune cells and bone marrow, are most active from ten in the evening until about three in the morning. Therefore, if a child goes to bed at eleven or twelve, his immune system (especially its "officers" - T-cells) will not be able to recover normally. Therefore, a systematic "torn" regime for a child is absolutely contraindicated precisely from the standpoint of immunity, and not just his mental health.

As for normal baby food, you need to pay attention to the constant presence of two components in food: vitamin D and iron. It is vitamin D that helps our cells fight viral infection. If earlier its prophylactic dose was considered to be 400 units per day, now at least 1000 units are prescribed. Statistics show that approximately two-thirds of children who live north of 42nd latitude have a decrease in vitamin D levels, and some of them are completely deficient.

An equally important component for immunity is iron. Its assistance in the efficient functioning of the immune system's T-cells is considered one of its main functions, in addition to the formation of hemoglobin. The ability of the body to respond with the “correct” inflammation to a bacterial or viral infection is impossible without a sufficient amount of iron in the blood. Therefore, it is necessary to raise the question not only of getting more of this element with food (the so-called heme iron in the form of meat, poultry and fish), but also about prescribing courses of iron preparations that are easily absorbed by the doctor.

There is a dangerous myth in Russia: drink pomegranate juice, eat beets, buckwheat and green apples, and you will have happiness in the form of iron. Will not! Because the absorption of iron from plant sources is approximately 5% of its total amount in them.

Today even doctors often argue about the importance of vaccination for children. What is your opinion on this matter?

Vaccinations are not meant to please doctors or drug companies. By and large, healthy immunity begins precisely in the maternity hospital, when a newborn receives his first vaccinations, and comes into this world already protected.

Vaccination was invented either for those diseases whose consequences are fatal, that is, from them there is a high risk of death (for example, with meningitis, rabies, tetanus). Or for those for whom there is no therapy (hepatitis B, mumps, measles, rubella, or the same covid). Yes, a person can easily get sick with them, but no one guarantees this.

Case in point: 10% of boys who recover from mumps become infertile. In this regard, I always have a question for “refusenik” parents: who gave you the right to doom a child to such a fate?!

There is a popular belief that only healthy people should be vaccinated. Not! Immune-compromised children, who have peculiarities in the development of the immune response, need it more. For them, the infections that vaccination protects against are more difficult to tolerate.

I categorically do not support the modern craze among parents, when, for example, one child gets chickenpox and several mothers bring their children to visit him for a “chickenpox party” (“rubella party”, etc.). I consider this to be deliberate harm to the health of a small person. After all, the consequences are unknown: if everything can go easily for one, then for another it will be a difficult process that requires hospitalization, and in rare cases (for example, with meningitis) lead to death. And at the same time, parents remain unpunished, which, in my opinion, is unfair. The child is not a thing. And in the new version of the Constitution, the priority of the state in protecting the health of children is just a red thread.

The immune system in the first months of life develops according to a certain plan

Scientists from the Karolinska Institute (Sweden) conducted a large-scale study of the development of the immune system in newborns from birth to three months.

The authors of the work consider the human immune system as sensory system for environmental factors. Like sight and hearing, she depends in its development on the channels of information input. Immune interaction systems of newborns with microbes of the intestines, skin and respiratory tract affects the risk of developing immune diseases in the future, such as allergies, asthma and type 1 diabetes.

Newborns are susceptible to infections, especially if they are born prematurely, but what is the reason is still not entirely clear. But since blood for analysis was usually taken from the umbilical cord after childbirth, such the samples did not reflect the changes that occur with the immune system after contact with bacteria. It is clear that research on the development of the immune system in children will help better protect newborns from infections, develop more effective vaccines and reduce the risk of developing immune diseases.

In a longitudinal study by Swedish scientists, involved 100 newborns born in the hospital Karolinska University, both premature and full term. Everyone has it the child during the first three months of life took 100 μl of blood - at the moment birth (cord blood), at the first, fourth and 12th week. method mass cytometry determined 58 populations of cells of the immune system, using immunoassay - 267 plasma proteins. Four preterm infants and four term infants also underwent transcriptome analysis at 1 and 12 weeks of age, to evaluate changes in gene expression.

Preterm labor is often caused by inflammatory processes, and to compare the state of the immune system in preterm and children born at term, the researchers analyzed the concentrations of proteins in cord blood. In children born significantly prematurely, it was found that in in particular, high expression of chemokines CXCL11 and interleukinin-8 (CXCL8) — pro-inflammatory cytokines that stimulate the migration of immune cells to the site infections. And full-term babies had higher levels of leptin — peptide hormone that regulates energy metabolism, which, according to the authors, associated with more significant fat accumulation in the last trimester.

The study showed that in the first months of a child's life the immune system undergoes dramatic changes. Difference between full-term and premature babies were significant at the beginning of life, but then decreased rapidly, and the development of the immune system was subject to general patterns in both groups of children. The driving force appears to have been contact with environmental antigens. On the other hand, the gut microbiomes of children differed significantly, full-term babies discharged home after a few days, and premature babies who spent months in the hospital grew up in completely different conditions. Therefore, the reason is not only in external factors: there must also be some physiological trigger processes common to all children. It is noteworthy that in children with dysbacteriosis, the normal development of the immune system has been broken.

Based on these observations, scientists proposed a model of stereotypical adaptive changes in the immune system under the influence of one or multiple environmental factors.

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