Everyone who is a parent knows that babies are prone to upper respiratory infections. Infants and young children are much less resistant than adults and do not have enough antibodies to allow the pathogen to detour. However, according to the current research data, children seem to be able to avoid developing severe patients with novel coronavirus pneumonia, and the impact of the virus on children is not as severe as that of adults. Many infectious diseases, from common chickenpox and measles, to the newly emerging Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), have similar features. At present, doctors do not fully understand the reasons for this phenomenon.
An article published dec. 10 in the journal Science Immunology may help explain why children are able to escape the severe effects of COVID-19. The article, titled "Transducing Infant T Cells To Develop a Powerful Lung Immune Response Through Enhanced T Cell Receptor Signaling," shows that the infant immune system is more powerful than most people think and beats the adult immune system in its performance against new pathogens. The study was supported by the National Institutes of Health (NIH) and the Helmsley Charitable Trust.
DOI: 10.1126/sciimmunol.abj0789
Compared to adults, it is widely believed that babies' immune systems are more fragile and not yet fully developed. Dr. Donna Farber, professor of microbiology and immunology at Columbia University's Waglos School of Clinical and Surgical Medicine and Professor george H. Humphreys II in the Department of Surgery, who led the study, argues that the comparison is not fair.
Observing how T cells respond to influenza antigens helps the researchers determine why naïve T cells from young mice (as shown above) respond faster and more intensely to pathogens than the same cells from adult mice. The colors in the image represent the different molecules involved in T cell activation. Image credit: Farber Lab/Columbia University Owen Medical Center
Infants do contract many respiratory diseases compared to adults due to viruses such as influenza and respiratory syncytial virus. But unlike adults, babies are seeing these viruses for the first time. "Adults don't get sick very often because our bodies record memories of these viruses, and it protects us," Farber said, "but everything babies encounter is completely new to them." ”
In the new study, Farber and colleagues tested only the ability of children's and adults' immune systems to respond to new pathogens to ensure fair play, essentially eliminating any effects from immune memory. To perform the head-to-head comparison, the researchers collected naïve T cells (CD4+ T cells) from infant and adult mice, respectively, and placed the cells in adult mice infected with the virus. Naïve T cells are immune cells that have never been activated by a pathogen.
In this race to eradicate the virus, infant T cells won a light victory: infant T cells in infant mice detected lower levels of the virus compared to adult cells, and infant cells multiplied faster and reached more cells at the site of infection, quickly building up a strong defense against the virus.
In this study, the researchers used an in vivo mouse cotransferment model to demonstrate that infant T cells produce a greater number of lung homing effector cells in response to influenza infection due to enhanced T cell receptor (TCR)-mediated signaling than adult T cells in the same host. Infant mouse T cells show higher sensitivity to low antigen doses than adult T cells, which originate from an interaction between T cells and antigen-carrying helper cells that drive immune synapses through actin-mediated signaling molecules. This enhanced signaling has also been observed in human infant and adult T cells.
Infants need to coordinate their immune responses to fight the challenges of multiple infections, especially respiratory infections, in the early stages of life. The findings provide a mechanism for how infants can control pathogen load and transmission, which is extremely important for designing targeted development strategies to promote the immune response at this vulnerable life stage.
"We're looking at naïve T cells that have never been activated, and surprisingly, they vary by age," Dr. Farber said, "which means that babies' immune systems are strong and efficient enough to clear pathogens at an early stage." An infant's immune system may in some ways even be better than an adult's because it is designed to respond to a large number of new pathogens. ”
The findings also appear to be playing a role in COVID-19 cases. "COVID-19 is new for everyone, so we're able to see natural, side-by-side comparisons of adult and infant immune systems, and kids are doing much better." Farber said, "Adults react more slowly when confronted with a new type of pathogen. This gives the virus the opportunity to replicate more, which is vulnerable to infection at this time. ”
The findings also help explain why vaccines are particularly effective in childhood, when T cells are very powerful. "Childhood is also the best time to get vaccinated, and you don't have to worry about getting multiple vaccinations within this window." Farber said, "All the children living in the world, especially before we start wearing masks, are exposed to a lot of neoantigens every day. They are already dealing with multiple infection contacts. ”
The study may lead to better vaccine design for children. "Most vaccine formulations and dosages are the same for all ages, but understanding the different immune responses in childhood suggests that we can use lower doses for children and can help us design vaccines that are more effective for this age group," Farber said.
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Resources:
[1]https://www.cuimc.columbia.edu/news/infant-immune-systems-are-stronger-you-think
[2] Puspa Thapa, Rebecca S. Guyer, Alexander Y. Yang, Christopher A. Parks, Todd M. Brusko, Maigan Brusko, Thomas J. Connors, Donna L. Farber. Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling. Science Immunology, 2021; 6 (66)
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