In the past, it has been difficult to examine how the neonatal immune system changes, because analyses have been based on samples taken from the umbilical cord directly after delivery. But researchers have now exploited a new technique for immune cell analysis to monitor how babies develop during the first few weeks of life outside the womb.1

“This is the first time we’ve pinned down how the human immune system adapts itself to birth and the new environment,” says Petter Brodin, MD, PhD, a physician and researcher at the Science for Life Laboratory and the department of women’s and children’s health at the Karolinska Institute. “We saw drastic changes in the babies’ immune system between each sampling, which shows that it is highly dynamic early in life.”

The study compared blood samples from 100 babies—both premature and full-term—taken during the first, fourth, and twelfth week after birth. The comparison was achieved using an advanced technique of immune cell analysis: mass cytometry in combination with extensive plasma protein analyses.

Only small amounts of blood—just a few drops from each baby—were needed to analyze all the white blood cells and hundreds of proteins circulating in the blood. The researchers were also able to show that babies who experienced abnormal development of the gut flora during their first weeks also exhibited a disorder of the immune system.

“Our results are important for better understanding the infection-sensitivity of newborn babies and the risks of premature birth,” says Brodin. “If we can monitor the development of the immune system and steer it in different directions, we make it possible to prevent autoimmune diseases and allergies, which are partly related to the development of the immune system, and to even develop better vaccines, tailored to the neonatal immune system.”

Brodin

Petter Brodin, MD, PhD, the Karolinska Institute.

Adaptation of the immune system is thought to be triggered by the microbes, bacteria, fungi, and so forth that the baby encounters outside the womb. The process begins primarily in the lungs, gut, skin, and mucosa—which is to say, the body’s points of contact with the outside world.

“What surprised us was how similar the changes were amongst babies,” says Brodin. “It seems as if all babies follow one and the same pattern, with their immune systems responding with exactly the same sequence of dramatic changes. It’s almost like a well-choreographed dance, a practiced routine.”

The researchers will now be broadening the study to encompass more babies, all of whom will be monitored into childhood. The broader study will enable the team to see which of the children develop diabetes, allergies, asthma, and inflammatory bowel disease.

“Many of these diseases can definitely be traced back to how a baby is born and how its immune system adapts to the external environment,” explains Brodin. “What we’re bringing to the table is the specific changes in the immune system that underlie this. It’s a piece of the puzzle that was formerly missing.”

The study was made possible through close collaboration with the Karolinska University Hospital.

“For ethical, practical, and logical reasons it’s difficult to put together a study like this,” says Brodin. “The key to our success is that those of us leading the study also work as doctors, and when we manage to combine patient-end work with the most advanced techniques, we make wonderful discoveries.”

The researchers who conducted the study are active at the Science for Life Laboratory, the Karolinska Institute, and the Karolinska University Hospital. For more information, visit the Karolinska Institute.

Reference

1. Olin A, Henchel E, Chen Y, et al. Stereotypic immune system development in newborn children. Cell. 2018;174(5):1277–1292.e14; doi: 10.1016/j.cell.2018.06.045.

Featured image: Neonatal care at the Karolinska University Hospital. Photo by Ann-Sofi Ingman courtesy of the Karolinska Institute.