The immune system of the newborn is shaped by the environment that was present at the maternal/fetal interphase, by the conditions encountered during the transition from the protected maternal environment to the outside world, and by the conditions encountered during the first weeks of life. However, the understanding of the forces that shape the newborn’s immune system has been hampered by experimental limitations—studies performed in human newborn rely mostly on cord blood samples, given the difficulty of obtaining blood samples during the first weeks of life.
Now, these experimental limitations have been overcome by the use of new techniques that require only a few drops of blood from each baby. Using these advanced techniques, which are based on the use of mass cytometry in combination with extensive plasma protein analyses, researchers from the Karolinska Institute in Sweden have characterized the changes occurring in the immune system during the first weeks of life.
For their study (Stereotypic Immune System Development in Newborn Children), published in the journal Cell a few months ago, the researchers compared blood samples from 100 babies, both premature and full-term, taken during the first, fourth and twelfth week after birth. Using their advanced technique, the researchers analyzed 58 immune cell populations by mass cytometry and 267 plasma proteins by immunoassays, thus obtaining a systems-level overview of immune system adaptation to postnatal life.
Peter Brodin, senior author of the study, said in a press release: “This is the first time we’ve pinned down how the human immune system adapts itself to birth and the new environment. We saw drastic changes in the babies’ immune system between each sampling, which shows that it is highly dynamic early in life.”
The researchers also found that changes in cell populations and plasma proteins followed a stereotypic pattern shared by all children, but not predictable from the analysis of cord blood samples. Surprisingly, the researchers found that children at different levels of maturity and exposed to different postnatal environmental conditions converge on a shared immune system developmental trajectory early in life. Thus, all babies appear to follow one and the same pattern, with their immune systems responding with exactly the same sequence of dramatic changes—almost like a well-choreographed dance.
The developmental trajectory also reflected interactions with microbes and, indeed, the researchers found that in a subset of children with gut bacterial dysbiosis, the development of the stereotypic immune system is hampered.
Brodin added: “Our results are important for better understanding the infection-sensitivity of newborn babies and the risks of premature birth. 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.”
After reading this blog post I immediately came to the idea that the new born body is microbe expectant. Working in the laboratory under Nancy Forger and Alexandra Castillo-Ruiz I helped work on a project that looked at how being born in a microbe free environment influences how your brain develops. We found that being born in a microbe free environment influences the amount of perinatal cell death that the brain undergoes. Cell death is a developmental event and is frequently used as a developmental measure. I would also be curious of whether the developmental time line is providing this choreographed immune development trajectory or the exposure to microbes is inducing it. In the womb we are in a relatively sterile environment. Have we evolved to be microbe expectant? Or are we going through the microbe invasion just as our ancestors did and it helps our immune system develop?
https://www.ncbi.nlm.nih.gov/pubmed/28890156
I am also curious about how our immune system develops and what triggers the stages of development. After reading an article about how both pregnant mothers and their newborn babies with gestational diabetes have similar gut microflora with high levels of glucose tolerant bacteria and abundance of certain viruses such as herpesvirus; I think the mother’s health and gut microflora composition plays an important role in how her child’s gut microflora composition will turn out.
I believe we need to do more research on the gut microbiome of newborn babies to determine how autoimmune diseases affect it and how to prevent harmful microbes from colonizing the gut microflora.
https://www.ncbi.nlm.nih.gov/pubmed/29760169
Newborns being microbe expectant is an interesting topic that I wanted to further explore. Ultimately, exposing your child to different microbes seems to benefit their immune system and overall health. One topic that I would like to explore further is the link between parasites and allergy. Allergy diseases are increasing worldwide and it seems to be linked with the decrease of parasitic infection. It seems to be because parasites induce a type of allergic-like inflammation. Research has shown that people with an effective immune response to parasites can be more susceptible to allergic reactions. That make sense because parasites in the U.S. today are scarce and it seems like everyone is allergic to something. Therapies are currently being developed derived from the helminth which is a type of worm to combat or prevent inflammatory diseases such as allergies.
https://www.ncbi.nlm.nih.gov/pubmed/29108604
The way the immune system develops in humans is really interesting and comes from a variety of sources, but something my mom has always told me is that when I have my own children, I should breastfeed them. One of the things she tends to highlight when she tells me this are the immunological benefits of breastfeeding– apparently my sister and I were very healthy children and she attributes that to her breastfeeding us. This blog post made me think of my mom and got me wondering how much more breastfed children are protected from pathogens compared to formula-fed babies, so I found a meta-analysis of many studies on this topic. As it turns out, my mom wasn’t making things up. Children who were breast fed for at least the first 6 months of their life tend to have better health outcomes than their formula-fed peers. Most notably, breastfed children are less likely to have asthma and allergic diseases. It’s nice to know that in the future I can take such a simple step to protect my kids!
https://www.ncbi.nlm.nih.gov/pubmed/28521318
I find your comment very interesting not to sound weird or anything, but breast milk is one of the most amazing things. For instance, when a baby is nursing there is supposed “backwash” that enters the mothers breasts and apparently this can tell the mother whether the baby is sick or not. If the baby is sick the mother will “donate” leukocytes to the baby to help fight its infection. The idea that your mother will help fight your infections is just amazing. Breast milk is really fascinating and another interesting thing that my mentor had told me once, is that mothers will produce diffrent breast milk composition based on whether the baby is a boy or a girl. I’ll include link to both articles if you’re interested but I’m primarily citing the leukocyte breast milk study for the “grade”.
Leukocyte: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232055/
Boy vs Girl breast milk in maquaces:
https://www.ncbi.nlm.nih.gov/pubmed/23446791
Award abstract on B V G breastmilk in humans:
https://nsf.gov/awardsearch/showAward?AWD_ID=1638167
I am a big supporter of breastfeeding and I strongly encourage moms around me to breastfeed their babies exclusively! When I was pregnant, I decided to breastfeed my baby because I wanted her to be as healthy as possible and provide her with antibodies she needs as my body produce them when she needed. You came up with something me and my mam believed in, as well you and your mam. My baby is healthy, and she suffered less from gases at her first few months compared with my friends’ babies. Breast milk has an important effect on the development of the neonatal immune system. That is what I found in this interesting article showing the benefit of breast milk over the formula on T-Lymphocyte subpopulation. They compared breast milk babies, formula and mix of both and measured their peripheral lymphocytes subsets (CD3, CD4, and CD8). What is interesting about this is babies on breast milk only had a higher CD8 and lower CD4 which make them less likely to have infections and allergies. This is why more and more people are encouraging breastfeeding and making supporting groups.
The previous link didn’t show in the comment
Yes, breastfeeding definitely helps the development of not only the immune system but the GI tract! Your baby may have had less gas than your friend’s because breastfeeding helps babies acquire their microbiomes, most of which are in their guts. In an article I read, the authors state that even though we know about all the benefits of breastfeeding, many hospitals don’t necessarily set mothers up to breastfeed or to be successful breastfeeding. Experts recommend at least 6 months of exclusive breastfeeding for better health outcomes. Here’s to hoping that hospitals change their practices when it comes to new mothers sometime soon!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686345/
I find it interesting that you mentioned how breastfeeding helps build newborns immunity. It reminded me of the vaginal delivery (VD) versus cesarean delivery (CD) topic. As science advances and technology improves, the percent of women who decide to have CD continues to rise, nearing the fifty percent marker here in the United States. Interestingly enough, some studies have linked the rise in CD to autoimmune diseases and allergic diseases as well. There are theories that suggest overly clean environments contribute to some childhood diseases. The argument in favor of VD is based on studies that show that the microbes the newborn is exposed to through VD are more beneficial for the newborns immune development. The mothers vaginal microflora aids in the development of the newborns intestinal tract. This study I found suggests that CD results in abnormal microbial seeding of the GI tract which would then lead to abnormal immunity development.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110651/
I’ve also read studies that prove/support significance of Vaginal Delivery (VD) over Cesarean Section (CS) mode of delivery. However, VD is not only beneficiary in development of strong immune system in the newborn infant, it also plays an important role in Cognitive Development of the child as well. I found an interesting study done in Australia by LSAC regarding this hypothesis. They studied cognitive performance of children varying from ages 4 to 9 (VD vs. CS born children) to observe the difference (if noticeable) in cognitive performance. According to the study results, VD born children show higher cognitive development than CS born participants. They suggest being precautious in planning CS if there is no life threatening possibilities from vaginal delivery.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597642/
Research regarding vaginal delivery versus cesarean section are numerous. Given the scientific findings that vaginal delivery is beneficial in the development of the infant’s immune system, I wondered if any methods have been developed to introduce the infant delivered cesarean section to the mother’s vaginal microbes. In a study, researchers introduced the infants to the mother’s by exposing them to maternal vaginal fluids at birth. The results showed that gut, oral, and skin microbiota improved in comparison to infants not exposed to the mother’s vaginal fluids. This method allows a partial restoration of the microbes passed from mother to infant delivered by cesarean section. One question raised during the review of this study was that if this method were to be introduced as a therapy for cesarean section delivered babies, how exactly would this be carried out? What if the mother has a vaginal infection or disease that could be harmful to the health of the infant? Would testing of the microbes in the vagina be tested before the child is born? All these specific questions will be thought out before any procedure to restore the microbes in an infant is carried out in a medical setting. I wonder if such therapies would be developed and established in medical settings before I have a child that might possibly be delivered by cesarean section.
https://www.ncbi.nlm.nih.gov/pubmed/26828196
Its always a marvel to see how amazing the immune system works. I couldn’t fathom the idea of giving my child immunity by just breast feeding them, then again I’m not a mother nor possess a child. Although this is a means of obtaining immunity in the infants first 6 months, I wonder exactly how the biochemical sequence of events panned out to the infant ultimately obtaining immunity. Please, can anyone help explain how this came to be? Thank you!
How immunoglobins from human milk are able to survive in the newborn stomach and pass through the digestive tract still need more research. However, samples were collected from mothers and their preterm infants after delivery between 7- 98 days. IgG and IgM were found to survive in the preterm babies stomachs while IgA was digested. Human milk also has anti-idiotypic antibodies that enhance infant response. Again more research should be conducted on the many benefits of breastfeeding and infant immunity.
https://www.ncbi.nlm.nih.gov/pubmed/29940583
I also wanted to know more about the importance of breastfeeding to an infant’s development. I was able to find an article that was looking for a correlation between pediatric asthma and breastfeeding. The incidence of pediatric asthma has increased substantially in the recent decades and is over 14%. Scientist believe this may be due to a decrease in breastfeeding. The scientist argue that children that are not breastfed at an early age fail to develop a diverse microbiota. This less diverse microbiota fails to optimally stimulate the infant’s immune system. The hypothesis is supported by observations that the gut microbiota is different in infants who develop asthma later in life compared to those who remain healthy. Thus, breastfeeding plays a crucial role in the development of asthma.
https://www.ncbi.nlm.nih.gov/pubmed/30140664
This article highlights the importance of nutrition in the development of neonates. The research states that vitamin A is important for the early development of lymphoid cells in the GI tract. There are variety of nutrients in breastmilk that regulate and induce immune response. For example, the long chain polyunsaturated fatty acid in milk change the concentration of different types of immune cell and cytokines. Alongside vitamin A, vitamin D correlates to gut mucosal immune function. These articles list out the various deleterious effects of nutrient deficiencies in neonates.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566995/
Autoimmune diseases are diseases that are caused when the immune cells of of our immune system recognizes and attacks healthy cells in out body. Type 1 Diabetes is a kind of autoimmune disease that results from immune system attack and destroy insulin-producing beta cells. A possible means of correcting this problem is through a patient undergoing continuous subcutaneous insulin infusion (CSII) pump therapy, or the less expensive multiple dose insulin (MDI) therapy. A study looked at the effectiveness of these treameants and discovered CSII pump therapy was more effiecient and no increased risk for weight gain or hypoglycemia. In an attempt to broaden our understanding of other autoimmune disease, please leave a comment that does so.
https://www.ncbi.nlm.nih.gov/m/pubmed/19694201/?i=4&from=/16912828/related
Newborns are susceptible to infection because of their under developed immune system, but the lactoferrin in the milk they drink helps bolster their anti-bacterial defenses. This is done through the iron sequestration, increases immune cell activation, T and B cells maturation and achieving immune homeostasis, amongst other activities.
https://www.ncbi.nlm.nih.gov/pubmed/30181493
This insight brings a good point to the topic of the different macronutrients present in breast milk. I do know that breast milk doesn’t start developing until late in the second trimester or early stages of the third trimester. So this brings the point of preterm babies. Even if a mother breast feeds her preterm newborn, are they still going to be receiving adequate nutrition and immunological protection from the mother? Most especially when is lactoferrin being produced in the breast milk? If is it produced after a stage where the child is already born, how helpful can it be? Or are there other things the female body can do to compensate for the early birth of the baby and needing to provide nutrients. Another question is that if the lactoferrin helps with T and B cells maturation, what can be said if this is not able to be produced in time by the mothers body? Are there other ways to help compensate these factors?
A study that was done using Indian women delivering at less than or equal to 34 weeks gestation (meaning preterm), was trying to see the variability in the micronutrition levels in breastmilk. As well as the energy content, if any, that is present in the breastmilk. The results from this study showed that there was an inverse correlation with the decline of protein concentration in human milk and the increase in postpartum days. In other words saying, the more days after the mother had given birth the more the protein concentration in her milk drops. On the other hand lactose, fat and energy concentrations went up. Whereas energy concentration goes up the most followed by fat and then lactose. Meaning the least present macronutrient seen in human milk after birth is lactose. The high amount of energy makes sense. I would be curious to see if this low lactose concentration has anything to do with the high number of lactose intolerant Americans that are present today. Maybe a solution can be seen in something as natural as breast milk, but more research will need to be done to look into this. The one fact is that though, preterm babies will most likely not meet their energy requirements from their mother if its solely breastfeeding. This also ties into immunity now because they will not be getting everything that they need to help protect them from foreign microbes.
https://www.ncbi.nlm.nih.gov/pubmed/28607212
This post has really inspired me into the thinking of mother’s saving their placenta. During pregnancy the placenta is responsible for supplying oxygen and nutrients to the baby. It also removes waste products from the babies food, and this is where the umbilical cord comes from. We know the umbilical cord is where the mothers immunity passes to the baby by the sharing of antibodies. So the concentration of all the nutrients the baby is getting is coming from the placenta. I watched a show where the mother had saved her placenta from birth, in a bottle up liquid form. She would put small droplets into her mouth, or into smoothies that she was making. In combination with being a breastfeeding mother. I know the immunological impact the umbilical cord has on the baby during growth in the fetus. So it would be really amazing to see if they’re any impacts seen in babies that are breastfeed by mothers ingesting placenta. More research needs to be done to see if this is actually a positive impact on the baby. The type of nutrition the babies are receiving play a huge impact into their immunological development.
I was intrigued to learn that the immune system develops in a similar pattern and trajectory in newborn babies. Before reading this article, I thought the environment played a more significant role in the development of a baby’s immune system.
I also found it interesting how gut-bacterial dysbiosis, or the unbalance of microbiota in the GI tract, can disrupt a child’s immune system development. This made me think, “is there a correlation between gut microflora and disease in newborn baby or neonate?”
Upon my research, I came across an article by Wang et al. that observed the impact of maternal health and colonization of microbiota on neonates. The research showed how pregnant women and neonates suffering from gestational diabetes had similar changes in their gut microbiome, specifically with the microbiome being more tolerant towards high levels of glucose and having an abundance of some viruses (herpesvirus and mastedonvirus).
This post got me interested in the possible prevention of allergies and autoimmune diseases via controlling immunological development. It turns out, not only is the infant microbiome important in immune development, the maternal prenatal microbiome could also be important. Can helping the mother’s microbiome prevent against allergies and immune diseases? Can exposure to microorganisms at a young age strengthen an infant’s immune system? A meta-analysis of several studies strongly suggested that when probiotics were given prenatally and postnatally the infants were less likely to contract eczema, and food allergies. It has also been shown that children with exposure to a farming environment in early life were far less likely to contract food allergies and asthma. The same study shows that children whose mothers were exposed to a farming environment during gestation were even less likely to contract food allergies and asthma. Because these problems are often associated with a deficient immune system, this indicates that altering the immune system development via exposure to microorganisms is a viable option to combat against autoimmune diseases and allergies. These results also indicate that there are steps the mother can take prenatally to help influence infant immune response. Unfortunately, the research in this area is limited and further studies would be required to provide conclusive evidence. As well, very little research has been conducted about the effects the maternal microbiome has on child immune development.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711986/
As I am a mother of three boys I totally understand the importance of maintaining an important immune system for newborns as well as keeping a stable immune system throughout childhood thus getting vaccines. However, as a mother, I also have become concerned with the early onset of children developing allergies. Do these vaccines and health preventions cause allergies earlier in children? For example, I did not receive the Chicken Pox vaccine an I was exposed to the virus. My brother, however, received the vaccine and also received shingles at the age of 9. I am a strong believer in breastfeeding and natural health precautions for newborns but when does over vaccination become an issue?
https://www.ncbi.nlm.nih.gov/pubmed/28346921
When it comes to the increase in the number of cases of allergies in children, I don’t know how much of it can be attributed to vaccines. Although there is the potential for any child to have adverse reactions to a vaccine I think part of what may lead to these adverse reactions or allergies is based of the child’s environment. I’ve heard that part of why we are seeing so many more allergies in children these days is partly due to the significant change in lifestyle our society has made including sanitation and this can have detrimental effects on our immune systems. One paper I found by Yu et al. investigated the effects that farm environments have on the pregnant woman and their children. Their work shows that this exposure provided some protection to the child and lessened the effects of allergies.
https://www.ncbi.nlm.nih.gov/pubmed/30140427
I must agree with the article there. I do believe that the less exposure and over dependancy of vaccines contribute to the increase of allergies.
This post discusses how the immune system of newborns are shaped by the environment that was present during their fetal stage, during birth, and during the first few weeks as a newborn. Originally, fully studying this topic is limited by the difficulty of obtaining newborn blood cord samples. However, now the new assessment techniques require just a few drops blood from the newborn infant. This process uses mass cytometry along with detailed plasma protein analyses to identify the changes occurring during its first few weeks of the newborn’s immune system.
In their study, the researchers compared blood samples from 100 newborns, including both pre-term and full-term births. The blood samples were taken at the first, fourth, and twelfth weeks post-birth. The analysis includes: 58 immune cell populations though mass cytometry and 267 plasma proteins done by immunoassays. This analysis provided a systems-level review of the infants’ immunological adjustment to newborn life.
The researchers found that cell population and plasma protein shifts followed a stereotypic pattern found in all of the infants, and that despite varying levels of maturity (pre-term or full-term) and exposures to varying newborn environments that their respective immune systems all went on the same developmental path at this stage in their young lives. However, if the infant’s immune system interacted with microbes already as newborns, then that stereotypical development of the neonatal immune system was hindered.
One of the researchers expressed that: “Our results are important for better understanding the infection-sensitivity of newborn babies and the risks of premature birth. 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.”
I was fascinated by how steering neonatal immune systems could prevent autoimmunity and allergies. I brief cursory review I found a review article “Breastfeeding and autoimmunity: Programing health from the beginning” that explains that breastfeeding‐induced protection may be due to early antigen‐specific tolerance induction, by both the transfer of antigens through the breast milk and the presence of various factors that affect the newborn’s immune maturation and responses. The presence of these antigens are involved in the “pathogenesis of multiple immune‐mediated diseases, such as soluble maternal semi‐allogenic HLA molecules, maternal cells, gliadin, ovalbumin, intact human insulin, and food allergens, such as peanut and bovine beta‐lactoglobulin.” So, the respective mother produces differently composed breastmilk due to her own previous antigen exposures and her immune responses to transferred antigens, “the permeability of her mammary gland epithelium, microbiome‐influencing factors, gut growth factors in her breast milk, and the presence of tolerogenic molecules.” This breast milk provides similar protections to her infant and therefore if the breast milk can be enhanced it could create a wider net of immunological protections to an even larger variety of antigens.
https://www-ncbi-nlm-nih-gov.ezproxy.gsu.edu/pubmed/29083070
After reading the blog post and learning how a baby’s immune system develops both during childbirth and the first few months after, I started to wonder how this would be impacted by diseases that cause significant damage to the immune system. Specifically, I wanted to know whether children born to HIV infected mothers but not necessarily infected themselves, would have an impaired immune response to their environment compared to babies not exposure to HIV. I found an article by Miyamoto et al. which tested the immune development of HIV exposed but uninfected (HEU) children by measuring the plasma levels of cytokines and immune cells and compared it to those of unexposed controls. They found that the immune system of the HEU children were like the controls for all cytokines except for IL-4 and MIP-1β, and for CD4+ T cells. The differences were seen from the groups of children that were 12 months old and from 6-12 years old.
https://www.ncbi.nlm.nih.gov/pubmed/28591258
After reading this article, I wanted to learn more about the effects of gut bacterial dysbiosis in premature babies. The imbalance microbial dysbiosis in preterm babies have been found to be cause Necrotizing enterocolitis (NEC). NEC is where the intestinal walls of the premature infant is invaded by bacteria because they had not yet formed symbiotic bacteria (in contrast to full term infants) in their flora as a defense mechanism. The invasion of these bacteria causes local infection and inflammation that will ultimately destroy the infant’s intestines. The mortality rate of preterm infants with NEC is 15-30%. Those that survive will suffer from long-term neurodevelopmental deficits. Overall, the full pathogenesis of NEC is not entirely known other than that it is caused by imbalance of gut bacteria and formula feeding. Researchers are still trying to utilize the Human Microbiome Project to find further evaluate the neonatal intestinal microbiome. I wonder if antibiotics could help protect infants born prematurely against diseases caused by the gut bacterial dysbiosis such as NEC, or potentially cause more harm by not allowing them to build their own immunity. I also wonder if probiotics could help build the normal flora to promote gut health and prevent NEC.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343300/
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