Innate Immunity and Breast Milk
This “quiescent mode” of innate immune system is part of a highly regulated .. A newborn ingests an estimated maternal cells per day with 80% a particularly important reciprocal relationship, affecting and affected by. No relationship was found between concentrations of innate factors and rotavirus vaccine response. Keywords: breast vaccine by acquired or innate immune factors present in breast milk. mother for involvement of the mother-infant pair. No relationship was found between concentrations of innate factors and rotavirus vaccine response. © The Author Innate Immune Factors in Mothers'Br east Milk and dose of the pentavalent rotavirus vaccine in corresponding infants. .. nate and acquired immunity score of breast milk between.
In this review, while we focus on the characteristics and status of ILCs in neonatal immune system, we also draw an analogy from a national defense perspective because of the great similarities between that and the immune system by providing the known biological counterparts of all five core operational elements, the five Ds of defense, detection, discrimination, deployment, destruction, and de-escalation, with special focus on innate immunity, maternal support, and influence during the neonatal and infancy periods.
However, neonatal immune system is a developing structure, evolves in a convoluted step-wise manner 1 — 4. Infantile immunity is a true elaborate system, simply because while it exits the friendly intra-uterine environment, it is entering the hostile microbe-laden external world.
In many ways, the immune system we are born with is the product of the immune environment during pregnancy 14.
It is crafted and built block by block and day by day, forged through continuous and never ending improvement during gestation. While still responding to all allo-antigens, the maternal immune system must be tolerant to the fetus, even though it is haplo-mismatched, or semi-allogeneic half of the antigens being of paternal, and therefore of foreign origin.
Innate Immunity of Neonates and Infants
This results in immunomodulation during pregnancy and extends to early life. Initially, the tolerogenic status of neonatal immunity was attributed to the immaturity and lack of memory within immune components during infancy. This premise of immune immaturity was replaced by the notion of immunodeviant characteristic of neonatal immunity 15. However, in light of recent discoveries, mounting evidence supports the concept that infantile immunity is in fact a highly regulated, but intellect, orchestrated, functional, and dynamic network of competent molecular and cellular components.
More recent data, such as those represented in the accompanying articles of this symposium, suggest that the mechanisms of inhibition may be further confounded by additional considerations.
Innate Immunity and Breast Milk
For example, the matrix in which the inhibitor is present may contain synergistic inhibitors, such that inhibitors thought to be weakly active may become highly effective inhibitors, such as with fatty acids. The location at which an inhibitor is produced and the location at which it is effective may result in a spatial specificity that would cause an inhibitor to act entirely differently in vitro from its role in vivo, such as with biocidal peptides.
Differences in resident microflora among individuals may influence the efficacy of a probiotic. Different states of inflammation may determine if specific immunomodulators are beneficial under a specific set of circumstances.
Individual differences in glycan expression determine to which pathogens an individual is susceptible and which human-milk oligosaccharides would be protective; expression of glycans in gut also differs at different stages of development.
Also, different strains of pathogens may have different binding specificities, again, determining which glycans would be effective inhibitors of these strains. Finally, all of these factors may interact. Thus, spatial and temporal specificity, synergy, individual differences and stages of development, and immunological states and context all must be taken into account when defining the protective agents in human milk that participate in the mucosal immunity of the infant.
Because this was the only major protective component recognized for some time, whose discovery coincided with the increasing recognition of the central role of antibodies in human defense, and the lower incidence of disease in breast-fed infants, the sIgA in milk was widely thought to account for the protection afforded to the nursing infant against pathogens. The mechanism for this protection is shown in Figure 1.
When the mother—infant nursing dyad is exposed to a novel enteric pathogen, the Peyer's patch in the maternal intestinal mucosa acquires the pathogen in a sample of luminal contents. The M cell presents the antigens of the pathogen to circulating B cells, priming the cell for antibody production.
When the B cell is in the proximity to the basolateral side of the mammary epithelial cell, the IgA that is produced is transported into the acinar cell on the basolateral side, and, as the IgA is transported to the apical side of the cell, the IgA acquires its carbohydrate chain to become sIgA that is excreted from the apical membrane into the milk.
The sIgA in milk enters the alimentary canal of the infant where it binds to the enteric pathogen, inhibiting disease. After the mother is exposed to a pathogen, many days elapse before the induction of protective antibody and its secretion into the milk and the gut of the infant.
- Evolution of the immune system in humans from infancy to old age
- Development of the Innate Immune Response: Role of the Maternal Microbiome
- Innate Immunity of Neonates and Infants
Assuming that both the mother and her infant are exposed to the pathogen simultaneously, this would leave the infant vulnerable to the pathogen were it not for other protective mechanisms. Other forms of infant mucosal protection were the topic of this series of reports and include protective components that are intrinsic constituents of human milk, which we define as components of an innate immune system of human milk, and probiotics, which are food-borne bacteria that confer some positive activity toward protecting the infant.
When the nursing dyad is exposed to an enteric pathogen, the Peyer's patch of the mother acquires the pathogen from the lumen of the gut, whereupon the M cell presents its antigen on the serosal side to the B cell, which migrates to the serosal side of the mammary epithelial cell and secretes IgA. As the IgA moves from the serosal to the luminal side of the mammary epithelial cell, it is glycosylated to form secretory IgA, which is secreted into the milk.
When the infant consumes the milk, the sIgA, which is resistant to digestion, binds to the pathogen, inhibiting its ability to infect the infant. Probiotics One of the early documented differences between breast-fed and artificially fed infants was the microflora of their gut. Breast-fed infants have a higher percentage of lactobacilli, especially Lactobacillus bifidus now Bifidobacterium bifidumwhereas artificially fed infant microflora has a composition that more closely resembles that of the adult gut.
A human-milk component, a glycan, was found to stimulate the growth of, and colonization by, L.
Another more direct mechanism for altering intestinal microflora is to feed beneficial bacteria, probiotics, in the diet to benefit from their presence in the gut. From the use of lactobacilli commonly found in traditional yogurts, the selection of probiotics that protect the recipient from diseases has advanced in the past several years to the highly popular and more effective Lactobacillus GG, an isolate with origins in the human gut.
Much work on Lactobacillus GG, and the continued search for other probiotics, was and is still being performed in Finland; Salminen and colleagues 2 describe the basis for the multiple criteria being used for the selection of new probiotics. Each probiotic has a specific target based on its specificity of binding to host cell receptors, which are usually glycans expressed on the cell surface of intestinal mucosa.
Likewise, specific probiotics are able to protect against specific pathogens. For a probiotic to be able to colonize the host, thereby extending its useful duration, the interdependence of microbiota must be considered. Administration of probiotics early in development has a greater chance of coinciding with a critical period of gut colonization and thus of producing lasting consequences.
Ultimately, we would like to be able to choose probiotics with long-term sequelae for prophylaxis against chronic conditions; for example, evidence is presented that specific probiotics early in life may attenuate or prevent the development of manifestations of allergy in later life. Thus, the search for effective probiotics has moved from looking for one or a few probiotics for treating acute infections by any intestinal pathogen to looking for complex combinations of probiotics that would balance the indigenous microflora in a way that has lifelong benefits to the recipient.
The innate immune system of human milk Several milk components have been found that are important nutrients but that have, or whose partial digestion products have, antipathogenic activity.
Innate Immunity and Human Milk | The Journal of Nutrition | Oxford Academic
These can be classified as multifunctional agents, and, because these are intrinsic components of milk, we will consider them as part of the innate immune system of human milk. Two of the most widely recognized have been the FFAs, and especially the monoglycerides, that are released as human-milk triglycerides are digested in the infant stomach, and lactoferrin, a major protein of human milk that has been reported to have several inhibitory mechanisms, including the sequestering of iron, which may be bacteriostatic, a direct antibacterial effect by the whole protein, and the release of peptides during its digestion.
These peptides inhibit many distinct pathogenic bacteria, most commonly through local disruption of the membrane, causing it to become leaky. Recent research is not only adding more recognized components to this category of multifunctional protective agents in milk but is also defining the conditions under which they are most active.
The examples in the accompanying articles are the FFAs and monoglycerides, the antibacterial peptides, and a protein structural conformer. Fatty acids and monoglycerides.Ch 19 Normal Newborn adaptation
In the adult, triglyceride is digested slowly, but, in nursing infants, as milk is entering the stomach, it is already releasing FFAs from the digestion of the milk triglycerides by lingual and gastric lipases. Thus, gastric contents of nursing infants already have appreciable fatty acids and monoglycerides, and these have been shown to be antiviral, antibacterial, and antiprotozoal.
This activity may augment the ability of the stomach to act as a barrier against ingested pathogens. An illustration of the ability of linoleate, at concentrations typical of the nursling's stomach, to destroy vesicular stomatitis virus is found in Figure 2 3.
In earlier studies, the Isaacs laboratory had defined oleic and linoleic acid as having very high activity at killing enveloped viruses and found that monoglycerides had the highest activity.
Of these, oleic acid is released from milk in the highest concentration, making it a primary source of protection to the breast-fed infant. However, when fatty acids are tested in combination, even those that show no inhibitory activity at the concentrations found in stomach aspirates may display potent activity when tested in combination.
Furthermore, these lipid activities may be further enhanced when tested in combination with inhibitory peptides 4. This implies that there may be many more bioactive milk components than those whose activity is apparent when they are tested separately.
More globally, this is just one example of how dependent we are on seemingly irrelevant conditions of assays for finding biological activities relevant to human protection and on how the synergies of these components might produce powerful protection from simple, common compounds.
Another point is the temporal and spatial specificity as compounds are released and then destroyed during specific phases of digestion at specific regions of the gut. This latter may be best illustrated by the release of bioactive peptides, described below.
Vesicular stomatitis virus a is incubated b for 30 min with linoleic acid at half the concentration found in gastric aspirate of nursing infants 0. The linoleic acid released from human-milk triglycerides makes the envelope of the viruses become leaky, ultimately destroying the virus under conditions that mimic those found in the stomach of nursing infants. The article by the Mietzner group 5 notes that, although human milk contains nutrients in proportions that should support profuse bacterial growth, it is highly resistant to bacterial overgrowth.
This is consistent with their conclusion that antimicrobial peptides are abundant in human milk, both pre- and postdigestion.