How Breastfeeding Transfers Immunity To Babies

How Breastfeeding Transfers Immunity To Babies

The study highlights an amazing change that takes place in a mother’s body when she begins producing breast milk. For years before her pregnancy, cells that produce antibodies against intestinal infections travel around her circulatory system as if it were a highway and regularly take an “off-ramp” to her intestine. There they stand ready to defend against infections such as cholera or rotavirus. But once she begins lactating, some of these same antibody-producing cells suddenly begin taking a different “off-ramp,” so to speak, that leads to the mammary glands. That way, when her baby nurses, the antibodies go straight to his intestine and offer protection while he builds up his own immunity.

This is why previous studies have shown that formula-fed infants have twice the incidence of diarrheal illness as breast-fed infants.

Until now, scientists did not know how the mother’s body signaled the antibody-producing cells to take the different off-ramp. The new study identifies the molecule that gives them the green light.

“Everybody hears that breastfeeding is good for the baby,” said Eric Wilson, the Brigham Young University microbiologist who is the lead author on the study. “But why is it good? One of the reasons is that mothers’ milk carries protective antibodies which shield the newborn from infection, and this study demonstrates the molecular mechanisms used by the mother’s body to get these antibody-producing cells where they need to be.”

Understanding the role of the molecule, called CCR10, also has implications for potential future efforts to help mothers better protect their infants.

“This tells us that this molecule is extremely important, so if we want to design a vaccine for the mother so she could effectively pass protective antibodies to the child, it would be absolutely essential to induce high levels of CCR10,” said Wilson.

Speaking broadly about the long-term applications of this research, BYU undergraduate Elizabeth Nielsen Low, a co-author on the paper, said, “If we know how these cells migrate, we’ll be able to hit the right targets to get them to go where we want them.”

Daniel Campbell is a researcher at the Benroya Research Institute in Seattle, a nonprofit organization that specializes in the immune system, and was not affiliated with this study.

“The molecular basis for this redistribution [of the mother’s cells] has not been well characterized, but Dr. Wilson’s work has begun to crack that code and define the molecules responsible for this cellular redistribution and passive immunity,” Campbell said. “It is important work that fundamentally enhances our understanding of how immunity is provided to the [baby] via the milk. Dr. Wilson’s study will certainly form the basis for many other studies aimed at uncovering how the immune system is organized, particularly at mucosal surfaces.”

To conduct their research, the team used so-called “knock-out mice” that had been genetically engineered to lack the CCR10 molecule. Whereas normal lactating mice had hundreds of thousands of antibody-producing cells in their mammary glands, the BYU team found that the knock-out mice had more than 70 times fewer such cells. Tests verified that the absence of CCR10 was responsible for the deficiency.

Surprisingly, the research also showed that CCR10 does not play the same crucial role in signaling antibody-producing cells to migrate to the intestine. Another molecule is their “traffic light.”

The findings will be published in the Nov. 1 issue of the Journal of Immunology.

The study was supported by Wilson’s grant from the National Institutes of Health, funding which continues for another 18 months and supports his and his students’ further investigation into the cells behind transfer of immunity in breast milk.

Breast Milk and Antibodies

Antibodies, or immunoglobulins, are found in breast milk. There are five basic forms: IgG, IgA, IgM, IgD and IgE. All 5 forms have been found in human breast milk, but the most prevalent type is IgA, also known as secretory IgA. It is also found in large amounts throughout the intestinal tract and respiratory system of adults. Two joined

IgA antibodies protect the antibody molecules from being reduced by gastric acid and digestive enzymes present in the intestinal tract and stomach.

 

It takes several weeks or even months after birth for infants to make secretory IgA on their own. Through breast milk, secretory IgA molecules are passed on to the nursing baby and help in many ways beyond their natural ability to bind to microorganisms and keep them away from the body’s tissues. Bottle-fed infants do not have the advantage of fighting ingested pathogens until they can produce secretory IgA on their own.

 

The medical establishment know that infants who are breastfed contract fewer infections than formula-fed babies. Breast milk protects against E. coli, salmonellae, shigellae, streptococci, staphylococci, pneumococci, poliovirus, and rotaviruses.  It is known that infants who receive formula can contract more sickness, meningitis, infections of the intestinal tract, ear, respiratory tract and urinary tract than do breastfed babies.

Antibodies transmitted to an infant are targeted against germs in the baby’s surroundings. A mother will begin producing antibodies when she comes in contact with a disease-causing agent. Antibodies made by the Mother are specific to her environment. The baby will then receive protection from infectious germs it will encounter the most in the first few weeks of life. Antibodies passed to the baby will disregard the useful bacteria found in the gut. This gut flora is used to get rid of the growth of harmful organisms, which will provide another measure of resistance. Secretory IgA molecules, unlike other antibodies, ward off diseases without causing inflammation.

Several other molecules in human milk prevent microbes from attaching to mucosal surfaces. Oligosaccharides, which are simple chains of sugars, can intercept bacteria, forming harmless complexes that the baby excretes. Breast milk also contains mucins that contain protein and carbohydrate. They are also capable of attaching to bacteria and viruses and eliminating them from the body.

There are other helpful molecules present in breast milk. A  molecule of a protein called lactoferrin, can bind to two atoms of iron. Since many pathogenic bacteria thrive on iron, lactoferrin can stop their spread. It is especially effective at reducing or slowing down the proliferation of organisms that can cause serious illness in infants such as Staphylococcus aureus. One of the oldest disease-resistance factors known in breast milk is the Bifidus factor, which promotes the growth of a beneficial organism called Lactobacillus bifidus. Interferon, which is found in colostrum that a mother produces during the first few days after birth, can be thought of as an antiviral agent. Fibronectin which is present in colostrum, can minimize inflammation and aid in repairing tissue damage. Colostrum is a natural and 100% safe vaccine since it contains large quantities of secretory immunoglobulin A, or IgA.

Immune cells are also in abundance in breast milk. They consist of white blood cells, which fight infection and activate other defenses. Cells such as neutrophils act as phagocytes in the infant’s intestinal tract for about 2 months after birth. Macrophages are present in about 40 percent of all the leukocytes in colostrum. In some experiments they have shown they are better capable than are their counterparts in blood. Macrophages in breastmilk also manufacture lysozyme, which increases the amount in the infant’s gastrointestinal tract. An enzyme called Lysozyme destroys bacteria by disrupting their cell walls. Macrophages in the digestive tract can get lymphocytes to action against invaders. B lymphocytes raise antibodies and T lymphocytes kill infected cells directly or provide direction to other chemical messages that will mobilize other components of the immune system. Breast milk lymphocytes proliferate in the presence of Escherichia coli, which is a bacterium that can cause severe illness in babies. However, they are less responsive than blood lymphocytes to germs. Breast milk lymphocytes also produce gamma interferon, migration inhibition factor, and monocyte chemotactic factor. All of which can strengthen the immune response.

There are studies showing that breast milk may induce an infant’s immune system to mature more quickly. Breastfed babies produce higher levels of antibodies in response to immunizations. Certain hormones in milk like cortisol and proteins such as epidermal growth factor, nerve growth factor, an insulin-like growth factor, and somatomedin C, can close up the leaky mucosal lining of the newborn. This makes it impossible for harmful pathogens to get though. Other compounds in breast milk stimulate a baby’s own production of secretory IgA, lactoferrin and lysozyme but are not known. Secretory IgA, lactoferrin and lysozyme are all found in the urine of breastfed babies. Breastfed babies cannot absorb these molecules from breast milk into their intestinal tract. The molecules are produced in the mucosa of the baby’s urinary tract. Therefore, breastfed babies have a lower risk of acquiring urinary tract infections.

Breast milk has the ability to protect infants against infection until they can protect themselves, along with providing them with all the nutritional requirements they need. Immune protection continues to improve and change dependent upon the needs of the infant and age throughout the duration of breastfeeding no matter how long that may be.  A baby may not necessarily receive enough of their mother’s  IgG immunities through breast milk to qualify as an immunization against a particular disease, but IgA, certain fatty acids, etc, in the breast milk active and do protect against illnesses. 
      
Dr. Jack Newman in How Breast Milk Protects Newborns, states: “Free fatty acids present in milk can damage the membranes of enveloped viruses, such as the chicken pox virus, which are packets of genetic material encased in protein shells.” The secretory IgA in breast milk also activates against the chicken pox virus in vitro.
 
As the baby grows, some of the immune factors in breast milk increase in concentration so older babies still receive plenty of immune factors. As a baby starts to nurse less and milk supply decreases, the concentration of immunities increases. [source: Goldman AS et al. “Immunologic components in human milk during weaning.” Acta Paediatr Scand. 1983 Jan;72(1):133-4.] 

List of Immune Factors In breast milk: 

alpha-Lactalbumin (variant) 
alpha-lactoglobulin 
alpha2-macroglobulin (like) 
ß-defensin-1 
Bifidobacterium bifidum 
Carbohydrate 
Casein 
CCL28 (CC-chemokine) 
Chondroitin sulphate (-like) 
Complement C1-C9 
Folate 
Free secretory component 
Fucosylated oligosaccharides 
Gangliosides GM1-3, GD1a, GT1b, GQ1b 
Glycolipid Gb3, Gb 
Glycopeptides 
Glycoproteins (mannosylated) 
Glycoproteins (receptor-like) 
Glycoproteins (sialic acid-containing or terminal galactose) 
Haemagglutinin inhibitors 
Heparin 
IgG 
IgM 
IgD 
kappa-Casein 
Lactadherin (mucin-associated glycoprotein) 
lactoferrin 
Lactoperoxidase 
Lewis antigens 
Lipids 
Lysozyme 
Milk cells (macrophages, neutrophils, B & T lymphocytes) 
Mucin (muc-1; milk fat globulin membrane) 
Nonimmunoglobulin macromolecules (milk fat, proteins) 
Oligosaccharides 
Phosphatidylethanolamine 
(Tri to penta) phosphorylated beta-casein 
Prostaglandins E1, E2, F2 alpha 
RANTES (CC-chemokine) 
Ribonuclease 
Secretory IgA 
Secretory leukocyte protease inhibitor (antileukocyte protease; SLPI) 
Sialic acid-glycoproteins 
sialylated oligosaccharides 
Sialyllactose 
Sialyloligosaccharides on sIgA(Fc) 
Soluble bacterial pattern recognition receptor CD14 
Soluble intracellular adhesion molecule 1 (ICAM-1) 
Soluble vascular cell adhesion molecule 1 (VCAM-1) 
Sulphatide (sulphogalactosylceramide) 
Trypsin inhibitor 
Vitamin A 
vitamin B12 
Xanthine oxidase (with added hypoxanthine) 
Zinc 
Unidentified factors