HOW BREAST MILK PROTECTSNEWBORNS

Someof the moleculesand cells

in humans milk actively help infants stave off infection by JackNewman As published SCIENTIFICAMERICAN December1995

Doctorshave long known that infants who are breast-fedcontractfewer infectionsthan do thosewho are given formula. Until fairly recently,most physicianspresumedthat breast-fedchildren fared better simple because milk supplied directly from the breastis free of bacteria.Formula,which must often be mixed with water and placed in bottles,canbecomecontaminatedeasily. Yet even infants who receivesterilized formula suffer from more meningitis and infection of the gut, ear, respiratory tract and urinary tract than do breast-fed youngsters. The reason,it turns out, is that mother'smilk actively helps newbornsavoid disease in a variety of ways. Suchassistance is particularly beneficialduring the first few months of life, when an infant often cannotmount an effectiveimmune responseagainstforeign organisms.And although it is not the norm in most industrial cultures,UNICEF and the World Health Organizationboth advise breast-fedto "two yearsand beyond." Indeed,a child's immune responsedoes not reachits full strength until agefive or so. All humansbabiesreceivesomecoverage in advanceof birth. During pregnancy,the mother passes antibodiesto her fetus through the placenta.These proteins circulate in the infant's blood for weeksto months after birth, neutralizing microbesor marking them for destructionby phagocytes-immune cells that consumeand break down bacteria,viruses and cellular debris. But breast-fedinfants gain extra protection from antibodies,other proteins and immune cells in human milk. Onceingested,thesemoleculesand cellshelp to prevent microorganismsfrom the body's tissues.Someof the moleculesbind to microbesin the hollow space (lumen) of the gastrointestinaltract. In this way, they block microbesfrom attachingto attachingto and crossingthrough the mucosa-the layer of cells,also known asthe epithelium, that lines the digestivetract and other body cavities. Other moleculeslessenthe supple of particular m~erals and vitamins that harmful bacterianeed to survive in the digestivetract. Certain immune cells in human milk are phagocytesthat attack microbesdirectly. Another setproduces chemicalsthat invigorate the infant's own immune response.

Breast Milk Antibodies

Antibodies, which are also called immunoglobulins, take five basic forms, denoted as IgG, IgA, IgM, IgD and IgE. All have been found in human milk, but

by far the most abundant type is IgA, specificallythe form known as secretory IgA, which is found in great amountsthroughout the gut and respiratory system
of adults. These antibodies consist of t:w joined ~gA molecules and a so-c~lled

secretorycomponentthat seems to shIeld the antibody moleculesfrom bemg ?egra.ded by the gastric acid and digestiveenzymesin the stomachand mtestmes. Infants who arebottle-fed have few meansfor battling ingestedpathogensuntil they begin making secretoryIgA on their own, often severalweeksor even months after birth. The secretoryIgA moleculespassedto the suckling child are helpful in ways that go beyond their ability to bind to microorganismsand keep them away from the body's tissues.First, the collection of antibodiestransmitted to an infant is highly targetedagainstpathogensin that children's immediate surroundings. The mother synthesizes antibodieswhen sheingests,inhalesor otherwisecomes in contactwith a disease-causing agent.Eachantibody shemakesis specificto that agent;that is, it binds to a single protein, or antigen,on the agentand will not wastetime attacking irrelevant substance. Because the mother makes antibodiesonly to pathogensin her environment, the baby receivesthe protection it most needs-against the infectious agentsit is most likely to encounterin the first weeksof life. Seconds, the antibodiesdelivered to the infant ignore useful bacterianormally found in the gut. This flora servesto crowd out the growth of harmful organisms, thus providing another measureof resistance. Researchers do not yet know how the mother's immune systemknows to make antibodiesagainstonly pathogenic and not normal bacteria,but whatever the processmay be, it favors the establishmentof "good bacteria"in a baby'sgut. SecretoryIgA moleculesfurther keep an infant from harm in that, unlike most other antibodies,they ward off disease without causinginflammation- a process in which various chemicalsdestroy microbesbut potentially hurt healthy tissue. In an infant's developing gut, the mucosalmembraneis extremely delicate,and excess of thesechemicalscan do considerabledamage. Interestingly, secretoryIgA canprobably protect mucosalsurfaceother than thosein the gut. In many countries,particularly in the Middle East,western SouthAmerican and northern Africa, women put milk in their infants' eyesto treat infectionsthere.I do not know if this remedy has ever beentested scientifically, but there are theoreticalreasonsto believeit would work. It probably doeswork at leastsomeof the time, or the practicewould have died out.

An Abundance of Help Molecules Severalmoleculesin human milk besidessecretoryIgA prevent microbesfrom attachingto mucosalsurfaces. Oligosaccharides, which are simple chainsof sugars,often contain domainsthat resemblethe binding sitesthrough which bacteriagain entry into the cells lining the intestinal tract. Thus, thesesugar can interceptbacteria,forming harmlesscomplexes that the baby excretes. In addition, human milk containslarge moleculescalled mucins that include a great deal of protein and carbohydrate.They, too, are capableof adhering to bacteria and viruses and eliminating them from the body. The moleculesin milk have other valuablefunctions aswell. Eachmoleculeof a protein called lactoferrin, for example,canbind to two atomsof iron. Because many pathogenicbacteriathrive on iron, lactoferrin halts their spreadby making iron unavailable.It is especiallyeffectiveat stalling the proliferation of organisms that often causeseriousillness in infants, including Staphylococcusaureus. Lactoferrin also disrupts the processby which bacteriadigest carbohydrates, further limiting their growth. Similarly, B12binding protein, as its name suggests, deprives microorganismsof vitamin B12. Bifidus factor, one of the oldest-known disease-resistance factorsin human milk, promotesthe growth of a beneficialorganismnamed Lactobacillus bifidus. Freefatty acidspresentin milk can damagethe membranes of envelopedviruses, such as the chickenpox virus, which are packetsof genetic material encased in protein shells.Interferon, found particularly in colostrumthe scant,sometimesyellowish milk a mother producesduring the first few days afterbirth - also has strong antiviral activity. And fibronectin, presentin large quantities in colostrum, can make certain phagocytes more aggressive so that they will ingest microbeseven when the microbeshave not beentaggedby an antibody. Like secretoryIgA, fibronectin minimizes inflammation; it also seems to aid in repairing tissuedamagedby inflammation. Cellular Defenses As is true of defensivemolecules,immune cells are abundant in human milk. They consistof white blood cells,or leukocytes,that fight infection themselves and activateother defensemechanism.The most impressiveamount is found in colostrum. Most of the cells are neutrophils, a type of phagocytethat normally circulatesin the bloodstream.Someevidencesuggests that neutrophils continue to act asphagocytesin the infant's gut. Yet they are lessaggressive than blood neutrophils and virtually disappearfrom breastmilk six weeksafter birth. So perhapsthey servesomeother functions, such asprotecting the breastfrom infection.

The next most commonmilk leukocyteis the macrophage, which is phagocytic like neutrophils and performs a number of oth-er protective functions. Macrophages make up some40 percentof aIr the leukocytesin colostrum.They are far more active than milk neutrophils, and recentexperimentssuggestthat they are more motile than are their counterpartsin blood. Aside from being phagocytic,the macrophages in breastmilk manufacturelysozyme,increasingits amount in the infant's gastrointestinaltract. Lysozymeis an enzymethat destroysbacteriaby disrupting their cells walls. In addition, macrophages in the digestivetract can rally lymphocytesinto action againstinvaders.Lymphocytesconstitutethe remaining 10percentof white cells in the milk. About 20 percentof thesecells are B lymphocytes,which give rise to antibodies;the rest are T lymphocytes,which kill infected cells directly or send out chemicalmessages that mobilize still other componentsof the immune system.Milk lymphocytesseemto behavedifferently from blood lymphocytes.Thosein milk, for example,proliferate in the presence of Escherichiacoli, a bacterium that can causelife- threateningillness in babies,but they are far lessresponsivethan blood lymphocytesto agentsposing lessthreat to infants. Milk lymphocytesalso manufactureseveralchemicals-including gamma-interferon, migration inhibition factor and monocytechemotacticfactorthat can strengthenan infant's own immune response. Added Benefits Severalstudiesindicate that somefactorsin human milk may induce an infant's immune systemto mature more quickly than it would were the child fed artificially. For example,breast-fed babiesproducehigher levels of antibodiesin response to immunizations. Also, certain hormonesin milk (suchascortisol) and smallerproteins (including epidermal growth factor,nerve growth factor, insulinlike growth factor and somatomedinC) act to closeup the leaky mucosal lining of newborn, making it relatively impermeableto unwanted pathogensand other potentially harmful agents.Indeed, animalsstudieshave demonstrated that postnatal developmentof the intestine occursfasterin animals fed their mother'smilk. And that also receivecolostrum,containing the highest concentrations of epidermal growth factor, mature even more rapidly. Other unknown compoundsin human milk must stimulate a baby'sown production of secretoryIgA, lactoferrin and lysozyme.All three moleculesare found in larger amountsin the urine of breast-fed babiesthan in that of bottlefed babies.Yet breast-fed babiescannot absordthesemoleculesfrom human milk into their gut. It would appearthat the moleculesmust be produced in the mucosaof the youngsters'urinary tract. In oth~r words, it seemsthat breastfeeding induceslocal immunity in the urinary tract. In support of this notion, recentclinical studieshave demonstratedthat the breast-fed infant has a lower risk of acquiring urinary tract infections.Finally, someevidencealso suggestthat an unknown factor in human milk may cause breast-fed infants to produce more fibronectin on their own than do bottle- fed babies.

All things considered, breast milk is truly a fascinating fluid that supplies infants with themselves. far more than nutrition. It protects-them against infection until they can protect

Immune Benefits of BreastMilk at a Glance

Component
I

Action
White Blood Cells
I

B lymphocytes Macrophages

Give rise to antibodiestargetedagainstspecific microbes Kill microbesoutright in the baby'sgut, produce lysozymeand activateother componentsof the immune system May act asphagocytes, injesting bacteriain baby's digestive system. Kill infected cells directly or send out chemicalmessageto mobilize other defenses. They proliferate in the presence of organismsthat causeseriousillness in infants.They alsomanufacturecompoundsthat can strengthena child's own immune response.
Molecules
I

Neutrophils T lymphocytes

Antibodies of secretoryIgA class B12binding

protein

Bind to microbesin baby'sdigestivetract and thereby prevent them from passingthrough walls of the gut in into body's tissues. Reduces amount of vitamins B12,which bacterianeed
in order to grow.

Bifidus factor

Promotesgrowth of Lactobacillus bifidus, a harmless bacterium,in baby'sgut. Growth of suchnonpathogenic bacteriahelps to crowd out dangerousvarieties Disrupt membranessurrounding certain viruses and destroy them. Increases antimicrobial activity of macrophages; helps to repair tissuesthat havebeendamagedby immune reaction'sin baby's gut. Enhances antimicrobial activity of immune cells.

Fatty acids Fibronectin

Gamma-interferon

Hormonesand growth factors

Stimulatebaby's digestivetract to mature more quickly. Oncethe initIally "leaky" membraneslining the gut mature, infants becomelessvulnerable to microorganisms. Binds to iron, a mineral many bacterialneed to survive. By reducing the availableamount of iron, lactoferrine thwarts growth of pathogenicbacteria. Kills bacteriaby disrupting their cell walls. Adhere to bacteriaand viruses,thus keeping such microorganismsfrom attachingto mucosalsurfaces. Bind to microorganismsand bar them from attaching to mucosalsurfaces.

Lactoferrin

Lysozyme Mucins Oligosaccharides

The Author
JACK NEWMAN founder the breast-feedingclinic at the hospital for sick Children in Toronto in 1984and servesas its director. He hasmore recently establishedsimilar clinics at DoctorsHospital and St. Michael'sHospital, both in Toronto. Newman receivedhis medical degreein 1970from the University of Toronto, where he is now an assistantprofessor.He completedhis postgraduate training in New Zealand and Canada.As a consultantfor UNICEF, he hasworked with pediatricians in Africa. He has alsopracticedin New Zealandand in Central and South America.

Further Reading
Mucosal :Immunity: The :Immunology of Breast Milk. H.B. Slade and S.A. Schwartz in Journal of Allergy and Clinical Immunology, Vol.80,No.3, pages 348356; September 1987. :Immunology of Milk and the Neonate. Edited by J. Mestecky et al. Plenum Press, 1991. Breastfeeding and Health in the 1980' s: A Global Epidemiologic Review. Allan S. Cunningham in Journal of Pediatrics, Vol. 118, No.5, pages 659666; May 1991.

System of Human Milk: Antimicrobial, Antinflammatory and Immunomodulating Properties. A.S. Goldman in Peaiatric Infectious Disease Journal, Vol. 12, No.8, pages 664-671;August.1993: Host-Resistance Factors and Inununologic Significance of Human Milk. In Breastfeeding: A Guide for the Medical Profession, by Ruth A. Lawrence. Mosby Year Book, 1994.
The Inunune