Importance of breast milk as a mode of passive immunisation in babies

Importance of breast milk as a mode of passive immunization in babies

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01) Introduction

02) Composition of breast milk

03) Passive Immunization

4. Components in breast milk which contribute to the passive immunization in babies

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4.1) Anti-infective

2) Ant allergic

3) Anti-inflammatory

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4) Drugs

05) Conclusion

Introduction

Breastfeeding provides unsurpassed natural nutrition to the newborn and infant. Human breast milk also contains numerous protective factors against infectious disease and may influence immune system development.If immune system development is significantly improved with the introduction of components of breast milk, then prematurely discontinued breastfeeding may facilitate pathogenesis of many chronic diseases later in life (e.g., autoimmune disorders)

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In addition to being the best source of nutrition for newborns

and infants, human breast milk also provides immunologic protection against many infectionsAlthough most of the immunologic benefit cited by researchers relates to protection from diarrheal diseases that are especially prevalent in developing countries(2,3) breastfeeding has also been shown to protect infants against extra intestinal infections, such as otitis media(4,6)and respiratory diseases.(7,10)

Breast-feeding maintains the maternal-fetal immunological link after birth, may favor the transmission of immune competence from the mother to her infant, and is considered an important contributory factor to the neonatal immune defense system during a delicate and crucial period for immune development. The protection from infections may be ensured either passively by factors with anti-infective, hormonal, enzymatic, trophic, and bioactive activity present in breast milk, or through a modulator effect on the neonatal immune

system exerted by cells, cytokines, and other immune agents in human milk.

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This essay will show how these factors of breast milk affect the passive immune system in babies.

Composition of Breast milk

Breast milk has all the necessary nutrients for infant in correct proportions including macro and micronutrients.

The first fluid produced by mothers after delivery is colostrum, which is distinct in volume,

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appearance and composition. Colostrum, produced in low quantities in the first few days

postpartum, is rich in immunologic components such as secretory IgA, lactoferrin,leukocytes, as well as developmental factors such as epidermal growth factor (4).Colostrumalso contains relatively low concentrations of lactose, indicating its primary functions to beimmunologic and trophic rather than nutritional. Levels of sodium, chloride and magnesiumare higher and levels of potassium and calcium are lower in colostrum than later milk.(1)

The nutritional components of human milk derive from three sources: Some of the nutrientsof milk originate by synthesis in the lactocyte, some are dietary in origin, and some originatefrom maternal stores. Overall, the nutritional quality of human milk is highly conserved, butattention to maternal diet is important for some vitamins and the fatty acid composition ofhuman milk.(4)

The macronutrient composition of human milk varies within mothers and across lactationbut is remarkably conserved across populations despite variations in maternal nutritional

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Status (13).The mean macronutrient composition of mature, term milk isestimated to be approximately 0.9 to 1.2 g/dL for protein, 3.2 to 3.6 g/dL for fat, and 6.7 to7.8 g/dL for lactose. Energy estimates range from 65 to 70 kcal/dL, and are highly correlatedwith the fat content of human milk. Macronutrient composition differs between preterm andterm milk, with preterm milk tending to be higher in protein and fat.

A study inDavis, California examined the association between maternal characteristics and the

composition of human milk macronutrients(4) and found that after 4 months postpartum, themacronutrient concentrations of human milk are associated with one or more of thefollowing factors: Maternal body weight for height, protein intake, parity, return ofmenstruation, and nursing frequency. This study also found that mothers who producehigher quantities of milk tend to have lower milk concentrations of fat and protein but higherconcentrations of lactose.

The proteins of human milk are divided into the whey and casein fractions or complexes,with each comprised by a remarkable array of specific proteins and peptides(4,1).The mostabundant proteins are casein, α-lactalbumin, lactoferrin, secretory immunoglobulin IgA,lysozyme, and serum albumin.(14)

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Non-protein nitrogen-containing compounds, includingurea, uric acid, creatine, creatinine, amino acids, and nucleotides, comprise ~25% of humanmilk nitrogen.

Human milk protein concentration is not affected by maternal diet, but increases with maternal bodyweight for height, and decreases in mothers producing higher amounts of milk.10

Human milk fat is characterized by high contents of palmitic and oleic acids, the formerheavily concentrated in the 2-position and the latter in the 1- and 3-positions of thetriglycerides. Fat is the most highly variable macronutrient of milk. Hind milk, defined as thelast milk of a feed, may contain two to three times the concentration of milk fat found inforemilk, defined as the initial milk of a feed.

The principal sugar of human milk is the disaccharide lactose. The concentration of lactosein human milk is the least variable of the macronutrients, but higher concentrations oflactose are found in the milk of mothers producing higher quantities of milk. (10) The other significant carbohydrates of human milk are the oligosaccharides, which compriseapproximately 1 g/dL in human milk, depending on stage of lactation and maternal geneticfactors. (1)

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Human milk provides the normative standard for infant nutrition. Nevertheless, manymicronutrients vary in human milk depending on maternal diet and body stores , including vitamins A, B1, B2, B6, B12, D,and iodine.(1)

Vitamin K is extremely low inhuman milk and thus, the American Academy of Pediatrics recommends an injection of thisvitamin to avoid hemorrhagic disease of the newborn(4).Vitamin D also occurs in lowquantity in human milk, particularly with low maternal exposure to sunshine, a circumstancenow common in populations worldwide

Human milk contains numerous growth factors that have wide-ranging effects on theintestinal tract, vasculature, nervous system, and endocrine system.

Intestinal maturation and repair: Epidermal growth factor (EGF)

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Found in amniotic fluid and breast milk, (1, 4) EGF is critical to the maturation andhealing of the intestinal mucosa

EGF is highest in early milk anddecreases over lactation.45,46 The average EGF level in colostrum is 2000-fold higher and inmature milk is 100-fold higher than in maternal serum.41 Further, preterm milk containshigher levels of EGF than term milk.(4)

Growth and development of the enteral nervous system: Neuronal growth factors (GDNF)

In human cells, breast milk-derived GDNF increases neuron survival and outgrowth.51

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Tissue growth: The insulin-like growth factor (IGF) superfamily

IGF-I and IGF-II, as well as IGF binding proteins and IGF-specific proteases, are found inhuman milk.(1, 4)Levels are highest in colostrum, and steadily decline over the course oflactation.(1,4). Enteraladministration of physiological levels of IGF-I stimulates erythropoiesis and increaseshematocrit.(1)

Regulation of the vascular system: Vascular endothelial growth factor (VEGF)

Angiogenesis is regulated primarily by the relative expression of VEGF and its antagonists.

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VEGF concentration is highest in colostrum in both preterm and term human milk, withpreterm milk containing less VEGF than term milk.(4)

Intestinal development and prevention of anemia: Erythropoietin (Epo)

Milk contains significant quantities of Epo, which is the primary hormone responsible forincreasing red blood cells (RBC).

Blood loss, intestinal pathology, and immaturity of thehematopoietic system all contribute to anemia of prematurity, which profoundly impactsgrowth and development. (4,1)

Growth-regulating hormones: Calcitonin and Somatostatin

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Calcitonin and its precursor procalcitonin are present in large quantities in milk.(4)

Somatostatin is rapidly degraded in the jejunum and not transferred through theintestinal wall, but delivery with milk protects it from degradation and maintains bioactivity within the lumen (1, 4).

Passive Immunization

the ability of an organism to resist disease, either through the activities of specialized blood cells or antibodies produced by them in response to natural exposure or inoculation (active immunity) or by the injection of antiserum or the transfer of antibodies from a mother to her baby via the placenta or breast milk (passive immunity)(7,8,10)

Passive immunization can be categorized as Natural and Artificial.

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Artificially prepared antibodies are introduced in congenital or acquired immunodeficiency,4,7where as naturally occurring passive immunity transfer of maternal antibody –mediated immunity through placenta or breast milk(3,4,7).

Mother’s previous exposure to antigens is directly proportional to the amount of antibodies present in the milk9. Although antibodies are proteins, they do not breakdown into peptides by the proteolytic activity of infant’s gastric enzymes(14).Thus they provide immunity throughout the digestive tract and systemic immunity without exerting any allergic symptoms (4, 7, 8, 10)for common diseases occur after birth.

Components in Breast milk which contribute to the passive immunization of babies

These components can be categorized into several groups according to their function.

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(1) Anti-infective

(2) Anti-allergic

(3) Anti-inflammatory

(4) Drugs

(01) Anti-infective properties

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The protective effect of breast-feeding against infections is called the Anti-infective propertiesin the newborn’s immature immune system.As compensation has the baby in the first months trans placental spoken transferred IgG from the mother.In addition, antibodies and other immune components transmitted through breast milk(3).Humoral and Cellular factors are responsible for infant immunological properties.(8)

Humoral factors

There are various protective factors present in human milk, including immunoglobulin (Ig), lysozymes, the bifidus factor and nutrient-carrier proteins which bind vitamin B12,folate,and iron(in lactoferin) and limit their availability for intestinal bacteria, especially E.coli.(8)

The immunoglobulins include IgC, IgM and IgD. The most important of these in man appears to be secretory IgA (sIgA).It defers antigenically from serum IgA. Secretory IgA is especially high in colostrum (2-4 mg/ml). sIgA is a compact molecule, and is resistant to proteolytic enzymes of the gastro-intestinal secretions and low stomach ph. Secretory IgAin human milk is in 10-100 times greater concentrations than in maternal serum.(3,8)

In older individuals, sIgA is normally produced by sub epithelial cells in the intestinal tract. (8)During the early weeks of life the neonate does not secret this antibody, so that IgA in colostrum and milk act as an antiseptic intestinal paint, protectingintestinal epithelial surfaces until the infant’s own immune mechanisms mature.

Bifidus factor is an N-containing carbohydrate. It is present in very high concentrations in colostrum.(3,8) It lost if breast milk is boiled. The bifidus factor in human milk (combined with the low pH of the intestinal contents) facilitates the growth of Lactobacillus bifidus (Bifidobacteria),which appears to have an intestinal guardian function, in particular checking the growth of undesirable, possibly harmful organisms, such as pathogenic E.coli.

Human milk contains large amounts of lactoferine (2 mg/100 ml) a powerful bacteriostatic.Lactoferin acts synergistically with sIgA. Lactoferin is an unsaturated iron binding compound which competes for iron with enteral organisms.(3)

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Lysozyme is a well-recognizedanti-infective substance found in breast milk(up to 2mg/100ml).This enzyme inhibits the growth of many bacterial species by disrupting the proteoglycan layer of the bacterial cell wall(3,7). And may play a role in protecting against various viruses, includingHerpes hominis virus. Fresh breast milk has been used in some traditional cultures as eye drops in the treatment of conjunctivitis. (12)

Other anti-infective substances which have a similar protective functions are interferon, derived fromlymphocytes, which may have anti-viral properties against neonatal infections with, for example, herpes virus(8)

Cellular effects

Human milk is a “live fluid” as is blood, with active enzymes (lysozyme, lipase), hormones (corticosteroids) and cells.

The primary cell in human milk appears to be the microphages (at least 2700 per µl), with lymphocytes, neutrophils and epithelial cells. The microphages secretelysozyme and lactoferrin. They are motile, amoeboid and phagocytic.

Lymphocytes are also abundant in human milk. They produce sIgA and interferon

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Human breast milk, and especially the early colostrum, contains measurable levels of leukocytes. Breast milk contains up to 4000 leukocyte like cells per micro liter during the first two weeks of life. Colostrum contains approximately 5_106 cells per mL, an amount that decreases tenfold in mature milk. (7,8,3)

Most of these leukocytes are macrophages and neutrophils, which phagocytes microbial pathogens. Lymphocytes, including T cells, natural killer cells, and antibody producing B cells, make up 10% of the leukocytes in human breast milk(8). There is evidence to suggest that these cells survive passage through the infant’s gastrointestinal system where they are absorbed and influence the infant’s immune response.(11)

Anti-allergic properties

Allergic diseases in early childhood due to food poisoning seem to be particularly common in all over the world. Many factors are responsible for food allergy in young children, but cow’s milk proteins such as α-lactalbumin and β-lactoglobulin are the commonest allergens. They are not present in human milk.(8,3)

The range of diseases due to milk protein intolerance is considerably high and includes atopicdermatitis (infantile eczema) , rhinitis failure to thrive ,otitis media, allergic gastroenteropathy and hypersensivity microhaemorrhages(11).

However breast feeding will not eliminate food allergies, not even completely to cow’s milk. It will however reduce the incidence very gradually and delay their onset.(8)

Anti-inflammatory properties

Although inflammation is a beneficial defense to the infant, an exaggerated inflammatory response will result in reduced intake, illness, and gut damage. It is not entirely clear whether the exaggerated or unchecked inflammatory response to an infectious challenge occurs only in the gut or whether this extends to the infant’s systemic immune system. The overall the balance of factors in breast milk appears to dampen the inflammatory response

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Cytokines such as IL (Interleukin)6, IL10, Interferon, TGFβ(transforming Growth Factor) and TNFR(Tumor Necrosis Factor Receptor) 1 and 11 are anti-inflammatory factors found in breast milk.(3,2)

HMOS (Human Milk Oligosaccharides) in breast milk also act as an anti-inflammatory substance.

Inflammation benefits the host as a defense mechanism7 and biological anti-inflammatoryof breast milk minimizes the symptoms without interfering the immune response of the infant(9)

Drugs/Chemical Toxicants

Potentially toxic chemical substances can be taken orally or intravenously by mothers and those drugs can be excreted in human milk.

Very recently (1970), a newly recognizeduncommon form of neonatal jaundice has been described associated with the excretion of 3-α, 2-β pregnanediol in the breast milk, which competes for glucuronyl transferase in the infant’s liver. This condition has never been associated withkernicterus or other type of brain damage.(3,8)

Few decades ago, protection from malaria was sought by administering anti-malarial drugs

to nursing mother but, weren’t success.3Some chemical toxicants in drugs can interferewith the metabolism of babies. Ex: Mercury can alter the genetically determined responseof Glucose 6-phosphate dehydrogenase and might cause hemolysis.(3,10)

Conclusion

After birth the infant is having an immature immune system. Its capacity to produce antibodies is low. To compensate this immunodeficiency breast milk provides immunological factors. Infants immune system gradually develop with the age. Accordingly the constituents of breast milk vary with stage of breast feeding.

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Breast milk contains lot of immunological factors. Early stage of breast milk it has more, rather than later.

By supplying immunity breast milk act as a dynamic, multifaceted fluid, containing nutrients and bio active factors needed for the infant’s health and development.

So breast milk is turned out to be the most reliable, safest and cheapest way of supplying nutrients and immunity for the infants. When breast milk provides its immunity it does not cause any other side effects too. So we can finally conclude breast milk as an important mode of passive immunization in babies

References

(01) Section on Human milk composition Ballard and Morrow pediatrics journal 2013. pg

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5263

(02) Section on breastfeeding and health outcomes .Diafericet al pediatrics

journal 2013. pg34,5

(03) Human milk in the modern world Jelliffe&Jelliffe. 2nd edition 1979. 85109

(04) Pubmed

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(05) The normal child.10th edition Roland S Illingworth .2005

(06) Text book of pediatrics .Nelson.19th edition. 2012.pg 28,160

(07) Immunology .Roitt&Brostoff .4th edition.1996

(08)Journal of nutrition. American society for nutrition. Department of Neonatology and Neonatal

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Intensive Care, SpedaliCivili, 25123 Brescia, Italy

(09) Breastfeeding, Immune response, and long health. Kelly M. Jackson, PhD, Professor, Medical

(11) Breastfeeding for Dummies, comparing formula and breast milk .Sharon Parkins, CarrolVannais

(12) Personal information

(13). Prentice, A. Regional Variations in the Composition of Human Milk. In: Jensen, RG., editor.Handbook of Milk Composition. Academic Press, Inc.; San Diego, CA: 1995. p. 919

(14). Jensen, RG. Handbook of Milk Composition. Academic Press, Inc.; San Diego, CA: 1995.

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