THE Mammary Gland-Infant Intestine Immunologic Dyad Intestine Immunologic Dyad

  • L Å Hanson
  • L Ceafalau
  • I Mattsby-Baltzer
  • M Lagerberg
  • A Hjalmarsson
  • R Ashraf
  • S Zamanand
  • F Jalil
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 478)

Abstract

The human infant has a very small immune system and needs the support of the mother with the transplacentally arrived IgG antibodies to protect tissues with inflammatogenic and energy-consuming defense. The mucous membranes, where most infections occur, need support via the specialized secretory IgA antibodies and the many other mucosal defense mechanisms provided via the mother’s milk. This defense is not inflammatogenic and energy-consuming.

We learn about additional defense factors in the milk, like the anti-secretory factor, which seems to protect against diarrhoea. The milk contains numerous growth factors and cytokines, like leptin, which may promote the development of the intestine as well as the immune system.

Results are appearing giving interesting evidence for enhanced protection against infection also after the termination of breastfeeding. This may occur via the priming of the infant’s immune system after uptake of anti-idiotypic antibodies and lymphocytes from the milk.

A breastfeeding motivation study in a large Pakistani village resulted in a 50% decrease of diarrhoea and infant mortality. Deep interviews with the mothers and the traditional birth attendants suggested that even better results may be obtained.

Key words

Breastfeeding passive protection active protection secretory IgA antibodies lactoferrin leptin antisecretory factor 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Adkins B. T-cell function in newborn mice and humans. Immunol Today 1999:20:330–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Brandtzaeg P, Nilssen DE, Rognum TO, and Thrane PS. Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol Clin North Am 1991:20:397–439.PubMedGoogle Scholar
  3. 3.
    Crabbé PA, Bazin H, Eyssen H, and Heremans JF. The normal microbial flora as a major stimulus for proliferation of plasma cells synthesizing IgA in the gut. Int Arch Allergy 1968:34:362–75.PubMedGoogle Scholar
  4. 4.
    Crabbé PA, Nash DR, Bazin H, Eysseb H, and Heremans JF. Immunohistochemical observations on lymphoid tissues from conventional and germ-free mice. Lag Invest 1970:22:448–57.Google Scholar
  5. 5.
    Goldblum RM, Hanson LA and Brandtzaeg P. The mucosal defense system. In: Stiehm E R, ed. Immunologic Disorders in Infants and Children. Philadelphia: W B Saunders, 1996:159–99.Google Scholar
  6. 6.
    Marchant A, Goetghebuer T, Ota MO, Wolfe I, Ceesay SJ, De Groote D, Corrah T, Bennett S, Wheeler J, Huygen K, Aaby P, McAdam KP, and Newport MJ. Newborns develop a Thl-type immune response to Mycobacterium bovis bacillus Calmette-Guerin vaccination. J Immunol 1999:163:2249–55.PubMedGoogle Scholar
  7. 7.
    Adlerberth I, Wold AE and Hanson LÅ. The ontogeny of the intestinal flora. In: Sanderson I R, et al, eds. Development of the gastrointestinal tract. Ontario: B C Decker, 1999.Google Scholar
  8. 8.
    Ellis-Pegler RB, Crabtree C and Lambert HP. The fecal flora of children in the United Kingdom. J Hyg (Camb) 1975:75:135–42.Google Scholar
  9. 9.
    Carlsson B, Kaijser B, Ahlstedt S, Gothefors L, and Hanson LÅ. Antibodies against Escherichia coli capsular (K) antigens in human milk and serum: their relation to the E. coli gut flora of the mother and neonate. Acta Paediatr Scand 1982:71:313–8.PubMedGoogle Scholar
  10. 10.
    Carlsson B, Ahlstedt S, Hanson LA, Lidin-Janson G, Lindblad B, and S S. Escherichia coli O antibody content in milk from healthy Swedish mothers and mothers from a very low socio-economic group of a developing country. Acta Paediatr Scand 1976:65:417–23.PubMedGoogle Scholar
  11. 11.
    Hanson LÅ, Carlsson B, Jalil F, Hahn-Zoric M, Karlberg J, Mellander L, Shaukat RK, Lindblad B, Thiringer K, and Zaman S. Antiviral and antibacterial factors in human milk. In: Hanson LA, ed. Biology of Human Milk. New York: Raven Press, 1988:141–57.Google Scholar
  12. 12.
    Glass RI, Svennerholm AM, Stoll BJ, Khan MR, Hossain KM, Huq MI, and Holmgren J. Protection against cholera in breast-fed children by antibodies in breast-milk. N Engl J Med 1983:308:1389–92.PubMedCrossRefGoogle Scholar
  13. 13.
    Cruz JR, Gil L, Cano F, Caceres P, and Pareja G. Breast-milk anti-Escherichia coli heat-labile toxin IgA antibodies protect against toxin-induced infantile diarrhoea. Acta Paediatr Scand 1988:77:658–62.PubMedGoogle Scholar
  14. 14.
    Ruiz-Palacios GM, Calva J and Pickering LK. Protection of breast-fed infants against Campylobacter diarrhoea by antibodies in human milk. J Pediatr 1990:116:707–13.PubMedGoogle Scholar
  15. 15.
    Hayani KC, Guerrero ML, Morrow AL, Gomez HF, Winsor DK, Ruiz-Palacios GM, and Cleary TG. Concentration of milk secretory immunoglobulin A against Shigella virulence plasmid-associated antigens as a predictor of symptom status in Shigella-infected breastfed infants. J Pediatr 1992:121:852–6.PubMedGoogle Scholar
  16. 16.
    Walterspiel JN, Morrow AL, Guerrero ML, Ruiz-Palacios GM, and Pickering LK. Secretory anti-Giardia lamblia antibodies in human milk: Protective effect against diarrhea Pediatrics 1994:93:28–31.PubMedGoogle Scholar
  17. 17.
    Hanson LÅ and Telemo E. Immunobiology and epidemiology of breastfeeding in relation to prevention of infections from a global perspective. In: Ogra PL, et al, eds. Mucosal Immunology. San Diego: Academic Press, 1999:1501–10.Google Scholar
  18. 18.
    Lonnerdal B and Iyer S. Lactoferrin: Molecular structure and biologocal function. Annu Rev Nutr 1995:15:93–110.PubMedCrossRefGoogle Scholar
  19. 19.
    Brock J. Lactoferrin: a multifunctional immunoregulatory protein? Imm Today 1995:16:417–9.Google Scholar
  20. 20.
    Tomita M, Takase M, Wakabayashi H, and Bellamy W. Antimicrobial peptides of lactoferrin. In: T W Hutchens et al, ed. Lactoferrin, Structure and Function. New York: Plenum Press, 1994.Google Scholar
  21. 21.
    Mattsby-Balker I, Roseanu A, Motas C, Elverfors J, Engberg I, and Hanson LÅ. Lactoferrin or a fragment thereof inhibits the endotoxin-induced interleukin-6 response in human monocytic cells. Pediatr Res 1996:40:257–62.Google Scholar
  22. 22.
    Ferenc Levay P and Viljoen M. Lactoferrin: A general review. Haematologica 1995:80:252–67.Google Scholar
  23. 23.
    Iyer S and Lönnerdal B. Review. Lactoferrin, lactoferrin receptors and iron metabolism. European Journal of Clinical Nutrition 1993:47:232–41.PubMedGoogle Scholar
  24. 24.
    Zimecki M, Mazurier J, Spik G, and Kapp JA. Human lactoferrin induces phenotypic and functional changes in murine splenic B cells. Immunmology 1995:86: 122–7.Google Scholar
  25. 25.
    Hutchens TW, Henry JH, Yip T-T, Hachey DL, Schanler RJ, Motil KJ, and Garza C. Origin of intact lactoferrin and its DNA-binding fragments found in the urine of human milk-fed preterm infants. Evaluation by stable isotopic enrichment. Pediatr Res 1991:29:243–50.PubMedGoogle Scholar
  26. 26.
    Goldblum RM, Schanler RJ, Garza C, and Goldman AS. Human milk feeding enhances the urinary excretion of immunologic factors in low birth weight infants. Pediatr Res 1989:25:184–8.PubMedGoogle Scholar
  27. 27.
    Wold A and Hanson LÅ. Defence factors in human milk. Curr Opin Gastroenterol 1994:10:652–8.Google Scholar
  28. 28.
    Rudloff S, Pohlentz G, Diekmann L, Egge H, and Kunz C. Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula. Acta Paediatr 1996:85:598–603.PubMedGoogle Scholar
  29. 29.
    Coppa GV, Gabrielli O, Giorgi P, Catassi C, Montanari MP, Varaldo PE, and Nichols BL. Preliminary study of breastfeeding and bacterial adhesion to uroepithelial cells. Lancet 1990:335:569–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Slaviková M, Lodinová-Zadniková R, Adlerberth I, Hanson LA, Svanborg C, and Wold A. Increased mannose-specific adherence and colonizing ability of Escherichia coli 083 in breast-fed infants. Adv Exp Med Biol 1995:371A:421–4.PubMedGoogle Scholar
  31. 31.
    Gothefors L, Olling S and Winberg J. Breastfeeding and biological properties of faecal Escherichia coli strains. Acta Paediatr Scand 1975:64:807–12.PubMedGoogle Scholar
  32. 32.
    Tullus K. Fecal colonization with P-fimbriated Escherichia coli between 0 and 18 months of age. Epidemiol Infect 1988:100:185–91.PubMedCrossRefGoogle Scholar
  33. 33.
    Pisacane A, Graziano L, Mazzarella G, Scarpellino B, and Zona G. Breast-feeding and urinary tract infection. J Pediatr 1992:120:87–9.PubMedGoogle Scholar
  34. 34.
    Mårild S, Jodal U and Hanson LÅ. Breastfeeding and urinary-tract infection. Lancet 1990:336:942.PubMedGoogle Scholar
  35. 35.
    Ceafalau LA, Engberg I, Dolphin G, Baltzer L, Hanson LA, and Mattsby-Baltzer I. Lactoferrin and peptides derived from a surface exposed helical region prevent experimental Escherichia coli urinary tract infection in mice. 1999. (In manuscript).Google Scholar
  36. 36.
    Ceafalau LA, Dolphin G, Baltzer L, Hanson LÅ, and Mattsby-Baltzer I. Anti-inflammatory activities of human lactoferrin and synthetic peptides thereof in experimental dextran-sulphate induced colitis in mice. 1999. (In manuscript).Google Scholar
  37. 37.
    Espinoza F, Paniagua M, Hallander H, Svensson L, and Strannegård ö Rotavirus infections in young Nicaraguan children. Pediatr Infect Dis J 1997:16:564–71.PubMedGoogle Scholar
  38. 38.
    Jayashree S, Bhan M, Kumar R, Bhandari N, and Sazawal S. Protection against neonatal rotavirus infection by breast milk antibodies and trypsin inhibitors. J Med Virol 1988:26:333–8.PubMedGoogle Scholar
  39. 39.
    Clemens J, Rao M, Ahmed F, Ward R, Huda S, Chakraborty J, Yunus M, Khan M, Ali M, and Kay Bea. Breast-feeding and the risk of life-threatening rotavirus diarrhea: Prevention or postponement? Pediatrics 1993:92:680–5.PubMedGoogle Scholar
  40. 40.
    Newburg DS, Peterson JA, Ruiz-Palacios GM, Matson DO, Morrow AL, Shults J, Guerrero ML, Chaturvedi P, Newburg SO, Scallan CD, Taylor MR, Ceriani RL, and Pickering LK. Role of human-milk lactadherin in protection against symptomatic rotavirus infection. Lancet 1998:351:1160–4.PubMedGoogle Scholar
  41. 41.
    Black ME and Armstrong D. Human-milk lactadherin in protection against rotavirus. Lancet 1998:351:1815–6.PubMedGoogle Scholar
  42. 42.
    Fornarini B, Iacobelli S, Tinari N, Natoli C, De Martino M, and Sabatino G. Human milk 90K (Mac-2 BP): possible protective effects against acute respiratory infections. Clin Exp Immunol 1999:115:91–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Casabiell X, Pineiro V, Tome MA, Peino R, Dieguez C, and Casanueva FF. Presence of leptin in colostrum and/or breast milk from lactating mothers: a potential role in the regulation of neonatal food intake. J Clin Endocrin Metab 1997:82:4270–3.Google Scholar
  44. 44.
    Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med 1999:130:671–80.PubMedGoogle Scholar
  45. 45.
    Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, and Diehl AM. Leptin regulates proinflammatory immune responses. FASEB J 1998:12:57–65.PubMedGoogle Scholar
  46. 46.
    Lönnroth I and Lange S. Inhibition of cyclic AMP-mediated intestinal hypersecretion by pituitary extracts from rats pretreated with cholera toxin. Med Biol 1984:62:290–4.PubMedGoogle Scholar
  47. 47.
    Göransson L, Lange S and Lonnroth I. Post weaning diarrhoea: focus on diet. Pig News Inform 1995:16:89–91.Google Scholar
  48. 48.
    Hanson LÅ, Lönnroth I, Lange S, Bjersing J, and Dahlgren U. Nutritional resistance to viral propagation. 1999. In: Nutrients and Viral Infections, from Molecular Biology to Public Health. Nutr Rev (In press).Google Scholar
  49. 49.
    Hanson LÅ. Breastfeeding provides passive and likely long-lasting active immunity. Ann Allergy Asthma Immunol 1998:81:523–33.PubMedCrossRefGoogle Scholar
  50. 50.
    Hawkes JS, Bryan D-L, James MJ, and Gibson RA. Cytokines (IL-1β, IL-6, TNF-α, TGF-β1 and TGF-b2) and prostaglandin E2 in human milk during the first three months postpartum. Pediatr Res 1999:46:194–9.PubMedGoogle Scholar
  51. 51.
    Bryan D-L, Hawkes JS and Gibson RA. Interleukin-12 in human milk. Pediatr Res 1999:45:858–9.PubMedGoogle Scholar
  52. 52.
    Letterio JJ. Maternal rescue of transforming growth factor-β1 null mice. Science 1994:264:1936–8.PubMedGoogle Scholar
  53. 53.
    Saarinen UM. Prolonged breast feeding as prophylaxis for recurrent otitis media. Acta Pediatr Scand 1982:71:567–71.Google Scholar
  54. 54.
    Wilson AC, Forsyth JS, Greene SA, Irvine L, Hau C, and Howie PW. Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study. BMJ 1998:316:21–5.PubMedGoogle Scholar
  55. 55.
    Silfverdal SA, Bodin L, Hugosson S, Garpenholt O, Werner B, Esbjorner E, Lindquist B, and Olcen P. Protective effect of breastfeeding on invasive Haemophilus influenzae infection: a case-control study in Swedish preschool children. Int J Epidemiol 1997:26:443–50.PubMedCrossRefGoogle Scholar
  56. 56.
    Silfverdal SA, Bodin L and Olcen P. Protective effect of breastfeeding: an ecologic study of Haemophilus influenzae meningitis and breastfeeding in a Swedish population. Int J Epidemiol 1999:28:152–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Howie PW, Forsyth JS, Ogston SA, Clark A, and V FC. Protective effect of breast feeding against infection. BMJ 1990:300:11–6.PubMedGoogle Scholar
  58. 58.
    Burr ML, Limb ES, Maguire MJ, Amarah L, Eldridge BA, Layzell JC, and Merrett TG. Infant feeding, wheezing, and allergy: a prospective study. Arch Dis Child 1993:68:724–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Porro E, Indinnimeo L, Antognoni G, Midulla F, and Criscione S. Early wheezing and breast feeding. J Asthma 1993:30:23–8.PubMedGoogle Scholar
  60. 60.
    Pabst HF, Grace M, Godel J, Cho H, and Spady DW. Effect on breastfeeding on antibody response to BCG vaccination. Lancet 1989:I:295–7.Google Scholar
  61. 61.
    Hahn-Zoric M, Fulconis F, Minoli I, Moro G, Carlsson B, Böttiger M, Räihä N, and Hanson LÅ. Antibody responses to parenteral and oral vaccines are impaired by conventional and low protein formulas as compared to breast-feeding. Acta Paediatr Scand 1990:79:1137–42.PubMedGoogle Scholar
  62. 62.
    Stein KE and Söderström T. Neonatal administration of idiotype or anti-idiotype primes for protection against Escherichia coli K13 infection in mice. J Exp Med 1984:160:1001–11.PubMedCrossRefGoogle Scholar
  63. 63.
    Okamoto Y, Tsutsumi H, Kumar NS, and Ogra PS. Effect of breast feeding on the development of anti-idiotype antibody response to F glycoprotein of respiratory syncytial virus in infant mice after post-partum maternal immunisation. J Immunol 1989:142:2507–12.PubMedGoogle Scholar
  64. 64.
    Hahn-Zoric M, Carlsson B, Jeansson S, Ekre 0, Osterhaus AD, Roberton DM, and Hanson LÅ. Anti-idiotypic to poliovirus in commercial immunoglobulin, human serum and human milk. Pediatr Res 1993:33:475–80.PubMedGoogle Scholar
  65. 65.
    Weiler IJ, Hickler W and Sprenger R. Demonstration that milk cells invade the suckling neonatal mouse. Am J Reproduct Immunol 1983:4:95–8.Google Scholar
  66. 66.
    Sheldrake RF and Husband AJ. Intestinal uptake of intact maternal lymphocytes by neonatal rats and lambs. Res Vet Science 1985:39:10–5.Google Scholar
  67. 67.
    Kumar SN, Stewart GL, Steven WM, and Seelig LL. Maternal to neonatal transmission of T-cell mediated immunity to Trichinella spiralis during lactation. Immunology 1989:68:87–92.PubMedGoogle Scholar
  68. 68.
    Tuboly S, Bernáth S, Glávits R, Kovacs A, and Megyeri Z. Intestinal absorption of colostral lymphocytes in newborn lambs and their role in the development of immune status. Acta Vet Hungar 1995:43:105–15.Google Scholar
  69. 69.
    Gustafsson E, Arvola M, Svensson L, Mattsson A, and Mattson R. Postnatally transmitted maternal B cells can cause long-term maintenance of serum IgG in B cell-deficient mice nursed by phenotypically normal dams. 1997. In manuscript.Google Scholar
  70. 70.
    Kois WE, Campbell DA, Jr., Lorber MI, Sweeton JC, and Dafoe DC. Influence of breast feeding on subsequent reactivity to a related renal allograft J Surg Res 1984:37:89–93.PubMedCrossRefGoogle Scholar
  71. 71.
    Deroche A, Nepomnaschy I, Torello S, Goldman A, and Piazzon I. Regulation of parental alloreactivity by reciprocal F1 hybrids. The role of lactation. J Reprod Immunol 1993:23:235–45.PubMedGoogle Scholar
  72. 72.
    Campbell DA, Jr., Lorber MI, Sweeton JC, Turcotte JG, Niederhuber JE, and Beer AE. Breast feeding and maternal-donor renal allografts. Possibly the original donor-specific transfusion. Transplantation 1984:37:340–4.PubMedGoogle Scholar
  73. 73.
    Zhang L, van Bree S, van Rood JJ, and Claas FHJ. Influence of breast feeding on the cytotoxic T cell allorepertoire in man. Transplantation 1991:52:914–6.PubMedGoogle Scholar
  74. 74.
    Hanson LA, Adlerberth I, Carlsson B, Jalil F, Karlberg J, Lindblad BS, Mellander L, Khan SR, Hasan R, Sheiku AK, and Söderström T. Breast feeding in reality. In: Hamosh M, et al, eds. Human Lactation 2. Maternal-Environmental Factors: Raven Press, 1986:1–12.Google Scholar
  75. 75.
    Fildes VA. Breast, Bottles and Babies: A History of Infant Feeding. 1986: Edinburgh University Press.Google Scholar
  76. 76.
    Adlerberth I, Carlsson B, de Man P, Jalil F, Khan SR, Larsson P, Mellander L, Svanborg C, Wold AE, and Hanson LA. Intestinal colonization with Enterobacteriaceae in Pakistani and Swedish hospital-delivered infants. Acta Paediatr Scand 1991:80:602–10.PubMedGoogle Scholar
  77. 77.
    Jalil F, Lindblad BS, Hanson LA, Khan SR, Yaqoob M, and Karlberg J. Early child health in Lahore, Pakistan: IX. Perinatal events. Acta Paediatr Suppl 1993:390:95–107.Google Scholar
  78. 78.
    Ashraf R, Jalil F, Zaman S, Karlberg J, Khan SR, Lindblad BS, and Hanson LA. Breast feeding and protection against neonatal sepsis in a high risk population. Arch Dis Child 1991:66:488–90.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • L Å Hanson
    • 1
  • L Ceafalau
    • 1
    • 2
  • I Mattsby-Baltzer
    • 2
  • M Lagerberg
    • 1
  • A Hjalmarsson
    • 1
  • R Ashraf
    • 3
  • S Zamanand
    • 3
  • F Jalil
    • 3
  1. 1.Department of Clinical ImmunologyGoteborg UniversityGöteborgSweden
  2. 2.Department of Clinical BacteriologyGoteborg UniversityGöteborgSweden
  3. 3.Departrnent of Social and Preventive PaediatricsKing Edward Medical CollegeLahorePakistan

Personalised recommendations