Skip to main content

Advertisement

Springer Nature Link
Log in

Immune Components of Colostrum and Milk—A Historical Perspective

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Key developments in the understanding of the immune functions of milk and colostrum are reviewed, focusing on their proteinaceous components. The topics covered include the immunoglobulins, immune cells, immunomodulatory substances, and antimicrobial proteins. The contributions of new technologies and the introduction of fresh approaches from other fields are highlighted, as are the contributions that mammary biology research has made to the development of other fields. Finally, a summary of some current outstanding questions and likely future directions of the field are given.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

Abbreviations

BPI:

bactericidal/permeability increasing protein

DHA:

docosahexaenoic acids

EPA:

eicosapentaenoic acid

IgA:

immunoglobulin A

IgG:

immunoglobulin G

LBP:

lipopolysaccharide binding protein

LC-PUFA:

long chain-polyunsaturated fatty acids

References

  1. Kitasato S. Das Verhalten der Cholerabacterien in der Milch. Z Hyg Infektionskrankh 1889;5:491–6.

    Google Scholar 

  2. Fokker AP. Ueber bacterienvernichtende Eigenschaften der Milch. Z Hyg Infektionskrankh 1890;9:41–55.

    Google Scholar 

  3. Ehrlich P. Ueber Immunität durch Vererbung und Säugung. Z Hyg Infektionskr 1892;12:183–203.

    Google Scholar 

  4. Isaacs CE. The antimicrobial function of milk lipids. Adv Nutr Res 2001;10:271–85.

    PubMed  CAS  Google Scholar 

  5. Newburg DS. Innate immunity and human milk. J Nutr 2005;135(5):1308–12.

    PubMed  CAS  Google Scholar 

  6. Ehrlich P, Brieger L. Beiträge zur Kenntnis der Milch immunisirter Thiere. Z Hyg Infektionskr 1893;13:336–46.

    Google Scholar 

  7. Campbell B, Petersen WE. Immune milk—a historical survey. Dairy Sci Abst 1963;25(9):345–58.

    Google Scholar 

  8. Famulener LW. On the transmission of immunity from mother to offspring. J Infect Disease 1912;10:332–40.

    CAS  Google Scholar 

  9. Orcutt ML, Howe PE. The relation between the accumulation of globulins and the appearance of agglutinins in the blood of new-born calves. J Exp Med 1922;36:291–308.

    CAS  PubMed  Google Scholar 

  10. Smith T, Little RB. The significance of colostrum to the new-born calf. J Exp Med 1922;36:181–98.

    CAS  PubMed  Google Scholar 

  11. Little RB, Orcutt ML. The transmission of agglutinins of Bacillus abortus from cow to calf in the colostrum. J Exp Med 1922;35:161–71.

    PubMed  CAS  Google Scholar 

  12. Ratner B, Jackson HC, Gruehl HL. Transmission of protein hypersensitiveness from mother to offspring: I. Critique of placental permeability. J Immunol 1927;14:249–65.

    CAS  Google Scholar 

  13. Ratner B, Jackson HC, Gruehl HL. Transmission of protein hypersensitiveness from mother to offspring: II. The role of colostrum. J Immunol 1927;14:267–74.

    CAS  Google Scholar 

  14. Ratner B, Jackson HC, Gruehl HL. Transmission of protein hypersensitiveness from mother to offspring: III. The rôle of milk. J Immunol 1927;14:275–90.

    CAS  Google Scholar 

  15. Smith T. The immunological significance of colostrum. I. The relationship between colostrum, serum, and the milk of cows normal and immunized towards B. coli. J Exp Med 1930;51:473–81.

    CAS  PubMed  Google Scholar 

  16. Ingram PL, Lovell R, Wood PC, Aschaffenburg R, Bartlett S, Kon SK, et al. Bacterium coli antibodies in colostrum and their relation to calf survival. J Pathol Bacteriol 1956;72:561–8.

    Google Scholar 

  17. Lascelles AK. A review of the literature on some aspects of immune milk. Dairy Sci Abstr 1963;25(9):359–64.

    Google Scholar 

  18. Richards CB, Marrack JR. Sheep serum gamma globulin. In: Peeters H, editor. Protides of the biological fluids bruges. Amsterdam: Elsevier Science; 1963. p. 154–156.

  19. Hanson LA. Comparative immunological studies of the immune globulins of human milk and of blood serum. Int Arch Allergy Appl Immunol 1961;18:241–67.

    PubMed  CAS  Google Scholar 

  20. Campbell B, Porter RM, Petersen WE. Plasmacytosis of the bovine udder during colostrum secretion and experimental cessation of milking. Nature 1950;166(4230):913.

    PubMed  CAS  Google Scholar 

  21. Lee CS, Lascelles AK. Antibody-producing cells in antigenically stimulated mammary glands and in the gastro-intestinal tract of sheep. Aust J Exp Biol Med Sci 1970;48(5):525–35.

    PubMed  CAS  Google Scholar 

  22. Blakemore F, Garner RJ. The maternal transference of antibodies in the bovine. J Comp Pathol 1956;66(4):287–9.

    PubMed  CAS  Google Scholar 

  23. Butler JE. Characteristics of bovine immunoglobulins and related molecules. Review of the bovine immunoglobulins. J Dairy Sci 1971;54(9):1315–6.

    PubMed  CAS  Google Scholar 

  24. Jones EA, Waldmann TA. The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. J Clin Invest 1972;51(11):2916–27.

    PubMed  CAS  Google Scholar 

  25. Kemler R, Mossmann H, Strohmaier U, Kickhofen B, Hammer DK. In vitro studies on the selective binding of IgG from different species to tissue sections of the bovine mammary gland. Eur J Immunol 1975;5(9):603–8.

    PubMed  CAS  Google Scholar 

  26. Barrington GM, Besser TE, Gay CC, Davis WC, Reeves JJ, McFadden TB, et al. Regulation of the immunoglobulin G1 receptor: effect of prolactin on in vivo expression of the bovine mammary immunoglobulin G1 receptor. J Endocrinol 1999;163(1):25–31.

    PubMed  CAS  Google Scholar 

  27. Smith KL, Muir LA, Ferguson LC, Conrad HR. Selective transport of IgGl into the mammary gland: role of estrogen and progesterone. J Dairy Sci 1971;54(12):1886–94.

    PubMed  CAS  Google Scholar 

  28. Lascelles AK, McDowell GH. Localized humoral immunity with particular reference to ruminants. Transplant Rev 1974;19(0):170–208.

    PubMed  CAS  Google Scholar 

  29. Barrington GM, Besser TE, Gay CC, Davis WC, Reeves JJ, McFadden TB. Effect of prolactin on in vitro expression of the bovine mammary immunoglobulin G1 receptor. J Dairy Sci 1997;80(1):94–100.

    PubMed  CAS  Google Scholar 

  30. Roux ME, McWilliams M, Phillips-Quagliata JM, Weisz-Carrington P, Lamm ME. Origin of IgA-secreting plasma cells in the mammary gland. J Exp Med 1977;146(5):1311–22.

    PubMed  CAS  Google Scholar 

  31. Weisz-Carrington P, Roux ME, Lamm ME. Plasma cells and epithelial immunoglobulins in the mouse mammary gland during pregnancy and lactation. J Immunol 1977;119(4):1306–7.

    PubMed  CAS  Google Scholar 

  32. McDermott MR, Bienenstock J. Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol 1979;122(5):1892–8.

    PubMed  CAS  Google Scholar 

  33. Tanneau GM, Oyant LHS, Chevaleyre CC, Salmon HP. Differential recruitment of T- and IgA B-lymphocytes in the developing mammary gland in relation to homing receptors and vascular addressins. J Histochem Cytochem 1999;47(12):1581–92.

    PubMed  CAS  Google Scholar 

  34. Finke D, Acha-Orbea H. Differential migration of in vivo primed B and T lymphocytes to lymphoid and non-lymphoid organs. Eur J Immunol 2001;31(9):2603–11.

    PubMed  CAS  Google Scholar 

  35. Hodgkinson AJ, Carpenter EA, Smith CS, Molan PC, Prosser CG. Adhesion molecule expression in the bovine mammary gland. Vet Immunol Immunopathol 2007;115(3–4):205–15.

    PubMed  CAS  Google Scholar 

  36. Wilson E, Butcher EC. CCL28 controls immunoglobulin (Ig)A plasma cell accumulation in the lactating mammary gland and IgA antibody transfer to the neonate. J Exp Med 2004;200(6):805–9.

    PubMed  CAS  Google Scholar 

  37. Crago SS, Kulhavy R, Prince SJ, Mestecky J. Secretory component of epithelial cells is a surface receptor for polymeric immunoglobulins. J Exp Med 1978;147(6):1832–7.

    PubMed  CAS  Google Scholar 

  38. Apodaca G, Katz LA, Mostov KE. Receptor-mediated transcytosis of IgA in MDCK cells is via apical recycling endosomes. J Cell Biol 1994;125(1):67–86.

    PubMed  CAS  Google Scholar 

  39. de Groot N, Van Kuik-Romeijn P, Lee SH, De Boer HA. Increased immunoglobulin A levels in milk by over-expressing the murine polymeric immunoglobulin receptor gene in the mammary gland epithelial cells of transgenic mice. Immunology 2000;101(2):218–24.

    PubMed  Google Scholar 

  40. Rosato R, Jammes H, Belair L, Puissant C, Kraehenbuhl JP, Djiane J. Polymeric-Ig receptor gene expression in rabbit mammary gland during pregnancy and lactation: evolution and hormonal regulation. Mol Cell Endocrinol 1995;110(1–2):81–7.

    PubMed  CAS  Google Scholar 

  41. Rincheval-Arnold A, Belair L, Djiane J. Developmental expression of pIgR gene in sheep mammary gland and hormonal regulation. J Dairy Res 2002;69(1):13–26.

    PubMed  CAS  Google Scholar 

  42. Brown WR, Newcomb RW, Ishizaka K. Proteolytic degradation of exocrine and serum immunoglobulins. J Clin Invest 1970;49(7):1374–80.

    PubMed  CAS  Google Scholar 

  43. Shuster J. Pepsin hydrolysis of IgA-delineation of two populations of molecules. Immunochemistry 1971;8(5):405–11.

    PubMed  CAS  Google Scholar 

  44. Phalipon A, Cardona A, Kraehenbuhl JP, Edelman L, Sansonetti PJ, Corthesy B. Secretory component: a new role in secretory IgA-mediated immune exclusion in vivo. Immunity 2002;17(1):107–15.

    PubMed  CAS  Google Scholar 

  45. Groves ML, Gordon WG. Isolation of a new glycoprotein-a and a gamma-G-globulin from individual cow milks. Biochemistry 1967;6(8):2388–94.

    PubMed  CAS  Google Scholar 

  46. de Oliveira IR, de Araujo AN, Bao SN, Giugliano LG. Binding of lactoferrin and free secretory component to enterotoxigenic Escherichia coli. FEMS Microbiol Lett 2001;203(1):29–33.

    PubMed  Google Scholar 

  47. Marshall LJ, Perks B, Ferkol T, Shute JK. IL-8 released constitutively by primary bronchial epithelial cells in culture forms an inactive complex with secretory component. J Immunol 2001;167(5):2816–23.

    PubMed  CAS  Google Scholar 

  48. Breed RS. The sanitary significance of body cells in milk.. J Infect Dis. 1914;14:93–9.

    Google Scholar 

  49. Holm GC. The types of leucocytes in market milk as related to bovine mastitis. J Am Vet Med Assoc 1934;35:735–46.

    Google Scholar 

  50. Nakajima S, Baba AS, Tamura N. Complement system in human colostrum: presence of nine complement components and factors of alternative pathway in human colostrum. Int Arch Allergy Appl Immunol 1977;54(5):428–33.

    PubMed  CAS  Google Scholar 

  51. Reiter B, Brock JH. Inhibition of Escherichia coli by bovine colostrum and post-colostral milk. I. Complement-mediated bactericidal activity of antibodies to a serum susceptible strain of E. coli of the serotype O 111. Immunology 1975;28(1):71–82.

    PubMed  CAS  Google Scholar 

  52. Smith CW, Goldman AS. The cells of human colostrum .I. In vitro studies of morphology and functions. Pediatr Res 1968;2(2):103–9.

    PubMed  CAS  Google Scholar 

  53. Mohr JA. The possible induction and-or acquisition of cellular hypersensitivity associated with ingestion of colostrum. J Pediatr 1973;82(6):1062–4.

    PubMed  CAS  Google Scholar 

  54. Beer AE, Billington RE, Head JR. Natural transplantation of leukocytes during suckling. Transplant Proc 1975;7:399–402.

    Google Scholar 

  55. Weiler IJ, Hickler W, Sprenger R. Demonstration that milk cells invade the suckling neonatal mouse. Am J Reprod Immunol 1983;4(2):95–8.

    PubMed  CAS  Google Scholar 

  56. Sheldrake RF, Husband AJ. Intestinal uptake of intact maternal lymphocytes by neonatal rats and lambs. Res Vet Sci 1985;39(1):10–5.

    PubMed  CAS  Google Scholar 

  57. Miller SC. Failure to demonstrate morphologically the presence of colostral or milk cells in the wall of the gastrointestinal tract of the suckling neonatal mouse. J Reprod Immunol 1981;3(3):187–94.

    PubMed  CAS  Google Scholar 

  58. Keller MA, Kidd RM, Bryson YJ, Turner JL, Carter J. Lymphokine production by human milk lymphocytes. Infect Immun 1981;32(2):632–6.

    PubMed  CAS  Google Scholar 

  59. Lawton JW, Shortridge KF, Wong RL, Ng MH. Interferon synthesis by human colostral leucocytes. Arch Dis Child 1979;54(2):127–30.

    PubMed  CAS  Google Scholar 

  60. Donnet-Hughes A, Duc N, Serrant P, Vidal K, Schiffrin EJ. Bioactive molecules in milk and their role in health and disease: the role of transforming growth factor-beta. Immunol Cell Biol 2000;78(1):74–9.

    PubMed  CAS  Google Scholar 

  61. Penttilla IA. Effects of transforming growth factor-beta and formula feeding on systemic immune responses to dietary beta-lactoglobulin in allergy-prone rats. Pediatr Res 2006;59:650–5.

    Google Scholar 

  62. Stavnezer J. Regulation of antibody production and class switching by TGF-beta. J Immunol 1995;155(4):1647–51.

    PubMed  CAS  Google Scholar 

  63. Sordillo LM, Shafer-Weaver K, DeRosa D. Immunobiology of the mammary gland. J Dairy Sci 1997;80(8):1851–65.

    Article  PubMed  CAS  Google Scholar 

  64. Gauthier SF, Pouliot Y, Saint-Sauveur D. Immunomodulatory peptides obtained by the enzymatic hydrolysis of whey proteins. Int Dairy J 2006;16:1315–1323.

    CAS  Google Scholar 

  65. Silanikove N, Shapiro F, Shamay A, Leitner G. Role of xanthine oxidase, lactoperoxidase, and NO in the innate immune system of mammary secretion during active involution in dairy cows: manipulation with casein hydrolyzates. Free Radic Biol Med 2005;38(9):1139–51.

    PubMed  CAS  Google Scholar 

  66. Elliott RB, Harris DP, Hill JP, Bibby NJ, Wasmuth HE. Type I (insulin-dependent) diabetes mellitus and cow milk: casein variant consumption. Diabetologia 1999;42(3):292–6.

    PubMed  CAS  Google Scholar 

  67. Yu WH. Scientific rationale and benefits of nucleotide supplementation of infant formula. J Paediatr Child Health 2002;38:543–9.

    PubMed  CAS  Google Scholar 

  68. Horrobin E. Low prevalences of coronary heart disease (CHD), psoriasis, asthma and rheumatoid arthritis in Eskimos: are they caused by high dietary intake of ecosapentaenoic acid (EPA), a genetic variation of essential fatty acid (EPA) metabolism or a combination of both? Med Hypothesis 1987;22:388–96.

    Google Scholar 

  69. Pastor N, Soler B, Mitmesser SH, Ferguson P, Lifschitz C. Infants fed docosahexaenoic acid- and arachidonic acid-supplemented formula have decreased incidence of bronchiolitis/bronchitis the first year of life. Clin Pediatr (Phila) 2006;45(9):850–5.

    Article  Google Scholar 

  70. Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, et al. Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin Exp Allergy 2003;33(4):442–8.

    PubMed  CAS  Google Scholar 

  71. Grulee CG, Sanford HN, Herron PH. Breast and artificial feeding: influences on morbidity and mortality of twenty thousand infants. J Am Med Assoc 1934;103:735–9.

    Google Scholar 

  72. Jarvinen KM, Suomalainen H. Leucocytes in human milk and lymphocyte subsets in cow’s milk-allergic infants. Pediatr Allergy Immunol 2002;13(4):243–54.

    PubMed  Google Scholar 

  73. Ruiz RG, Kemeny DM, Price JF. Higher risk of infantile atopic dermatitis from maternal atopy than from paternal atopy. Clin Exp Allergy 1992;22(8):762–6.

    PubMed  CAS  Google Scholar 

  74. Han Y-S, Park H-Y, Ahn K-M, Lee J-S, Choi H-M, Lee S-I. Short-term effect of partially hydrolysed formula on the prevention of development of atopic dermatitis in infants at high risk. J Korean Med Sci 2003;18:547–51.

    PubMed  CAS  Google Scholar 

  75. Saarinen KM, Savilahti E. Infant feeding patterns affect the subsequent immunological features in cow’s milk allergy. Clin Exp Allergy 2000;30(3):400–6.

    PubMed  CAS  Google Scholar 

  76. Gdalevich M, Mimouni D, David M, Mimouni M. Breast-feeding and the onset of atopic dermatitis in childhood: a systematic review and meta-analysis of prospective studies. J Am Acad Dermatol 2001;45(4):520–7.

    PubMed  CAS  Google Scholar 

  77. Fleming A. On a remarkable bacteriolytic element found in tissues and secretions. Proc Roy Soc Ser Biol Sci 1922;93:306–17.

    CAS  Google Scholar 

  78. Bordet J, Bordet M. Le pouvoir bacteriolytique du colostrum et du lait. Compt Rend 1924;179:1109–13.

    CAS  Google Scholar 

  79. Jones FS, Little RB. The bactericidal properties of cow’s milk. J Exp Med 1927;45:319–35.

    CAS  PubMed  Google Scholar 

  80. Salton MR. The properties of lysozyme and its action on microorganisms. Bacteriol Rev 1957;21(2):82–100.

    PubMed  CAS  Google Scholar 

  81. Jolles P, Jolles J. Lysozyme from human milk. Nature 1961;192:1187–1188.

    CAS  Google Scholar 

  82. Chandan RC, Shahani KM, Holly RG. Lysozyme content of human milk. Nature 1964;204:76–7.

    PubMed  CAS  Google Scholar 

  83. Auclair JE. Studies on the antibacterial properties of cow’s milk. PhD Thesis, University of Reading 1953.

  84. Wright RC, Tramer J. Factors influencing the activity of cheese starters. The role of milk peroxidase. J Dairy Res 1958;25:104–18.

    Article  CAS  Google Scholar 

  85. Theorell H, Akeson A. Highly purified milk peroxidase. Ark Kemi Mineral Geol 1943;B17(7):1–6.

    Google Scholar 

  86. Jago GR, Morrison M. Anti-streptococcal activity of lactoperoxidase III. Proc Soc Exp Biol Med 1962;111:585–8.

    PubMed  CAS  Google Scholar 

  87. Sorensen M, Sorensen SPL. The proteins in whey. C R Trav Lab Carlsberg 1939;23:55–99.

    CAS  Google Scholar 

  88. Schäfer KH. Elektrophoretische Untersuchengen zum Milchweissproblem. Monatsschr Kinderheilkd 1951;99:69.

    Google Scholar 

  89. Oram JD, Reiter B. Inhibition of bacteria by lactoferrin and other iron-chelating agents. Biochim Biophys Acta 1968;170(2):351–65.

    PubMed  CAS  Google Scholar 

  90. Kirkpatrick CH, Green I, Rich RR, Schade AL. Inhibition of growth of Candida albicans by iron-unsaturated lactoferrin: relation to host-defense mechanisms in chronic mucocutaneous candidiasis. J Infect Dis 1971;124(6):539–44.

    PubMed  CAS  Google Scholar 

  91. Schardinger F. Ueber das Verhalten der Kuhmilch gegen Methylenblau und seine Verwendung sur Unterscheidung von ungekochter und gekochter Milch. Z Unters Nahr Genussm 1902;5:1113–21.

    CAS  Google Scholar 

  92. Green DE, Pauli R. The antibacterial action of the xanthine oxidase system. Proc Soc Exp Biol Med 1943;54:148–50.

    CAS  Google Scholar 

  93. Lipmann F, Owen CR. The antibacterial effect of enzymatic xanthine oxidation. Science 1943;98:246–8.

    PubMed  CAS  Google Scholar 

  94. Gyorgy P, Dhanamitta S, Steers E. Protective effects of human milk in experimental staphylococcus infection. Science 1962;137:338–40.

    PubMed  CAS  Google Scholar 

  95. Reiter B, Oram J. Bacterial inhibitors in milk and other biological fluids. Nature 1967;216:328–30.

    CAS  Google Scholar 

  96. Masson PL, Heremans JF, Dive C. An iron-binding protein common to many external secretions. Clin Chim Acta 1966;14:735–739.

    CAS  Google Scholar 

  97. Masson PL, Heremans JF, Schonne E. Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med 1969;130(3):643–58.

    PubMed  CAS  Google Scholar 

  98. Harmon RJ, Schanbacher FL, Ferguson LC, Smith KL. Concentration of lactoferrin in milk of normal lactating cows and changes occurring during mastitis. Am J Vet Res 1975;36(7):1001–7.

    PubMed  CAS  Google Scholar 

  99. Masson PL, Heremans JF. Metal-combining properties of human lactoferrin (red milk protein). 1. The involvement of bicarbonate in the reaction. Eur J Biochem 1968;6(4):579–84.

    PubMed  CAS  Google Scholar 

  100. Goldsmith SJ, Eitenmiller RR, Barnhart HM, Toledo RT, Rao VN. Unsaturated iron-binding capacity of human milk. J Food Sci 1982;47:1298–304.

    CAS  Google Scholar 

  101. Arnold RR, Brewer M, Gauthier JJ. Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms. Infect Immun 1980;28(3):893–8.

    PubMed  CAS  Google Scholar 

  102. Tomita M, Bellamy W, Takase M, Yamauchi K, Wakabayashi H, Kawase K. Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. J Dairy Sci 1991;74(12):4137–42.

    Article  PubMed  CAS  Google Scholar 

  103. van der Strate BW, Beljaars L, Molema G, Harmsen MC, Meijer DK. Antiviral activities of lactoferrin. Antiviral Res 2001;52(3):225–39.

    PubMed  Google Scholar 

  104. Reiter B. The lactoperoxidase-thiocyanate-hydrogen peroxide antibacterium system. Ciba Found Symp 1978;65:285–94.

    PubMed  Google Scholar 

  105. de Wit JN, Hooydonk ACM. Structure, functions and applications of lactoperoxidase in natural antimicrobial systems. Neth Milk Dairy J 1996;50:227–44.

    Google Scholar 

  106. Kussendrager KD, van Hooijdonk AC. Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications. Br J Nutr. 2000;84(Suppl 1):S19–S25.

    PubMed  CAS  Google Scholar 

  107. Bjorck L, Rosen C, Marshall V, Reiter B. Antibacterial activity of the lactoperoxidase system in milk against pseudomonads and other gram-negative bacteria. Appl Microbiol 1975;30(2):199–204.

    PubMed  CAS  Google Scholar 

  108. Reiter B, Marshall VM, Bjorck L, Rosen CG. Nonspecific bactericidal activity of the lactoperoxidases-thiocyanate-hydrogen peroxide system of milk against Escherichia coli and some gram-negative pathogens. Infect Immun 1976;13(3):800–7.

    PubMed  CAS  Google Scholar 

  109. Bjorck L, Claesson O. Xanthine oxidase as a source of hydrogen peroxide for the lactoperoxidase system in milk. J Dairy Sci 1979;62:1211–5.

    Google Scholar 

  110. Hunt J, Massey V. Purification and properties of milk xanthine dehydrogenase. J Biol Chem 1992;267(30):21479–85.

    PubMed  CAS  Google Scholar 

  111. Tubaro E, Lotti B, Santiangeli C, Cavallo G. Xanthine oxidase increase in polymorphonuclear leucocytes and macrophages in mice in three pathological situations. Biochem Pharmacol 1980;29(3):1945–8.

    PubMed  CAS  Google Scholar 

  112. Bungener W. Influence of allopurinol on the multiplication of rodent malaria parasites. Tropenmed Parasitol 1974;25(3):309–12.

    PubMed  CAS  Google Scholar 

  113. Chipman DM, Sharon N. Mechanism of lysozyme action. Science 1969;165(892):454–65.

    PubMed  CAS  Google Scholar 

  114. Cohn ZA, Hirsch JG. The isolation and properties of the specific cytoplasmic granules of rabbit polymorphonuclear leucocytes. J Exp Med 1960;112:983–1004.

    PubMed  CAS  Google Scholar 

  115. Leffell MS, Spitznagel JK. Association of lactoferrin with lysozyme in granules of human polymorphonuclear leukocytes. Infect Immun 1972;6(5):761–5.

    PubMed  CAS  Google Scholar 

  116. Lahov E, Regelson W. Antibacterial and immunostimulating casein-derived substances from milk: casecidin, isracidin peptides. Food Chem Toxicol 1996;34(1):131–45.

    PubMed  CAS  Google Scholar 

  117. Medzhitov R, Janeway CA Jr. Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 1997;9(1):4–9.

    PubMed  CAS  Google Scholar 

  118. Lehrer RI, Ganz T. Defensins of vertebrate animals. Curr Opin Immunol 2002;14(1):96–102.

    PubMed  CAS  Google Scholar 

  119. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 2004;75(1):39–48.

    PubMed  Google Scholar 

  120. Goldammer T, Zerbe H, Molenaar A, Schuberth HJ, Brunner RM, Kata SR, et al. Mastitis increases mammary mRNA abundance of beta-defensin 5, toll-like-receptor 2 (TLR2), and TLR4 but not TLR9 in cattle. Clin Diagn Lab Immunol 2004;11(1):174–85.

    PubMed  CAS  Google Scholar 

  121. Swanson K, Gorodetsky S, Good L, Davis S, Musgrave D, Stelwagen K, et al. Expression of a beta-defensin mRNA, lingual antimicrobial peptide, in bovine mammary epithelial tissue is induced by mastitis. Infect Immun 2004;72(12):7311–4.

    PubMed  CAS  Google Scholar 

  122. Armogida SA, Yannaras NM, Melton AL, Srivastava MD. Identification and quantification of innate immune system mediators in human breast milk. Allergy Asthma Proc 2004;25(5):297–304.

    PubMed  CAS  Google Scholar 

  123. Murakami M, Dorschner RA, Stern LJ, Lin KH, Gallo RL. Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk. Pediatr Res 2005;57(1):10–5.

    PubMed  CAS  Google Scholar 

  124. McDonald TL, Larson MA, Mack DR, Weber A. Elevated extrahepatic expression and secretion of mammary-associated serum amyloid A 3 (M-SAA3) into colostrum. Vet Immunol Immunopathol 2001;83(3–4):203–11.

    PubMed  CAS  Google Scholar 

  125. Maes P, Damart D, Rommens C, Montreuil J, Spik G, Tartar A. The complete amino acid sequence of bovine milk angiogenin. FEBS Lett 1988;241(1–2):41–5.

    PubMed  CAS  Google Scholar 

  126. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 2003;4(3):269–73.

    PubMed  CAS  Google Scholar 

  127. Egesten A, Dyer KD, Batten D, Domachowske JB, Rosenberg HF. Ribonucleases and host defense: identification, localization and gene expression in adherent monocytes in vitro. Biochim Biophys Acta 1997;1358(3):255–60.

    PubMed  CAS  Google Scholar 

  128. Rosenberg HF, Domachowske JB. Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. J Leukoc Biol 2001;70(5):691–8.

    PubMed  CAS  Google Scholar 

  129. Donaldson L, Vuocolo T, Gray C, Strandberg Y, Reverter A, McWilliam S, et al. Construction and validation of a bovine innate immune microarray. BMC Genomics 2005;6:135.

    PubMed  Google Scholar 

  130. Swanson KM, Henderson HV, Farr VC, Davis SR, Oden K, Stelwagen K, et al. The use of microarrays to investigate gene regulation in the bovine mammary gland during Streptococcus uberis mastitis. Proc NZ Soc Anim Prod 2004;64:14–6.

    Google Scholar 

  131. Stein T, Morris JS, Davies CR, Weber-Hall SJ, Duffy MA, Heath VJ, et al. Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3. Breast Cancer Res 2004;6(2):R75–R91.

    PubMed  CAS  Google Scholar 

  132. Clarkson RW, Wayland MT, Lee J, Freeman T, Watson CJ. Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression. Breast Cancer Res 2004;6(2):R92–R109.

    PubMed  CAS  Google Scholar 

  133. Hogarth CJ, Fitzpatrick JL, Nolan AM, Young FJ, Pitt A, Eckersall PD. Differential protein composition of bovine whey: a comparison of whey from healthy animals and from those with clinical mastitis. Proteomics 2004;4(7):2094–100.

    PubMed  CAS  Google Scholar 

  134. Smolenski G, Haines S, Kwan FY, Bond J, Farr V, Davis SR, et al. Characterisation of host defence proteins in milk using a proteomic approach. J Proteome Res 2007;6(1):207–15.

    PubMed  CAS  Google Scholar 

  135. Takakura N, Wakabayashi H, Yamauchi K, Takase M. Influences of orally administered lactoferrin on IFN-gamma and IL-10 production by intestinal intraepithelial lymphocytes and mesenteric lymph-node cells. Biochem Cell Biol 2006;84(3):363–8.

    PubMed  CAS  Google Scholar 

  136. Bowdish DM, Davidson DJ, Hancock RE. Immunomodulatory properties of defensins and cathelicidins. Curr Top Microbiol Immunol 2006;306:27–66.

    Article  PubMed  CAS  Google Scholar 

  137. Hodgkinson AJ, Cannon RD, Holmes AR, Fischer FJ, Willix-Payne DJ. Production from dairy cows of semi-industrial quantities of milk-protein concentrate (MPC) containing efficacious anti-Candida albicans IgA antibodies. J Dairy Res 2007;74(3):269–75.

    PubMed  CAS  Google Scholar 

  138. Finlay BB, Hancock RE. Can innate immunity be enhanced to treat microbial infections? Nat Rev Microbiol 2004;2(6):497–504.

    PubMed  CAS  Google Scholar 

  139. Caccavo D, Pellegrino NM, Altamura M, Rigon A, Amati L, Amoroso A, et al. Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application. J Endotoxin Res 2002;8(6):403–17.

    PubMed  CAS  Google Scholar 

  140. Kerr DE, Plaut K, Bramley AJ, Williamson CM, Lax AJ, Moore K, et al. Lysostaphin expression in mammary glands confers protection against staphylococcal infection in transgenic mice. Nat Biotechnol 2001;19(1):66–70.

    PubMed  CAS  Google Scholar 

  141. Sun H-C, Xue F-M, Qian K, Fang H-X, Qiu H-L, Zhang X-Y, et al. Intramammary expression and therapeutic effect of a human lysozyme-expressing vector for treating bovine mastitis. J Zhejiang Univ Science B 2006;7:324–330.

    CAS  Google Scholar 

Download references

Acknowledgement

The authors wish to acknowledge the efforts of Claire Miller and the staff at the AgResearch, Ruakura Information Services section in procuring the sometimes obscure original literature.

Author information

Authors and Affiliations

  1. Dairy Science and Technologies Section, AgResearch, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand

    Thomas T. Wheeler & Alison J. Hodgkinson

  2. Dairy Goat Co-operative (NZ) Ltd., Hamilton, New Zealand

    Colin G. Prosser

  3. Vialactia Biosciences Ltd., P. O. Box 109-185, Newmarket, Auckland, New Zealand

    Stephen R. Davis

Authors
  1. Thomas T. Wheeler
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Alison J. Hodgkinson
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Colin G. Prosser
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Stephen R. Davis
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Thomas T. Wheeler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wheeler, T.T., Hodgkinson, A.J., Prosser, C.G. et al. Immune Components of Colostrum and Milk—A Historical Perspective. J Mammary Gland Biol Neoplasia 12, 237–247 (2007). https://doi.org/10.1007/s10911-007-9051-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-007-9051-7

Keywords