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The effects of milk proteins on immunity:
Mechanisms and implications
RJJ van Neerven
FrieslandCampina Research, Wageningen, The
Netherlands
Cellbiology and Immunology Group, Wageningen
University, Wageningen, the Netherlands
Milk is a natural, complete food full
of functional components
It has two main functions:
•
•
promoting development & growth
and protection against infections
Paul Ehrlich: Transfer of immunity by milk
Maternal immunization of animals and
subsequent breastfeeding protected
suckling mice against the toxins abrin
and ricin (1892)
Paul Ehrlich
(1854-1915)
Transfer of immunity by milk
Quote from : Kauffmann
Nature Immunol 2008
Transfer of immunity by milk: factors involved
Most of these factors are also
present in cow’s milk !
Verhasselt, Mucosal
Immunology 2010
Effects of farming on allergy development:
Evidence from multiple epidemiological
studies
•
Effect on asthma, rhinitis and wheezing
•
Effect of stable and animal exposure
•
Effect of milk consumption
•
Effect of heating of raw milk
Protective effect of exposure to milk and stables
on development of allergy
Riedler et al
Lancet 2001
Epidemiological studies on the effect of farm
milk consumption on allergies
Adapted from von Mutius and Vercelli
Nat. Rev. Immunol 2011
Heating status and milk protein levels are linked
to the protective effect of farm milk on asthma
Loss et al
J Allergy Clin Immunol, 2011
Raw milk consumption is associated with
fewer upper airway infections in early life -1
Pasture study: A prospective birth cohort of 1100 children in 5 countries
Reference group for milk types is UHT Shop milk.
* Statistically
significant
Loss et al
JACI in press
Raw milk consumption is associated with
fewer upper airway infections in early life -2
Pasture study: A prospective birth cohort of 1100 children in 5 countries
Reference group for milk types is UHT Shop milk.
* Statistically
significant
Loss et al
JACI in press
Binding of bovine IgG to human airway pathogens
Specificity of bovine immunoglobulins:
Agglutination of pathogenic bacteria
Human serum IgG (IV Ig) and bovine milk IgG (bIg)
bind to human RSV and influenza
IV Ig
bIg
Den Hartog et al
Submitted
Bovine IgG can prevent in vitro infection of
human cells by human RSV
50
00
50
Inhibition RSV (%)
hibition 150
of HEp-2 infection by RSV-GFP
100
Therapeutic Ab
Synagis
Human serum Ig
IVIg
Bovine milk Ig
boIg
50
0
-50
-4
0
-2
0
2
4
Concentration Ig (log(ug/ml))
Den Hartog et al
Submitted
Functions of immunoglobulins
Binding to bacteria, viruses and allergens
• Igs neutralise pathogens
• Igs induce phagocytosis and killing of pathogens
• Igs induce and enhance immune responses
+
Bovine IgG promotes phagocytosis of pathogens
by human MoDC
Den Hartog et al
Submitted
How can raw milk consumption protect against
respiratory infection and allergy ?
Adapted from
van Neerven et al
JACI 2012
RSV infections are linked to otitis and asthma
Acknowledgements
WUR CBI:
Huub Savelkoul
Gerco den Hartog
FrieslandCampina
Laurien Ulfman
Anouk Feitsma
Elise van de WegSchrijver
Talitha Eshuis
Andre Groeneveld
Margrethe Jonkman
Rolf Bos
UMCU/WKZ
Jeanette Leusen
Gerco den Hartog
University Munich
Erika von Mutius
Georg Loss
Marcus Ege
WUR HMI
Nico Taverne
Jerry Wells