164 D
. Kelly, A.G.P. Coutts Livestock Production Science 66 2000 161 –167
an infectious challenge. The major immune cell Neonatal cells also have a limited ability to activate
types involved in mediating innate responses are the specific adaptive arm of the immune system
macrophages, neutrophils and natural killer cells. Fairhurst et al., 1998.
These cells are capable of discriminating self from non-self and recognise molecular arrays or patterns,
3.1. Disease susceptibility of neonates such as lipopolysaccharides or techoic acids, that
seem to be shared among groups of pathogens. These Although the cellular apparatus of the immune
structures are recognised by pattern recognition system is in place and mucosal and systemic anti-
receptors expressed on activated macrophages that body responses can be detected early in life, a
induce killing mechanisms including phagocytosis functional deficit in immune function persists for
and opsonisation. For many years the innate immune some time leaving the neonate susceptible to bacteri-
system has been seen as a separate entity from the al and viral attack. Aspects of the immune function
adaptive system. However, recent studies have which account for the impaired responses to antigen
shown that they have a more integrative function challenge have been proposed and include enhanced
where the innate system functions to initiate and intestinal permeability and immaturity in T and B
regulate the adaptive response Jullien et al., 1997. cell function. However, in the neonate, a major
The adaptive immune responses are initiated follow- limitation to mounting appropriate immune responses
ing antigen uptake and presentation to T and B cells. appears to relate to deficiencies in antigen presenta-
The major route of antigen uptake has long been tion and, in particular, the function of APCs Ridge
considered to be via M cells which are located on et al., 1996; Jullien et al., 1997. The neonate is also
organised lymphoid structures referred to as Peyer’s very deficient in anti-polysaccharide antibodies to
Patches. Antigens are transported into the gut associ- encapsulated pathogens Fairhurst et al., 1998 and
ated lymphoid tissue and are presented to T and B this has been attributed to deficiencies in the CD1
cells by antigen presenting cells APCs, a process system of antigen recognition and presentation. The
that involves antigen recognition and has inherent CD1 system is also thought to be an important
fine molecular specificity. Antigen-primed T and B antigen presentation pathway that links together the
lymphocytes migrate through the lymph and reach innate immune system and the adaptive response
the peripheral blood, where they home to mucosal Jullien et al., 1997. This may explain why the
effector sites, including the mammary gland. In this neonate fails to mount strong and appropriate im-
way the maternal experience of environmental an- mune responses. The neonate is therefore immuno-
tigens is passed to the sucking neonate. The role of logically suboptimal and, given an appropriate level
enterocytes and dendritic cells in antigen uptake and of pathogen exposure, the mucosal surfaces are
presentation to APCs Kaiserlian and Etchart, 1999 readily colonised by harmful micro-organisms.
is currently very topical and it is considered that immunological outcome may be determined as a
result of the communication and crosstalk between
4. Early nutrition and the developing intestine
these cell types. and immune system
Resistance to infection relies on a harmonious balance between the innate and adaptive antigen-
Maternal colostrum and milk not only provide the driven immunity. However, in the neonate the
newborn with nutrition but also confer passive adaptive arm of the immune system has not de-
immunity and generally protect against gastrointesti- veloped and, hence, during this period of vulnerabili-
nal and respiratory diseases. In addition, maternal ty, cells of the innate immune system, predominantly
milk may have the capacity to directly stimulate macrophages, neutrophils and NK cells, clear large
immune function. Although the precise mechanisms quantities of foreign antigen. Furthermore, although
whereby maternal milk confers protection are poorly the neonatal cells are functional, they are present in
defined, it is likely that they involve altered intestinal lower numbers, are less chemotactic and have lower
physiology, microbiology and immunology. The enzyme
activity than
their adult
counterparts. mode of action of factors in milk which confer
D . Kelly, A.G.P. Coutts Livestock Production Science 66 2000 161 –167
165
protection can be grouped into four main categories express the surface antigen CD45RO, which is
and comprise maturational, immuno-modulatory, an- associated with immunological memory Bertotto et
ti-inflammatory and anti-microbial effects. al., 1990. They are also loaded with ligands such as
CD40L Bertotto et al., 1996. These cells are 4.1. Maternal milk and maturation of the intestine
thought to be taken up by the neonate and to compensate for the immature function of neonatal
Colostrum and milk feeding have been shown to cells by providing potent activation signals leading to
promote the maturation of the developing intestinal strong active immune responses Bertotto et al.,
epithelium. Lactase expression specific and total 1996; Xanthou, 1997. It has also been proposed that
was found to decline significantly in colostrum-fed milk-borne cytokines are important regulators of
animals when compared with colostrum-deprived immune responses. For example, human colostrum
animals. The levels of sialylation and fucosylation on has been shown to stimulate the release of cytokines
epithelial cells indicated that intestinal cells from from peripheral blood mononuclear cells PBMCs,
colostrum-fed animals were phenotypically mature thus altering the cytokine milieu or background
Kelly et al., 1993. Differences in glycosylation against which immunological decisions are made
patterns over Peyer’s Patch epithelium were also Bessler et al., 1996. Among all the factors that are
observed. This suggests that the adherent flora in known to control T cell development and function,
colostrum-fed animals may be qualitatively different cytokines are considered to be the most important
over Peyer’s Patch epithelium and hence the antigens Delespesse et al., 1998.
sampled may also differ. The possibility that such It is interesting that the defence factors in human
differences influence the priming of the immune milk function without causing inflammation and in
system is considerable, since the nature and dose of fact a number of maternal milk constituents have
antigen have a dramatic effect on the immunological been reported to have anti-inflammatory activity.
outcome. Lactoferrin and fragments thereof has been shown to
inhibit the endotoxin-induced interleukin 6 IL6 4.2. Maternal milk and immune modulation
release from human monocytic cells Mattsby-Bal- tzer et al., 1996. The cytokine IL10 and TGFb have
The immuno-modulatory effects of maternal milk been reported in maternal milk and are recognised to
have been investigated using antibody responses to have immuno-suppressive and anti-inflammatory ac-
vaccines as indicators of immunity Pickering et al., tivities Letterio et al., 1994; Garofalo et al., 1995.
1998. The results from these studies are very Maternal TGFb has been shown to be important to
controversial. However, a well-executed randomised the survival of TGFb-null mice by reducing the
trial Pickering et al., 1998 recently reported that diffuse and lethal inflammation caused by gene
breast-fed infants do exhibit enhanced specific anti- disruption Letterio et al., 1994.
body titre to some vaccines. Similarly, immuno- phenotypic differences in lymphocyte populations
4.3. Maternal milk and anti-microbial function have been reported following exposure to maternal
milk. These differences include a decrease in the The protection afforded by maternal milk has been
ratio of CD4 1 :CD8 1 cells and a greater number largely attributed to the presence of secretory IgA.
of NK cells Hawkes et al., 1999. This difference is However, milk contains a large number of other
consistent with age-related changes, suggesting that components with anti-microbial activity including
maternal milk induces maturation of the developing complex carbohydrates, glycoproteins, glycolipids,
immune system. The mechanism whereby maternal glycosaminoglycans, mucins and oligosaccharides.
milk induces these effects is largely unknown. The oligosaccharides comprise the third most abun-
Recent studies suggest that maternal lymphocytes in dant constituent in milk and contain a myriad of
milk may fulfil an important role in modulating structures. Those with homology to cell surface
neonatal immune responses. Maternal lymphocytes pathogen receptors may inhibit pathogen interactions
are present in milk in a very activated state and with host mucosal tissues and therefore protect
166 D
. Kelly, A.G.P. Coutts Livestock Production Science 66 2000 161 –167
against infection. A large number of constituents will address this question at a mechanistic level, will
which interfere with pathogen binding have been unravel further virtues of maternal feeding.
reported in milk. Lactadherin is a milk glycoprotein that inhibits rotaviral infection Newburg et al.,
1998. IgA and mucin prevent the attachment of
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5. Conclusions
