The acquisition of passive immunity in the new-born piglet

The acquisition of passive immunity in the new-born piglet

Livestock Production Science 78 (2002) 13–23 www.elsevier.com / locate / livprodsci The acquisition of passive immunity in the new-born piglet a, b J...

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Livestock Production Science 78 (2002) 13–23 www.elsevier.com / locate / livprodsci

The acquisition of passive immunity in the new-born piglet a, b J.A. Rooke *, I.M. Bland a

Animal Biology Division, SAC, Craibstone Estate, Bucksburn, Aberdeen AB21 9 YA, Scotland, UK b Writtle College, Chelmsford CM1 3 RR, UK

Abstract Because of the epitheliochorial nature of the porcine placenta, the new-born piglet must acquire maternal immunoglobulins from ingested colostrum and milk for passive immune protection until the immune system of the piglet becomes fully developed. Concentrations of IgG in piglet plasma depend on the amount of colostrum ingested, IgG concentrations in colostrum and the timing of gut closure (when intact IgG can no longer be absorbed by the gastro-intestinal tract of the piglet). Much of the available information concerning IgG absorption by the piglet and the mechanism and timing of gut closure has been derived from studies using artificially-fed piglets. It is now recognised that, in addition to changes in colostrum IgG concentrations in the first 24 h of life, colostrum contains many bio-active compounds whose concentrations also change rapidly in the first 24 h of life. Modern sows are expected to rear increased numbers of physiologically less mature piglets and producers are faced with pressures to reduce antibiotic usage. Therefore it is critical that piglets absorb adequate amounts of IgG for disease protection. The review assesses the maternal supply of IgG and piglet absorption of IgG in naturally suckling piglets of modern genotype. Nutritional and other factors which may influence acquisition of IgG by the piglet are discussed and relationships between acquisition of passive immunity and development of active immunity addressed.  2002 Elsevier Science B.V. All rights reserved. Keywords: Piglet; Colostrum; Immunoglobulin G; Gut closure

1. Introduction Pre-weaning mortality of piglets is an important loss to the pig industry. Recent UK data (Meat and Livestock Commission, 2001) show that more than 10% of piglets born alive die before weaning and the problem is intractable since the level of mortality has changed little in the last 10 years (Varley, 1995). *Corresponding author. Tel.: 1 44-1224-711-060; fax 1 441224-711-292. E-mail address: [email protected] (J.A. Rooke).

Crushing by the sow, starvation, infection and abnormalities are the immediate causes of mortality with, in most surveys, crushing by the sow and starvation being the most frequent (Varley, 1995). Although inadequate colostrum intake is primarily implicated in deaths due to starvation and hypothermia, a suboptimal intake of colostrum may result in an inadequate transfer of maternal immunoglobulins to the new-born animal and therefore increased susceptibility to infection not only in the immediate postnatal period (Drew and Owens, 1988) but also after weaning (Varley et al., 1986). Passive transfer of

0301-6226 / 02 / $ – see front matter  2002 Elsevier Science B.V. All rights reserved. PII: S0301-6226( 02 )00182-3

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immunity via colostrum is important in major farm livestock species as the epitheliochorial nature of the placenta in these species prevents the transfer of immunoglobulins across the placenta which occurs, for example, in the human. As transfer of intact macromolecules across the gastro-intestinal tract is only possible for a short time after birth, this period is particularly important. The new-born piglet is therefore reliant on immunoglobulin G (IgG) absorbed from colostrum for humoral immune protection until its own immune system has sufficiently matured to respond (to produce antibodies against) to foreign antigens. Thus, the concentrations of IgG in the plasma of piglets shortly after birth are positively correlated with survival (Hendrix et al., 1976) and in addition dead piglets had lower serum IgG concentrations than comparable surviving piglets (Klobasa et al., 1981; Drew and Owens, 1988). It is not therefore surprising that traits such as birth order and time to suckle which imply successful early suckling are positively correlated with survival (Tuchscherer et al., 2000). The pig industry is currently subject to pressures which may make the producer more reliant on successful suckling by the piglet to obtain adequate passive immune protection. Amongst these are economic pressure which reduces labour inputs and thus supervision of the farrowing house; pressures to reduce use of antibiotics and therefore the ability to treat piglets with sub-optimal colostrum intakes and finally the move away from systems based on farrowing crates to systems which potentially reduce piglet welfare and increase mortality. This paper reviews current knowledge on the acquisition of passive immunity by the new-born piglet with particular emphasis on the naturally suckling piglet and explores opportunities for enhancing immunoglobulin uptake by the piglet.

2. Immune status of the new-born piglet The new-born piglet is immunologically underdeveloped at birth both from lack of exposure to antigens and underdevelopment per se. Immunoglobulins can be detected in the blood of new-born unsuckled piglets (Bianchi et al., 1992) although not in the same molecular form as present in mature

animals (Porter and Hill, 1970). Foetuses can produce IgG and IgM in response to mitogen stimulation in utero (Tlaskalova-Hogenova et al., 1994) and spontaneously immunoglobulin-producing B cells have been isolated from foetal piglets (Cukrowska et al., 1996). Gaskins (1998) recently reviewed the development of active cellular immunity in the piglet and concluded that most aspects of the system were immature at birth. For example, T lymphocytes were present in the lamina propria of the intestine but in lower numbers than at 4 weeks of age and with a higher proportion of the CD2 2 CD4 2 CD8 2 subset. The ability of intestinal T cells to respond to mitogens was less well developed in the neonate and the numbers of antigen-presenting cells were lower. Similarly, blood mononuclear cells responded less well in the neonate to a T-cell-dependent antigen (Hammerberg et al., 1989) and the numbers of immunoglobulin-secreting cells in spleen and bone marrow were lower at 1 than 4 weeks of age (Bianchi et al., 1999). Thus, most components of the immune system of the piglet are present at birth but are functionally undeveloped and several weeks of life are necessary before the immune system becomes fully developed. In relation to synthesis of IgG, when piglets were reared on bovine colostrum, porcine IgG was detected in serum from about 7 days of age (Klobasa et al., 1981; Drew and Owens, 1988). However, the absorption of maternal IgG was considered to repress the active synthesis of IgG by the piglet when measurements were based on changes in piglet serum concentrations. Similarly, no IgA or IgM positive cells were detected in the gut of the piglet until about 10 days of age and IgM rather than IgA was the dominant type (Butler et al., 1981).

3. Acquisition of passive immunity Since the new-born piglet is immunologically ¨ and the time lag before its immune system naıve develops fully covers at least the period from birth until weaning, the piglet is dependent on the sow for immune protection during that period. Given the epitheliochorial nature of the porcine placenta, the maternal supply of passive immunity occurs postnatally from immunoglobulins, other bioactive peptides such as growth factors and cytokines and cells

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in colostrum and milk (Schanbacher et al., 1997). Critically important is the supply of IgG in colostrum because of the short time window during which the new-born piglet is able to absorb intact immunoglobulins and transfer them to the bloodstream. For successful transfer of passive immunity, several factors are of importance. The lactational secretions of the sow must contain adequate amounts of the appropriate immunoglobulin (i.e. IgG before gut closure and IgA post-closure); the immunoglobulins must be delivered intact to the site of absorption or functional activity, and finally in the case of IgG, the immunoglobulins must be absorbed intact and delivered to the circulation of the piglet.

4. Composition of colostrum Colostrum is characterised by a high concentration of IgG and relatively lower concentrations of IgA and IgM (Curtis and Bourne, 1971; Klobasa and Butler, 1987; Klobasa et al., 1987). The concentration of IgG in colostrum is several-fold higher than in sow plasma and declines rapidly during the first 24 h of secretion. In mature milk, IgA rather than IgG is therefore the dominant immunoglobulin. The initial concentration of IgG in colostrum is very variable even within sows on the same unit (Klobasa and Butler, 1987; Bland and Rooke, 1998). Parity, season and genotype have been suggested as factors that influence colostrum IgG concentrations (Inoue et al., 1980; Klobasa and Butler, 1987). Between different parts of the udder, caudal teats tended to have lower IgG concentrations than cranial teats (Inoue et al., 1980; Bland and Rooke, 1998). The amount of IgG available to an individual piglet is therefore influenced by a variety of factors, many of which are poorly understood. Indeed the entire process of colostrogenesis is not well described in the pig. Bourne and Curtis (1973) have shown that essentially all IgG and IgM are derived from the serum of the sow and, as in the cow, the uptake is mediated by specific receptors on mammary epithelial cells (Huang et al., 1992). The mechanisms controlling colostrogenesis in cattle clearly involve lactogenic hormones (see review by Barrington et al., 2001) but detailed information on the control of the IgG receptor is lacking. In the pig, such information

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would be desirable as a basis for understanding the variability in colostrum IgG concentrations. In addition to immunoglobulins, colostrum contains leukocytes and other immunologically active cells. Leukocytes are absorbed from colostrum (Tuboly et al., 1988; Williams, 1993) and migrate to mesenteric lymph nodes and other tissues of the piglet where they exert an immunomodulatory effect on piglet responses to mitogens (Williams, 1993). Bianchi et al. (1999) have attributed the relatively high frequency of IgG secreting cells in the spleen, lymph node and bone marrow of 1-week-old piglets to colostrum-derived cells. This is an aspect of passive immune acquisition that deserves further attention. Colostrum contains a variety of growth factors including insulin-like growth factors (IGF) 1 and 2, insulin (Burrin et al., 1997), epidermal growth factor (EGF, Odle et al., 1996) and transforming growth factor-beta (Xu et al., 1999). The amounts of these factors in colostrum and their impact on the acceleration of intestinal tissue growth and maturation of the gut resulting from colostrum ingestion have recently been reviewed (Xu et al., 2000). In general, the concentrations of growth factors in colostrum fall over the first day of life and therefore any positive effects of growth factors may be diminished in later borne piglets. Since the ability of the piglet to transfer IgG from the gut to the bloodstream disappears in the first 24 to 36 h of life (see below) the change of the dominant immunoglobulin from IgG to IgA over the same period is in keeping with the need of the piglet to acquire IgG for passive humoral immune protection in the first 24 h of life and then continuing protection from IgA in milk at mucosal surfaces thereafter. Since the antigenic specificity of IgG and IgA reflects the maternal experience of environmental antigens, immunity acquired through colostrum and milk will protect the piglets against these antigens but not against novel antigens.

5. Intake and absorption of colostrum As the intake of colostrum by piglets suckling the sow is difficult to quantify, most studies describing the uptake of macromolecules by the neonatal piglet

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have relied upon feeding piglets known amounts of a standard colostrum or administering exogenous markers. In so-doing, the rapidly changing composition of colostrum over the first day of life and effects of natural suckling are not taken fully into account. However, these defined studies have provided a basis for describing the mechanisms of IgG uptake and delivery to the circulation of the piglet. Delivery of intact immunoglobulins to the small intestine, where absorption of intact proteins takes place, is facilitated by two factors. At birth and in the first days of life, the dominant gastric protease in the stomach is chymosin rather than pepsin (Sangild et al., 2000) which predominantly results in the clotting of milk. Secondly, colostrum contains protease inhibitors which facilitate absorption, as feeding of colostrum from which trypsin-inhibitors had been removed (Carlsson et al., 1980) or added to (Westrom et al., 1985), respectively, decreased and increased transfer of IgG to the serum of the piglet. The immunoglobulins in colostrum are rapidly taken up by non-specific pinocytosis into the enterocytes of the small intestine of the new-born piglet and localised in vacuoles (Payne and Marsh, 1962; Clarke and Hardy, 1971). The ability of foetal enterocytes to endocytose immunoglobulins is present before birth as demonstrated both in utero (Sangild et al., 1999) and in piglets which have been born prematurely (Sangild et al., 1997). However, enterocytes synthesised postnatally lack the ability to endocytose intact proteins (Smith and Jarvis, 1978; Smith and Peacock, 1980). The complete replacement of the foetal population postnatally by these ‘adult’ enterocytes takes up to 19 days (Smith and Jarvis, 1978) and at 8 days of age 38% of the cell population of the villus is still of the foetal type (Smith and Peacock, 1980). This rate of cell replacement in the villus is therefore unable to explain the cessation of macromolecule transfer to the circulation of the piglet after 24 to 36 h of life. Cells are still able to take up macromolecules after cessation of transfer (Clarke and Hardy, 1971; Ekstrom and Westrom, 1991) and the small intestine of the suckled piglet at 1 day of age contains swollen epithelial cells with substantially increased protein contents (Xu et al., 1992). Therefore, the critical event in controlling the transfer of intact immuno-

globulins to the circulation of the piglet is cessation of transfer across the basolateral membrane of the enterocyte. For this reason, the term ‘gut closure’ is defined as cessation of transfer of IgG to the circulation of the piglet rather than cessation of uptake into the enterocyte from the gut.

5.1. Gut closure Since the interval between birth and gut closure is the critical window during which absorption of intact immunoglobulins can take place, an understanding of gut closure is necessary in attempts to improve passive immunity in the piglet. That closure takes place as early as 24 h of age in suckling pigs was first noted by Speer et al. (1957) and has been since confirmed many times. Factors influencing closure have been investigated in detail as the new-born piglet has proved a convenient experimental model to investigate the absorption of intact proteins. That fasting piglets delays closure has long been established (Lecce and Morgan, 1962; Payne and Marsh, 1962). Further studies with fractionated colostrum or pure substances established that it was the intake and absorption of nutrients rather than any specific component of colostrum that induced closure as simple sugars such as glucose (Lecce, 1966) or lactose (Werhahn et al., 1981) induced closure. The amount of nutrients absorbed also influenced closure with a minimum amount of glucose being required (Lecce, 1966). The mechanism by which the amount of nutrients absorbed induces closure is not clear. Leary and Lecce (1978) demonstrated that closure took place at the same time in an isolated segment of intestine as in the remainder of the small intestine and therefore the factor(s) inducing closure was present in the circulation of the piglet. Mehrazar et al. (1993) maintained piglets by intravenous infusion and noted that absorption of protein from a test dose administered gastrically was reduced after 1 day of age and completely suppressed at 5 days of age indicating the importance of absorbed nutrients in initiating closure. Several hormones may be involved in the signal for closure. Svendsen et al. (1986) showed that administration of insulin to new-born piglets decreased transmission of marker proteins 12 h after

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birth in conjunction with increased concentrations of serum insulin. However, in studies on the effect of colostrum on neonatal protein synthesis, Burrin et al. (1995) concluded that colostrum-derived insulin made only a small contribution to the rise in serum insulin concentrations observed in colostrum-fed piglets. Therefore, in the suckling piglet, the observed effect of insulin in reducing macromolecule absorption may be secondary to nutrient intake. This would seem more likely than a primary effect especially in the light of the later observations by Svendsen et al. (1990) that in piglets where macromolecule absorption was enhanced, increased concentrations of serum insulin were also observed at birth. Addition of insulin-like growth factor-1 (IGF1) to colostrum increases epithelial cell tight junction length (Zarrinkalam et al., 1999). However, since IgG absorption is by pinocytosis, this effect is more likely to be relevant to exclusion of pathogens. More data are available on the effects of glucocorticoids on IgG absorption. Increasing maternal cortisol by treatment with ACTH has been associated with increased serum IgG concentrations in the newborn (Bate and Hacker, 1985), IgG concentrations at 48 h of age were positively correlated with cortisol concentrations at birth (Sangild et al., 1997) and administration of metapyrone (an inhibitor of adrenal cortisol synthesis) reduced IgG concentrations at 3 days of age (Patt and Eberhardt, 1976; Sangild et al., 1993). Thus, glucocorticoids have a stimulatory effect on uptake of macromolecules. However, the above studies do not differentiate between increased absorptive capacity for IgG prior to gut closure and a delay in gut closure. Since in general, cortisol has a stimulatory effect on gut maturation (Sangild et al., 2000) it is more likely that the effect of increased cortisol on plasma IgG concentrations is mediated by enhanced uptake rather than delayed closure. Indeed, administration of ACTH to the sow for 7 days prior to farrowing depressed IgG uptake by the piglet (Bate et al., 1991). The decrease in IgG concentrations was attributed to exogenous ACTH anticipating the peri-natal maternal surge in cortisol concentrations and prematurely stimulating maturation of the gastro-intestinal tract. From the above, the evidence for a direct role of insulin and cortisol in stimulating gut closure is not strong and the domi-

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nant factor initiating closure in the piglet is most probably the intake and absorption of a critical amount of nutrients.

5.2. Specificity of immunoglobulin G absorption Absorption by the gut of the new-born piglet is saturated by increasing amounts of colostrum or individual nutrients, e.g. glucose or protein (Lecce et al., 1964; Pierce and Smith, 1967). It has been suggested that absorption is saturable because an individual enterocyte is only able to take up a finite amount of material by pinocytosis. There has been debate concerning the specificity of transmission of intact macromolecules to the circulation of the piglet. Certainly there is no good evidence for the receptormediated uptake and transfer of IgG that occurs in man and rat. Many studies have observed the appearance in piglet blood of a range of dosed heterologous proteins and other macromolecules indicating a lack of selectivity of absorption. However, less attention has been paid to selective absorption in the naturally suckling piglet. Klobasa et al. (1981) demonstrated absorption of IgA, IgG and IgM by suckling piglets and observed variability between piglets in the extent of uptake of immunoglobulins. This might in part be related to the possibility of different routes of absorption as Butler et al. (1981) noted that while IgG was located in villus cells, IgA and IgM were located in crypt cells. Carlsson et al. (1980) measured the appearance of IgG, albumin and b-lactoglobin in piglet serum and found that compared to concentrations in colostrum, b-lactoglobin concentrations in serum were lower than IgG and albumin. More recently, using bovine colostrum-fed piglets, Kiriyama (1992) and Harada et al. (1999) have shown selective transfer to serum and cerebrospinal fluid of components of colostrum by electrophoretic characterisation of proteins. Using the same approach, Bland and Rooke (unpublished observations) have attempted to quantify the transfer of different proteins to piglet serum. Table 1 shows that of the proteins in colostrum only the concentrations of IgG light and heavy chains and a protein of molecular weight 45 kD increased when piglets consumed colostrum, thereby indicating selective uptake of protein from colostrum. Concentrations of IgG de-

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Table 1 Concentration of proteins (mg / ml) in sow colostrum and piglet plasma determined by SDS–polyacrylamide electrophoresis Molecular weight (kD) 11 16 23 29 45 58 75 91

Protein

IgG light chain

IgG heavy chain Albumin a

Colostrum

11.1 29.5 23.6 25.8 6.8 43.2 5.4 3.9

Piglet plasma 0h

12 h

1.6 2.4 0.6 0.2 ND a ND 10.6 2.4

0.3 2.9 9.4 0.2 8.6 12.9 6.0 4.0

ND, none detected.

termined either by electrophoresis or by ELISA in both colostrum and piglet plasma were similar, indicating that IgG was absorbed intact. Therefore, there is evidence that protein absorption in the piglet is to some extent selective towards IgG. The fate of the various protein growth factors in colostrum has recently been reviewed by Xu et al. (2000) who concluded that absorption of growth factors such as IGF-1 and EGF from colostrum was limited probably because their actions are local to the gut and receptor-mediated. In summary, absorption and transmission of IgG to the circulation of the piglet takes place when the gastro-intestinal tract of the piglet is predisposed to absorption of intact macromolecules. Factors involved are the low proteolytic activity present in the stomach and intestines, the presence of protease inhibitors in colostrum and the population of foetal enterocytes in the intestines. Available evidence also suggests that uptake of IgG is to some extent selective. Colostrum intake specifically stimulates the functional maturation of the piglet’s gastrointestinal tract (see review by Xu et al., 2000) in the first 24 h of life and also appears to be the main factor that stimulates gut closure. Gut closure is stimulated by colostrum in a dose-dependent manner perhaps with the involvement of the perinatal cortisol surge in initiating gut maturation. Functionally, this process ensures that if the suckling piglet has an adequate colostrum intake, sufficient IgG is absorbed in a minimum time thus reducing the chances of invasion by potentially pathogenic macromolecules

prior to gut closure. Questions that arise are what constitutes an adequate intake of colostrum and IgG in the suckling piglet; are there occasions when this intake is not achieved and can intake and absorption of IgG be manipulated.

6. Acquisition of passive immunity in the normal suckling piglet The normal suckling piglet has to deal with a constantly changing environment as it attempts to suckle and so obtain nutrients and immunoglobulins as the composition of colostrum changes rapidly with time and there is competition between siblings for access to teats. In this situation the total colostrum intake of individual piglets and the amounts of IgG derived from colostrum vary widely. Using correction factors for metabolic and urinary losses (Fraser and Rushen, 1992), Bland et al. (1999) estimated colostrum intakes for normally suckling piglets over the first 24 h of life. Estimated colostrum intakes varied widely (348 g / kg live-weight / 24 h, S.D. 46) as did estimated IgG intakes (10.4 g / kg live-weight / 24 h, S.D 3.7). The mean estimate of colostrum intake was, however, similar to other reported values for suckling pigs (Le Dividich et al., 1997). There were differences between litters in estimated IgG intakes which were related to differences in colostrum IgG concentration rather than total colostrum intake indicating the importance of colostrum IgG concentration. However, there was no significant

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Fig. 1. Relationship between IgG intake of piglets over the first 24 h of suckling and plasma IgG concentrations after 24 h suckling (different symbols denote piglets from different litters).

relationship between colostrum IgG intake and concentrations of IgG in piglet plasma at 24 h of age (Fig. 1) although there were suggestions of curvilinearity. The main conclusion to be drawn from these data is that in piglets that have the opportunity to suckle colostrum from the start of lactation, the supply of IgG in colostrum over the first 24 h of life does not limit the acquisition of IgG by the piglet. However, since in normally suckling piglets, the concentration of IgG in colostrum that any piglet first encounters will be determined by its position in the birth order and the length of farrowing, IgG acquisition by piglets late in the birth order may be prejudiced by low colostrum IgG concentrations. Klobasa et al. (1981) withheld piglets from the sow for periods up to 24 h and observed a progressive reduction in plasma IgG concentrations in the piglets. Bland et al. (2000) used a similar approach and delayed suckling for 8 and 12 h but also estimated colostrum intakes and showed, in agreement with Klobasa et al. (1981), that plasma IgG concentrations decreased as the delay in suckling increased. Colostrum intakes did not differ between groups of piglets that suckled immediately or after a delay and therefore the

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reduced piglet plasma IgG concentrations resulted from lower colostrum IgG concentrations. These reduced plasma IgG concentrations were still evident at 4 weeks of age. These observations emphasise the importance of colostrum IgG concentrations as piglets born late in the birth order to a sow producing colostrum with low IgG concentrations would have reduced plasma IgG concentrations and therefore be at risk. Other factors can reduce colostrum intake by a piglet, many of which act by reducing the ability of a piglet to compete successfully with its litter-mates. A low birth-weight piglet is less able to compete first because of its smaller size; secondly, it has a larger surface area in relation to weight and is therefore more sensitive to effects of cold stress (Le Dividich and Noblet, 1981) and thirdly, a true runt piglet differs physiologically from its litter-mates and has an increased risk of mortality (Rooke et al., 2001). Any piglet that suffers hypoxia during birth will be slower to reach the udder and suckle and therefore likely to have a reduced colostrum intake (Herpin et al., 1996). Finally, the entire litter may be prejudiced if premature (Milon et al., 1983). Any of the above factors will have a greater effect on colostrum intake if the number of piglets in a litter exceeds the number of functional teats.

6.1. Factors affecting acquisition of IgG by suckling piglet There may therefore be a need in some circumstances to increase the amounts of IgG absorbed by the piglet. As discussed previously, the variability in colostrum IgG concentrations is poorly understood and there is a scarcity of data on its heritability and indeed whether IgG concentration is consistent between lactations in the same sow. Other factors which influence IgG uptake by the piglet relate to the viability of the piglet per se and therefore its ability to compete successfully and suckle; the efficiency of transmission of IgG from the lumen of the intestine to the bloodstream and the length of time prior to closure when transmission of IgG is possible. Delaying closure is not a desirable option because of the increased risk of transmission of pathogens. Svendsen et al. (1990) reported that absorption of

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a test dose of bovine serum albumin was positively associated with piglet weight and the maturity of the piglet and was also positively correlated with piglet plasma insulin concentrations. Treatment of piglets with oestradiol (Bate and Hacker, 1982) reduced birth to suckling interval which may increase IgG intakes by increasing intakes of early high IgG concentration-containing colostrum and increasing sow plasma cortisol concentrations have been associated with increased piglet serum IgG concentrations (Sangild et al., 1999). However, piglet birth-weight is difficult to manipulate and it would be preferable to improve piglet IgG absorption by less invasive methods than hormone administration, such as manipulation of the diet of the sow. In general it is difficult to change the protein composition of colostrum. For example, King et al. (1996) found that reducing the protein concentration of the diet of the sow from 179 to 80 g / kg did not reduce the protein concentration of colostrum. However, manipulation of the antioxidant vitamin content of the diet of the sow has been shown to influence the IgG status of the piglet. Nemec et al. (1994) observed non-significant increases in plasma IgG when twice or fourfold vitamin E requirements were included in the diet of the sow. More recently, Bland et al. (2001) reported significantly increased plasma IgG concentrations after 12 and 24 h suckling in piglets whose dams were fed diets with increased concentrations of vitamins A, C and E (one- and threefold NRC requirements). No differences between treatments were observed in colostrum IgG intakes. Further data analysis suggested that the time of closure was unchanged by vitamin supplementation suggesting that net efficiency of absorption of IgG was increased in response to vitamin supplementation. Antipatis et al. (2001) observed decreased plasma IgG concentrations in both normal and runt piglets at 12 h of age when the diet of the sow was made deficient in vitamin A. Finally, Pinelli-Saavedra et al. (2001) recorded increased IgG concentrations in piglets at 21 days of age when sows were fed diets supplemented with both vitamin E and C. Taken together, these reports suggest that supplementation of the diet with antioxidant vitamins above requirements has the potential to increase IgG concentrations in the piglet, possibly through increased efficiency of absorption. The mechanisms by which

antioxidant vitamins increased efficiency of absorption are unclear and warrant further investigation.

6.2. Relationship between passive immune acquisition and active immune development Klobasa et al. (1981) modified the amounts of colostrum IgG absorbed by piglets by delaying suckling for varying times and found that the appearance of IgG synthesised by the piglet was progressively delayed as the amount of IgG absorbed from colostrum increased. Thus, there was a negative relationship between development of active immunity and the acquisition of passive immunity, with serum IgG concentrations not reaching a minimum until 5 weeks of age. However, a weakness of observations based on serum or plasma concentrations is that no account is taken of the growth of the piglet and consequent expansion of plasma volume. Recent observations (J.A. Rooke, unpublished data) of the dilution of a specific maternal IgG in piglet plasma from birth to 35 days of age (1 week postweaning) which took into account piglet weight, haematocrit and estimates of blood volume have led to the conclusions that in normally suckling piglets there was no evidence for appearance of IgG synthesised by the piglet before 7 days of age. However, by 14 and 21 days of age, 0.33 and 0.44, respectively, of plasma IgG was not of maternal origin. Thus synthesis of IgG by the normally suckling piglet begins much earlier than previously realised. Indeed, piglets deprived of colostrum and therefore maternal IgG (Klobasa et al., 1981; Drew and Owens, 1988) begin to synthesise IgG from 7 days of age. In addition when concentrations of plasma IgG at 7 and 28 days of age were compared (Fig. 2) a positive curvi-linear relationship was found between IgG at 7 and 28 days of age implying that the amount of IgG at 28 days of age, which includes newly synthesised IgG, was positively related to maternal IgG present at 7 days of age.

7. Conclusions This review has suggested that in normal suckling piglets, the concentrations of maternally-derived IgG in plasma are largely independent of colostrum IgG

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Acknowledgements SAC receives financial support from the Scottish Executive Environment and Rural Affairs Department.

References

Fig. 2. Relationship between piglet serum IgG concentrations at 7 and 28 days of age.

intake above an intake of | 5 g IgG / kg live-weight over the first 24 h of life. However, delayed suckling or low maternal IgG concentrations may prevent the piglet achieving this intake. As concentrations of IgG in maternal colostrum are very variable, an improved understanding of factors influencing colostrum IgG concentrations is desirable. The transmission of colostrum IgG to the piglet can be manipulated nutritionally, as demonstrated by the effects of maternal dietary fat soluble vitamin concentrations. Finally, recent evidence suggests that the synthesis of IgG by the piglet is positively related to the amount of maternal IgG absorbed and thus reinforces the importance of an adequate IgG intake from colostrum in the first day of life before gut closure for piglet growth and survival. There is a need to improve understanding of colostrogenesis in the sow with the aim of increasing colostrum IgG concentrations throughout the first day of life. Future research should focus on providing a quantitative definition of the amount of IgG which constitutes an adequate intake which needs to be established in relation to passive immune protection, active immune development and the consequences for animal health and welfare throughout life. The role of cells and growth factors present in colostrum in the development of the immune system of the piglet should also be investigated further.

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