Transfer of maternal colostral leukocytes promotes development of the neonatal immune system Part II. Effects on neonatal lymphocytes

It has been established that maternal leukocytes, conditioned by the mammary environment, cross the neonatal gut and circulate in the newborn calf. However, the impact of these cells on the development of neonatal immunity remains to be determined. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal adaptive immunity by examining the expression of surface markers on neonatal lymphocytes. At birth, neonatal calves were fed whole colostrum, or colostrum that had the maternal cells removed (cell-free colostrum), from their respective dams. Peripheral blood samples were collected at regular intervals over the first 4 weeks of life and lymphocytes were evaluated for surface expression of cellular markers. The results of these studies demonstrated that calves receiving whole colostrum had fewer CD11a positive lymphocytes in circulation during the first 2 weeks of life and this marker was expressed at a lower density than calves receiving cell-free colostrum. In addition, calves receiving whole colostrum also had a higher percentage of lymphocytes expressing the activation markers CD25 and CD26 by 7 days after birth. During the first week of life, lymphocytes from calves receiving whole colostrum had a higher density of MHC class I expression on their surfaces than cells from calves receiving cell-free colostrum. In general, these results indicate that transfer of maternal cells with colostrum allows for more rapid development of lymphocytes and maternal cells appeared to enhance their activation.     

Transfer of maternal colostral leukocytes promotes development of the neonatal immune system I. Effects on monocyte lineage cells

Although it has been established that maternal leukocytes traffic from colostrum into the neonatal circulation, the effects of these cells on neonatal immunity are only beginning to be understood. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal antigen presenting cells. At birth, groups of neonatal calves received whole or cell-free colostrum (CFC) from their respective dams. Peripheral blood samples were obtained over the first 4 weeks of life, and expression of surface markers associated with cellular activation and physiological stress were monitored on monocyte lineage cells. Calves receiving cell-free colostrum at birth expressed elevated levels of CD11a, CD11c, and CD14, compared to calves receiving whole colostrum (C). Calves receiving cell-free colostrum had an elevated number of monocytes in the peripheral blood during the first 2 weeks of life, however, these cells expressed lower levels of expression of CD25 and MHC class I compared to calves receiving whole colostrum. The most significant differences in marker expression occurred within the first 7 days of life.     

Uptake of colostral leukocytes in the intestinal tract of newborn calves

The role of colostral immunoglobulins for the protection of newborn calves has been studied extensively, but little is known about the importance of colostral leukocytes. To study the uptake of colostral leukocytes in the intestine of calves and to determine preferential sites for this uptake, FITC-labelled colostral cells derived from the respective dams were injected into intestinal loops with/without Peyer's patches of three male Holstein Frisian calves about 5h post natum. In adjacent loops, PBS was injected as control. Loops were excised after an exposure of 1.5-2h. FITC-labelled material and cells were detected by the direct immunoperoxidase method in paraplast sections. Twenty-five consecutive sections were evaluated from each localization. Uptake of labelled material and cells was observed in all three calves in the jejunal Peyer's patch and in two calves in the ileal Peyer's patch as well. In the jejunal Peyer's patch, labelled material and cells were present in epithelium, domes and sinuses around lymphoid follicles, whereas in the ileal Peyer's patch, they were found in the sinuses only. These findings confirm that uptake of colostral leukocytes through the intestinal barrier is possible and that the preferential route of uptake is through follicle-associated epithelium of Peyer's patches.     

The influence of colostral leukocytes on the immune system of the neonatal calf. III. Effects on phagocytosis

The influence of colostral leukocytes on the activity of phagocytic cells from the blood of calves, in particular the concentration of neutrophils (PMN) in blood, ingestion of Streptococcus agalactiae, reduction of NBT-dye and activity of lysozyme, was investigated for four weeks using four groups. The calves received either complete colostrum (COL+, n = 16), cell depleted colostrum (COL-, n = 16), cell-supplemented milk-substitute (MS+, n = 7) or pure milk-substitute (MS-, n = 6). Calves of the COL+ group had a significantly lower PMN concentration in their blood on day 2 and a significantly higher activity of lysozyme during their first three weeks of life as compared to the COL- animals. A postnatal increase in number of ingested Streptococcus agalactiae test bacteria per 100 phagocytic cells occurred later in the COL+ calves than in the COL-. No difference between both COL groups in NBT-reduction was observed. The calves of the MS+ group showed higher lysozyme activity and a retarded increase in the ingestion of test bacteria during the first week of life as compared to the MS-. The MS+ group had a transient neutrophilia on the second day of life while the concentration of PMN was not altered in the MS- from the first to the second day.     

The effects of cold stress on neonatal calves. II. Absorption of colostral immunoglobulins.

Newborn calves were subjected to cold stress and made hypothermic by immersion in water at 15 to 17 degrees C. Cold stress delayed the onset and significantly decreased (P less than 0.05) the rate of absorption of immunoglobulins (IgM, IgG1 and IgG2) up to 15 hours after first feeding of pooled colostrum. However, the net absorption of colostral immunoglobulins was not affected. The possible deleterious effect of cold stress on absorption of colostral immunoglobulins by newborn calves under range conditions is discussed.     

The influence of colostral leukocytes on the immune system of the neonatal calf. I. Effects on lymphocyte responses

The influence of colostral leukocytes on lymphocyte counts in the blood of calves and on lymphocyte responses, in particular the Concanavalin A-induced blastogenic response in vitro and the formation of antibodies against sheep erythrocytes, was investigated for four weeks postnatum using four experimental groups. The calves received either complete colostrum (COL+, n = 16), cell-depleted colostrum (COL-, n = 16), colostral cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during their first three days of life. In contrast to the calves fed with cell-depleted colostrum (COL-) the calves fed with complete colostrum (COL+) showed no decrease of lymphocyte numbers in the blood on the second day of life, uniform blastogenic responses to two different Concanavalin A concentrations, slightly enhanced antibody formation against sheep erythrocytes and a high spontaneous proliferation of mononuclear cells during the first week of life. In the calves fed with milk-substitute supplemented with colostral cells (MS+) a higher blastogenic response to Concanavalin A and an intensified formation of antibodies against sheep erythrocytes was observed as compared to the MS- calves. A passage of vital colostral lymphocytes through the intestinal wall is postulated. They seem to stimulate and regulate the blastogenic response and enhance the T-helper cell-dependent formation of antibodies against sheep erythrocytes in calves.     

The influence of colostral leukocytes on the immune system of the neonatal calf. II. Effects on passive and active immunization

The influence of colostral leukocytes on the concentration of immunoglobulins and antibodies against an enterotoxigenic strain of E. coli in the sera of newborn calves was investigated for four weeks using four experimental groups. The calves received either complete colostrum (COL-, n = 16), cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during the first three days of life. The cows were not specifically immunized. The sera of the COL+ calves had significantly higher concentrations of antibodies against E. coli mainly of IgG1 specificity on the second day of life as compared to those of the COL-. The sera of the COL+ calves contained significantly more IgM on days 2 and 5 and slightly more IgA during the first week. Both COL groups had equal concentrations of serum IgG. It appears that colostral leukocytes which are an integral part of the colostrum enhance the passive immunity of the neonatal calf, especially in regard of antibodies and immunoglobulin classes which are essential for intestinal immunity. The concentration of IgM in the sera of the MS+ calves was reduced, that of IgG did not rise to appreciable amounts; the IgA synthesis started one week later as compared to the MS- group. The administration of isolated colostral cells led to an impairment of the natural active immunization.     

The influence of colostral leukocytes on the immune system of the neonatal calf. IV. Effects on bactericidity, complement and interferon; synopsis.

The influence of colostral leukocytes on the bactericidity of whole blood of calves against a strain of E. coli and on the activities of haemolytic complement and interferon-alpha (the antiviral activity of sera resisting an acidic treatment at pH 2 for 6 h) in the serum was investigated during a period of 4 weeks using 4 experimental groups. The calves received either complete colostrum (COL+, n = 16), cell-depleted colostrum (COL-, n = 16), cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during their first three days of life. The bactericidity of whole blood of the COL+ group was significantly higher on the second and third days of life while the activity of haemolytic complement was lower after the first week as compared to the COL- group. No interferon-alpha was detectable in the sera of both COL groups. The bactericidity of the MS groups was significantly lower than that of the COL groups after the first day of life. It was significantly lower in the MS+ group after one week of life while the activity of haemolytic complement was higher than that of the MS- group. Three out of 5 MS- and only one out of 7 MS+ calves had low titres of interferon-alpha in their sera on the third day. Three out of 6 MS- calves died and 5 out of 7 MS+ animals. The mean day of death was 4.0 in the MS- and 8.4 in the MS+ group. Based on the in vitro results of this and the previous three communications it can be concluded that leukocytes which are an integral part of normal bovine colostrum, influence immunological reactions of the calf and that they may enhance its defence against infection. Colostral leukocytes in the absence of humoral components of the colostrum are not able to prevent fatal losses in the calves due to natural infection, although their influence on immune responses of the calves was detectable in vitro.     

Adsorption of colostral antibodies against classical swine fever, persistence of maternal antibodies, and effect on response to vaccination in baby pigs.

OBJECTIVE: To determine kinetics of antibody absorption, persistence of antibody concentrations, and influence of titers on vaccination of baby pigs with a vaccine against classical swine fever (CSF). ANIMALS: 15 sows and their litters. PROCEDURE: Farrowings were supervised. Initial time of suckling was recorded. In the first experiment, blood samples were collected at farrowing, 2 and 4 hours after suckling, and hourly until 10 hours after initial suckling. Samples were assayed for CSF antibodies, using a serum neutralizing (SN) test. A second experiment included 33 baby pigs vaccinated as follows: 10 prior to ingestion of colostrum, 18 between 1 and 4 hours after ingestion of colostrum, and 5 at 12 hours after ingestion of colostrum. Fourteen pigs were vaccinated when 7 weeks old, and 15 pigs were not vaccinated. At 10 weeks of age, pigs were challenge-exposed with virulent CSF virus. Blood samples were collected and assayed for CSF antibodies and p125 antigen and p125 antibodies. RESULTS: CSF antibodies were detected in pigs beginning 2 hours after suckling. Colostral antibodies persisted for > 7 weeks (half-life, 79 days). Vaccination of pigs before suckling provided effective protection from severe disease after challenge-exposure. However, vaccination of neonates with antibody titers was not effective, because 19 of 23 (82%) pigs succumbed after challenge-exposure. All pigs vaccinated when 7 weeks old resisted challenge-exposure, whereas all unvaccinated control pigs succumbed. CONCLUSIONS AND CLINICAL RELEVANCE: Vaccination before ingestion of colostrum conferred good protection against CSF in baby pigs. Vaccination of 7-week-old pigs that had decreasing concentrations of passively acquired antibodies was efficacious.     

Decay of acquired colostral antibodies to Actinobacillus pleuropneumoniae in pigs

The main objective of this study was to estimate the decay of acquired colostral antibodies to Actinobacillus pleuropneumoniae serotype 2 in pigs. Data were obtained from pigs in an isolated cohort of 47 pigs born to five sows seropositive to A. pleuropneumoniae serotype 2. The pigs were examined serologically at 18 different times from birth until an age of about 22 weeks, using an A. pleuropneumoniae serotype 2-specific blocking enzyme-linked immunosorbent assay. Antibody concentration was expressed as an OD% derived from the optical density of the sample and the median from eight wells without serum on the same plate. A non-linear mixed model assuming a constant rate of decay (half-life) was specified and fitted to the serological data. To estimate the between-pig variability of different components, between-pig random effects of each component of the model were estimated. The estimated average half-life of acquired colostral antibodies was approximately 2 weeks, but there was a considerable variation between pigs (half-life ranged from 1-3 weeks). The duration until acquired colostral antibodies were no longer detectable ranged from 2 weeks to 2 months postpartum among the pigs in the study, mainly depending on the initial level of acquired colostral antibodies to A. pleuropneumoniae serotype 2.     

Neural invasion of two virulent suid herpesvirus 1 strains in neonatal pigs with or without maternal immunity.

The neural invasion of two virulent Suid Herpesvirus 1 (SHV1) strains was examined in neonatal pigs with or without maternal immunity. One-week-old pigs with comparable levels of maternal immunity (SN-titer = 12-48) were intranasally inoculated with 10(7.0) TCID50 of either of the Ka or E21 strains. The invasion of the strains was examined in the nasal mucosa and in three neuronal levels of the trigeminal nervous pathway as well as in three levels of the olfactory nervous pathway by virus titration and immunohistochemistry (IHC). In control pigs without specific antibodies, both strains invaded up to the end level of each neural pathway. In pigs with maternal immunity, the Ka strain invaded only up to the 2nd level of each pathway with titers being significantly lower (p<0.05) than in the negative controls. However, the E21 strain invaded up to the end levels in both neural pathways of immune pigs with virus titers being similar to those observed in non-immune pigs (p>0.05). IHC revealed that maternal antibodies can protect against a fibroblast-mediated spread of the Ka strain in the lamina propria of the nasal mucosa, as well as against a local spread of the Ka and E21 strains from neurons to their satellite cells in the trigeminal ganglion. In conclusion, the nature of virus strain determines the invasion of SHV1 within the nervous system of maternally-immune neonatal pigs.     

Protein digestibility of porcine colostrum by neonatal pigs

Colostrum plays an important role in neonatal growth and development. However, little is known about the digestion of macronutrients in colostrum of any species. This study was conducted with the neonatal piglet model to determine the digestibility of proteins in porcine colostrum. Twelve, 1-d-old, male piglets were selected from 3 litters (4 pigs/litter) and housed individually in metabolism crates with heating lamps to maintain a temperature of 35 °C. Colostrum (13 L) was collected from 400 sows (30 to 40 mL/sow) within 12 h postpartum after injection of oxytocin. All piglets were fed colostrum containing 0.25% (DM basis) chromium oxide as an external marker based on the following feeding program: 6 meals/d for an entire 3-d period; with 40 mL/meal for d 1 (240 mL/d), 55 mL/meal for d 2 (330 mL/d), and 70 mL/meal for d 3 (420 mL/d). Colostrum was hand-fed using baby milk bottles. Entire fecal samples with the chromium green color were collected each day after colostrum feeding. Fecal collection was terminated before the fading of the green color. Fecal samples were weighed (10.3 ± 1.0 g/pig), stored in − 20 °C, freeze-dried, and thoroughly ground for chemical analysis. Blood samples were collected at 0900 h of d 3 to obtain plasma samples for amino acid and immunoglobulin (Ig) G analysis. Digestibilities of crude protein and DM in colostrum, defined as the percentage of ingested colostral crude proteins and DM that disappeared in the gut, averaged 96.9 ± 0.4% and 98.3 ± 0.2%, respectively. Digestibility of total amino acids (protein-bound plus free amino acids) in the colostrum was 98.3 ± 0.1%, with the values being 98.5 ± 0.3, 98.2 ± 0.4, and 98.3 ± 0.3%, respectively, for Lys, Thr, and Arg. Plasma and colostral IgG content were 3.4 ± 0.3 and 3.8 ± 0.7 g/L, respectively. In conclusion, protein-bound and free amino acids in porcine colostrum were highly digestible and available to neonatal pigs.     

Review article: colostral leukocytes and their significance for the immune system of newborns

The colostrum contains a comparably high concentration of leukocytes as the peripheral blood. The majority of them are vital leukocytes, namely neutrophils, macrophages and lymphocytes. There is some evidence in mouse and man that lymphocytes from the gut-associated lymphoid tissue home selectively to the peripartal mammary gland. The phagocytic cells may be involved in the transportation of certain immunoglobulins into the neonate. In vitro colostral leukocytes exhibit a variety of immunological activities such as blastogenesis after mitogenic and antigenic stimulation, cytotoxicity and phagocytosis, but the medium milk confines these activities in comparison with those of blood leukocytes. Intact colostral leukocytes reach the gut of the gut of the newborn and may even cross the intestinal wall, gaining access to the neonates system and influencing its immunologic reactions, e.g. hypersensitivity and antibody-formation. The knowledge on the significance of colostral leukocytes for the protection against infection of the neonate is still limited.     

Effect of colostral antibody on bovine leukemia virus infection of neonatal calves

Pairs of newborn calves were exposed to bovine leukemia virus (BLV) when they were given their 1st colostrum feeding. Calves that were given 10(6) BLV-infected lymphocytes in colostrum free of BLV-specific antibody became infected. Calves that were fed 10(7), 10(8), or 10(9) infected lymphocytes in colostrum that contained BLV-specific antibody did not become infected. One of 2 calves inoculated intradermally with 250,000 infected lymphocytes was protected by colostral antibody, but the other was not. Colostral antibody titers in the unprotected calf decreased normally until the calf was 4 months old and then increased markedly; this pattern indicates that the presence of colostral antibody may have prolonged the latent period of the BLV infection.     

Passive transfer of colostral immunoglobulin G in neonatal llamas and alpacas

OBJECTIVE: To evaluate precolostral hypogammaglobulinemia in neonatal llamas and alpacas, to determine when postcolostral peak serum IgG concentrations develop, to determine whether differences in postcolostral serum IgG concentrations between llamas and alpacas exist, and to determine postcolostral half-life of serum IgG in llamas and alpacas. DESIGN: Prospective observational study. ANIMALS: 29 llama and 10 alpaca crias. PROCEDURE: Blood samples were collected prior to suckling and on days 1, 2, and 3 after parturition and analyzed for serum IgG concentration by use of a commercial radial immunodiffusion assay. Additional samples were collected on days 8, 13, and 18 from 8 crias to determine mean half-life of IgG. RESULTS: Llamas and alpacas are born severely hypogammaglobulinemic. Mean serum IgG concentrations for day-1, -2, and -3 samples for llamas were 1,578 mg/dl, 1,579 mg/dl, and 1,401 mg/dl, respectively, and for alpacas were 2,024 mg/dl, 1,806 mg/dl, and 1,669 mg/dl, respectively. Peak serum immunoglobulin concentration developed between days 1 and 2. Mean half-life of IgG for all crias was 15.7 days. CONCLUSIONS AND CLINICAL RELEVANCE: Although increased mortality has been linked to failure of passive transfer, it is clearly possible to raise crias that have low serum immunoglobulin concentrations. Llamas and alpacas do not differ significantly with respect to immunoglobulin absorption or IgG concentration in neonates. The optimal sampling time for passive transfer status is between 1 and 2 days.     

Immunomodulating effects of levamisole in chicks immunocompromised by infectious bursal disease virus

Summary Immunomodulating effects of levamisole in experimentally IBD induced immunosuppressed 7-days old White Leghorn chicks have been observed. For this, infectious bursal disease (IBD) virus (Poona strain) was used. All the chicks were immunised with sheep red blood cells to monitor antibody responses. A group of chicks each from infected (PS-L) and uninfected (PBS-L) groups were given 4 injections of levamisole hydrochloride at the daily dose of 1·5 mg per 100g body weight starting from the second day post inoculation with IBD virus. Serum samples were collected and the haemagglutination titre against sheep red blood cells was determined. IBDV infected chicks showed a significant decrease in HA titre compared with uninfected control chicks. In levamisole treated IBDV infected birds the HA titres were comparable to those of uninfected controls. However, uninfected chicks treated with levamisole showed no significant increase in HA titre to SRBC compared with uninfected untreated control chicks.

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Efectos Inmunomoduladores Del Levamisol En Pollitos Comprometidos Inmunologicamente Debido A La Infeccion Con El Virus De La Enfermedad De Gumboro (Virus De La Bursitis Infecciosa Aviar)

Resumen Se observaron los efectos inmunomoduladores del levamisol en pollitos White Leghorn de siete dias deprimidos inmunológicamente debido a la infección con el virus de la bursitis infecciosa aviar (cepa Poona). Todas las aves fueron inmunizadas con eritrocitos de oveja para controlar la respuesta humoral. Un grupo de pollitos, formado por animales provenientes tanto de grupos infectados como de no infectados, recibió 4 inyecciones de hidrocloruro de levamisol a una dosis diaria de 1·5 mg por 100 g de peso corporal, comenzando el segundo día despues de la inoculación con el virus de la bursitis infecciosa aviar. Se tomaron muestras de suero y se determinaron los titulos hemaglutinantes contra los eritrocitos de oveja. Los pollitos infectados con el virus de la bursitis infecciosa aviar presentaron titulos reducidos en comparacion con los controles no infectados. En las aves infectadas tratadas con levamisol, los títulos hemaglutinantes fueron comparables a aquellos de los controles no infectados. Sin embargo, los pollitos no infectados tratados con levamisol no mostraron incrementos significativos de titulos hemaglutinantes comparados con los pollitos controles no infectados y no tratados.

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Effets Immunomodulateurs Du Levamisole Sur Des Poulets Immunodeficients Par Le Virus De La Maladie De Gumboro

Résumé Les effets immunomodulateurs du lévamisole ont été observés sur des poulets Leghorn blanc de 7 jours, rendus immunodéficients par une maladie de Gumboro expérimentale. Dans ce but, le virus (souche de Poona) de la maladie de Gumboro a été utilisé. Tous les poulets ont été immunisés avec des globules rouges de mouton, afin de contrôler les réponses d'anticorps.Chaque poulet provenant soit des groupes infectés (PS-L), soit des non-infectés (PBS-L), a reçu 4 injections quotidiennes de chlorydrate de levamisole de 1,5 mg par 100 g de poids vif, à partir du 2e jour après l'inoculation du virus de la maladie de Gumboro.Des échantillons de sérum ont été prélevés et le titre des anticorps hémagglutinant des globules rouges de mouton a été déterminé. Les poulets infectés avec le virus de la maladie de Gumboro ont montré une chute significative du titre d'hémagglutination par rapport aux poulets témoins non-infectés. Chez les poulets infectés avec le virus de la maladie de Gumboro et traités au lévamisole, les titres d'hémagglutination étaient comparables à ceux des poulets non-infectés. Cependant, les poulets non-infectés et traités au lévamisole n'ont montré aucune hausse significative du titre des anticorps hémagglutinant des globules rouges de mouton, en comparaison avec celui des poulets témoins non-infectés et non-traités.

     

The implication of maternal effects for genetic improvement of litter size in pigs

Gilts raised in large litters produce smaller litters than those raised in small litters. These maternal influences affect the regression coefficient of additive genetic on phenotypic value. Over a range of plausible values, this regression coefficient, and thus genetic change, decreased 5–10% due to maternal effects. So the genetic impact of maternal effects on litter size is minimal. In a selection experiment, selected breeding gilts are raised in large litters. This results in a negative maternal influence on litter size which is mainly environmental. This influence can be eliminated to a large extent by standardization of those litters from which gilts are going to be selected. Selection for fertility seems to be possible if the requirements (accurate correction for fixed effects, optimization of herd management, high selection intensity, standardization of litters and accurate estimation of breeding values) are fulfilled.