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.     

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.     

The influence of colostral antibodies on the postvaccinale humorale immune response in neonatal calves

The aim of this study was to evaluate the efficiency of vaccination of young calves and to see whether maternal antibodies may influence the immunological response in calves. For this project 20 matched-pairs of cows and their offspring were selected. Of each pair, one cow received a placebo 8 and 4 weeks before term (group A) and the other was vaccinated against Feline Leucose Virus, FeLV, with Leucogen? (group B). All calves received colostrum from their respective mother shortly after birth and all calves were vaccinated with Leucogen? 10 days after birth. Blood samples from the cows and calves were taken during the whole study period (till four weeks after calf vaccination). An ELISA test was done in the lab to define the FeLV antibody concentration. 30 % of the vaccinated cows showed a seroconversion, 13 out of 20 vaccinated cows passed the antibodies onto their calves. 11 calves of group B did not convert in comparation of only 4 of group A. All seroconverted calves had low antibody concentration before their vaccination. Calves of group B with a low passive antibody level at the beginning showed a higher seroconversion as compared to calves with higher antibody concentrations of the same group. Two thirds of the calves without maternal antibodies reacted adequately to the vaccination. Therefore, an early vaccination of calves can be recommended.     

The influence of antibiotics on the immune system III. Investigations on the cellular functions of chicken leukocytes in vitro

Tetracyclines are bacteriostatic antibiotics widely used in veterinary medicine. It is reported here that the tetracycline analogue oxytetracycline (OxyTC) interferes with the mitogenic response of chicken leukocytes. A dose-dependent suppression of lectin stimulation of peripheral blood and spleen leukocytes was observed. The kinetics of the DNA-synthetic activity were seriously affected. The antimicrobial agent does not seem to have any effect on interleukin 2 (IL-2) production, whereas the uptake of ³H-thymidine by IL-2-dependent T cell blasts was severely reduced.

It is concluded that the T cell blast is the target for OxyTC.     

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.     

Immunomodulating effects of intestinal absorbed maternal colostral leukocytes by neonatal pigs.

Intestinal absorption of fluorescein isothiocyanate-labelled maternal colostral leukocytes (FITC-CL) was studied in 49 neonatal colostrum-deprived (CD) pigs from nine Minnesota miniature sows. Within 2 h postfeeding (pf), maternal FITC-CL were absorbed from the sibling's digestive tract and migrated into blood. The peak appearance of FITC-CL in blood occurred in samples at 5 and 7 h pf. By 24 h pf, cells were detected in liver, lung, lymph nodes, spleen and gastrointestinal tissues. To confirm intercellular migration of FITC-CL, gastrointestinal explant cultures from neonatal CD pigs were used. Maternal FITC-CL were observed to intercellularly migrate in 24 to 48 h pf between duodenal- and jejunal-epithelial cells to lamina propria cells and submucosal spaces. Fluorescein isothiocyanate-labelled maternal colostral leukocytes were not absorbed via ileal explant cultures. Unlike FITC-CL, maternal FITC-peripheral blood mononuclear leukocytes (FITC-PBL) were not absorbed either in vivo or in vitro by gastrointestinal tissues. When maternal FITC-PBL were intravenously administered to siblings they were distributed in blood and organs similar to FITC-CL. Following exposure to FITC-labelled cells, treated- and mock (untreated)-pigs were compared on the basis of PBL proliferative responses to phytomitogens. Sibling CD-pigs fed maternal FITC-CL showed higher PBL T-cell responses to phytohemagglutinin (PHA) and concanavalin A (ConA), and a significant stimulation (p < or = 0.01) of B-cell responses to pokeweed mitogen (PWM). Pigs fed FITC-PBL showed little PBL responses to PHA, ConA and PWM over PBL from mock pigs. Similarly, the influence of noncellular constituents of colostrum were also assessed by proliferative studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of a rapid specific test for detecting colostral IgG1 in the neonatal calf

A commercially available latex agglutination test was used to measure the concentration of IgG1 in bovine plasma and the results were compared with radial immunodiffusion and zinc sulphate turbidity methods. For concentrations of IgG1 up to 80 g/litre there were highly significant (P less than 0.001) correlation coefficients between the latex agglutination test and radial immunodiffusion, and between the latex agglutination test and zinc sulphate turbidity method (0.93 and 0.74 respectively). The coefficient of variation for the latex agglutination test ranged from 8.1 per cent to 17.9 per cent. IgG1 concentration was measured using the latex agglutination test in whole blood on a farm, in whole blood at a laboratory and in plasma at a laboratory. The correlation coefficients were highly significant (P less than 0.001) in all cases. The latex agglutination test is easy to use, rapid and specific. It is suitable for checking the colostral status of young calves on commercial farms.     

Hematology of the neonatal calf. III. Frequency of congenital iron deficiency anemia.

The hematocrits of 258 Holstein-Friesian and Jersey calves were determined during the first 3 days following birth. Hematocrit values of 25% or less were observed in 15.8% of the calves and hematocrits of 20% or less were observed in 6.9% of calves from apparently normal dams. The serum iron concentration of neonatal calves with hematocrits of 25% or less was significantly lower than the value recorded in calves with hematocrits above 25% and there was a direct correlation between PCV and serum iron concentration. The data presented suggested that prenatal development of iron deficiency is an important cause of anemia in neonatal dairy calves. Factors which may be important in pathogenesis are discussed.     

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.     

Maximising the absorption of colostral immunoglobulins in the newborn dairy calf

Various systems of early post natal management of the newborn calf were examined to determine which would consistently achieve high serum concentrations of maternally derived immunoglobulins, and to examine the factors which might influence this transfer. Early assisted sucking of colostrum to satiation produced consistently high serum concentrations of absorbed immunoglobulins with a mean of 27.17 +/- 8.92 zinc sulphate turbidity (ZST) units for 100 calves. No significant increase in the serum concentrations of absorbed immunoglobulins occurred when calves, which had been assisted to suck immediately after birth, were permitted to remain with their dams and encouraged to suck again at 12 hours (29.20 +/- 9.40 ZST units). Despite early assisted sucking, a small proportion of calves may remain hypogammaglobulinaemic because of the low concentration of immunoglobulins in their dams' colostrum; leakage of colostrum from the udder before calving was the major cause of these low immunoglobulin concentrations. A highly significant correlation was demonstrated between the colostral immunoglobulin concentrations and the passively acquired serum immunoglobulin concentrations of the calves. With this intensive system of early assisted sucking the breed of the calf did not significantly influence the absorption of colostral immunoglobulins.     

The influence of colostral antibodies on the immunization of lambs against adenoviruses

The effect of colostral antibodies on the immune response in lambs following adenovirus vaccination was studied. Young lambs of different ages, born from vaccinated ewes, were vaccinated with an inactivated and aluminium hydroxide-adsorbed sheep adenovirus vaccine. In a group of lambs vaccinated at 5–7 days of age, the titre of humoral antibodies declined in parallel to unvaccinated controls. In lambs vaccinated at 24–35 days of age, antibody titres to adenovirus stabilised and persisted after an initial fall. Cell mediated immunity, as measured by blastogenic responses of circulating lymphocytes, was stimulated in both groups, but higher numbers of IgG-producing cells became evident in the group of lambs vaccinated at 24–35 days of age.