The maturation of the immune system.
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Biomedical subjects
Publications and source records attributed to U Dahlgren.
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The ability of Langerhans cells (LC) from rat oral mucosa to internalize and process antigens and to participate in the induction of T cell mitogenesis was examined. To purify LC from epithelial cells, monoclonal anti-class II antibodies and immunomagnetic beads were employed. Suspensions of epithelial cells, containing LC, were found to be effective in mediating a Con A-induced T cell proliferation. Depletion of class II molecule-expressing LC reduced the proliferation of T cells by 80%. Presentation of ovalbumin (OA) to primed T cells was found to be dependent on the concentration of OA and the number of LC. Partially purified LC were five times as effective in inducing proliferation of primed T cells as the untreated suspension of epithelial cells. The data suggest that LC obtained from rat oral mucosa can generate accessory signals, process antigens and serve as antigen-presenting cells.
Bystander suppression of delayed-type hypersensitivity (DTH) and the antibody response to human serum albumin (HSA) were studied in young normal rats and in young rats made partially tolerant to ovalbumin (OVA) by feeding an OVA-containing diet for 4 weeks from weaning. At 2 months of age, the animals were intracutaneously immunized with a mixture of OVA and HSA in Freund's complete adjuvant (FCA) at one site of the back, or separately at two different sites on the back. All rats made orally tolerant to OVA showed a significantly reduced IgE and IgG anti-OVA antibody production and DTH response to OVA, compared to the controls. OVA-fed rats subsequently immunized with a mixture of OVA + HSA had significantly lower IgE and DTH responses to HSA than the controls. When rats were immunized with OVA and HSA at two different sites, however, there was no difference in the response to HSA between the OVA-fed rats and the control rats, which rules out the possibility of shared epitopes between the antigens. Ear-challenge with the mixture of OVA + HSA gave a significantly lower DTH reaction in the tolerant rats immunized with a mixture of the antigens, compared to the control rats. However, suppression of the DTH reaction was not seen when tolerant and control rats were immunized with HSA alone and challenged with the mixture of OVA + HSA in one ear. These results present evidence that young rats orally tolerant to one antigen show a suppressed T-cell and antibody response to an unrelated antigen, provided that the two antigens are given in a mixture during the inductive phase. There was no evidence for bystander suppression of the T-cell response at the effector site.
The IgE immune response was studied in female athymic, nude (Lewis rnu/rnu) and euthymic (Lewis +/+) rats infected with the nematode Nippostrongylus brasiliensis. During the course of the infection, serum IgE levels were followed using an enzyme-linked immunosorbent assay technique (ELISA), while the surface expression and occupancy of IgE receptors on peritoneal mast cells were quantified using flow cytometry after immunolabelling with anti-IgE. The results show that the up-regulation of IgE receptors, which takes place on the mast cells of both athymic and normal rats during the early phase of the immune response, is more pronounced and longer-lasting in normal rats than in athymic ones, thereby suggesting that T cells are necessary for a full response to the parasite infection. The increased IgE occupancy observed on the mast cells during the early phase of the parasite immune response was not reflected in the serum IgE levels, which remained low during the entire infection period in athymic rats. In euthymic rats, on the other hand, there was a pronounced increase in serum IgE, as well as an increase in IgE occupancy on the mast cells, all reaching a peak level after 2 weeks of infection. However, there was no significant correlation between the serum IgE concentration and IgE occupancy or the density of IgE receptors on the mast cells of the individual euthymic rats. This indicates that the quantification of IgE occupancy on the mast cells may be a better way of detecting low-level IgE responses than the measurement of serum IgE. These findings, which were obtained in female Lewis rats, when compared with our previous findings in male rats of the same strain, suggest that sex differences may exist in terms of the intensity and duration of the IgE immune response to the parasite infection.
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Colostrum was collected from Swedish, Indian and Japanese mothers. The samples were as a mean, collected 4.00-4.25 days after delivery of term infants. The level of specific IgA antibody to 2S, 7S and crude soybean antigen were measured by the enzyme-linked immunosorbent assay (ELISA). The avidity of the IgA antibodies to 7S soybean antigen was also measured with an ELISA system using different molarities of potassium thiocyanate for elution of the specific IgA antibody from solid phase-bound antigen. The level of specific IgA antibody to 7S and crude soybean antigen in the milk of the Indian mothers was significantly higher than in the milk of the Japanese mothers (p less than or equal to 0.01). In contrast, the avidity expressed as the molarity of KSCN for 50% elution of IgA antibody to 7S soybean antigen in the milk of the Japanese mothers was significantly higher than in the milk of the Indian mothers (p less than 0.01).
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Most infections reach man via the mucosal membranes, and more than half of the lymphoid system is found in connection with mucosae. The major antibodies found on mucous membranes are secretory IgA, which function primarily by binding microorganisms and thereby preventing their contact with the host tissues. The optimal mode of immunization to obtain a secretory IgA response is not well defined. Repeated mucosal exposure with antigen may result in oral tolerance, with decreasing circulating antibodies but a remaining secretory IgA response. The secretory IgA response is usually short-lived and can be difficult to boost. IgM as well as IgG antibodies may add to host defence at the mucosal level, but when engaged, they usually induce inflammation in host tissues. Analogues to bacterial receptors on mucosal epithelium may be present in exocrine secretions such as human milk. During an attack on the host, it is possible that such receptor analogues may aid in the prevention of attachment of bacteria to mucous membranes used as an initial site. A number of non-specific host factors support mucosal defence. One of them is lactoferrin. Lactoferrin deficiency seems to result in recurrent bacterial infections, suggesting its importance in normal host defence.
The immune response of the mammary gland is dominated by local production of secretory IgA antibodies (SIgA). These milk antibodies, amounting to about 0.5-1 g/day throughout lactation, are directed against food proteins and microorganisms often present in the intestine. This is presumably explained by the enteromammaric link: after antigenic exposure in the Peyer's patches of lymphoid cells they home to various exocrine glands, including the mammary gland. Similarly, lymphoid cells from the bronchial mucosa, may contribute to the antibody-producing cell population in the mammary gland. SIgA antibodies against common foods like cow's milk and soy proteins are regularly found in milk if such proteins are part of the mother's diet. It is possible, but unproven, that milk antibodies can decrease the exposure of the infant's intestinal mucosa to foreign food proteins introduced during continued breast-feeding. Milk SIgA antibodies do not prevent intestinal colonization by microorganisms, against which the milk antibodies are directed. The SIgA antibodies are thought to exert protection primarily by preventing contact between the microorganisms and the mucosal membranes. In this manner, human milk blocks attachment of otitis media-causing strains of pneumococci and H. influenzae to retropharyngeal cells, possibly explaining why breast-feeding may prevent otitis media. Milk antibodies have anti-attachment capacity, but there is also low molecular weight material in the milk with this capacity. It probably consists of analogues to the oligosaccharide receptor for pneumococci on the retropharyngeal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mucosal defense is provided by a number of host factors countering the specific virulence factors of the many microorganisms infecting the mucous membranes. Secretory IgA antibodies presumably play an important role. Increase of the sIgA antibodies may most advantageously be attained by parenteral immunization, following mucosal priming. This was demonstrated in a rat model, where it was also noted that antigen injection into PP induced high milk IgA antibody levels. In man, parenteral vaccination against polio increased the sIgA antibody levels in the milk of mothers previously exposed naturally to the poliovirus. The response was relatively short-lived. In the previously unexposed, there was little or no response. By contrast peroral immunization with live poliovirus vaccine did not increase, or even decrease, the milk sIgA poliovirus antibody levels. Although salivary sIgA antibodies against antigens of colonizing E. coli appear during the first days of life, they are slow to increase. This deficiency is richly compensated for by all the sIgA antibodies that are provided the baby through the milk. No transfer of dimeric IgA into the milk could be shown in lactating rats, in contrast to what has been reported in mice. There is no evidence for a contribution to milk sIgA from serum in man. Close to parturition, human milk often contains some 7S IgA and various sizes of free SC, in addition to the dominating 11S sIgA. A few days later there is almost exclusively monomeric SC and 11S sIgA. IgG antibodies also play a role at the mucosal level. IgG2 antibodies against the bacterial polysaccharide capsule are as slow to appear as sIgA in ontogeny, possibly explaining the prevalence of infections with encapsulated bacteria and the poor response to polysaccharide vaccines in early childhood. Other defense factors preventing infections by way of mucous membranes may be important. Thus, oligosaccharides present in human milk seem to specifically prevent pneumococcal attachment to retropharyngeal cells. This anti-attachment capacity, in addition to that provided by milk and salivary IgA antibodies, may explain why breast-fed babies have less otitis media than formula-fed ones.