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Biomedical subjects

S Ahlstedt

Publications and source records attributed to S Ahlstedt.

At least 127 records · Page 7Linked to original sources

The immune response of the mammary gland and its significance for the neonate.

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)

Animals↗

Mononuclear cells, mast cells and mucous cells as part of the delayed hypersensitivity response to aerosolized antigen in mice.

Mice (BALB/c) exposed to picryl chloride (PiCl) on their shaved abdomen and untreated animals were after 7 days exposed to daily aerosolized trinitrophenylated dog serum albumin (TNP-DSA). Mice exposed to PiCl tended to respond earlier and more strongly with both delayed hypersensitivity (DH) and IgG antibodies in serum and bronchial washings than did mice exposed to aerosol only. Picryl chloride sensitization resulted in spontaneously proliferating axillary lymph node cells, which could not be further stimulated with antigen or mitogen. Histological examination of lung tissue of aerosol-sensitized animals revealed an increase in mononuclear cells and mast cells around bronchioli and mucous cells, particularly in those animals exposed for prolonged periods and sensitized with PiCl prior to aerosol. Sensitization of mice with aerosolized TNP-DSA administrated in two 2- and 1-week periods with a 4-week interval responded with DH and IgG antibody in a dose dependent fashion irrespective of presensitization with PiCl. In bronchial washings IgG antibodies were found particularly after two 2-week periods of exposure. The cells taken from the axillary or brachial lymph nodes showed spontaneous proliferation. Culture of the cells to achieve mast cell maturation resulted in no or very low numbers of mast cells in the lymph nodes.

Aerosols↗

Mucosal immunity.

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.

Adult↗

IgA antibodies in rat bile are not solely derived from thoracic duct lymph.

The IgA level in rat bile was significantly decreased by drainage of the thoracic duct, and passively administered IgA antibodies to Escherichia coli O antigen decreased similarly. In contrast, specific IgA antibodies against E. coli O antigen raised by immunization in the Peyer's patches did not diminish significantly in the bile. Rats immunized in the Peyer's patches with sheep erythrocytes had IgA-forming cells in the thoracic lymph nodes, in the mesenteric lymph nodes, and in the spleen. Perfusion of the liver of immunized animals significantly decreased the bile levels of the IgA antibodies. It seems that IgA antibodies reach the bile not only via the thoracic duct but also via lymph ducts originating from thoracic lymph glands and the spleen.

Animals↗

Immunoglobulin E and immunoglobulin G4 antibodies to cow's milk in children with cow's milk allergy.

The presence of cow's milk specific antibodies of immunoglobulin E and G4 classes were studied in 47 children with a positive clinical history of cow's milk allergy. The children were challenged with cow's milk orally. The clinical diagnosis was verified by immediate reactions in 25 patients while 22 had late reactions or were provocation test negative in spite of the clinical history. There was no relation between levels of cow's milk specific IgG4 antibodies and provocation test results, i.e. neither with immediate or late reactions. Total IgE was elevated above +1 SD for age in 31 of 41 tested patients. Of these, 29 had immediate type reactions to cow's milk, wheat flour and/or egg white, while only two of 10 children with IgE of less than +1 SD had a demonstrable allergy to any of these foods. The sensitivity of the total IgE determinations for the diagnosis of food allergy was 94% and the specificity was 80%. Specific IgE antibodies to cow's milk were demonstrated in 11 of 14 children with immediate reactions and in three of 15 who were provocation test negative or had only late reactions. This means a sensitivity of 79% and a specificity of 80%. At least one of the four patients with specific IgE but negative provocation test results had earlier shown an immediate reaction when challenged with cow's milk, indicating that the specific IgE antibodies were not truly "false" positive reactions but a consequence of previous allergy. Our results confirm an association between elevated total serum IgE and food allergy and an association between positive RAST to cow's milk and positive provocations in young children. We did not find any evidence for specific IgG4 antibodies playing a role in these patients.

Animals↗

Relation between mucous cells and lymphoid tissue in rat intrapulmonary airways.

The distribution of mucous cells in rat intrapulmonary airways was investigated by conventional light microscopic technique. A striking association was found between differentiation of epithelial mucous cells and accumulation of lymphoid tissue in the lamina propria of bronchioli. Nodular accumulations of lymphoid tissue, covered by a lymphoepithelium, as well as differentiation of mucous cells, increased with age. This normal development was accelerated in rats exposed to aerosolized ovalbumin.

Aging↗

Effects of fibrinogen fragment and proteolytic enzyme on the immune system in mice.

The immunomodulating ability of fibrinogen fragment (Hol-DSK) and proteolytic enzyme with fibrinolytic activity from Aspergillus oryzae was analysed in CBA/Ca, C57Bl, C3H/HeJ and NMRI mice. Suppressive effects on the blastogenic response to mitogens were noted. No consistent suppressive effect, but sometimes an enhancing one, was recorded on the antibody responses to protein antigens. Administration of Hol-DSK or proteolytic enzyme shortly after the immunization resulted in a slight inhibition of the development of delayed hypersensitivity to picryl chloride in C57Bl but not in CBA mice. When similar administration was done simultaneously with administration of the challenging antigen of picryl chloride or sheep red blood cells in immunized mice, significant impairment of the delayed-type hypersensitivity reaction was noted. The modulating effects by Hol-DSK did not alter the in vitro bacteriocidal effects of peritoneal exudate cells from mice on Escherichia coli.

Animals↗

Cow's milk protein intolerance in children is connected with impaired lymphoblastic responses to mitogens. Preliminary report.

The lymphoblastic responses of peripheral blood lymphocytes to mitogens were analyzed in 36 infants and children aged 1-28 months. The patients had confirmed or suspected cow's milk protein intolerance (CMPI). Immediately after a positive provocation test 12 out of 14 patients with repeatedly confirmed CMPI showed more than 30% decrease of their lymphoblastic responses to pokeweed mitogen and concanavalin A compared with their initial values. In 10 infants the response to phytohemagglutinin was similarly decreased. In 4 out of 12 infants with previously confirmed CMPI, but with no reaction at challenge, similar decreases were seen to some of the mitogens. In patients with suspected CMPI, but with no obvious reaction to the challenge with cow's milk, generally an increase of the lymphoblastic responses was seen compared with the initial values.

Animals↗

Antibody responses to honey-bee venom and monomethoxy-polyethylene glycol-modified honey-bee venom in mice.

Antibody responses of the IgE isotype were raised in mice with honey-bee venom (HBV) administered in alum or by daily injections without adjuvant. The sensitized mice were treated with single injections of HBV modified with monomethoxy-polyethylene glycol. By such treatment with modified but not with natural HBV, suppression of the IgE antibody responses was achieved. The IgG antibody responses, in contrast, were unchanged or enhanced.

Adjuvants, Immunologic↗

Immune responses in rats sensitized with aerosolized antigen. Antibody formation, lymphoblastic responses and mast cell and mucous cell development related to bronchial reactivity.

Rats of BN X Wi/Fu strain were immunized by aerosol exposure to 0.001-1% of ovalbumin (OA) without using any adjuvant for 2- or 1-week periods with 4-week intervals. The immunization, particularly with the highest dose, induced antibody formation of IgE, measured with RAST, and of IgG and IgA, measured with ELISA. Regional lymph node cells from immunized animals showed spontaneous proliferation which was suppressed by syngeneic spleen cells. The cell mixture could be stimulated by addition of specific antigen or mitogen, while cultures of peripheral lymph node cells showed a less consistent increase in lymphoblast formation. Histological examination of the lungs of immunized animals revealed a rapid onset of inflammation with accumulations of mononuclear cells and also increased numbers of mast cells. There was some dose-response relationship between antigen concentration and cell accumulations. The immunization also seemed to induce differentiation of epithelial cells to mucous cells. Intravenous provocation of animals immunized with 0.01-1% OA aerosol resulted in clinical bronchial reactivity assessed as increased transpulmonary pressure. This airway response was attenuated by pretreatment with indomethacin. Animals immunized with 1% OA did, however, not respond to challenge. These animals showed a decreased response to serotonin compared with nonimmunized controls. In summary, the described animal model seems to provide a tool for studies of the asthmatic reaction.

Aerosols↗

Induction of humoral immunity and pulmonary mast cells in mice and rats after immunization with aerosolized antigen.

Rats (BN X Wistar) and mice (CBA/Ca) were immunized by exposure in 10-day periods to an aerosol of ovalbumin (OA). In rats this immunization resulted in IgE antibodies detectable at very low levels in bronchial washings, whereas IgG, IgA and IgM antibodies were recorded both in serum and in bronchial washings. In mice, exposure to aerosolized antigen resulted in specific IgE and IgG antibodies in serum. The levels of IgM antibodies were low and no IgA antibodies could be recorded with the enzyme-linked immunosorbent assay (ELISA). Histological examination of lung tissue from immunized rats and mice revealed increased numbers of cells with characteristics of both immature and mature mast cells. In addition, in the rats these cells were more closely located to the bronchi in immunized than in control animals. In the latter animals the mast cells were located around the blood vessels. Immature mast cells were located in the bronchiole-associated lymphatic tissue (BALT) which showed a marked proliferation in immunized animals. The findings indicate that sensitization via the airways provides possibilities to develop a model in rodents for studies of IgE-mediated allergy in the lung.

Aerosols↗

The kinetics of leucocyte migration into rabbit knee joints elicited by preformed immune complexes with different in vitro characteristics.

Immune complexes were formed in vitro with antibodies obtained from rabbits immunized with bovine serum albumin in Freund's complete (FCA) or incomplete (FIA) adjuvant. The antibodies were mixed with different amounts of antigen. Immune complexes formed at maximum precipitation proportions were efficient in complement activation, whereas immune complexes formed at antigen excess had weak complement-activating properties. When injected into rabbit knee joints, the immune complexes formed at maximum precipitation proportions with FCA or FIA antibodies caused a moderate leucocyte migration into the joints with maximum cell counts 6-8 hr after injection. Injection into the joints of immune complexes formed with FCA antibodies at antigen excess induced a pronounced leucocyte migration with maximum numbers 18 hr after injection. Immunofluorescent studies indicated that these immune complexes became associated with the leucocyte membrane, whereas immune complexes formed at maximum precipitation proportions were found in the leucocyte granulae, indicating that only the complement-activating immune complexes were efficiently eliminated.

Animals↗

Antibody-dependent cell-mediated cytotoxicity against Escherichia coli O antigens.

Antibodies against Escherichia coli O antigen from rabbits immunized with formalin-killed bacteria were tested for cytotoxic capacity in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay with human lymphocytes as effector cells and autologous papainized erythrocytes coated with O antigen as target cells. The cytotoxic titres were compared with the titres obtained with three methods of antibody quantitation. It was found that ADCC recorded antibodies with similar sensitivity as the enzyme-linked immunosorbent assay (ELISA) for IgG, but was much more sensitive than the ammonium sulphate precipitation (ASP) and indirect haemagglutination (IHA) using beta-mercaptoethanol reduced sera. The ADCC titres were found to correlate very well with the titres obtained with ASP, ELISA and IHA for IgG but not for IgM, which is in accordance with a previous notion that ADCC is primarily mediated via IgG antibodies. ADCC should be considered as a possible immunopathologic mechanism in renal parenchymal damage in connection with urinary tract infections.

Animals↗