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B Haneberg

Publications and source records attributed to B Haneberg.

At least 37 records · Page 2Linked to original sources

[What is the purpose of mucosal antibodies? Relevance to colonization with group B streptococci].

The surface area of the mucosae is extremely large and its contact with the external environment is of vital importance. Most infectious agents use the mucosae as their portal of entry. Some microorganisms, however, colonize the mucosal surfaces without causing disease, and may even be beneficial by contributing to the digestion of food or by excluding pathogens. An important part of the immune system operates in the mucosae, the principal mediator substance of this local immune system being secretory IgA. Other antibody isotypes are usually found in small amounts in exocrine fluids, but IgG predominates in secretions of the uterine cervix. These mucosal antibodies may eliminate microbes, or they may coexist with persistent colonization. In a recent study, we found increased levels of IgA and IgG antibodies to group B streptococci in the cervical secretions of women colonized with these bacteria. Group B streptococci are often transmitted to the infant during delivery, and are a major cause of severe infection in newborns. We have used this study as a background for discussing the role of mucosal antibodies. Presumably, group B streptococci may be eradicated by reenforcing the local antibody response, and a mucosal vaccine will be evaluated in the near future.

Antibodies, Bacterial↗

Nasal immunization with group B streptococci can induce high levels of specific IgA antibodies in cervicovaginal secretions of mice.

We have studied the cervicovaginal antibody responses in mice, by ELISA, following mucosal immunizations with group B streptococci (GBS) serotype III/R4. Immunizations were carried out either: (1) rectally with GBS alone; (2) rectally with GBS plus cholera toxin (CT); (3) nasally with GBS alone; (4) nasally with GBS+CT; or (5) nasally under general anesthesia with GBS+CT. Nasal immunizations with GBS alone led to at least tenfold higher levels of specific IgA-antibodies to GBS in cervicovaginal secretions than with any other immunization. These mucosal antibody levels were higher than after rectal immunizations, and 2-17 times higher than the corresponding IgA antibody levels in sera. Markedly lower cervicovaginal antibody levels were found in mice which had received GBS together with CT as a mucosal adjuvant than in mice immunized by the same routes with GBS alone. Our observations indicate that a nasal vaccine consisting of GBS might induce sufficient antibody levels to protect against genital colonization of these bacteria.

Adjuvants, Immunologic↗

Distribution of monoclonal antibodies in intestinal and urogenital secretions of mice bearing hybridoma 'backpack' tumours.

Mice bearing IgA hybridoma 'backpack' tumours have been used to demonstrate that secretion of a single monoclonal IgA can protect against mucosal infection, but the relevance of this model to normal IgA protection is not clear. The authors analysed the distribution of specific monoclonal and total antibodies in bile, local intestinal secretions, cervical-vaginal secretions, urine and serum of mice bearing anti-cholera toxin (CT) IgA and IgG backpack tumours, with and without bile duct ligation. Backpack tumours resulted in high levels of both anti-CT and total IgA or IgG in serum, and IgA (but not IgG) in bile. Secretions recovered by absorbent filter 'wicks' from mucosal surfaces throughout the intestines of backpack tumour mice contained significant concentrations of monoclonal anti-CT IgA, but total IgA levels were as in normal mice. Neither monoclonal nor total IgA levels on mucosal surfaces were altered by bile duct ligation. Furthermore, anti-CT monoclonal IgA levels in local intestinal secretions of backpack tumour mice were comparable to specific polyclonal IgA levels previously elicited by mucosal immunization with CT. Thus, IgA-mediated protection against enteric challenge in the backpack tumour model may be a valid predictor of protection provided by natural mucosal immunization in vivo. High monoclonal IgA levels in bile, urine and the female genital tract, however, may not reflect the situation in normal immunized mice.

Animals↗

Colonization in the rectum and uterine cervix with group B streptococci may induce specific antibody responses in cervical secretions of pregnant women.

We have studied the relationships between genital or rectal carriage of group B streptococci (GBS) with the levels of systemic and mucosal antibodies to GBS in 200 women at about week 17 of pregnancy. Secretions from the uterine cervix were collected with absorbent cylindrical wicks for quantification of antibody levels with whole cell enzyme-linked immunosorbent assay. GBS were cultured from the cervix (with or without concomitant rectal colonization) of 13.5%, from the rectum (with or without concomitant cervical colonization) of 12%, and from both culture sites of 8.5% of the women. Serotypes Ia, II, and III were predominant. Compared with culture-negative women, the group of women colonized rectally had markedly elevated levels of both immunoglobulin A (IgA) and IgG antibodies to GBS in cervical secretions and also had a moderate but significant elevation of IgA antibodies in sera. Women colonized only in the cervix had increases of specific IgA and IgG antibodies in cervical secretions, but their serum antibody levels were not elevated. In cervical secretions, the increase in antibody levels in the groups of colonized women was most pronounced for the IgG isotype, indicating a mucosal immune response involving IgG as well as IgA. A close correlation was found among the levels of antibodies to each of the three GBS serotypes tested. Evidence for such cross-reacting antibodies to different serotypes of GBS, as well as to group A streptococci, was also obtained from absorption experiments. Altogether, our results show that undiluted secretions for antibody determination can be easily collected from the uterine cervix with absorbent wicks and demonstrate that colonization of GBS in the rectum and the uterine cervix may induce a systemic as well as a pronounced local immune response in the female genital tract. The findings may have implications for the development of a mucosal vaccine against GBS disease.

Adolescent↗

Systemic and mucosal antibody responses to group B streptococci following immunization of the colonic-rectal mucosa.

The cervico-vaginal mucosa is poorly designed for inducing a mucosal immune response, but it can effect such a response evoked at other mucosal sites. This study was undertaken to determine whether colonic-rectal immunization with group B streptococci (GBS) might induce a local cervico-vaginal immune response. Mice were immunized with either fragmented GBS rectally, whole GBS rectally, or whole GBS subcutaneously. Cholera toxin (CT) was used as an adjuvant for the rectal immunizations. Following colonic-rectal immunization with whole GBS, the mean anti-GBS IgA antibody level in vaginal secretions was 735 kU/ml, with individual values reaching 3480 kU/ml. Corresponding levels of IgA antibodies never exceeded 10 kU/ml in serum and intestinal secretions, or 90 kU/g in feces. In vaginal secretions IgA antibodies to GBS also constituted a much larger fraction of total IgA than in serum, intestinal secretions and feces. Immunizations with fragmented GBS produced much lower IgA responses. Anti-GBS IgA response at the inductive site in the colon-rectum was not significant, as opposed to a strong anti-CT IgA response. Except in serum, the anti-GBS IgG responses to colonic-rectal immunizations were generally low, or absent. The results may provide a basis for the development of mucosal vaccines against GBS-infection.

Administration, Rectal↗

Evaluation of a rapid enzyme immunoassay for detection of genital colonization of group B streptococci in pregnant women: own experience and review.

We have compared an enzyme immunoassay (ICON Step B, Hybritech) with cultures for demonstration of genital carriage of group B streptococci (GBS) in pregnant women, and studied the relationship between vaginal and rectal carriage of this organism. Pertinent literature has also been reviewed. Two hundred pregnant women at gestational week 17 were included. Swabs from the uterine cervix were tested for GBS by ICON Strep B immunoassay and ordinary cultures on blood agar. Additional swabs from the rectum were tested by cultures. The percentage of women with GBS in cervical secretions was 13.5% (27/200) by cultures and 4% (8/200) by the ICON Strep B immunoassay. The overall sensitivity of the immunoassay was 7.4%, and the specificity 96.5%. In conclusion, the sensitivity of rapid enzyme immunoassays is too low for accurate screening of GBS in the genital tract of pregnant women.

Adolescent↗

Induction of specific immunoglobulin A in the small intestine, colon-rectum, and vagina measured by a new method for collection of secretions from local mucosal surfaces.

In order study patterns of local antibody responses following mucosal immunization of mice via different routes, a method for collection of secretions directly from mucosal surfaces was developed. Mice were immunized on days 0, 10, 17, and 24 by administration of cholera toxin into the oral cavity, stomach, colon-rectum, or vagina. At sacrifice on day 32, absorbent wicks were placed in the oral cavity and, via an applicator tube, into the vagina and distal colon-rectum and along the entire small intestine after flushing of luminal contents. Protein was quantitatively extracted from wicks, and specific anti-cholera toxin immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay. Concentrations of specific IgA in secretions at various mucosal sites were dramatically influenced by the route of immunization. Oral immunization effectively induced IgA in saliva, and the intragastric route was optimal for induction of IgA in the small intestine. High levels of specific IgA appeared on the colonic-rectal mucosal surface only after rectal delivery of antigen. Oral, gastric, and rectal immunizations also produced distant responses in the vagina. Following vaginal immunization, however, neither local nor distant IgA responses were detected. These results suggest that vaccines intended for protection of colonic-rectal and vaginal mucosal surfaces might best be administered by the rectal route.

Animals↗

[AIDS in the Third World. Africa suffers most].

AIDS is now world-wide, and the HIV infection is spreading rapidly via the heterosexual route. Among the Third World countries those in sub-Saharan Africa are the hardest hit, it is estimated that one in 40 of the adult population is already infected. Half of the victims are women, who will give birth to a large number of infected children. The clinical picture of full-blown AIDS in an African patient is not very different from elsewhere. However, other AIDS-related conditions seem to be influenced by a variety of endogenic pathogens which might explain the development of the typical wasting syndrome, i.e. "Slim" disease. Tuberculosis is the most typical opportunistic infection in Africa, and adds another dimension to the misfortune. The outlook is gloomy in the light of the potential for widespread disruption of normal social and economic activities.

Acquired Immunodeficiency Syndrome↗

Immunoglobulin E in the feces of children and adolescents from some tropical and subtropical countries.

Eighteen of 27 individuals, aged from 6 months to 19 years (mean 5 years, 7 months), from countries in the tropics or the subtropics had either intestinal parasitic infestations or intestinal enteropathogenic bacterial infections or both. Fourteen of those with intestinal pathogens had detectable concentrations of IgE in their fecal extracts, ranging from less than 0.5 to 420 IU/ml extract (mean 33 IU/ml). This rate of occurrence was significantly higher than the number of IgE-positive fecal extracts in a group of 54 healthy nonallergic Norwegian children (p less than 0.001), but did not differ from that of a group of 40 allergic children (p greater than 0.20). The individuals with intestinal helminthic infection had the highest fecal IgE concentrations. Of the 9 individuals who did not have any demonstrable intestinal pathogen, low concentrations of IgE could be detected in feces from only 2, which did not differ from the rate in the healthy Norwegian controls. The concentrations of IgE in the feces of the subjects from tropical/subtropical regions correlated linearly with the corresponding serum concentrations of IgE (r = 0.69; p less than 0.001). The results indicate that the combined load of intestinal pathogens, including helminths, protozoa, and enteropathogenic bacteria, may stimulate IgE production in the gut.

Adolescent↗

Automated differential leukocyte counts in newborn infants. Comparison of Coulter VCS and Technicon H1 with manual counts.

There was good agreement between results obtained with Coulter VCS/Technicon H1 and manual counting with respect to neutrophils and eosinophils. Coulter VCS overestimates the lymphocyte percentage compared to manual counting and to H1. If, however, the percentage of so called "naked" cells are added to the percentage of manually counted lymphocytes, the agreement between VCS and the manual method is improved. The alarms given by the two instruments are of little value in detecting left shift or nucleated red blood cells.

Automation↗

Improved automated differential counts of leukocytes from newborn infants using pre-dilution of blood samples.

A method for automated differential leukocyte counting using peroxidase staining and light scatter (H1) failed to present results in more than 25% of blood samples from newborn infants. These failures were mostly seen at or below 2 weeks of age, and with high concentrations of haemoglobin F (HbF). Dilution of the blood with equal amounts of isotonic saline made the problem disappear almost completely. The results of differential counts on such diluted blood samples also compared more favourably with traditional manual counts of blood smears than did the results obtained with undiluted blood. The present method with blood diluted 1/2 is therefore recommended for routine use in newborn infants.

Automation↗

Inhibition of in vitro lysozyme release from human granulocytes and monocytes by non-steroidal anti-inflammatory agents.

A selective zymosan-induced release of lysozyme from freshly prepared human blood granulocytes and monocytes was inhibited by indomethacin, sulindac, piroxicam and ibuprofen. This effect was slightly more marked for granulocytes than for monocytes. Salicylic acid, acetylsalicylic acid and naproxen, even at high concentrations, did not inhibit the enzyme release from either cell type. Since all these nonsteroidal anti-inflammatory agents are cyclooxygenase inhibitors, these findings suggest that lysozyme release is independent of prostaglandin biosynthesis.

Anti-Inflammatory Agents, Non-Steroidal↗

Standardization of a chemiluminescence method for the measurement of meningococcal opsonins using ethanol fixed meningococci.

A chemiluminescence (CL) method using polymorphonuclear leukocytes (PMNLs) and an automatic photoluminometer was used to measure serum opsonins to viable and inactivated group B meningococci. Continuous mixing at 37 degrees C both during opsonization and phagocytosis was essential for optimal CL responses. The CL response increased rapidly during an opsonization time up to 7.5 min, and with PMNL and bacteria concentrations up to 37.5 X 10(5) and 3.8 X 10(7) cells/ml, respectively. Opsonized ethanol fixed meningococci gave CL responses similar to those of viable meningococci, but had a better reproducibility. Using the ethanol fixed bacteria, the variation of PMNLs from different donors, the day-to-day variation, and the coefficient of variation of the CL responses, were all less than 10%. The opsonic activity of convalescent sera from 10 patients with meningococcal disease was markedly higher than that of sera obtained during the acute phase of the disease. Thus, this standardized CL assay using ethanol fixed bacteria is a highly reproducible and sensitive method for measuring serum opsonins to meningococci.

Ethanol↗

Antimicrobial therapy and case fatality in meningococcal disease.

The effect of different initial antimicrobial treatments on the case fatality rate (CFR) was evaluated in 112 consecutive patients with meningococcal disease. The overall CFR was 9.8%. 85 patients received initial therapy with chloramphenicol in addition to benzylpenicillin or other antimicrobials, and 27 patients benzylpenicillin or other antimicrobials without chloramphenicol. Patients treated with chloramphenicol had a lower CFR than those not given chloramphenicol (5% vs. 26%; p = 0.004). However, severely ill patients were treated more often with penicillins, and adjustment for the severity of disease on admission to hospital demonstrated that this difference in favour of chloramphenicol was slight and nonsignificant (p = 0.58). High doses of benzylpenicillin and no chloramphenicol were also associated with a higher CFR than low doses. However, the difference was not significant (p = 0.22). More extensive studies should be carried out to evaluate the effect of benzylpenicillin doses and chloramphenicol on the outcome of meningococcal disease.

Adolescent↗