B. Andersson

Defence of mucous membranes by antibodies, receptor analogues and non-specific host factors

SummaryMost 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.ZusammenfassungBeim Menschen gelangen Infektionen zum größten Teil über die Schleimhäute in den Organismus; mehr als die Hälfte des lymphatischen Systems findet sich in Verbindung mit den Schleimhäuten. Sekretorisches IgA stellt die wichtigste Antikörperklasse der Schleimhäute dar; seine Funktion besteht primär darin, daß es Mikroorganismen bindet und damit ihren Kontakt mit den Geweben des Wirtes verhindert. Wie durch Immunisierung am besten eine Antwort von sekretorischem IgA erzielt werden kann, ist bislang nicht hinreichend geklärt. Wiederholte Antigenexposition von Schleimhäuten kann eine orale Toleranz hervorrufen, bei der es zu einer Verminderung der zirkulierenden Antikörper kommt, während die Antwort von sekretorischem IgA erhalten bleibt. Für gewöhnlich hält die Antwort von sekretorischem IgA nur kurze Zeit an, eine Boosterung ist schwierig. IgM — und IgG-Antikörper unterstützen wahrscheinlich die Abwehr im Bereich der Schleimhäute, doch kommt es in der Regel zu einer Entzündung der Gewebe, wenn diese Antikörper beteiligt sind. Exokrine Sekrete wie die Muttermilch enthalten wahrscheinlich Analoga zu Rezeptoren für Bakterien auf dem Schleimhautepithel. Es ist möglich, daß solche Rezeptorenanaloga das Anheften von Bakterien an den Schleimhäuten verhindern helfen, die als primärer Angriffsort beim Eindringen der Erreger dienen. Eine Reihe unspezifischer Wirtsfaktoren unterstützen die Abwehr im Schleimhautbereich. Dazu gehört Lactoferrin. Lactoferrin-Mangel führt offensichtlich zu rezidivierenden bakteriellen Infektionen, was auf seine Bedeutung für die normale Abwehr schließen läßt.

Nasopharyngeal Bacterial Flora in Otitis Prone Children Treated with Immunoglobulin

The present study was undertaken to evaluate possible beneficial effects of regularly given, long term immunoglobulin prophylaxis of children below 2 years of age with recurrent acute otitis media (RAOM). The nasopharyngeal bacterial flora and the frequency of acute otitis media (AOM) and secretory otitis media SOM were studied. Every second of 44 children with 3 or more periods of AOM during the last year received immunoglobulin intramuscularly (Gammaglobulin Kabi 165 mg/l, 0.45 ml/kg b.w.) every third week for 6 months, while the other 22 children served as controls. All children were followed for 12 months. Immunoglobulin prophylaxis neither influenced the nasopharyngeal flora, nor the frequency of AOM or SOM periods. Children with AOM or SOM more often harbored bacterial pathogens in their nasopharynx than children with normal middle ear status. Also, the immunoglobulin prophylaxis did not influence the increased frequency of bacterial pathogens in the nasopharynx of children attending public day care or family day care as compared to those taken care of at home.

Role of Attachment for the Virulence of Streptococcus pneumoniae

Adherence of microorganisms to mucosal surfaces is a general phenomenon among microorganisms infecting the human host. Its role for persistence and colonization as well as production of local inflammation is well established. This paper describes the adhesion of Streptococcus pneumoniae to human epithelial cells. Strains from various anatomical sites or diseases are compared for attaching capacity. Isolates from the same host but at different times are also compared. The molecular mechanisms, the so-called adhesin-receptor interactions, are partially described. The pneumococcus recognizes a sugar sequence; GlcNAc beta 1-3Gal; on the surface of the host epithelial cell. Glycoconjugates containing this disaccharide act as receptors for adhering pneumococci. The adhesin in pneumococcal attachment is less well characterized. It is a heat and trypsin sensitive component, most likely a peptide, which forms a bridge between the receptor and an anchoring site in the pneumococcal cell wall. Receptor active saccharides are part of the adhesion-inhibitory activity found in human milk.

Inhibition of Attachment of Streptococcus Pneumoniae and Haemophilus Influenzae by Human Milk

Human milk inhibited the attachment of Streptococcus pneumoniae and Haemophilus influenzae to human pharyngeal or buccal epithelial cells. Infant formulas and cow and buffalo milk showed a lower inhibitory activity against pneumococci and enhanced the adhesion of H. influenzae. The antiadhesive effect against S. pneumoniae was found in both the high- and the low-molecular-weight fractions of milk. The inhibitory activity in the high-molecular-weight fraction was independent of specific antibody content; it was present after immunoadsorption and in the milk from IgA-deficient women. The inhibitory activity in the low-molecular-weight fraction was in part explained by the content of oligosaccharides corresponding to the carbohydrate moieties of the neolactoseries of glycolipids, which have previously been shown to act as receptors for attaching pneumococci. The antiadhesive activity against H. influenzae was restricted to the high-molecular-weight fraction of the milk and was unaffected by immunoadsorption. Milk may protect against otitis by reducing colonization.

Reduced frequency of acute otitis media in breast-fed infants

The finding that breast-milk inhibits bacterial attachment in vitro(1) provided the basis for a clinical study of the protection by breast-feeding in children below one year of age. 493 infants were enrolled in the study. Breast-fed infants between 4 and 12 months had a significantly lower frequency of upper respiratory tract infections compared to the other feeding groups. In the age group 0 to 3 and 8 to 12 months of age the exclusively breast-fed children had a significantly lower frequency of acute otitis media.