Specific Mucosal IgA Responses Research Articles

Pilot study of human experimental challenge with neisseria lactamica

Introduction: Neisseria lactamica is a non pathogenic commensal bacteria commonly found in the upper respiratory tract of infants. Its carriage dynamics have been extensively studied in young children and a clear correlation has been documented between colonisation by N. lactamica and protection from meningococcal disease. This is thought to be due to common antigens resulting in a cross protective immune response. Objectives: The aim of this study was to inoculate Neisseria negative healthy adult volunteers, with live N. lactamica and monitor their specific mucosal and systemic immune response, then analyse their serum bactericidal antibody response against 6 UK prevalent meningococcal B strains. Methodology: 9 individuals were inoculated with live N. lactamica, resulting in 5 successful colonisations. Colonisation was confirmed using nasopharyngeal swabs and gargles. Saliva and blood samples were taken at 0 weeks, 2, 4, 7, and 12 weeks. Findings: Results demonstrated a specific mucosal IgA and systemic IgG immune response to colonisation by N. lactamica. The specific mucosal IgA response from baseline to 12 weeks, comparing non colonised and colonised individuals was significant, p value Z0.0159. Baseline specific IgG and peak fold rise for each individual, using a Mann Whitney test, demonstrates a value of pZ0.063 in colonised individuals. Discussion: Most interestingly colonised individuals demonstrate a greater range of SBA responses to different meningococcal strains, than the non colonised group. Within the colonised individuals 2 volunteers had a significant (greater than 4 fold rise) response to 4 different meningococcal strains. Overall, all volunteers mounted a response to at least one strain of meningococci, it is likely that individual exposure to N. lactamica is resulting in a booster response of one or more specific antigens which are found on the outer membrane of these different strains of meningococci. These results support the hypothesis that colonisation by Neisseria lactamica does result in cross protection against meningococci. MATRIX METALLOPROTEINASE DRIVEN TISSUE DESTRUCTION IN CENTRAL NERVOUS SYSTEM TUBERCULOSIS IS REGULATED BY NFjB Justin Green, Shruti Dholakia, Rachel Moores, Lucinda Rand, Paul Ekington, Jon Friedland Imperial College, London, United Kingdom

IL-6-deficient mice exhibit normal mucosal IgA responses to local immunizations and Helicobacter felis infection.

Using IL-6-deficient (IL-6 -/-) or wild-type mice, we investigated whether IL-6 is involved in the intestinal adjuvant activity of cholera toxin (CT) and to what extent IL-6 is required for mucosal IgA responses against soluble protein Ags or live Helicobacter felis infection. In naive IL-6 -/- mice we found normal total IgA levels in serum, bronchial and intestinal lavage and unaltered frequencies of IgA plasma cells in intestinal lamina propria. In Peyer's patches (PP) and mesenteric lymph nodes (MLN) IgA-producing cells were as frequent in IL-6 -/- as in wild-type mice. Immunohistochemical analysis of PP revealed germinal centers that co-localized IgA+ cells, indicating B cell activation and isotype switching in situ in the intestinal immune inductive site. Phenotypic analysis of the distribution of conventional B-2 cells (B220+CD5-/Mac-1-) and B-1 cells (B220+, CD5+/Mac-1+) in intestine-associated tissues gave comparable results in IL-6 -/- and wild-type mice. The ability to respond with mucosal IgA following oral and intranasal immunization with specific Ag, KLH or OVA, in the presence of CT adjuvant or to live H. felis infection was similar in IL-6 -/- and wild-type mice. CT exerted strong and comparable adjuvant functions in IL-6 -/- and wild-type mice. Repeated oral immunizations with CT alone stimulated immune protection against CT-induced diarrhea in ligated loops that was of similar magnitude in IL-6 -/- and wild-type mice. We conclude that, although IL-6 has been ascribed a crucial role in terminal differentiation of IgA B cells in vitro, we found no evidence to support the notion that IL-6 is critically required for IgA B cell development or specific mucosal IgA responses in vivo.

Parenteral immunization causes antigen-specific cell-mediated suppression of an intestinal IgA response.

Rats immunized s.c. with cholera toxin (CT) or toxoid (CTd) show antigen-specific suppression of the jejunal IgA anti-CT response to subsequent enteric doses of CT. We determined whether this effect was partly cell-mediated and studied the suppressor cell response involved. Spleen cells from s.c.-immunized rats suppressed the jejunal anti-CT response in adoptive recipients when cell transfer was at, or 4 days before, intraduodenal priming with CT. Transferred suppression was antigen-specific, and the suppressor cells were nylon wool-nonadherent. Increasing the s.c. dose of CT from 0.1 to 40 micrograms, and the interval between immunization and cell harvest from 2 to 16 wk, each increased the suppressive effect of a constant spleen cell inoculum. After s.c. immunization, suppressor cells were present in the spleen within 1 to 2 wk, among TDL within 4 to 8 wk, and in Peyer's patches and thymus within 8 to 16 wk; this sequence suggested they arose in the spleen and later migrated to mucosae and the thymus. Prior splenectomy did not alter the suppressive effect of s.c. CT, however, nor did it prevent suppressor cell appearance among TDL, indicating that suppressor cells also arose from nonsplenic sites. Transferred suppressor cells acted by interfering with the development of specific immunologic memory within Peyer's patches during enteric priming; transfer of suppressor cells at the time of enteric boosting had no effect upon the secondary mucosal anti-CT response. We conclude that the suppressive effect of s.c. immunization on a specific mucosal IgA response is due largely to the action of systemically derived suppressor cells upon the primary mucosal immune response within Peyer's patches. This sequence resembles the mirror image of oral tolerance, which involves the suppression of systemic IgG and IgM responses by suppressor cells that arise in Peyer's patches and migrate to the spleen after antigen feeding.