Recovery from live influenza virus infection is known to induce heterosubtypic immunity. In contrast, immunity induced by inactivated vaccines is predominantly subtype specific. In this study, we investigated the heterosubtypic protective immunity induced by inactivated influenza virus. Intranasal immunization of mice with inactivated influenza virus A/PR8 (H1N1) provided complete protection against the homologous virus and a drift virus within the same subtype, A/WSN (H1N1), but not against the heterosubtypic virus A/Philippines (H3N2). However, coadministration of inactivated virus with cholera toxin as an adjuvant conferred complete heterosubtypic protection, without observed illness, even under conditions of CD4+ or CD8+ T-cell depletion. Analysis of immune correlates prior to challenge and postchallenge indicated that humoral immune responses with cross-neutralizing activity in lungs and in sera play a major role in conferring protective immunity against heterosubtypic challenge. This study has significant implications for developing broadly cross-reactive vaccines against newly emerging pathogenic influenza viruses.
intranasal ͉ mucosal adjuvant ͉ mucosal immunity ͉ redirection ͉ secretory IgA
Wu H-Y, Nguyen HH, Russell MW. Nasal Lymphoid Tissue (NALT) as a Mucosal Immune Inductive Site. Scand J Immunol 1997;46:506-513 Intranasal (i.n.) immunization is a very effective route for inducing mucosal immunity, but the cellular mechanism responsible for regulating and disseminating these responses is not fully understood. The authors studied the role of nasal lymphoid tissue (NALT) as a mucosal inductive site by using highly purified NALT cells obtained by a new method of mechanical isolation. The NALT cells, like Peyer's patch (PP) cells, were smaller in size and less granular than lymphocytes from salivary glands (SG) and small intestinal lamina propria (LP). The NALT cells isolated from i.n. immunized mice contained antigen-specific antibodysecreting cells (ASC) predominantly of immunoglobulin (Ig)A isotype, similar to those also recovered from salivary glands in a time course study. However, the higher proportion of smaller sized spots formed by NALT cells in ELISPOT assays suggested that these cells were less differentiated precursors of those found in salivary glands. This was supported by the fact that after i.n. immunization, IgA ASC appeared in NALT, as well as in mucosal effector sites SG and LP, but none or very few in another mucosal inductive site, PP. In contrast, after intragastric (i.g.) immunization, IgA ASC were detected in PP, along with the SG and LP, but none or very few in NALT. Furthermore, after i.n. immunization, lymphocytes from NALT but not PP proliferated in response to the specific antigen in culture. These findings imply that NALT served as an inductive site for IgA antibody responses at mucosal effector sites.
This study develops and empirically tests the interrelationships between service quality, customer satisfaction, and customer loyalty in a retail banking context. Increasingly intense competitiveness and fundamental changes in the business environment nowadays are forcing firms to implement a customer-focused strategy which raises the importance of customer-related constructs such as customer satisfaction, service quality, and customer loyalty in explaining a firm's performance. In particular, they are essential for competitiveness in industries where the exchanges are complex and customers are closely involved in the decision-making process, such as the banking industry. In this study, first, a research model about the interrelationships between service quality, customer satisfaction, and customer loyalty is suggested. Then a survey is conducted with retail banking customers about these constructs, which results in 261 valid respondents. The hypotheses are then proposed and tested using confirmatory factor analysis (CFA) and the structural equation modelling technique (SME). The analysis reveals that service quality and customer satisfaction are important antecedents of customer loyalty and customer satisfaction mediates the effects of service quality on customer loyalty. These findings suggest that there are non-linear relationships between three constructs and emphasize the need to treat customer loyalty management as a process which includes plenty of factors interacting with each other.
Heterosubtypic immunity, defined as cross-reactive immune responses to influenza virus of a different serotype than the virus initially encountered, was investigated in association with virus-specific cytotoxic T lymphocyte (CTL) responses induced in systemic and mucosa-associated lymph nodes after immunization via different routes. Mice immunized by the pulmonary route with live nonpathogenic influenza virus, strain Udorn (H3N2), survived challenge with mouse-adapted pathogenic influenza virus, strain PR/8/34 (H1N1). These mice developed strong heterosubtypic CTL responses in spleen, cervical lymph nodes (CLN), and mediastinal lymph nodes (MLN). Alternately, only 20% of mice immunized intravenously, intraperitoneally, or intranasally survived the challenge; all of these developed CTL responses in spleen and CLN, but not in MLN. Direct correlation between short-term and long-term memory heterosubtypic CTL responses induced in MLN and host recovery after lethal infection indicates that these CTL responses may play an important role in heterosubtypic immunity. Furthermore, induction and maintenance of memory CTL in regional mucosa-associated lymphoid tissues are highly dependent on mucosal immunization. The results implicate the mechanism of heterosubtypic immunity and should be an important consideration in the development of protective mucosal vaccines against variant strains of influenza and HIV.
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