Transport of polymeric immunoglobulin A (plgA) in rat salivary glands has been investigated by combined morphological and biochemical techniques in vivo and in vitro. The distribution of IgA and its cellular receptor secretory component (SC) was observed by immunoperoxidase staining of cryosections from parotid and submaxillary gland, showing serous acinar cells are the site of IgA transport into saliva. Binding of horse radish peroxidase specific IgA to parotid serous acinar cells in vitro, observed by electron microscopy, shows that only the basolateral domain of acinar cells possesses exposed SC. A combination of new cell fractionation methods and standard western blotting techniques shows that SC present on basolateral plasma membrane of parotid acinar cells has a molecular weight (mwt) >100,000 and shows a high affinity for plgA in vitro. The existence of a 73,000 mwt SC occurring with plgA in cellular fractions of parotid gland suggest cleavage of SC occurs prior to secretion. The kinetics of plgA trancytosis was studied using isolated parotid acini. Bound plgA was secreted into the incubation medium as slgA, within thirty minutes of incubation at 37°C. Secretion of plgA was initially rapid but slowed over a 2hr period of incubation at 37°C. In addition to facilitating plgA transport serous acinar cells also synthesise and secrete a diverse range of other salivary proteins which are packaged into secretion granules and secreted directly through the apical plasma membrane. It is improbable that one complex secretory pathway facilitates both bulk secretion of salivary protein and transport of plgA. Therefore secreted proteins must be selectively segregated during secretion into saliva. Secretion of proteins from acinar cells in vitro shows proteins are released at two distinct rates.

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Anti-idiotype antisera were raised in rabbits to two monoclonal antibodies, Fd-1 and Fd-2, with specificity for each of the two antigenic epitopes found on the ferredoxin (Fd) molecule. The anti-idiotype antisera (anti-Fd-1 and anti-Fd-2) were used to demonstrate that one of the idiotypes (Fd-1) was expressed at significant levels in most anti-Fd antisera raised in BIO.BR mice while the second idiotype (Fd-2) was infrequently expressed. Examination of anti-Fd sera raised in other mouse strains demonstrated that expression of the Fd-1 idiotype mapped to the IgH gene complex and was found in the antisera of all mouse strains examined with the Ig-1[sup=b] allotype. When splenocytes from Fd-immune B10.BR mice were treated with anti-Fd-1 and transferred to irradiated syngeneic recipients, the adoptive secondary response was significantly higher in animals receiving treated cells as opposed to control animals which received normal rabbit serum treated cells. This response produced a net increase in antibody to both epitopes and the relative amount of Fd-1 idiotope was not significantly altered. Further studies with separated cell populations showed that the overall increase of anti-Fd antibody produced was attributable to the effects of the anti-idiotypic serum on a population(s) of T cells. Treatment of mice with the Fd-1 monoclonal antibody (which should react with anti-idiotypic cells) had an analogous effect to that of the anti-idiotype. Treated mice produced heightened levels of antibodies directed to both epitopes of Fd. Treatment of mice with second anti-idiotype, anti-Fd-2, was found to enhance the anti-Fd response of B10.BR mice and abrogate the non-responder status of DBA/2 mice. Additional evidence indicates that the Fd-2 idiotype could be expressed on a suppressor cell population which may be a predominant regulatory element in both BIO.BR and DBA/2 mice. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

Madariaga virus (MADV) has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien Province. We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. In addition, by applying a catalytic, force-of-infection (FOI) statistical model to two serosurveys from Darien Province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically. In 2017, MADV and VEEV IgM seroprevalences were 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%, VEEV: 16.8%, Una virus (UNAV): 16.0%, and Mayaro virus: 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households, raising questions about its vectors and enzootic transmission cycles. Insomnia was associated withMADVand VEEV infections, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in Aruza and Mercadeo, respectively. The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased-potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially in some locations of eastern Panama. / National Institute for Health Research / Revisión por pares

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

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Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.