Background: Adjuvants are essential in the induction of immunity by vaccines and interact with receptors, including the Toll-like receptors (TLRs). Responsiveness of these receptors differs between... Show moreBackground: Adjuvants are essential in the induction of immunity by vaccines and interact with receptors, including the Toll-like receptors (TLRs). Responsiveness of these receptors differs between and within populations, which impacts vaccine effectiveness. Objective: Here we examine how the innate cytokine response towards TLR ligands differs between high and low socioeconomic status (SES) school-aged children from Makassar, Indonesia. Methods: We stimulated whole blood from children, of which 27 attended a high SES school and 27 children a low SES school, with ligands for TLR-2/1, -2/6, -3, -4, -5, -7, -9 and measured pro- (TNF) and anti-inflammatory (IL-10) cytokines released. Results: In the low SES there is an increased pro-inflammatory response after 24 h stimulation with TLR-2/1 ligand Pam3 and TLR-4 ligand LPS compared to the high SES. Comparison of the response to LPS after 24 h versus 72 h stimulation revealed that the pro-inflammatory response in the low SES after 24 h shifts to an antiinflammatory response, whereas in the high SES the initial anti-inflammatory response shifts to a strong proinflammatory response after 72 h stimulation. Conclusion: We observed differences in the TLR-mediated innate immune response between children attending low and high SES schools, which can have important implications for vaccine development Show less
The studies present in this thesis fall into two broad areas: the first focusing on filarial infection, Ig (immunoglobulin)E levels and risk factors for infection, while the second deals with the... Show moreThe studies present in this thesis fall into two broad areas: the first focusing on filarial infection, Ig (immunoglobulin)E levels and risk factors for infection, while the second deals with the possible associations between nematode infection and allergy. Compared to ELISA, RAST is superior in detecting filarial specific IgE in endemic area of Brugia malayi. Levels of filaria-specific IgE and IgG4 in children up to 10 years correlated with maternal antibody levels. Genetic factors had a more pronounced effect in children than in adults. The use of objective measurements, such as skin prick test (SPT) and IgE levels are required when conducting epidemiological studies of allergic diseases in Indonesia. Study on risk factors of allergy in Indonesia showed that nutritional status of children in the high socioeconomic school negatively associate with SPT and IgE positivity but we did not show a statistically significant role for helminths in inhibiting SPT responses. In endemic area of lymphatic filariasis, genetic factors contribute significantly to both total and allergen-specific IgE, whereas environmental factors influence the clustering of SPT positivity. By using several TLR ligands it was demonstrated that the dynamics of cytokine production following the innate immune stimulation can differ according to helminth infection status. Show less
