Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses

Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-gamma-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-gamma responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-gamma responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria

Семантичні зміни в лексичному складі російської та української мов

Использование вычислительной техники и радиоэлектроники способствовало формированию специальной группы лексических единиц. Номинация новых явлений и понятий является актуальной проблемой нынешнего этапа развития языка. Изменение семантического наполнения – это один из способов решения данной проблемы. Расширение или сужение семантического объема слов способствует обогащению лексической системы, а именно терминологии.Використання обчислювальної техніки та радіоелектроніки спричинило формування спеціальної групи лексичних одиниць. Номінація нових явищ та понять є актуальною проблемою теперішнього етапу розвитку мови. Зміна семантичного об'єму – це один із засобів вирішення даної проблеми. Звуження або розширення семантичного наповнення сприяє збагаченню лексичної системи, а саме термінології.Using of radio-electronic devices forced the formation of a special group of lexical units. The nomination of new processes and notions is an actual problem of today's language development. Semantic changes of existing units is one of the decisions of the problem. Widening and narrowing of semantic meanings promotes the enrichment of lexical system, especially the system of terminology

T-/NK-cell frequencies and the occurrence of malaria during the first 12 months of life.

<p>T-/NK-cell frequencies and the occurrence of malaria during the first 12 months of life.</p

Multivariate (LMM) analyses of alterations in circulating T- and NK-cell subset frequencies in peripheral blood as a function of infants’ age and of <i>P</i>. <i>falciparum</i> infection at delivery.

<p>Multivariate (LMM) analyses of alterations in circulating T- and NK-cell subset frequencies in peripheral blood as a function of infants’ age and of <i>P</i>. <i>falciparum</i> infection at delivery.</p

Frequencies of cell subsets in infants' peripheral blood during the first year of life.

<p>Curves include dots representing mean with SEM (standard error of the mean). The statistical significance of differences indicated refers to analyses of variances for repeated measures. ***, p <0.001.</p

T and NK cell cord blood frequencies as immunological predictors of malaria in infants.

<p>T and NK cell cord blood frequencies as immunological predictors of malaria in infants.</p

Characteristics of the study population (n = 158 mother/infant pairs).

<p>Characteristics of the study population (n = 158 mother/infant pairs).</p

Frequencies of cell subsets in infants' peripheral blood over time segregated on the basis of presence or absence of maternal infection at delivery.

<p>(white for negative and hatched for maternal infection). Curves include dots representing mean with SEM (standard error of the mean).</p

Flow diagram of birth cohort study.

<p>217 pregnant women were enrolled under 24 weeks of gestation and their infants were longitudinally followed-up from birth to 12 months of age. For the Treg/Teff part: 59 newborns were excluded (52 newborns < 3 blood samples collected and 7 newborns HIV+ or unknown HIV serostatus in the mother). Data from 158 infants were included for analyses. For the CD4, CD8, NK part: 67 newborns were excluded (60 newborns < 3 blood samples collected and 7 newborns HIV⁺ or unknown HIV serostatus in the mother). Data from 150 infants were included for analyses.</p