Human Immunotoxicity of Developmental PCB Exposure
发育过程中接触 PCB 的人体免疫毒性
基本信息
- 批准号:9899989
- 负责人:
- 金额:$ 55.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-25 至 2024-02-28
- 项目状态:已结题
- 来源:
- 关键词:16 year oldActivities of Daily LivingAcute bronchitisAddressAdolescenceAdolescentAffectAgeAge-MonthsAntibodiesAntibody ResponseAntibody-mediated protectionB-LymphocytesBCG LiveBCG VaccineBacille Calmette-Guerin vaccinationBiological Response ModifiersBirthCategoriesCellsChemicalsChildChildhoodClinicalCollectionCommunicable DiseasesDataDeveloped CountriesDevelopmentDevelopmental ProcessDiagnosisEnvironmentEnvironmental ExposureExogenous FactorsExposure toFlow CytometryFood ChainFrequenciesFutureHealthHumanImmuneImmune systemImmunityImmunoglobulin AImmunoglobulin GImmunologic MarkersImmunosuppressionIndividualInfantInfectionInvadedKnowledgeLifeLower Respiratory Tract InfectionLymphocyteMeasurementMeasuresMemoryMemory B-LymphocyteMethodsMycobacterium bovisNoseOutcomePeripheralPharyngeal structurePhasePhysiciansPolychlorinated BiphenylsPopulationPredispositionPrevention strategyPrimary PreventionProcessPublic HealthResearchRespiratory Tract InfectionsSerumShapesSlovakiaT cell responseT memory cellT-LymphocyteT-Lymphocyte SubsetsTh1 CellsThymus GlandTimeTissuesUmbilical Cord BloodVaccinationVaccinesWorkbasecohortearly childhoodearly life exposureemerging adultenvironmental agentexposed human populationfightingfollow-upimmune functionimmune system functionimmunotoxicityin uteroinfancyinnovationpathogenpharmacokinetic modelphysiologically based pharmacokineticspollutantpostnatalprenatalpublic health relevancerespiratoryrespiratory morbidityresponsevaccine efficacyvaccine response
项目摘要
Emerging experimental and observational data suggest that the immune system is susceptible to the influence
of early life exposure to exogenous factors. The immune system begins to develop in utero, and continues to
undergo tightly regulated developmental processes through adolescence and early adulthood. However,
knowledge remains scant regarding how environmental exposures earlier in life modify susceptibility of immune
cells to functional deficits throughout childhood and into adolescence, especially for the human immune system.
Current evidence that environmental exposures perturb human immune function during early life is primarily
limited to infants and young children. Presently, there is almost no information about how these observations
relate to immune function during other critical developmental stages, such as adolescence. The objective of this
project is to define how exposure to a specific category of environmental agents, polychlorinated biphenyls
(PCBs), during key developmental periods, affects immune functions throughout childhood and into
adolescence. The proposed work builds directly on findings that higher infant PCB levels are strongly associated
with lower vaccine responses and greater respiratory morbidity in a birth cohort in eastern Slovakia. The
proposed work will examine adaptive immune function and infection in 400 adolescents from this cohort. Building
on our finding that 6-month PCB levels were inversely associated with anti-BCG specific antibody levels, our
first aim will determine IgG- and IgA-specific anti-BCG and -MMR levels at 45 months, and 7 and 16 years of
age. Leveraging extensive pre- and postnatal exposure data, this will allow the estimation of age-specific PCB-
antibody associations, as well as permit the estimation of vaccine response trajectory over time. This aim is
particularly important since vaccines administered in infancy are intended to create durable responses that
contribute to protection as children age. Our second aim examines PCB exposure in relation to functionality of
distinct B cell and T cell subsets. Higher PCB concentrations are associated with lower antibody levels to
vaccination in several studies. However, the mechanism is not known, and specific lymphocyte sub-types and
functional capacity remain poorly characterized: data from this aim will help fill this knowledge gap. In the third
aim, we will use PCR-based methods to measure the frequency of 22 common respiratory pathogens over a 1-
year period of follow-up, including asymptomatic and symptomatic collections. We will also abstract physician-
diagnosed lower respiratory tract infections (LRTIs) from birth through 16 years. With these measured endpoints,
associations between pre- and postnatal PCB concentrations and symptomatic and asymptomatic respiratory
infection will be assessed. By extending research with this established cohort from birth to adolescence, we will
obtain new information about how this category of common pollutants impacts the human immune system.
新出现的实验和观察数据表明,免疫系统容易受到这种影响
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Todd Jusko其他文献
Todd Jusko的其他文献
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{{ truncateString('Todd Jusko', 18)}}的其他基金
Human Immunotoxicity of Developmental PCB Exposure
发育过程中接触 PCB 的人体免疫毒性
- 批准号:
10112909 - 财政年份:2019
- 资助金额:
$ 55.02万 - 项目类别:
Human Immunotoxicity of Developmental PCB Exposure
发育过程中接触 PCB 的人体免疫毒性
- 批准号:
10348766 - 财政年份:2019
- 资助金额:
$ 55.02万 - 项目类别:
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