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OECD Series on Adverse Outcome Pathways

An Adverse Outcome Pathway (AOP) describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure to a stressor and leads to an adverse health effect in humans or wildlife. AOPs are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. These AOPs are available in the AOP-Wiki, an interactive and virtual encyclopaedia for AOP development. Following their development and review, the endorsed AOPs are published in the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude regular updates or new contributions to a given AOP. While the AOP-Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP.

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Adverse Outcome Pathway on impaired interleukin-1 receptor type I (IL-1R1) signaling leading to impaired T-cell dependent antibody response

Stressors that exhibit immunosuppression might act by different mechanisms, i.e. alter the number of cells involved in the immune response, the ability of the cells to produce cytokines, chemokines, antibodies or growth factors, the composition of the subpopulations of cells present at the site of the response, or the function of the cells. This Adverse Outcome Pathway (AOP) describes how impairment of the signaling receptor IL-1R1 in T cells can lead to impaired T cell activation and antibody production, leading to increased susceptibility to infection. The AOP focuses on the blocking of binding of IL-1 to IL-1R1, leading to the Inhibition of Nuclear factor kappa B (NF-kB). This AOP is referred to as AOP 277 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

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