Fig. 2.

Schematic representation of a simplified narrative scenario model of integrating DAMP-promoted innate and adaptive immune responses (in terms of uncontrolled, dysregulated responses) in both the exposome and the AOP concept. Any infectious or sterile stress/injury (i.e., environmental stressors) are mediated (1) directly by exogenous DAMPs, or (2) indirectly by stress/injury-induced endogenous DAMPs, which interact with PRMs on or in cells of the innate immune system (in the case of infectious injury, together with MAMPs). Following recognition of DAMPs (plus MAMPs, respectively), PRM-bearing cells get activated to trigger innate immune inflammatory responses or, in the presence of nonself or altered-self antigens, to promote antigen-specific adaptive immune responses. DAMP-triggered innate immune effector responses, when uncontrolled and dysregulated, result in pathologies such as acute/chronic (auto)inflammatory diseases, DAMP-shaped, antigen-specific adaptive immune responses, when uncontrolled and dysregulated, can lead to immune pathologies such as autoimmune or allergic diseases. Totality: all environmental chemicals acting as stressors (“stressogens”) on a particular receptor or biological pathway in a functional assay [according to Smith et al. (2015)]. AO adverse outcome, AOP adverse outcome pathway, APCs antigen-presenting cells, CTLs cytotoxic T lymphocytes, DAMPs damage-associated molecular patterns, DCs dendritic cells, KE key event, MAMPs microbe-associated molecular patterns, MIE molecular initiating event, MØ macrophages, PMNs polymorphonuclear neutrophils, PRMs pattern recognition molecules.

Sources: Smith et al. (2015), Escher et al. (2017), Leist et al. (2017) and Vinken et al. (2017)