1.2 Combined exposure to nanomaterials and other agents Studies on mixtures usually focus on a group of related substances ( Holmstrup et al., 2010 Orr et al., 2020 Fair et al., 2021 Tooker et al., 2021), while the environment provides co-exposure to many substance pollutant classes at the same time ( Soares et al., 2022). However, much less is known regarding the more realistic circumstance of exposure to a combination of contaminants, in which we expect the combined exposure to have effects substantially different from the sum of individual pollutant’s effects. Abundant cross-sectional and some longitudinal information is available on the immune effects caused by a number of individual pollutants, based mainly on experimental in vitro and in vivo models, in which animals or cells are exposed to the polluting agents ( Joubert et al., 2020). Notably, the effect on immunity of the individual history of exposure (immunobiography) is a leading concept in the efforts of predicting possible inadequacy in immune reactivity to future challenges ( Franceschi et al., 2017).

The recent concept of the exposome, the measure of all exposures experienced by individuals through their lifetime ( Rappaport, 2011), fully applies to the interaction between pollutants and immunity, since the immune system has a memory (in vertebrates both innate and adaptive immune memory develop), which biases immune reactions to new challenges. Alterations in immune responses caused by air and water pollutants can hamper human and environmental health, both in terms of inadequate reactivity (immunosuppression, increased susceptibility to infections and diseases) and in terms of excessive response (pathological inflammation, allergies, autoimmunity) (e.g., Reinmuth-Selzle et al., 2017).

Pollutants of different origins and nature can have an impact on immunity (e.g., Glencross et al., 2020). This encompasses a homeostatic role of patrolling and controlling the body tissues and organs, and a defensive role to face an external environment filled with microorganisms, particles and molecules of different nature, block the entry of potential threats and adapt to changes in the environment ( Murphy et al., 2022). The immune system of all living organisms has developed in order to preserve the integrity and functionality of the organism in the face of external invaders such as viruses, bacteria or pollutants.

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