Nanotechnology has a role of growing importance in development of novel industrial and medical applications. Silver nanoparticles (nanoAg) are some of the most researched types of nanomaterials for potential use in medicine due to their significant antimicrobial properties. Their use in medical applications is limited due to their potential toxicity to human cells and tissue. Although the toxicity of silver nanoparticles is well known, there is a distinct lack of information on combined biological effects of nanoAg and other types of materials or nanomaterials. In order to develop safe nanoAg-enabled products, it is paramount to determine if interactions of nanoAg with other materials could pose additional health hazard compared to nanoAg alone. Polystyrene is a biologically inert material with widespread use in industrial and medical applications, and polystyrene nanoparticles (nanoPS) were used to assess the effects of nanometrial mixtures on model immune cell lines, Jurkat and THP-1. Nanoparticles were characterized using atomic force microscopy, as well as dynamic and electrophoretic light scattering techniques. The effects of nanoAg and nanoPS on cell survival, induction of apoptosis, oxidative stress parameters, DNA damage, immune response and changes in cell mechanical properties were analyzed. Nanoparticle uptake was visualized with confocal microscope and quantified using flow cytometry. Results have shown that nanoAg and nanoPS do not interact in water suspensions or in cell culture media, and that nanoAg/nanoPS mixtures had an augmented, detrimental impact on Jurkat and THP-1 cells compared to individual nanoparticle types. These results present an important contribution for understanding impact of nanomaterials on human health, and for development of novel and safe applications of nanotechnology in medicine.