In vitro test methods to evaluate the effects of chemicals on innate and adaptive immune responses

The immune system comprises innate and adaptive immunity. Both arms of the immune response function differently and are represented by different populations of cells. A variety of cells are involved in these two type of immune response. Innate immune response includes neutrophils and other types of granulocytes, macrophages, natural killer (NK) cells, innate lymphoid cells, and mast cells. Adaptive immune responses involve T cells and B cells. Then, macrophages and dendritic cells (DCs), which act as antigen-presenting cells (APCs), link the innate and adaptive immune responses because they can present antigens to T cells in the context of MHC class II molecules and stimulate their proliferation and effector functions after being stimulated via pathogen recognition receptors. Therefore, to detect the immunotoxicity of chemicals, in vitro test methods must adequately assess their immunotoxic effects on both the innate and adaptive immune responses. On the other hand, considering the complexity of immune response, it would seem impossible for a limited number of in vitro test methods to detect all of the immunotoxicants that could affect the immune system. Except for chemicals that either naturally target or are synthesized to target specific receptors or intracellular signaling molecules, however, it is conceivable that chemicals induce immune dysfunction by a limited number of cellular responses to deforming or damaging cellular macromolecules, such as membrane lipids, proteins, and/or DNA, so called cellular stress responses. In this section, we summarize the mechanism of chemicals to induce immunotoxicity and introduce several in vitro methods to detect immunotoxicants.