This is a review of immunotoxicological effects of arsenic, cadmium, mercury and lead with a view to the balance of interactions between metallic toxicants and the essential metals copper, selenium and zinc. Working hypothesis at the outset was that, singly and combined, metals predictably impact the human immune system and that resulting risk could be quantitated. A tentative objective was to prototype an adverse outcome pathway for one or more metals centered upon a key event in regulatory T-cell differentiation. Such an adverse outcome would be over- or underperformance, i.e. immunosuppression or autoimmunity.