Immune responses between individuals are highly variable. Some of this variability can be attributed to differences in age, sex, genetics and environment. However environmental effects on immune responses can be more challenging to study due to their ephemeral nature. By studying diverse immune responses of 1,000 healthy donors we recently identified significant effects of cigarette smoking on inflammatory responses to bacterial stimulation, as well as induced T cell responses. Interestingly the effects on inflammatory responses were lost soon after smoking cessataion, while the effects on T cells were maintained for many years through specific epigenetic modifications. We are now extending this integrated immune profiling approach to other diverse immune phenotypes as well as a longitudinal assessment of the same donors, and extension to other ages, populations and patient cohorts. We believe that this wil improve our understanding of the factors that shape differential immunity and help develop new strategies for the preventation and management of disease.