The 3rd edition of the computational methods for the immune system function workshop has been held in San Diego, CA, in conjunction with the IEEE International Conference on Bioinformatics and Biomedicine (BIBM 2019) from November 18 to 21, 2019. The workshop has continued its growing tendency, with a total of 18 accepted papers that have been presented in a full day workshop. Among these, the best 10 papers have been selected and extended for presentation in this special issue. The covered topics range from computer-aided identification of T cell epitopes to the prediction of heart rate variability to prevent brain injuries, from In Silico modeling of Tuberculosis and generation of digital patients to machine learning applied to predict type-2 diabetes risk.