Understanding how the adaptive immune system works is of monumental scientific importance. It is remarkable, then, that despite the sophisticated modeling technologies available today, there are no human-relevant in vitro platforms mimicking the adaptive immune system in a physiological environment. Rather, state-of-the art models involve animals or in vitro systems that capture isolated elements of the immune response (e.g., activation by tumor cells). The challenge in developing immunized in vitro models is that adaptive immune cells cannot be co-cultured with non-autologous tissue, as they become activated and destroy it. We propose a groundbreaking paradigm that tackles this challenge, while advancing the greater ideal of personalized medicine. The approach builds on my expertise with the Organ-on-a-Chip: a microfluidic platform comprising human tissue that closely mimics organ functionality. I will create a novel platform integrating six vascularized Organ-Chips, all originating from iPSCs derived from a specific individual, which have been differentiated into specific tissue types. This fully isogenic platform will accommodate the donor’s adaptive immune cells: Because they originate from the same source, they will not be activated. Indeed, preliminary results support this hypothesis. The resultant system, Immune-Me-on-a-Chip, will constitute a first-of-its kind personalized-immunized-human platform for studying human physiology and biological threats. I will use the system to explore fundamental biological questions: (i) understanding how different isogenic and non-isogenic tissues interact with the immune system, e.g., in organ transplantation; and (ii) identifying how pathogens (antibiotic-resistant E. coli), as well as antibiotic treatment, affect human physiology and the immune response. This research will revolutionize the study of human physiology in general and of immunity in particular, and will open the door to a new era of personalized medicine.