Our immune system is an evolutionary masterpiece. Every day it protects us from the thousands of different viruses, bacteria and other microbes that attempt to invade our bodies. Without a functioning immune system, we would not survive. One of the immune system’s marvels is its ability to identify pathogens and differentiate them from the body’s own cells. The microbes that threaten our health do not wear a uniform – they all have different appearances. Many have also developed similarities to human cells, as a form of camouflage. So how does the immune system keep track of what to attack and what to protect? Why doesn’t the immune system attack our bodies more frequently? Researchers long believed they knew the answer to these questions: that immune cells mature through a process called central immune tolerance (see image). However, our immune system turned out to be more complex than they believed. Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi have been awarded the 2025 Nobel Prize in Physiology or Medicine for their discoveries concerning peripheral immune tolerance.