Immunology expert Allan Kirk, MD, PhD, discusses what compels the immune system to respond to danger, and how our immune systems change over time. Dr. Kirk is a transplant surgeon and the chair of the Department of Surgery. He is also professor in the Departments of Immunology and Pediatrics at Duke. Transcript: LK Welcome to HeadScratchers, a mini-cast from the Duke University School of Medicine. We ask Duke experts to help us understand the questions in science that have us scratching our heads. Today, we're speaking with Dr. Allan Kirk, a transplant surgeon and the chair of the Department of Surgery here at Duke. Dr. Kirk, what causes a person's immune system to weaken? AK The immune system is best envisioned as a way of sensing your environment, just like your nerve system. As it senses what's around you, it's continuously making decisions about what's important to respond to. And, if it's gonna respond, whether it's gonna be aggressive and try to attack it, or whether it's going to be passive and allow it. Each time it makes one of those decisions, it changes a little bit and becomes better. It develops memory. So nobody's immune system is the same. And in fact, a person's immune system is not the same day to day. Even identical twins have completely different immune systems by the time they're just a few weeks old, based on what they've been exposed to. But in general, time and exposure eventually leads to immune exhaustion. So the natural history of an immune cell as it responds, is to eventually become exhausted, meaning it can't respond anymore, so that you're not continuously having an immune response to something. Fortunately, you can make more of your immune system. But as you grow older, the things that help you make your immune system, like your thymus and your bone marrow, become less good at it, and you slowly run out of immune cells. The most common cause for your immune system weakening is just, then, living a long time -- which is a good thing. LK What types of factors go into the immune system’s decision to respond or not? AK Really, the immune system works hard to stay off unless something dangerous impels it to go on. When you're considering a context, you're looking for something called danger. That's actually an immunological term. And there are molecules that are associated with danger, with inflammation, with pain. And those things drive an immune system to assume that it's a dangerous context and make an aggressive immune response. Whereas, if those signals are not there, the assumption is that things are fine and there's no need to have an immune response. So something that's harming you, you should respond to, and something that's not, you should accept. In fact, if we would act more like our immune system, we might get along better. LK Thanks for listening. This podcast was produced by the Duke University School of Medicine, music by Blue Dot Sessions. Visit us online at headscratcherspodcast.duke.edu. You can also find us on all your favorite podcast players. Don't forget to hit the subscribe button -- and if you like us, leave us a review. Medical Disclaimer & Terms of use at https://bit.ly/2LrjWdh