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Speaker 1: Welcome to BrainStuff, a production of iHeart Podcasts. Hey BrainStuff, Lauren Vogelbaum here. In the human body, some of our organs are in the spotlight. We're pretty attuned to what our heart and lungs and skin are doing at any given time because their status is easily observable. And when something goes wonky with them, it's fairly immediately obvious. Other organs are more the working quietly in the background types. They're no less important. They're all working together to keep you alive and kicking. But when they're working well, they're not attracting any attention. The thymus is definitely one of those. The thymus is a small gland that sits in the center of your upper chest, right above your heart and just behind your sternum. It's an organ of your immune system, and specifically of your lymphatic system. As far as fluids in our body go … Blood gets all the glory. It's the spotlight fluid. But alongside your blood circulatory system, you have a parallel network of vessels and tissues for moving around lymph. Okay, what the stuff is lymph? The cells in your body are generally not packed in tightly. There's fluid surrounding them called interstitial fluid. This is where your blood cells deliver oxygen and nutrients to your tissues, and where those tissues deposit their waste materials. Your blood picks up most of that, but some of it, and some of the interstitial fluid it's floating in, can build up, and that's where your lymphatic system kicks in. Lymph capillaries will pull in the excess fluid and stuff and transport it through a series of hundreds of lymph nodes throughout your body to, A, screen and filter it for anything unuseful, and B, return anything useful to your bloodstream, or right before your blood gets pumped back through your heart. Once this fluid and stuff is in your lymphatic system, it's called lymph, named after Lympha, the ancient Roman goddess of fresh water. The lymphatic system is considered part of your immune system because a big category of the unuseful stuff it screens for is invaders like microbes that could make you sick. The main type of bodily cells hanging out in the lymphatic system are lymphocytes, which are types of white blood cells. These cells can identify and either destroy invaders or mark them for destruction. We humans have a few types of lymphocytes, but the ones we're concerned with today are called T-cells because they develop or mature or receive their professional training in the thymus. T-cells are really important to your adaptive immune system, that is, the branch of your immune system that learns as it fights invaders. T-cells can specialize to serve in a number of different functions. Some are specially designed to kill particular cancer cells or bodily cells that are infected with a virus or bacteria. Some will remember a prior invader and can signal other white blood cells to help coordinate future attacks against it. And some can even help prevent other white blood cells from attacking your body's healthy cells by accident. The thymus regulates all of this by producing and releasing specific hormones. But it does most of this job during your childhood. Like, by the time you hit puberty, the bulk of its work is done. The T-cells it's created will last you for the rest of your life. But your thymus itself will slowly decrease in size and function, its active cells being replaced with fatty tissue over the years. Today, let's look into this odd and quiet but important organ and how it works, plus what can go wrong when it's not working as expected. Humans noted the existence of the thymus in antiquity. It sits right over your heart. It's grayish pink in color and and consists of two sort of knobby main lobes, each composed of many smaller lobes or lobules, all protected by a thin covering. Each lobule is made up of a thicker outer layer and a less dense inner layer of cells. Your circulatory system brings blood to and from the thymus, and lymphatic vessels carry lymph out of it. But we essentially had no idea what the thymus does until the 1960s. We knew it had something to do with the lymphatic system because people had observed lymphocytes in it and saw the lymph vessels flow out of it. But it was really mysterious because it didn't seem to display any changes during an immune system response to illness. And taking it out of an adult didn't really seem to affect the function of their immune system, which we now know makes sense. That's because the human thymus does a lot of its job before we're even born. We're still learning the nitty-gritty and how it can vary from person to person. Until pretty recently, a lot of studies about the thymus have been in mice. But basically, the thymus is the training and testing ground where T-cells must develop and then prove that they're capable of doing their job before they go to work out in your lymphatic system. T cells begin life in your bone marrow, along with a different kind of lymphocyte called B cells. B cells stay and develop in the bone marrow, but the proto-T cells, called thymocytes, travel to the thymus. There, they undergo a series of developments and tests. First, they have to prove that they can check the ID of a cell or other molecule that might be a threat. And then they have to prove that they won't react too strongly to anything that presents an ID, marking it as coming from inside your own body. After all, you want your immune system to eliminate dangerous invaders, but not your own healthy cells. You want them to be competent, but also self-tolerant. The vast majority of thymocytes do not pass these tests and are killed off during the process, like over 95% of them. Yet your body produces enough of them, and your thymus screens enough of them, that you build up a more or less lifetime supply of T-cells early on. These will hang out in your lymphatic system, awaiting to ID a threat. The thymus also produces T-cells that specialize to prevent
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your other immune cells from attacking healthy tissue, and T-cells that act more like first line of defense innate immune cells. But again, most of this happens when you're really young. As early as one year of age, your body might start going through what's known as thymic involution, which is a fancy way of saying it shrinks. We are born with enough T-cells to last us a lifetime if we have to. The thymus stays active until puberty kicks in, and then begins shrinking and being replaced with fatty tissue at a rate of around 3% a year until we reach middle age, around 40 years or so, at which point that rate slows to more like 1% a year. One thing we still don't know is why. It seems like it would be useful for our bodies to continue producing T-cells throughout our lives. And a lot of the medical issues associated with aging, like increased risk of serious illness from infectious diseases, increased occurrence of cancer, and increased occurrence of autoimmune diseases like arthritis, they're all linked to our immune systems not functioning as well as we age. Yet almost all animals that have a thymus go through thymic involution. Some researchers have proposed that the biological cost of keeping your thymus running is simply too expensive. It is true that activity really drops off when our reproductive hormones kick in during puberty. Evolutionarily speaking, maybe the body focuses its energy on your immune system keeping you alive until you hit a reproductive age, and then puts that energy into making you capable of reproducing. Other researchers have suggested that turning down the thymus' capacity after childhood may have some protective effect that we don't understand yet. We really don't know. A lot of science is being done to better comprehend what the thymus does for us later in life, including whether boosting its capacity could help prevent some of those immune system-related health issues that we see as we age. What we do know is that it's not good when your thymus works strangely or doesn't work at all. There's a disorder some babies are born with called DeGeorge syndrome, where the thymus is underdeveloped or missing altogether. This severely decreases the capacity of the infant's immune system and may require a thymus transplant. In adults, unexpected changes to the thymus have been linked to a few immune-related conditions. Those changes can include hyperactivity in the thymus, and also cysts, tumors, and cancers of the thymus. Some of the conditions linked to these changes include a disorder called hypogammaglobulinemia, which just means that your body doesn't produce enough antibodies to fight off germs, meaning you'll get sick a lot. There's also pure red cell aplasia, in which for some reason your body doesn't produce enough red blood cells, often because your immune system is attacking your bone marrow, meaning you'll experience anemia. And there's one we talked about recently on the show, myasthenia gravis, in which your immune system attacks the point of communication between your nerves and your muscles, leading to muscle weakness that starts around the eyes and can proceed through the face, limbs, and body. If you or a loved one experiences any of these symptoms, talk to a healthcare professional. They'll be able to help you rule out other issues and reach a diagnosis, and figure out a treatment plan that works for you. Those changes in the thymus, like growths, like tumors, aren't always noticeable unto themselves. They're sometimes only found during an x-ray or CT scan for something else entirely. But because of how the thymus is situated in the upper center of the chest, thymus tumors can press against a bunch of stuff that doesn't like being pressed. This can result in chest pain, shortness of breath, hoarseness of voice, coughing, trouble swallowing, and the most immediately seriously, a blocking of blood coming down from the head, which can cause swelling in the face and neck, and headaches or feeling lightheaded. Definitely talk to a healthcare professional if you see or experience any of those symptoms. Again, they'll be able to help you figure out what you're dealing with and prevent any danger from blocked veins, which can become deadly. Different types of thymus tumors have different options for treatment. Not all of them will spread, but you want to get that diagnosis to put you on the right path. Even if we don't understand everything about organs like the thymus that seem to just putter along in the background, we're learning more all the time. What we've assessed just since the 1960s has changed our understanding of T-cells and thus informed how we think about everything from vaccines to cancer therapies to the human microbiome. Here's hoping that future research will help us unlock even more about human health. Today's episode was written by me, Lauren Vogelbaum. The Brain Stuff is a production of iHeart Podcasts and is produced by Tyler Klang. For more shows from iHeart Podcasts, visit the iHeart Radio app, Apple Podcasts, or wherever you listen to your favorite shows.