{"id":18086,"date":"2019-01-10T14:38:20","date_gmt":"2019-01-10T19:38:20","guid":{"rendered":"https:\/\/www.med.unc.edu\/medicine\/news\/chairs-corner\/podcasts\/the-science-behind-autoimmune-disease-with-meghan-free-phd\/"},"modified":"2025-10-23T13:12:11","modified_gmt":"2025-10-23T17:12:11","slug":"autoimmune-science","status":"publish","type":"episode","link":"https:\/\/www.med.unc.edu\/medicine\/news\/chairs-corner\/podcast\/autoimmune-science\/","title":{"rendered":"The Science Behind Autoimmune Disease &#8211; with Meghan Free, PhD"},"content":{"rendered":"<figure class=\"thumbnail wp-caption alignright\" style=\"width: 310px\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2018\/12\/autoimmune-science-image2.jpeg\" alt=\"Meghan Free, PhD\" width=\"300\" height=\"200\" \/><figcaption class=\"caption wp-caption-text\">Meghan Free, PhD<\/figcaption><\/figure>\n<p>This is Episode One of &#8220;Autoimmune Disease: Pieces of the Picture,&#8221; a new Chair&#8217;s Corner podcast series. Dr. Ron Falk and Dr. Meghan Free begin this series with a conversation about what goes wrong in the cells of the human body during an autoimmune disease process. Dr. Free is a basic science researcher whose work focuses on the autoimmune disease vasculitis; she is an Assistant Professor of Medicine in the UNC Division of Nephrology.<\/p>\n<div class=\"image-section\"><\/div>\n<div class=\"alert alert-grey\">\n<p>&#8220;We know in patients with autoimmune disease that there are breaks in tolerance, that there are certain genes or certain receptors or proteins, that are either misfolded, dysregulated \u2013 there\u2019s something amiss within those pathways that causes your body to mistake yourself for an antigen.<\/p>\n<p>&#8211; Meghan Free, PhD<\/p>\n<\/div>\n<!--[if lt IE 9]><script>document.createElement('audio');<\/script><![endif]-->\n\t<div class=\"wp-playlist wp-audio-playlist wp-playlist-light\">\n\t\t\t<div class=\"wp-playlist-current-item\"><\/div>\n\t\t<audio controls=\"controls\" preload=\"none\" width=\"1118\"\n\t\t\t><\/audio>\n\t<div class=\"wp-playlist-next\"><\/div>\n\t<div class=\"wp-playlist-prev\"><\/div>\n\t<noscript>\n\t<ol>\n\t\t<li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/03\/science-of-autoimmunity.mp3'>Science Behind Autoimmune Disease - with Dr. Meghan Free<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/autoimmunity-common-threads.mp3'>Common Threads in Autoimmune Disease<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/autoimmunity-t-cells.mp3'>T cells, B cells, and self-antigens<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/autoimmunity-tolerance.mp3'>Tolerance, and how T cells & B cells learn their functions<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/autoimmunity-allergy.mp3'>The difference between an autoimmune disease and an allergy<\/a><\/li><li><a class=\"thumbnail img-thumbnail\" href='https:\/\/www.med.unc.edu\/medicine\/wp-content\/uploads\/sites\/945\/2019\/01\/autoimmunity-prodrome.mp3'>What is a prodrome?<\/a><\/li>\t<\/ol>\n\t<\/noscript>\n\t<script type=\"application\/json\" class=\"wp-playlist-script\">{\"type\":\"audio\",\"tracklist\":true,\"tracknumbers\":true,\"images\":true,\"artists\":true,\"tracks\":[{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/03\\\/science-of-autoimmunity.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Science Behind Autoimmune Disease - with Dr. Meghan Free\",\"caption\":\"\",\"description\":\"\\\"Science Behind Autoimmune Disease - with Dr. Meghan Free\\\" from Autoimmune Disease: Pieces of the Picture by UNC Department of Medicine: Dr. Ron Falk. 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Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"2:27\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/autoimmunity-t-cells.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"T cells, B cells, and self-antigens\",\"caption\":\"\",\"description\":\"\\\"autoimmunity-t-cells\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"1:50\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/autoimmunity-tolerance.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"Tolerance, and how T cells & B cells learn their functions\",\"caption\":\"\",\"description\":\"\\\"autoimmunity-tolerance\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"4:42\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/autoimmunity-allergy.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"The difference between an autoimmune disease and an allergy\",\"caption\":\"\",\"description\":\"\\\"autoimmunity-allergy\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"1:38\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}},{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/uploads\\\/sites\\\/945\\\/2019\\\/01\\\/autoimmunity-prodrome.mp3\",\"type\":\"audio\\\/mpeg\",\"title\":\"What is a prodrome?\",\"caption\":\"\",\"description\":\"\\\"autoimmunity-prodrome\\\". Released: 2019.\",\"meta\":{\"year\":\"2019\",\"length_formatted\":\"2:22\"},\"image\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64},\"thumb\":{\"src\":\"https:\\\/\\\/www.med.unc.edu\\\/medicine\\\/wp-content\\\/plugins\\\/media-library-assistant\\\/images\\\/crystal\\\/audio.png\",\"width\":48,\"height\":64}}]}<\/script>\n<\/div>\n\t\n<p><strong>Ron Falk, MD:<\/strong> Hello, and welcome to the Chair\u2019s Corner from the Department of Medicine at the University of North Carolina.<\/p>\n<p>We begin today a series that will concentrate on autoimmune disease. What causes it, what is it, and how can patients find experts who can help them and figure out the best treatments that will make them feel better? We\u2019ll be joined in this series by several experts to help us explore these and other topics, and take a close look at some specific types of autoimmune diseases and treatments.<\/p>\n<p>Today, we\u2019ll look at current research in autoimmunity and we welcome Dr. Meghan Free who is an Assistant Professor at the University of North Carolina in the Division of Nephrology, and she specializes in autoimmune disease and the basic science that underpins what causes how people react to themselves. Her studies focus on very important cells that are players in autoimmune disease \u2013 T cells, and B cells, and the role they play in various disorders.<\/p>\n<p>Welcome, Meghan Free.<\/p>\n<p><b>Meghan Free, PhD:<\/b> Thank you.<\/p>\n<h3><span class=\"blue\">Common Threads in Autoimmune Disease<\/span><\/h3>\n<p><b>Falk:<\/b> Meghan, your research focuses really on translational science of a particular form of autoimmune disease, and that is inflammation of blood vessels called vasculitis. There are so many different autoimmune diseases. Help us understand some common threads that you and others have observed that link these autoimmune diseases together.<\/p>\n<p><b>Free:<\/b> I think that\u2019s one question that often times comes to mind with patients with autoimmune diseases: What caused my disease? Was there anything that I could have done to prevent that? We know through research that there isn\u2019t one gene that causes autoimmune disease, but through various research studies we know that there are certain genes that have come up in numerous autoimmune diseases. One of those genes is called HLA, or human leukocyte antigen. That is a gene that codes for a protein receptor that basically tells your immune system what\u2019s in your immune system: is it bacteria, is it a virus, is it yourself? And there are certain HLA\u2019s that predispose people to Type I diabetes or vasculitis or rheumatoid arthritis. But that gene alone doesn\u2019t cause disease. We know that there are different environmental factors that can also predispose people and what we\u2019re starting to understand is it\u2019s the combination of all these events that often lead to autoimmune disease.<\/p>\n<p><b>Falk:<\/b> So it\u2019s the combination of your genes and the environment that interact and result in a break in what\u2019s called tolerance. We\u2019ll talk about tolerance in a moment. It\u2019s now a reaction to oneself. You\u2019re not supposed to have your immune system react to you, you\u2019re supposed to have your immune system react to bacteria, viruses, or foreign substances. Now you\u2019ve broken through normal, regulatory pathways and you\u2019re reacting to some protein in your body, yourself. What you\u2019re saying is that\u2019s a consequence of some alteration \u2013 a genetic background that now has come in contact with an environmental stimulus.<\/p>\n<h3><span class=\"blue\">T cells, B cells, and self-antigens<\/span><\/h3>\n<p><strong>Falk: <\/strong>What is a T cell and what is a B cell?<\/p>\n<p><strong>Free:<\/strong> Most people know that we all have white blood cells that float around in our blood. White blood cells is a heterogenous population of immune cells. There are two portions of the immune system that can be categorized. You have your innate immune system \u2013 which are your first responders, things like neutrophils and monocytes. There is also the adaptive immune system. Some people think that these cells are a little smarter, because they\u2019ve been trained more, they have specific targets, and those are B cells and T cells. B cells are the ones that make our antibodies, which, in patients with autoimmune disease, they have antibodies to self, that\u2019s what is tested for in the clinical labs. T cells are also specific for self in patients with autoimmune disease.<\/p>\n<p><strong>Falk:<\/strong> What is a self-antigen?<\/p>\n<p><strong>Free:<\/strong> A self-antigen is any protein that is supposed to be in our body. So, it can be a liver protein, it can be a bone protein, a kidney protein: anything that, basically is internal to our own person.<\/p>\n<p><strong>Falk: <\/strong>Some patients make antibodies-instead of to a bacteria or to a virus, make antibodies to that self. Antigen to that self-protein.<\/p>\n<p><strong>Free: <\/strong>Correct. If the self-antigen is known in the disease, that is known often times what is tested for in the clinical labs. Patients with vasculitis are tested to see if they have anti-neutrophil cytoplasmic autoantibody.<\/p>\n<p><strong>Falk: <\/strong>Or in rheumatoid arthritis, they\u2019re tested for antibodies to citrullinated proteins. There are lots of tests in the clinical lab that are looking for antibodies to a self-antigen.<\/p>\n<h3><span class=\"blue\">Tolerance, and how T cells &amp; B cells learn their functions<\/span><\/h3>\n<p><strong>Falk:<\/strong> So what is tolerance? What is a break in tolerance?<\/p>\n<p><strong>Free:<\/strong> The number one function of the immune system, in my view, is supposed to be able to discriminate self from non-self. What that means, like you\u2019ve alluded to, is that your immune system is supposed to be very good at protecting your body from external antigens, be it bacteria, viruses, other foreign pathogens, while preserving the self. You don\u2019t want to harm yourself. So tolerance is the mechanism by which your immune system discriminates bacteria from your lungs, from your kidneys, and so on.<\/p>\n<p>That is often taught very early in life \u2013 the T cell is taught in the thymus, the B cell is taught in the bone marrow. We know in patients with autoimmune disease that there are breaks in tolerance, that there are certain genes or certain receptors or proteins, that are either misfolded, dysregulated \u2013 there\u2019s something amiss within those pathways that causes your body to mistake yourself for an antigen. That can also happen through something called molecular mimicry, wherein your body is trained to respond to bacteria or virus and something has happened to yourself, that either the protein becomes misfolded or misexpressed, and it now looks like that bacterial protein or looks like a viral protein. That\u2019s why a lot of times we see patients present initially with a respiratory illness or the flu that then can lead to autoimmune disease.<\/p>\n<p><strong>Falk:<\/strong> You used an interesting word choice. You said that T cells and B lymphocytes \u2013 you used the word that these cells were \u201ctaught.\u201d What does that mean? Help us understand that.<\/p>\n<p><strong>Free:<\/strong> I think of it in a rudimentary way in that T cells and B cells essentially \u2013 they\u2019re born, they go to school, and they learn what they\u2019re supposed to learn. A more scientific way to think about it is that, in your thymus, for example, which is this organ right above your heart, your T cells go there and there are cells that are called medullary thymic epithelial cells. They know all the proteins in your body and they present little pieces of all these different proteins to your T cells. If your T cell reacts too strongly to your self-protein, that cell will become deleted.<\/p>\n<p><strong>Falk:<\/strong> This is during development, in utero.<\/p>\n<p><strong>Free:<\/strong> Yes. It\u2019s educated by deletion, but also if those cells react too strongly to self, they can be taught to become a regulatory T cell, which provides an anti-inflammatory response during times of inflammation.<\/p>\n<p><strong>Falk: <\/strong>Your work and others have shown that there are, in humans with various forms of autoimmune disease \u2013 in your work, vasculitis \u2013 there are cells that are no longer listening to lessons that they may have learned and are proliferating and are not being able to be regulated by other forms of T cells.<\/p>\n<p><strong>Free: <\/strong>In vasculitis in particular, there are two anomalies that we have found with T cells. One of those, as we\u2019ve alluded to, is the regulatory T cell type, or the anti-inflammatory T cell. These are cells that are supposed to keep your immune system under check and not allow too much inflammation to go on. We know in patients with vasculitis that those cells don\u2019t function as they\u2019re supposed to.<\/p>\n<p><strong>Falk:<\/strong> That\u2019s true of other autoimmune disease.<\/p>\n<p><strong>Free:<\/strong> Right, they\u2019ve seen it in lupus, they\u2019ve seen it in a number of other autoimmune diseases. That goes back to the common threads of autoimmune disease. We don\u2019t know exactly why those cells don\u2019t function as they\u2019re supposed to. We have hints and clues that the genetics of those cells may be amiss. The flip side of that coin is that there are effector T cells that are supposed to be inflammatory and do their job when appropriate. There is a population of those cells in patients with vasculitis that have expanded beyond their normal means and are exceedingly pro-inflammatory and can\u2019t be kept in check by those nonfunctioning regulatory T cells. So it\u2019s a perfectly bad storm of two different populations not functioning appropriately.<\/p>\n<h3><span class=\"blue\">The difference between an autoimmune disease and an allergy<\/span><\/h3>\n<p><b>Falk:<\/b> What\u2019s the difference between an autoimmune disease and an allergy?<\/p>\n<p><b>Free:<\/b> Both instances can be seen as states of a hyper immune system. That the white blood cells are responding to something inappropriately, they are overly inflammatory towards something. The biggest difference is that allergy is a reaction to something external: a peanut protein, or a pollen \u2013 something that is external to your body. While autoimmune disease, you are having an inflammatory response to something that is an internal protein.<\/p>\n<p><b>Falk:<\/b> That\u2019s a beautiful differentiation. Just in summary, then, there are genetic reasons for people to have an autoimmune disease, there are environmental triggers that may cause the disease, they can cause a flare. There are T cells and B lymphocytes that have been taught during development to be under control; there are T cells that are there to regulate other T cells, and B cells there to regulate other B cells. This is a beautiful balance between regulatory components that are supposed to keep the immune system in check, and somehow, in the process of an autoimmune disease, are no longer functioning like they\u2019re supposed to. That\u2019s really this concept of breaking tolerance to your own protein.<\/p>\n<h3><span class=\"blue\">What is a prodrome?<\/span><\/h3>\n<p><b>Falk:<\/b> Most patients with an autoimmune disease don\u2019t come in with a sign on their forehead that says \u201cI have rheumatoid arthritis.\u201d They start with vague symptoms; they come in with not necessarily specific findings, and that is known as a \u201cprodrome.\u201d How would you explain a prodrome from a scientific perspective?<\/p>\n<p><b>Free:<\/b> The best way that I think about it is there are so many pieces to an autoimmune disease that go wrong, essentially. Something goes wrong with T cells, B cells, neutrophils in the case of vasculitis, and often times all those pieces don\u2019t go wrong at the same time. It\u2019s an additive effect. Maybe when you see a patient the first time, only the regulatory T cell component has gone bad. That then leads to dysregulation of B cells and dysregulation of neutrophils. It\u2019s only over the course of time that more and more symptoms occur as these dysregulations in the immune system are also occurring.<\/p>\n<p><b>Falk:<\/b> The body actually can self-heal in some of those circumstances. So once that process has begun, there is the possibility for the immune system to gain control again and thwart an autoimmune disease from occurring. That process is happening on a regular basis in most of us as we are exposed to different factors in the environment. So a prodrome may be this possibility of the immune system becoming out of check and producing inflammatory signals.<\/p>\n<p><b>Free:<\/b> The other issue there, and I think you see a lot in vasculitis, is that the same function that our system is playing in autoimmune disease \u2013 those same immune cells are also responsible for a response to a respiratory infection, and sometimes it\u2019s hard to decipher if a person\u2019s respiratory symptoms are due to a mere infection, or is this early vasculitis?<\/p>\n<p><b>Falk:<\/b> Meghan, thank you so much for this introduction to the science behind autoimmune disease that begins this series for patients on autoimmune disease in general. Thanks so much.<\/p>\n<p><b>Free:<\/b> Thanks for having me.<\/p>\n<p class=\"MsoNormal\"><span style=\"line-height: 1.43em\">*<\/span><\/p>\n<p>&nbsp;<\/p>\n<div class=\"alert alert-blue width:100% \">\n<p><strong>Visit these sites for information referenced in the podcast conversation.<\/strong><\/p>\n<ul>\n<li><a class=\"external-link\" title=\"\" href=\"http:\/\/unckidneycenter.org\/about\/directory\/meghan-free\" target=\"_blank\" rel=\"noopener\">View Dr. Free&#8217;s profile<\/a><\/li>\n<li><a class=\"external-link\" title=\"\" href=\"http:\/\/unckidneycenter.org\/research\/unc-kidney-center-labs\" target=\"_blank\" rel=\"noopener\">Read more about the UNC Kidney Center labs<\/a><\/li>\n<\/ul>\n<\/div>\n<p>\/\/<\/p>\n","protected":false},"excerpt":{"rendered":"<p><!-- description --> <\/p>\n<p class='lead'>This is Episode One of &#8220;Autoimmune Disease: Pieces of the Picture,&#8221; a new Chair&#8217;s Corner podcast series. Dr. Ron Falk and Dr. Meghan Free begin this series with a conversation about what goes wrong in the cells of the human body during an autoimmune disease process. Dr. Free is a basic science researcher whose work focuses on the autoimmune disease vasculitis; she is an Assistant Professor of Medicine in the UNC Division of Nephrology.<\/p>\n","protected":false},"featured_media":4111,"menu_order":0,"template":"","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","_links_to":"","_links_to_target":""},"podcast-category":[634,692,639],"class_list":["post-18086","episode","type-episode","status-publish","has-post-thumbnail","hentry","podcast-category-podcast-autoimmune-disease-series","podcast-category-kidney-autoimmune-podcasts","podcast-category-podcast","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>The Science Behind Autoimmune Disease - with Meghan Free, PhD | Department of Medicine<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/medicine\/news\/chairs-corner\/podcast\/autoimmune-science\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The Science Behind Autoimmune Disease - with Meghan Free, PhD | Department of Medicine\" \/>\n<meta property=\"og:description\" content=\"This is Episode One of &quot;Autoimmune Disease: Pieces of the Picture,&quot; a new Chair&#039;s Corner podcast series. Dr. Ron Falk and Dr. Meghan Free begin this series with a conversation about what goes wrong in the cells of the human body during an autoimmune disease process. 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