Team Igas Resident Evil 1.5 Download
Mariu Carlton
Vicky Whittemore: Okay. So, good morning, everyone. It's my pleasure to welcome you to the second in our series of webinars as part of the ME/CFS Research Roadmap Webinar Series. Today we're going to be focused on the immune system. And I'll just give some brief introductory comments. I should introduce myself. I'm Vicky Whittemore. I'm a program director at NINDS, where I oversee grants on ME/CFS, as well as work together with my colleagues at NIAID and across NIH, and Dr. Koroshetz, director of NINDS, to coordinate the Trans-NIH ME/CFS Working Group.
So, I'd just like to recognize all of the members of our Research Roadmap Working Group of Council. All of these individuals have been busy organizing each of the eight. We now have added one, so there'll be eight webinars in this series. And my special thanks go out to the chairs of each of the working groups, as well as all of the members of each of the working groups. And today, special thanks to Derya Unutmaz from the Jackson Laboratories and all of the members of the Immune System Webinar Planning Group who have worked to organize our webinar today. And I also would like to thank the NIH team working with me at NINDS that's really been sort of here in the background and helping to support this whole effort. My deepest appreciation to all of you for your extra work and hard work to make this happen.
So, I would just like to point you to the website where you can go to get more information about the webinar series as well as click on the link that links you over to the website where you can register for each of these upcoming webinars between -- there's one upcoming next week, two in November, one in December, and two in January. So, just some guidance for webinar participants today. So, the goal of these webinars is to identify research priorities for research in each of these topic areas.
So, as I said, today we're focused on immune system involvement in ME/CFS. So, we've asked the speakers to address what do we know, what don't we know, and what do we need to know to really accelerate the research to move forward toward clinical trials. So, this is not your typical research conference or research webinar. So, the focus really is getting into looking at those questions and research priorities for research going forward. So, the questions for each speaker will be addressed after each presentation. So, put your questions in the Q&A. It's likely we will not be able to address all of the questions we receive. We've asked the speakers to answer questions in the Q&A that we might not be able to get to. And we're not able to answer questions related to your individual health issues. So, please refrain from asking those types of questions. This is not a patient conference. And so, we really cannot answer those kinds of questions in this forum. So, your questions should focus on clarifying things that the speaker said or focus on research priorities in this area of ME/CFS research.
So, we will have an opportunity for additional feedback. You can send an email to this mecfsresea...@ninds.nih.gov, email address, and we will respond to that and take your feedback. The best way to receive announcements and updates from NIH is to sign up for this NIH ME/CFS listserv by going to this link, And so, watch for announcements coming soon to participate in discussion on a crowdsourcing platform called IdeaScale. We'll be posting the research priorities that came from the Nervous System webinar back in August very soon. And subsequently, we'll be posting the research priorities for each of these webinars for additional community input and feedback.
So, with that, I will turn it over to the chair of the Immune Webinar Planning Group, Derya Unutmaz, who's a professor at the Jackson Labs in Connecticut. So, thank you. And I'll turn it over to you, Derya.
Derya Unutmaz: Thank you very much, Vicky. I'd like to also start by thanking you and NIH and all the supporting team for initiating and organizing this really fantastic series of webinars. And I welcome all the attendees. So, today, we're going to focus on immunology. And we have a very, very fantastic group of speakers. And hopefully, we'll have some discussions around the questions. It's a very tight schedule, so I want to get started right away and introduce our first speaker, Dr. Nancy Klimas. She is a professor of medicine at the Department of Clinical Immunology, College of Osteopathic Medicine, and the chair of the Department of Clinical Immunology at Nova Southeastern University. I'm sure a lot of you know Nancy because she has been involved in ME/CFS for many, many years. She's been recognized for her outstanding clinical work and basic research work as well. She's also studied Gulf War illness, fibromyalgia, and recently Long COVID. So, without further ado, Nancy, the floor is yours.
Nancy Klimas: Now, I'm good. I was going to double down on the thank you back. Thank you very much for inviting me. And I'm really pleased to be here. So, I was asked to give sort of the clinician and clinical immunologist type of overview to get this session started using these key questions that Vicky just reviewed. So, the focus of this talk and all the talks is to review what we know, what we need to know, and where do we go from here. And the double-down focus is how do we get to effective clinical therapy in ME/CFS. That's the ultimate goal. So, what do we know? We have been working on immunology for a long, long time in this field. My group, and many, many other groups have published hundreds and hundreds of papers on the role of the immune system or the biomarkers of the immune system, or the effects of the immune system. And we know a lot, a whole lot. So, we know there's inflammation. We know there's neuroinflammation. We know there are issues with immune competence, pathogen surveillance, and pathogen control. There's newer work, which you'll hear a lot about today, on immune senescence and immune exhaustion, and very exciting work in autoimmunity. Again, the speakers today will be focusing on that. And so, we have all these areas that have a considerable knowledge base. And then we have more literature on specific cells. And this field has initially focused, as much of immunology has focused, on the role of the lymphocyte in human disease, chronic disease. It's a very important cell, and it does a lot of things. And a lot of our literature is based on lymphocyte function, lymphocyte subtypes, and so on.
But there are other cells that are engaged in this illness and matter, and perhaps matter a lot. One which deserves a lot of attention is the role of the mast cell. There's a condition called chronic mast cell activation. We think of mast cells as allergy cells, but in fact, they're very inflammatory cells that can get on a slow kind of weak thing and cause a lot of symptoms and misery. Platelets matter, and we're learning that a lot more in Long COVID. Macrophages matter, they're the first step in any memory type of immune response. And neutrophils, pretty much completely ignored neutrophils, which are virtually half of the immune system. And so, these are all potential targets for clinical intervention and for a better understanding of what's going on in this illness. And they also can reflect things that tell you important knowledge. For instance, an antibody response to a virus might be the only thing we can find that says there was a virus or there is a virus. Sometimes we can't find the actual bug, but we can see its immune signature. And so, these things all matter.
So, to start with inflammation and neuroinflammation, it's been described many times in many ways. There's some knowledge about general immunology that matters when you're trying to interpret all these types of papers. When we think about inflammation, we often fall back on models of autoimmunity like rheumatoid arthritis where there's complement activation, immune complexing, and a whole cascade of things that happened that respond to classic autoimmune types of drugs like non-steroidal anti-inflammatories. But in ME/CFS, what we actually see is a signature that's more obviously inflammatory in the cytokine panel, in the chemical messages that the immune system's making that promote not just inflammation but a lot of immune functions. And that this inflammatory cytokine signal is accentuated when you exercise. So, you'll see many studies, and some presented today, about how we use exercise in our research to actually see the signal and actually see the cascade of events that follows such a challenge that have intervention points. I call this getting in front of the tail of the dog.
Often what we see in a patient is how they feel today and what's circulating, but when we use the exercise challenge, we can see what happens first, second, third, and fourth and hope to treat the first. So, that we're not having to treat all these other downstream events. So, it's an exciting way to approach this illness, which is, of course, made worse by exercise. And so, it gave us this real opportunity, I think, to use this way, this kind of window into understanding the illness. So, what we have then is a lot of bench work, basic science, cool modeling work to tell us that there is inflammation and that there's neuroinflammation. I'll go into that in a moment. But what we do not have is a lot of targeted clinical trials that focus on that. In fact, we have very few and practically none. And so, these targeted studies with biologics haven't happened very much. And the physicians that are treating this and know it's there are left with a bag of tricks that is basically using their clinical knowledge and things that they can actually use and have reimbursed by third-party payers or aren't so expensive the patient couldn't afford it themselves. And it's predominantly nutraceuticals.
Now, nutraceuticals are drugs, and they need study. But we are doctors seeing patients with an immune signature, and we're going to treat it any way we know how. And this is somewhere in the space where most of us are actually trying to treat this illness. In Long COVID, there's also evidence of thrombosis and micro thrombosis. So, if you think about the body's bloodstream, and you see the great big arteries, the heart, the aorta, then the next bunch of vessels that are kind of the size of your finger, and then the next bunch of vessels that are about the size of straws, they get smaller, smaller, smaller until they're threads, and this is the microvasculature. And the microvasculature's really letting one cell through at a time in this speeding kind of way. They're rushing through delivering oxygen and glucose to the distal tissues, to the fingertips and the skin and the organs, and so on. And in Long COVID, what we've seen is that there's evidence of micro thrombotic events and endothelial inflammation, the lining of the blood vessels, and that these are also targetable areas for intervention. We don't know if this is new knowledge. And we should have been looking there along more closely, although some people have in ME/CFS. But we do know that in Long COVID, that's another targetable point for intervention.
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