How Our Immune System Works – PediaCast 462

Show Notes 


  • The immune system is making headlines during the COVID-19 pandemic. We go beyond the headlines and provide you with a foundation of how this fascinating system works. Dr Becky Scherzer and Dr Ben Prince help us explore antigens and antibodies, B cells and T cells, macrophages and natural killer cells. You’ll also learn about weakened immune systems and over-zealous cytokine storms. We hope you can join us!


  • The Immune System 
  • COVID-19 Pandemic




Announcer 1: This is PediaCast.


Announcer 1: Welcome to PediaCast, a pediatric podcast for parents. And now, direct from the campus of Nationwide Children's, here is your host, Dr. Mike.

Dr. Mike Patrick: Hello, everyone. And welcome once again to PediaCast. It is a pediatric podcast for moms and dads. This is Dr. Mike coming to you from my home. 

It's Episode 462 for May 20th, 2020. We're calling this one "How Our Immune System Works". I would like to welcome all of you to the program.

So there has been a lot of talk about the immune system in recent weeks. Probably more talk about it in the news ever since I've been alive. And of course, the immune system is interesting and just by its very nature, today's episode is going to be a little more sciencey than some of our more recent episodes where we've covered lots of social, physical, mental, academic aspects surrounding this pandemic, sort of more big global issues. 


We did mental fitness during a pandemic, physical fitness, academic fitness and then most recently preventing child abuse during a pandemic. So really kind of big social sort of topics that are absolutely very, very important, that's why we cover them. But today, we're going to delve into the science a little bit more of the immune system. And still, our primary audience is parents and so we want to explain things in terms you can understand but without diluting the science of it. 

So that's going to be our goal as we just sort of explore how the immune system works. And interestingly, this was recorded a couple of weeks ago. And in that very short amount of time, a new thing popped up in kids that initially was called pediatric multisystem inflammatory system. That has changed already, there's a name change already. And both the World Health Organization and the CDC have settled in on multisystem inflammatory syndrome in children, or MISC. So you're going to be seeing and hearing about that.


It's basically, at its core an inflammatory syndrome, so there's widespread inflammation throughout the body. So it's your body's immune system that is causing this. And it appears to occur following an infection with SARS-CoV-2, which is the virus that causes the disease, COVID-19.

And a lot a of these kids, and there had not been very many, this is a rare disorder, so I want to preface with that. But in a lot of these kids, they didn't necessarily know that they had COVID-19 disease. So you can have very mild disease symptoms or no symptoms at all, and then still have this widespread inflammatory response which can cause lots of problems. 


Now, the doctors in the crowd and the pediatrician in the audience, this is going to sound familiar. There are other diseases processes caused by inflammation following a mild viral infection, sort of at the less extreme end of the spectrum. You can see hives that occur, or urticaria that occur following a viral infection which is  the immune system kind of on overdrive. And even though the virus may not have been that severe. 

And then, on the other end of the extreme is something like Kawasaki disease where we do see widespread inflammation in the body including in blood vessels which can cause the eyes to look red without drainage because it's not really an infection. The lips can look red and cracked because of inflamed blood vessels. 


You can have a rash that looks sort of different on different parts of the body, swollen hands and feet, peeling skin on the fingers. Again, all related to the immune system. And in Kawasaki disease, we worry about heart inflammation and in particular, in the coronary arteries, which bring oxygen to the heart muscle.  And so an aneurysm can occur, which is sort of ballooning out of the blood vessel wall. That's one of the main things that we worry about with Kawasaki disease. 

So this is sort of similar to that but doesn't necessarily meet all the criteria for Kawasaki in some kids that has met the criteria and others that hasn't. Also abdominal pain and possibly vomiting have been associated, and possibly diarrhea as well, has been associated with this. And so, the World Health Organization and the CDC, they put out some criteria for diagnosing this and being on the lookout for it. 


The biggest thing from a parent's point of view is that when kids get this, they have a fever. And by definition, a fever is 100.4 degrees Fahrenheit or higher, that last for a couple of days and there may be some other symptoms associated with it. So I think you're going to hear a lot of things about this. And the most important thing for parents is just to be in touch with your child's pediatric provider. So if they have a fever that's lasting for a day or two, just check in. 

And that may end up just being a quick conversation on the phone. It may be a telehealth visit, it might be "Hey, come on into the office and let's take a look at this." And in the early stages, it may be, "Hey, let's just watch this fever and make sure nothing else is going on." And then if the fever is progressing, it's lasting longer, we're out now of three four days of fever, or there are other concerning symptoms beginning to appear, then you and your doctor can work together. 

Ultimately, it's going to take bloodwork to diagnose this and kids who have it will likely end up needing to be admitted to the hospital to watch and you won't know if that's going on or not without the bloodwork. But that doesn't mean that every kid with a fever for a day or two needs bloodwork.


So again, the best thing is just to touch base with your doctor if your child develops a fever of 100.4 degrees Fahrenheit or higher and let them sort of work through and walk down this path with you of whether your child actually need something done or not. The most important thing is to keep in mind that this is rare. 

We're seeing lots of cases of it in hotspots only because there were a lot of viral infections. And so, if you have a condition that follows a viral infection that's rare, you're going to see more of it when there's a lot more viral infection in the general population. And so, as hotspots of COVID-19 illness develop, a few weeks or even a couple of months down the road is when you're going to start to see these types of delayed inflammatory processes from the immune system going on. 


So it's not surprising that we're seeing it in sort of the New York area right now because there's so much COVID disease. But we probably will see it in other areas of the country as this pandemic evolves. So again, just be on the lookout for fever and if that happens to your child, touch base with your doctor and they'll let you know when it's time to worry and exactly what you need to do. 

So, just like with this multisystem inflammatory syndrome, there's been a lot of talk about the immune system lately. As I mentioned at the beginning, it's probably the most coverage that's it's gotten in the news since I've been alive. And it's probably the most exposure that you've have to many concepts related to the immune system as well.

There's been talk about folks with weakened immunity. Also, overzealous responses of the immune system, like a cytokine storm, that was kind of in the news during the height of this. And probably a phrase that you have not heard of before COVID-19, cytokine storms. 


We talked about PCR testing for viruses, and antibodies, and antibody testing, immunizations with headlines sort of pivoting away from anti-vaccine groups to those who want a COVID vaccine now and fast. But and this has always been the case, vaccine scientists care about safety and effectiveness. 

So if a vaccine can be made for COVID, it's going to take some time. Now, as a doctor, I have always found the immune system fascinating because it is a complex interwoven body system with lots of pieces parts. And with so much interest landing upon the immune system in these days of COVID-19, I thought it would be helpful and interesting to lay down the foundation for you regarding how the immune system works. 

So we're going to talk to you today about antigens and antibodies, yes, but also B cells and T cells, macrophages, and other phagocytes, memory cells, and my favorite, natural killer cells, got to love those, especially in the early stages of viral infection, they're very important. 


To help us step through the immune system, I have a couple of really terrific guests joining me this week, Dr. Becky Scherzer, she is Section Chief of Allergy and Immunology at Nationwide Children's Hospital and Dr. Ben Prince, also an allergist and immunologist here at Nationwide Children's.

Before we get to them, I do want to remind you, you can find PediaCast in all sorts of places. We are in the Apple Podcast app, Google Podcasts, iHeart Radio, Spotify, SoundCloud, and most mobile podcast apps for iOS and Android. 

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So, let's take a quick break. We'll get our expert guests connected with the studio and then we will be back to talk lots more about the immune system. That's coming up right after this.



Dr. Mike Patrick: Dr. Becky Scherzer is Section Chief of Allergy and Immunology at Nationwide Children's Hospital and a professor of Pediatrics at the Ohio State University College of Medicine. Dr. Ben Prince is also an allergist and immunologist at Nationwide Children's and an assistant professor of Pediatrics at Ohio State.

They're here to talk about our immune system and how it works. So, let's give a warm PediaCast welcome to Dr. Scherzer and Dr. Prince. Thank you both so much for joining us today. 

Dr. Benjamin Prince: Thanks for having us.

Dr. Rebecca Scherzer: Yeah, we appreciate the invitation.

Dr. Benjamin Prince: Really excited.

Dr. Mike Patrick: And I appreciate you guys taking the time out of your busy schedules to talk to us about the immune system. Because I think right now, more so than any other time since I've been alive, there is more focus right now on the immune system than there ever has been before. And as physician, I find the immune system fascinating. But I think it's also really misunderstood by a lot of people and so, hopefully, we'll shine some light today. 

We're not going to make parents into immunologists, but hopefully, we will be able to shed some light on exactly how everything comes together and work.


So Ben, if you could start us off, sort of what is the big picture overview that you would give of the immune system?

Dr. Benjamin Prince: So the immune system is actually a really complex system that we're going to kind of generalize a little bit today, but it's made up of various organs, tissues, cells, and molecules that all work together to protect us from invading organisms. They help remove toxins from our body and also help clear tumor cells. And this whole process is kind of what we generally call immunity. 

It's actually a pretty amazing system. I mean, I get pretty psyched about it, but I mean, I'm biased. But it does a lot of stuff, it has to discriminate between what is our own body and what is foreign to our body. It has to discriminate between harmful bacteria, the commensal bacteria, the good bacteria that help live in amongst us in our body and make those symbiotic relationship. 


And in fact, those bacteria make up about 90% of our body, so it really has to do some discrimination there. And then once it responds to an invading pathogen that might be going on, it has to kind of then go back down and kind of regress and go back to homeostasis level where it's just sort of in surveillance and monitoring again. 

Dr. Mike Patrick: I just want to point out, you did say that bacteria or microorganisms make up about 90% of our body, compared to our cells. Is that what you're saying?  

Dr. Benjamin Prince: Yeah, so I think that that's a big shocker. It's something that I tell a lot of parents. You don't think about it, but if you took your body and you separated every cell out and you cull your cell, the cells that have your own DNA, and then other cells that don't have your DNA, you're only about one-tenth you, which is I think pretty striking.


And well, you have many people that are germophobes and whatnot, there are a lot of great bacteria that live on our skin, in our gut, in our respiratory tract that do a lot for us and allow us to live and kind of carry on our lives. 

Dr. Mike Patrick: Yeah, yeah, absolutely. And it's amazing then that the immune system can differentiate between friend and foe, so to speak. Because they're all microorganisms, so which ones are allowed to be here, and which ones aren't is pretty amazing.

One other term that I wanted to define right here at the beginning, because I have the feeling we'll start kind of using it as we're discussing this and that's antigen. What is antigen?

Dr. Benjamin Prince: So I'm going to talk about it in a little bit, but antigens are really, they're a specific molecule that's a part of your immune system called adaptive immune system recognizes and responds to. 


And so we call it antigen, but it's what your antibodies or certain receptors on cells that make up your adaptive immune system, which is one arm of your immune system, are specific and recognize and have to respond to. In contrast, the other arm, which is your innate immune system, which is I think we'll dive into a little bit as well. 

Dr. Mike Patrick: There's also, as we think about immunity, there's a difference between active immunity and passive immunity. What's the difference between those two terms? 

Dr. Benjamin Prince: I think it's a great question. Active immunity is really kind of what it sounds like. It is an individual's ability to actively develop protected immunity against a microbe or a toxin that occurs over period of days to weeks. And this optimum response results in immunologic memory, it is long lasting.

One example of active immunity would be either just exposure to something naturally, if you catch a cold with this virus and you would be re-exposing particularly in that season, you're likely not to get that infection again because you've developed active immunity. 


And then, another example would just be through vaccination. So we are able to develop active immunity through the vaccines that we give the population.

Dr. Mike Patrick: And passive immunity. 

Dr. Benjamin Prince: So passive immunity is a little bit different. It's when you're actually, you're giving immunologic protection that's usually conferred pretty rapidly. And it's through adaptive transfer of serum or antibodies or other cells such as lymphocytes from somebody's who's immunized, so who's protected against something, to somebody who's not immunized. 

An example of this that some parents might know and lots of pediatricians definitely know is in fact the humanized monoclonal antibody palivizumab or Synagis, which is a neutralizing antibody against diffusion protein of RSV, which is a virus that causes severe illness, particularly in really young infants.


And in giving this kind of monoclonal antibody during times when RSV is around, we can confirm passive immunity to that individual and it helps protect that young child or person at risk from developing a really severe RSV infection. 

But as soon as that you stop giving it, it goes away. There's no memory there, there's no long-lasting response. 

Dr. Mike Patrick: Yeah, you give those antibodies and then they're gone after a few weeks or so or however long till the body can metabolize them. And since you're not making it yourself, then you don't have that immunity anymore. 

And then, this is what, as we hear about folks with COVID getting plasma transfusions from people who had the infection before, you're kind of thinking about the concepts of passive immunity when we're using that as a treatment for this disease, right?

Dr. Benjamin Prince: Exactly, and I mean, I'm glad you brought that up because that's really how it applies. So in regard to COVID, there's been use of the investigation use of convalescent plasma, which are essentially purified antibodies that are taken from individuals who have recovered from COVID-19 and then used to treat patients who have serious or immediate life-threatening infections.


And this is not the first time that this has been done. Similar things like this have been used in other severe respiratory infections, viral infections such as SARS-CoV-1, which occur back in 2003 and even the 2009-2010 H1N1 influenza virus pandemic as well.

Dr. Mike Patrick: And then, in addition to active and passive immunity, we also hear about herd immunity or community immunity as kind of the newer term for it. Describe what that is. 

So community immunity which is a tough one to say or herd immunity, has to use that, it refers to the indirect protection or protected immunity that occurs for a non-immune individual when a sufficient proportion of the population is immune to contagious disease. And that's either through vaccination or because of prior illness. 

So again, in this kind of immunity, the non-immuned individual is still susceptible to the infection. They're not protected but because they're not exposed to people who have the disease, because the people around them are immune, they are then protected from getting that disease. 


And when you talk about what percentage of the population has to be protected for this to occur, it really ranges. There's a wide range anywhere from 40% to 95% and that kind of relates to how contagious that infection is. The more contagious that that infection is, the more higher percentage of the population has to be immune before that herd immunity occurs. 

Dr. Mike Patrick: So if there aren't people in the community who can give you the disease, then you're not going to get it. So you're really relying on everyone else's immunity not to give you the organism. 


Dr. Benjamin Prince: Exactly. And let me point out one really quick thing, and it's before even the COVID stuff came out, it's something that we were often talking about in regard to some of the other vaccinations that are commonplace and given to kids. So for example, measles, we have seen a resurgence in measles and it's not taking over completely, and that's partially because of herd immunity.

But as more and more people don't get vaccinated to measles, then that herd immunity, the level, the threshold that needs to be there for herd immunity to continue to occur drops. And then you can get more and more people who are not immune that they can transmit it or confer the disease. 

Dr. Mike Patrick: Yeah, that's important and we'll talk more about the adaptive immune system and the antibodies and all of that in a bit. But it is an important concept because even if you have been vaccinated, you still rely on community immunity to a degree because some folks don't respond to the vaccine like you would expect them to and have immunity that's protective. And then also, that immunity can wane over time for some folks.

And then, of course, there's those who can't get vaccines, or they have weakened immune systems and so we're really protecting all of us by maintaining community immunity.


Dr. Benjamin Prince: I agree. I couldn't agree more and that's actually one of the really groundbreaking things that vaccination has done for us, is it's wiped out, even though not 100% of the population is immune to these diseases that we haven't seen in a long, long time, it is the fact that herd immunity still exist that the majority of the population is protected, that we haven't seen a resurgence of this. But that could very well change if we stop vaccinating children and adults, too, because of this.

Dr. Mike Patrick: Dr. Scherzer, I want to bring you in. We have talked about different types of immunity, and we call it the immune system. And typically, in the body, a system is kind of, you know, it's a set of organs and tissues that are in one place. So like the respiratory system is in one specific place. But the immune system, really, incorporates lots of organs and tissues around the body. 


So I wanted to just sort of take an overview of the different components of the immune system. And as we go through this, hopefully, this doesn't get too cheesy, but I came across an article from the Children's Hospital of Philadelphia and their Vaccine Education Center. And they had a fantastic police force example as they describe the immune system. And so, if you think about the Police Academy and detectives and beat officers and they've kind of put that, overlaid that on to the immune system. 

So as we talk about this, I'm just going to chime in now and then, and say, oh yeah, that's whatever. And I'm going to put a link in the show notes after this episode, 462, over at to the Vaccine Education Center over at the Children's Hospital of Philadelphia. Because it really is well done and helps to explain these things.

So Becky, if you want to just go ahead and just jump in and just kind of talk to us about the different components of the immune system in the human body. 


Dr. Rebecca Scherzer: Sure, thank you. And that is a wonderful resource, so it will be wonderful if that is linked in to this PediaCast. So one of the reasons that, and again, I'm biased like Dr. Prince, that the immune system is so fascinating is it does play a role really everywhere in your body. And there are so many different parts of your body that are involved in the immune system, many that I think a lot of people know about and some that people may not know about. 

So just kind of going through some of the different parts of the immune system, ones that I think a lot of folks know about are tonsils. So tonsils play a big role in your immune system. They're collections of certain cells called lymphocytes, which help you fight off infection. 

And so, they play an important role. Certainly, there are situations where tonsils do need to be removed, but I think that's taken very seriously because we do know that is a part of your immune system that can be a benefit. 


Another part of the immune system that I think people know about but may not think about as the immune system is the liver. So the liver plays a role on lots of different things that need to happen in your body. I think immunology may not be one that people think about, but the liver is where some very essential proteins of the immune system are synthesized. So when your liver is not functioning well, your immune system may not function as well just because you can't synthesize those proteins.

Places like the blood, so we all think about our blood and we think about the fact that it keeps oxygen levels up and it's an important of our circulation. But that blood also carries around a lot of cells and proteins of the immune system and takes it from one part of the body to another part of the body. So if you have an infection in your toe, the blood helps bring some of the immunology cells to where the infection is or where those cells are kind of like little fighters need to be to really help us fight off infection. 

So those are some of the things that places or organ system that people might think about as we went through the spot. There are also plenty of places in the immune system that people may not think about. We all have something called a thymus. And the thymus is an organ. It's kind of in your upper chest, kind of in front of your heart. And this is a really important place of your immune system because it's where some of the most important cells of the immune system go to school.


So that is where they go, and they get their education and really learn how to function and help our immune system. So the thymus is... 

Dr. Mike Patrick: That's the police academy. The police academy is that.


Dr. Rebecca Scherzer: I'm sure the thymus is listed as the police academy because it is important schooling process for the immune system. 

But there's also your bone marrow. So bone marrow is very important. Bone marrow is where a lot of the primitive immune cells are located and really where these cells start their development. So if somebody's bone marrow isn't functioning, there's lots of parts of the immune system that are not going to work as they should, because we really need functioning bone marrow for that. 

Lymph nodes, I think most people listening to this will have kids, or help take care of kids. We all see kids with these kind of growing lymph nodes especially with infection and lymph nodes are a collection of different kinds of immune cells, different kinds of cells called T cells and B cells. 


These are really, will help you fight off a lot of different kinds of infections, including bacterial infections and viral infections. Another important part of your immune system is lymphatic tissue, which is found through mucous membranes in the body, but also through your gastrointestinal tract. So your gastrointestinal tract is a huge part of our immune system. And the lymphatic tissue there is really where we have a lot of cells that contain different kinds of antibodies that help us look for infection. 

And if you think about the place where a lot of foreign things come in, it is certainly through your GI tract. And so that's why it's important that we have a good functioning immune system there. I think there's lots of different parts of the immune system. I very much suggest going and looking at the police academy because it sounds like a wonderful resource.


Dr. Mike Patrick: Yeah, in terms of that analogy, the bone marrow and the thymus are the police academy, where those cells start out. And then, the lymph nodes were the police stations.

Dr. Rebecca Scherzer: Oh, love it! That's great.

Dr. Mike Patrick: And then, another important organ in the immune system is the spleen, right? Tell us about that one. 

Dr. Rebecca Scherzer: Yeah, spleen is very important. The spleen is a collection of different kinds of cells that you find in the immune system. So there are T cells there and B cells there and monocytes. And it's a place where really organisms and different kinds of cells in the immune systems can interact with each other. 

So there's a lot of interaction that goes on there. It helps stimulate an immune response. We know this is a very important organ system. And as part of  this organ system, people without spleen, and there are patients that are born without spleens, or there are patients who ended up having their spleen removed for different reasons, we know that they would be considered immunocompromised, because it's such an important part of the immune system. 

Dr. Mike Patrick: And one stat that really surprised me, in addition to 90% of our body being bacteria, but that 25% of every heartbeat actually gets filtered through the spleen. Like a quarter of our blood with every heartbeat goes to the spleen. 


And so it really is a filter system where our blood, some organism gets in the blood. It's got a good chance of being encountered by the immune system in the spleen, and just really drives home how important that it is. 

And then I also wanted to mention the skin, right? The skin is really part of our immune system, correct? 

Dr. Rebecca Scherzer: Oh, definitely and we'll talk about that a little later when we talk about physical barriers. Because there's so many different important parts, if you think about the mucous membrane and your sinuses in your mouth. All of those different areas play such a huge role, even when you think of things like urine. 

Urine is very acidic, that also is another place that we have some kind of immune process. So there are so many parts of your body. And again, this is why immunology is very cool, is it plays the role really everywhere in so many ways throughout the body. 


Dr. Mike Patrick: It is just fascinating, really is. Now, another sort of dividing line that we have mentioned already that I think we should define a little bit more is the innate immune system versus the adaptive immune system. So let's start with the innate immune system. Becky, what exactly is that?

Dr. Rebecca Scherzer: So the innate immune system is kind of your body's ability to respond to something that you're born with. Now, I say that as most of us are born with this. There are very many different kinds of primary immunodeficiency disorders that children can be born with. That can lead you not having a normal innate immune system. But the innate immune system is a non-specific in most cases defense mechanism that comes into play immediately in a couple of hours of when you see this antigen or this appearance in your body.

So your body, there's something there that's not supposed to be there, it makes this non-specific response. And these mechanisms can include a lot of things, like physical barriers, just like you mentioned, the skin, chemicals in the blood. And then the immune cells that can kind of attack and go after, I think of it as a Pac-Man, kind of come around and kind of gobble up some of these infections. 


So it's just there, and again, it's not very specific for what's coming in. Whereas, adaptive immunity is created, so it's not something you just form. It's created in response to exposure to a foreign substance. So it's a process that occurs. And that doesn't happen quite as quickly. That can take multiple hours, days into exposure to something to be able to make that adaptive response. So innate is immediate, whereas adaptive is a slower process. 

Dr. Mike Patrick: And that's why kids when they start going to daycare or they'd been home and then suddenly they go to school and they're exposed to a lot of microorganisms, it seems like they're sick all the time because then you are needing to rely on that adaptive immune system. You haven't built up the immunity to things yet, is that correct? 


Dr. Rebecca Scherzer: Oh, that is. I always tell families, there's going to be that timeframe where they have lots of infections, when they go to daycare, when they go to preschool or kindergarten. Because you do, your body has to see a lot of these different kinds of infections, and then hopefully build up some of these memory cells. So the next time you get exposed, you may not have as significant of an infection because your body is able to adaptively respond to that infection or that exposure. 

Dr. Mike Patrick: Yeah. So we talked about physical barriers being skin and mucous membranes. Other physical barriers could include like cough. You physically have a cough in order to keep bacteria from getting down into the lungs or we have mucus that traps bacteria. Even vomiting and diarrhea, if you have do have organisms that are entering to the GI tract, it helps to get rid of those things. I mean, those are still sort of in a way, physical barriers, right? 


Dr. Rebecca Scherzer: Oh, definitely, I mean, you think about sweat, mucous membranes, tears, saliva, they all contain enzymes that can help kill pathogens. Again, the uric being acidic, it's often too acidic for many pathogens. And then, if you start thinking about the GI tract in the stomach, which is very acidic, it definitely can kill pathogens that enter the GI tract in either food or water. 

So definitely, there are lots of ways that our body kind of just inherently in most people knows how to help at least start fighting some of these infections when you get exposed. 

Dr. Mike Patrick: And we've talked about all of these bacteria that make up our body and sometimes we call that the good bacteria. But by having good bacteria, that also limits the space where the bad bacteria can live, right? So good bacteria even plays a role in our immune system. 

Dr. Rebecca Scherzer: Oh definitely, so good bacteria, I think a really great prime example's in the gut. And it keeps the immune system there kind of prime to more effectively fight infection from what might be a pathogenic or a bacteria that can get you sick. I mean, this is why we really consider before we start someone on antibiotic. 


Definitely, if you need antibiotics, we want people to take as appropriately written, that is for sure. But we don't like people to get antibiotics if they don't need it because they can kind of change that delicate balance between good bacteria and maybe not so good bacteria. And in some ways, that can compromise your immune response. 

So again, if you need antibiotics, we 100% want you take it. But if we don't need antibiotics or if we don't need what we call broad spectrum antibiotics, then we can give you very focused antibiotics that will just hopefully be able to treat what infection is occurring at that time, that will allow that delicate balance to continue. 

Dr. Mike Patrick: And then, you mentioned cells sort of gobbling up other cells. Talk to us a little bit more about that. These are just you don't necessarily need an antibody, if they come across something that they don't like, will they just eat them up? How does that work?


Dr. Rebecca Scherzer: So different cells, they work in different ways. I always think so, macrophages, which are a type of white blood cells, I always of them like I said as Pac-Man. They kind of encircle and bring it in. They also could help stimulate other immune cells. They've kind of been described as kind of lawyers. They kind of go after them and just kind of go around. 

And then there's lots of other cells that play a role. As you start thinking about different kinds of cell or we call them lymphocytes, they are a different kind of subcategories of these lymphocytes and they play a role sometimes in very specific kinds of infections. And we need them all to work in balance so that we're able to fight off different kinds of infections. 

So for example, T cells play a really important role of fighting off many kinds of infections including viral infections. They're also important and if you don't have a balance and you can see them many of the immune cell, if you have too many or they're working sometimes too hard, you can get autoimmunity, because of these kinds of cells, too. 


B cells also play a role. They help us fight bacterial infections, and then there's something called NK cells. And they help fight sometimes very specific types of infections such herpes infections.

So again, different cells play roles in different parts of your immune system and that ends up coming to be very important with patients with immunodeficiency disorders because a lot of times, what kind of infections we'll think about or treatment options we'll think about will be based on what kind of cell is not functioning in your immune system. 

Dr. Mike Patrick: One really cool-sounding cell is the natural killer cell. Is that the NK cell you were talking about? 

Dr. Rebecca Scherzer: That is the NK cell. 

Dr. Mike Patrick: Natural killer, I don't know, that's kind of a cool thing.


Dr. Mike Patrick: And these are cells that oftentimes fight viral infections while you're waiting for an antibody response because it kind of attach to infected cells and see, "Hey, there's something in this cell that's not supposed to be there," and actually kill the human cell in order to subsequently kill the virus that's in it, right?


Dr. Rebecca Scherzer: Definitely. Again, they all work together and play a really important role, and knowing what type of cell is there or not there in somebody that you're considering a primary immunodeficiency disorder really will help you determine what you need to do to help treat it. Because certain immunodeficiency disorders, we have treatments that we can give you and will keep you safe. Other things, we will need to consider something like a bone marrow transplant for. 

Because again, these cells are such critical part of your immune system, you really need them to function. And so that you don't have issues with recurrent infections or severe infections. 

Dr. Mike Patrick: Great point. With our police example, the innate immune system is described as the beat cops that are taking care of local crime and keeping the peace. 


Dr. Rebecca Scherzer: This is awesome. 

Dr. Mike Patrick: They're just hanging around. I know, I want this, I love this. That's why I think it's really brings it to life. 


And then, the other thing I wanted to mention with all of these different components, there is a really complicated signaling system in that the immune system uses chemicals called cytokines that allows these cells, even though they may be in different distance places in the body, to communicate with one another, right?

Dr. Rebecca Scherzer: Oh, definitely. The immune system is very intricate. And definitely, an infection in one part of your body brings in another part of your body to be functioning and coming in to help. One of the cells we did not mention was neutrophils. And I think it's a great example of a cell that travels all over the place depending on what you need. 

So neutrophils are actually what makes up puss. So when you think about different kinds of abscesses or puss, that's what neutrophils are. And they migrate to an area of infection very rapidly, within minutes. So the area that's infected sends up this kind of alert signals and through different kinds of cytokines and inflammatory responses, it says, "We need this kind of cells here." And neutrophils go immediately to the site of infection.


Dr. Mike Patrick: That's really cool. So like the macrophage, it will gobble it up and then send chemical signals that go through to the blood. And suddenly, these neutrophils are like "Hey, I need to get to a specific place." There's got to be a lot of this we don't understand completely, right? 

Dr. Rebecca Scherzer: Oh, definitely. I'm not going to name how many years ago it was in my immunology training, but I think of how much we've known in the past, well, I'm kind of dating myself, for the past 15 to 20 years, and it is amazing what we know now and how we can diagnose immunodeficiency now compared to that time. 

Dr. Mike Patrick: Absolutely. All right, if the innate immune system is like the beat cops on the street, the adaptive immune system are the Special Forces. This is the SWAT team. So Ben, tell us about the adaptive immune system. 

Dr. Benjamin Prince: Right. 

Dr. Mike Patrick: More coolness, this is really cool.

Dr. Benjamin Prince: It is really cool. I have to say one thing. I'm going to regress just for a second in medical school. When we were talking about neutrophils, one of my professors, she just described them as when you see puss, as we often were like, "Oh, puss!" Like "Aah!" But you have to be reverent for pus, right? Those are your neutrophil soldiers that had given their lives so that you can go on. So I always thought that was cool.


Dr. Mike Patrick: I love it. 

Dr. Benjamin Prince: But as far as the adaptive immune system, so as Becky kind of allude to, it actually it's named accordingly because it adapts to previous exposures and previous infections. And unlike the innate immune system that recognizes characteristic patterns that are particularly certain pathogens or foreign material, the adaptive immune system has the ability to recognize and respond to very specific foreign substances. And we already talked about those, in immunology, we call those antigens. 

The cells that make up the adaptive immune system are going to be your T lymphocytes, as Becky was kind of saying T cells, which mature in the thymus that she describes you, and then B cells or B lymphocytes that mature in the bone marrow.


And then, the last piece of the adaptive immune system is going to be the antibodies that are made from activated T cells or plasma cells. And all three of those things play a significant role in the adaptive immune response. 

Just like I wouldn't love one child more than the other. I think the both the innate immune system and the adaptive immune systems are very very important. Defects in the adaptive immune system leads to some of the most severe immune deficiencies. So it is really, really an important part of your immune system that you want to have working for you. 

Although as Becky said, the innate immune system, the beat cops, they're going to be right there on the street taking care of stuff immediately. The adaptive immune system does take some time to work, but it can function at a much more specific level, as I mentioned. And then, the other thing that's really important  to think and remember about the adaptive immune system is it also has the ability, unlike the innate immune system, to generate immunologic memory. 

So, once you've been exposed to something and you have seen it, your adaptive immune system responds to it, certain cells will hang around and remember that. And then, if you are re-exposed that again, it's able to create a more quick and robust response than you had at that first time. 


Another thing that I can kind of compare and contrast between the adaptive and the innate immune system is the innate immune system, it doesn't change at all. It is the same from the time that you're born to the time that you pass on. So if you have a defect there, it stays that way. If you have a well working innate immune system, nothing changes. It recognizes the same things from day one till the end. 

Where the adaptive immune system really changes and adapts depending on what you're exposed to. So depending on things that you see, even though you had, you may start off as identical twin, for example, as the exact same genetic material, but as one person is exposed to different things, their adaptive immune system is going to respond differently and kind of protect you differently than the other person that was exposed to different things.


Dr. Mike Patrick: I mean, just so incredibly interesting. Let's delve into some of the individual component parts of the adaptive immune system, kind of walk us through an antigen sort of enters the body. And their cells called antigen presenting cells and dendritic cells, they're kind of the thing that this antigen first meet. Sort of walk us through that process.

Dr. Benjamin Prince: Sure, absolutely. So generally speaking, when a pathogen invades the body, it's going to come in through the skin or mucosa. And well designed, that's where your dendritic cells sort of hang out, in that area. And what they do is they see that, they phagocytose it or they engulf it.  And then, they carry that, that pathogen back to lymph nodes, and the lymph nodes, you think of it as police station, I sometimes say home, but that's where your B and T cells, that's where they hang out together and they're looking for, is there something that they be concerned about. 


So these dendritic cells are one kind of an antigen presenting cell and they take them back to the lymph nodes and they present that antigen or actually small pieces of the protein from that pathogen to T cell through a molecule called an MHC class II molecules that's on their surface. 

And in that interaction, that's how kind of how, that's the link between the innate immune system and the adaptive immune system. And that's when we sort of start the big guns to kind of get involved and start to rev up. And still, you have a few days before it's running in full force, but that initiates that response. 

The T cells, there are a few different kinds of T cells and your T cells are in fact very important. The T cell, the dendritic cell or your antigen presenting cell is going to be showing this piece of that pathogen, too. It's generally speaking going to be a CD4 or a helper T cell. And these helper T cells, I don't know what the analogy is, but I usually call them the general of immune system.


Dr. Mike Patrick: Yeah, yeah, police chief and sergeants. 

Dr. Benjamin Prince: There you go. So they are extraordinarily important, and they do a lot for us. So there are a few different kinds of Th helper T cells. And they send  signals. We've talked about cytokines that are both other immunologic cells to help trigger them to proliferate and differentiate, to be more specific in attacking whatever pathogen might be trying to invade the immune system. 

They also are very integral in helping regulate the immune system as well. So after you have this really robust immune response, you have what are called regulatory T cells that kind of contract the immune system and kind of bring it back down to homeostasis, that sort of monitoring days when you're not having an active infection, while still leaving some memory cells, some memory B cells, some memory T cells, some long-lived plasma that long term secrete antibodies hanging around, just in case that pathogen would come around again. Go ahead.


Dr. Mike Patrick: One of the terms that has really been in the news is cytokines. And so we hear about like a cytokine storm with really bad outcomes in COVID and if we think back to the 1918 flu pandemic that a lot of young people died, and we think it was just their overactive immune system, and that really is what we're talking about here, right? That the helper T cells use the cytokines to get things moving, but then we want to pull it back in. You don't want your SWAT team mowing down the whole neighborhood. You really want to have some control over this. That's where the regulatory T cells come in, right?

Dr. Benjamin Prince: Exactly, exactly. So I think the cytokines are, they're just sort of messengers. Maybe when you were in school, you were passing note to your friend. These are the cells passing notes to their friends, their immune cells, or they're passing notes to other non-immune cells to try to help take care of the infection. And then, once things are kind of taken care of, go back down and regress and contract in a very systematic manner that's actually really well controlled and kind of go back to that homeostasis. 


And I think, one of the things that you bring up I think is really important in that, you know, a lot of times, when we get sick, when we get a viral infection, we feel bad. If we get a fever, we get what we call myeologist or aches and pains, and we get all these other symptoms that are some of the worst symptoms of having an infection, and we jump right to that stupid virus or whatever. And it's actually not the virus, it's your immune's response to the virus that a lot of those symptoms come from. 

So that, as you can imagine, even in a normal response, you sort of feel some of these complications, these sort of collateral damage from your immune system reacting to the virus. If you have an unchecked response, it's even more significant. Then, you can have respiratory distress that can occur. You could have an organ damage. You could have all these other things that are the results of just unchecked inflammation and a lack of bringing things back down and regulating it back to where it should be. 


Dr. Mike Patrick: And just to give you an idea of how complicated all of this is. There are at least 50 different cytokines that have been identified, each are a different message that they're giving to the immune system. So these are kind of like, if you think about our police example, these are the call number. Like we get a 348 over on West Fit Street. That's a specific message and each of these cytokines represent a different message. And we're really just beginning to learn how all of these interacts together, right? 

Dr. Benjamin Prince: Exactly. There are many different classes of cytokines that not only do certain tasks, so either cause you to have a fever or ramp up your initial response or tell other cells to "Oh, we're seeing a bacterial infection. We need the cells that are important for bacterial infections to come do things." Or "Hey, you know, we're seeing a viral infection, we need those kinds of cells to come around." 


So there's those kinds of cytokines, but there's also another group of molecules, not to make this even more complicated, that are called chemokines. And so, chemokines are sort of like if you're on a highway, think of them as like the road signs that tell cells, important cells that need to get where the infections ongoing, that tell them how to get there and where they need to go. So there are several small molecules that really kind of connect everything altogether and allow the immune system to work in a very coordinated and controlled manner. 

Dr. Mike Patrick: Before we get to antibodies and B cells, which is another really important part of the adaptive immune system, you mentioned fever. And for a lot of parents out there, we deal with fevers when your kid is sick often. So the question becomes is the fever doing anything for the immune system? Why do we have fever? 


Dr. Benjamin Prince: And the fever actually does. The fever is actually designed to help make it a non-ideal environment for whatever pathogen that's trying to invade to body to be able to replicate and carry on its normal day. We don't like fevers, it doesn't make us feel good, but neither do the pathogens. So it is actually part of your body's way of making the host or yourself an environment that is not optimal for that pathogen to survive and sort of take over.

Dr. Mike Patrick: And so it's a balance really, right? We want our kids to be comfortable, you want to treat a fever if the fever is really affecting the quality of life of the kid. But if the kid is happy and playful and they have a 102 fever, do we necessarily have to treat that every time? 


Dr. Benjamin Prince: Not necessarily, and even some of the complications from having rapidly increased fever such as febrile seizure and things like that, there's a lot of data that even when you treat the fever some of those things still occur. Now, I will say it's not fun to have a fever. And so, there is some benefit in giving antipyretics or your Tylenols, your Motrin, ibuprofens, those kinds of medications, your nonsteroidal anti-inflammatory drugs, to help bring down the fever so that that individual doesn't feel awful. 

And then, there are certain situations where a fever can get so high that can have other side effects as well and cause brain injury and things like that. So just as in anything else, it's important to think of things, too much of something can also be bad.

Dr. Rebecca Scherzer: Oh, I'm sorry. 

Dr. Mike Patrick: And so... No, no, go ahead, Becky. Go ahead.

Dr. Rebecca Scherzer: Just kind of thinking along those lines, I've said several times now that the immune system is really a delicate balance. We want it to work well. But sometimes, as you mentioned, when we talk about COVID-19, it can also be exuberant and that can lead to problems. 


So when you think about  autoimmune disease or times where your immune system is going a little bit overboard, as I think we definitely have seen being reported with COVID-19, that a lot of the issues aren't just from the infection, but a kind of overwhelming immune response. We are starting to see more and more medications that are out there to treat things like autoimmune disease, and different ways that your immune system is overactive. And sometimes those are being looked up for different kinds of infections to actually we want your body to be able to respond to an infection, we want the immune cells to be able to respond. 

But sometimes, the cytokines, if things that are going a little bit again overboard, we want to be able to bring it down, and so that's why when you look at the news or read the news, starting to think there's some of the medication being used to dampen down the immune system. That's why we don't want to stop your body from fighting the infection, but we also want to make sure those cells aren't doing more harm than good.


Dr. Mike Patrick: And this really plays into the complexity of medicine, to begin with. And that, as doctors, we're looking at so many data points to come up with what the right answer is. And the same thing, just simply with the kid with the fever, there's going to be instances where you do want to treat it. Then there's going to be instances where it's okay to let it ride. And really, parents having a conversation with their child's doctor and where that doctor can look at all the data points and really give you an idea of what you need to do. 

And a lot of times, this is where the art of medicine also comes in because it's not all cookie cutter, like each kid can be a little bit different, right? 

Dr. Benjamin Prince: Absolutely. And just to echo what Becky said, we don't know everything with every disease. We're still learning. For example, with COVID-19, there are some instances where maybe what you're seeing, the complications from the disease are the result of that secondary inflammatory response that's causing damage. But then, other times, in patients that have a weakened immune system or immune deficiency or have a hard time controlling the virus, it could be the result of ongoing viral replication and proliferation. 


So even in just things like corticosteroids, you may see under those, whether it helps or not, the verdict's still out. And some of these other medications, we're really not sure. And even within one disease or one kind of COVID-19, as you said, it is an art. And you have to take each patient that comes to you and what might be the proper treatment too for this patient that you're seeing in front of you might not be the same treatment that you would consider in the next person that you see, depending on what the complications are that you're seeing from the disease. 

Dr. Mike Patrick: Let's move on antibodies and B cells. What are their roles in the adaptive immune system?

Dr. Benjamin Prince: So B cells, so I usually call B cells the artillery or the snipers. I don't know what the thing is there.

Dr. Mike Patrick: So the SWAT officers and their weapons are the antibodies. 


Dr. Benjamin Prince: Yeah, there you go. So B cells are actually another form of antigen presenting cell. And what a B cell does is that it recognizes pieces of a pathogen or a foreign molecule. And it can recognize anything from a sugar to a protein to a lipid. But when it recognizes it, and it causes the B cell receptor, which is in a lot of ways very similar to the T cell receptor, that you have a diverse amount of them. They're very specific for certain things. They kind of change depending on what you're exposed to. 

When it recognizes something, it kind of goes and talks to its friends using those cytokines and those we talked about. So it might have a conversation with a T cell. And then that T cell, whether decides, "Is this something you should be worried about?" And if it says, "Yeah, this is something that I recognize as well," then there's some signals that go on. 


And there's just not signal and the receptor, the direct receptor, but there's close stimulation that happens and in other cytokines that go out that kind of communicate back and forth, that then tell that B cell to activate, to go on and start producing, instead of just B cell receptor, a secreted protein called antibody.

And an antibody kind of looks like a fork or a Y. And it has at the very end of it is whatever initially recognize that pathogen or that piece of that pathogen on the B cell receptor is going to be identical to the secreted antibody that B cell secretes. And so, once it gets those signals from the T cell, the B cell will activate and either turn into a short-lived or a long-lived plasma cell, that they're just warehouses and machinery to just churn out that artillery or those bullets, and those bullets being the antibodies. 


And antibodies, they play a  huge role, so the connection here is this is actually what we're utilizing in vaccines, right? Like this is the big piece of the adaptive immune system that are sort of gone to take care of the problem. But there are a lot of different ways that antibodies work to help control an infection.

So the first way is in neutralization. So if you have a pathogen or a microbe that needs to access a certain receptor to get into that cell that cause a problem, antibodies can block that. And they can also neutralize toxins and things like that. And that's what we actually are doing when you're getting a tetanus vaccine. So when you're getting a tetanus vaccine, you're actually creating antibodies towards the tetanus toxoid, and they're neutralizing antibodies that prevent that toxin from causing problems. 

So that's one of the big ways that antibodies are affected in helping the immune system. There are other ways that they can play a role, too. So I think Becky talked a little bit of those Pac-Man cells, those phagocytes. And there are some pathogens, some bacteria, that their virulence factor, the way that they invade the immune system is that they have this sugar capsules. 


So they're not sweet, but they're made of polysaccharide. And it actually makes it so that your pathogens, oh, excuse me, so that your phagocytes, those macrophages, those neutrophils, things like that, they have a hard time grabbing on to them and ingesting them. So the Pac-Man cell can't do his job. 

And so, there's a process called axenization where the antibody will bind, recognize and bind to that sugar capsule is normally very slick and slippery. And it kind of acts as a handle that that phagocyte can grab on to and then do its job. So that's another way that antibodies can be effective. 

And then, one final way that I'll just throw out there as well is in the process called antibody dependent cell-mediated cytosis or a cytotoxicity. And we talked about that natural killer cell. I think this is really cool. So Becky mentioned there's this natural killer cell, that all it does is go around and when it sees certain things that it knows are not right, it will kill that cell to help prevent a viral infection. 


But it can't recognize specifics. So it's very general and it recognize a certain pattern and there's very basic things that it can see. But antibodies can help make that natural killer cell much more specific. And what happens is an antibody can recognize like a viral cortical for example on the outside of the cell or something on the outside of the cell that's clearly not supposed to be there. 

And then, those natural killer cells have receptors that then recognize that tail piece of the antibody and give it a signal to that killer cell. So it's another way that the innate immune system and the adaptive immune system sort of work together and you create a much more specific response to an infection, but it's actually done and mediated through the process of an innate cell, a natural killer cell. So antibodies do a whole lot for us and they are very very important. 


Dr. Mike Patrick: Really amazing and you could spend an hour just talking about antibodies, right? I mean, there's the IgGs, and IgMs, and IgA and there's different antibodies and they each do a little bit something different. One thing I did want to mention, the IgM antibodies are actually like five antibodies together. And so, in our police example, these were the five citizens that we're keeping as suspect at the scene of the crime until the police could arrive. 

So I had to point that out, because I think that was pretty funny. And then, so then, how does memory exist? So like you make these antibodies, and how do we then remember them so that we can get a jumpstart on fighting an infection the next time that that organism comes along. 

Dr. Benjamin Prince: Yeah, so memory, again, one of the integral pieces of why the adaptive immune system is so important. In that initial response, in that initial immune activation to whatever is invading, there's a whole process. 


And this is why it takes several days, and where you form effective antibodies, you form very specific T cells, you form very specific B cells. And during the context, during the process of that just initial infection, the initial responders, the B cells and T cells, the antibodies that initially responded and recognize that pathogen are not nearly as good as at the end of the infection. 

So there's a lot of different reasons why those cells just in the process of seeing that same pathogen become better at recognizing it and getting rid of it over the course of that infection. So once you take care of that, it's really important to hang on to those cells, you don't do that whole process all over again. 

And so what happens is you have memory T cells which we briefly mentioned, memory B cells, and then this long-lived plasma cells that all they do is they kind of the huge clonal expansion goes away, but you still have a few guys that hang out and they just sort of police the different lymph nodes, the different secondary lymphoid tissues or those police stations. And they say, "Hey, we got a problem here? Anybody reaction okay?"


And if they recognize that same pathogen again, you don't have to go through that whole process again. They can much more quickly and much more effectively activate the adaptive immune system and take care of that pathogen. And that's the exact reason why we get vaccines is you want to expose that patient or that person to more of a less deadly form of whatever you're trying to vaccinate or immunized them to. So that when they come across the real deal, you don't have to go through that whole process again. They've already seen it, you have that memory there. 

Dr. Mike Patrick: Becky, there is so much research right now going into creating a COVID vaccine against SARS-CoV-2. And some really interesting, again, we could do an entire episode just on vaccine development. We can do a whole series of episodes on vaccine development. And this is really giving us a  chance to learn some new techniques in a very fast track sort of way making new vaccines. 

But let's talk about one vaccine that we know about with the flu vaccine. Just describe how that works and why do we need a flu shot every year? 


Dr. Rebecca Scherzer: So vaccines, as Dr. Prince had mentioned, they can be such an important part of the immune system and how we respond to infections. The goal is that we have vaccines that help prevent diseases that can be dangerous or even deadly. And again, just like Dr. Prince was saying, part of it is that the vaccine works with your natural defenses to help really be able to say "Okay, I was exposed to this through the vaccine. And some vaccine, you just need one, and some vaccine, you need multiple ones to really get your immune system to respond to it."


But should you get exposed outside of the vaccine setting to that infection, your body is ready to go. That squad team is ready to head out and immediately take care of what the infection is. So that's why vaccines can be such an important part of really of any body of any ages.

We talked about herd immunity and that's a big part of why vaccines are such an important part because they do allow protection for folks who cannot receive vaccines for lots of reasons. Either their own immune systems don't work well, or they've been weakened or they're on certain medications that won't allow them get vaccines.

So when we talk about herd immunity or community immunity, that's what the goal is why we vaccinate and through childhood and adulthood depending on the vaccine. So we do give flu shots every year and this is because flu virus has evolved so quickly. So last year's vaccine is out of date. So what folks do is they'll look ahead, months and months ahead of flu season to what they think is coming from the specific different kinds of flu strains. And that is why every year, you need a new vaccine. 


Again, last year's is out of date and probably will not help you unless the same strain come through your community. And flu virus is actually also ones that can change and adapt pretty quickly. And so again, you need a new vaccine to help protect you every year. Every year, you want your body, when it gets vaccinated to produce those immune cells as antibodies. And that's really why we're going to give it year to year to make sure you got the right antibodies or the right protection for that particular year. 

Dr. Mike Patrick: Well, what we would need is to find the protein on a flu virus that is common to all the strains of flu viruses, right? 

Dr. Rebecca Scherzer: Yeah. 

Dr. Mike Patrick: If we wanted to make one vaccine that would last from year to year, and that still alludes us, right? 

Dr. Rebecca Scherzer: Oh, definitely. And even thinking through the vaccines that you don't receive, that is often is the flu vaccine. You do have waning immunity to vaccines. Again, we give you several of them in childhood to help really kind of prime and then get your immune system ready to face that infection should you get it not in the vaccine setting. 


But we definitely know that you could have waning immunity, is what we call it. So that's why sometimes we need booster immunizations as you go through into young adulthood and then to adulthood. 

Dr. Mike Patrick: So vaccines present us with an antigen that our immune system can respond to and make antibodies, but to do that in a safe way that does not cause harm. Then when the real disease or pathogens comes along, then you're able to mount a quick response, in a nutshell. 

Dr. Rebecca Scherzer: That's exactly it. And again, most of the vaccines out there were really looking to prevent diseases that can be dangerous or even deadly. 

Dr. Mike Patrick: Ben, what sort of things lead to, we talked about a  weakened immune system. And we see such huge variability, even with COVID, and we have all of these folks who are completely asymptomatic with it and then others who have just devastating disease. Why does the immune system differ so much from one person to another? 


Dr. Benjamin Prince: Well, I think that's actually a really good question. And one that I oftentimes will address very frequently in amongst parents and patients in my clinic. And one of the reasons is there is a huge just normal variation in the amount of the factions that, for example, kids get yearly. And it's one of the hardest things that pediatricians have to do is to try and differentiate, okay, of these children who are getting infections, which ones have a truly weakened immune system and which ones, you know, is this just normal variation because of a multitude of other factors. 

And so, I always point out that the average child will have eight to ten respiratory infections per year. That's basically something every six weeks, you're going to have a respiratory tract infection. And in certain situations, that cause increased overexposure to pathogens such as older siblings or attending school or daycare. This can go up to 10 to 12 infections per year. 

And if you think about the normal, the mean duration of an infection about eight days, many many days, these children are ill. And a lot of the times what I'm seeing patients in my immune clinic, most of them don't have an immune problem. Just for certain situations, they just have maybe a little bit on the upper end of that normal variation. 


I think the big things to point  out that differentiates a person that has a true immune problem from just sort of normal variation is that a healthy child is still going to grow and develop normally. They're not going to have severe deep seated or persistent infections. And they're not going to have infections with atypical pathogens or require frequent antibiotic use or hospitalizations. 

And so, once if I am seeing that stuff, then I start to think of either primary or secondary reasons to why this patient might have an underlying immune problem. And without going into a ton of detail, when I say a primary immunodeficiency, I'm referring to over 400 identified genetic or inherited disorders or defects in the cells or tissues of the immune system that result in it not working appropriately and not function correctly. 


Even though this is why I'm getting lots of referrals, they are much much more rare than secondary reasons why people have immune problems or immunodeficiencies. And secondary immunodeficiencies result from a variety of factors that can affect the host that has a normal immune system. And this can include anything from environmental conditions to metabolic diseases to infectious agents and drugs. One of the most common reasons worldwide, not seen as commonly here in the United States, but worldwide, malnutrition is a big one that leads to a secondary immune deficiency. 

Age can also play a role, so really, really, young kids, their adaptive immune system that we talked so much about, their antibody system doesn't work as well. And that's actually one of the reasons why you have that passive immunity that we've also talked about that's transferred from mom in utero to help protect them during that time. But if they're premature, they didn't get that antibody across placenta to help protect them for those few months of life, they can just be intrinsically immunodeficient.


And then, on the other extreme, elderly people, so the extreme of that would be they're also at increased risk of infection. And it's just because as Becky mentioned, the thymus that's really robust and there in the beginning of life, it involutes with age. So you don't have as robust, you don't have as many new T cells that are there that helping you out. And you're sort of still then relying on some of those ones that are hanging around from the different infections that you've seen over the course of your lifetime. 

And so, we could go on and on and on, other examples of secondary cause of infection includes metabolic diseases like diabetes, uremia from kidney or liver disease, certain immunosuppressive medications such as steroids. Anatomic abnormalities, so we talked about how important that spleen is or people that don't have a spleen, that's an example of an anatomic reason why they might get infections and other kinds of things as well. 


Smoking is another one, even allergic disease, as I'm evaluating kids that are having frequent respiratory tract infections, I'm thinking do they have underlying component of AR, or allergic rhinoconjunctivitis? Do they have eczema that might be predisposing them to skin infections because their barrier is disrupted? Do they have asthma that ultimately leads to more frequent pneumonias and things like that? 

So there are many, many, many reasons. And by far, the majority of patients that I've seen in clinic, if they do have an immune problem, it often tends to be one of those secondary reasons. And the good news is a lot of them, we can modulate them, we can affect them. And we can treat better control of chronic disease or we can better control asthma. We can better control allergies. We can remove smoking from the environment. And so, the good news is some of these things, we can control and help augment. 


Dr. Mike Patrick: And really, that does come back around then to the variety of severity that we see with COVID, and some folks being completely asymptomatic and just the viruses in your nose and you can pass it on to other people for a while, but your immune system is taken care of it. And then, you have older folks whose immune system may not be working as well, but you can also have younger folks whose immune system overreacts. And when we're thinking about a process that is as complicated as this is, there's just so many points where things can go right and there's so many points where things can go wrong. 

And then, when you have a new virus that none of us have immunity to, and then you're going to magnify all these little problems, because there's so many people having, the rare thing is not rare anymore because so many people are infected at once. Is that an adequate description?


Dr. Benjamin Prince: I couldn't agree more. So right, so a lot of the high-risk populations, you can see some overlap. So we just talked about some of those risk factors, right? So some of those risk factors of COVID, while we don't know all of them right now, but the common ones that had been described are older age, hypertension, coronary heart disease, obesity, diabetes. Those are the same kind of secondary immunodeficiencies that we just kind of address and talk about. 

But then, on the other hand, you have young kids that are having, seem to have more complications later on in the disease where it's more maybe that regulation of the immune response that's ultimately leading to acute respiratory distress syndrome, the systemic inflammatory response, the organ failure... All that stuff is really a result of not being able to kind of tone things back down.

And so, that goes back to... it is an art, and it depends on why we think that disease is causing a severe complication. And then, when we figure that out, if we can, what would be the next best medication to give to try to help that patient?


Dr. Mike Patrick: I find it interesting that as I watch the news, oh, we found out that COVID is doing this, and now it's doing that and now, it's doing this, and this other thing. And all these things it's doing but they're all things that viruses always do. We just see it on a much smaller scale because we don't have so many people getting infected at the same time with it to see that all magnified. 

Dr. Rebecca Scherzer: Now, totally, I mean, your body's naive to this until you have been exposed to it, so it is, it's making and some patients are very largely response to that, to the infection and then not able to calm down the immune system. We are just seeing it in such high numbers because again it is novel. 

Dr. Mike Patrick: Well, this has been a fascinating discussion that has lasted over an hour now. But I knew it would, because this is just so interesting. We could go on, there are still things that I want to ask that I haven't had a chance to, but we do need to come to a close. 


If you are listening to this, and you're thinking, yeah, this is really fascinating, I want to learn more, I would really highly suggest that you check out the Vaccine Education Center at the Children's Hospital of Philadelphia. And I'm going to put a link to that in the show notes for this episode, 462, at 

It really goes into again, the human immune system, types of immunity, parts of the immune system, development of it, how everything comes together and works. And what happens when the immune system does not work properly. And there's so much of a spotlight on the immune system these days. I think you'd find that information quite fascinating and I would encourage folks to check it out. 

All right, well, Dr. Becky Scherzer and Dr. Ben Prince, both with Allergy and Immunology here at Nationwide Children's Hospital, thanks again for stopping by and educating all of us.

Dr. Benjamin Prince: Thanks for having us. It was fun.

Dr. Rebecca Scherzer: Thank you for inviting us. 



Dr. Mike Patrick: We are back with just enough time to say thanks once again to all of you for taking time out of your day and making PediaCast a part of it. Really do appreciate that. 

Also, thanks to our two guests, Dr. Becky Scherzer and Dr. Ben Prince, both with Allergy and Immunology here at Nationwide Children's Hospital. 

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Thanks again for stopping by. And until next time, this is Dr. Mike saying stay safe, stay healthy, and stay involved with your kids. So long, everybody.


Announcer 1: This program is a production of Nationwide Children's. Thanks for listening. We'll see you next time on PediaCast.

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