Immune Platoon!

can you share your circulatory system? Joining me today is Philip Detmer, writer and creator of Kurtz kustok a k A in a Nutshell, which is a beautiful YouTube channel that teaches science and biology with absolutely gorgeous animations and clear entertaining narration. He's also the author of the book Immune, which is like going on to get to know you, meet and greet with your own immune system. Welcome Philip, Hey,

thanks for having. The immune system is one of those things where you don't think about it too much day to day. Uh, you only think about it when you're actually sick, and then you're like, oh, right, this is a thing most people don't really have, like a concept of the immune system. If you try to visualize it, like, you don't see anything sort of accurate actually, because as you said, it's it's not a thing like, yeah, this is enormous complex stance of like trillions of things doing

this stuff at the same time. I read the Immune Book and it's really really nice. I really like how clear the explanations are, because I think something like the immune system is so complex it can feel really intimidating. One thing I think is hard for people to imagine is like, where is the immune system. Do we have an organ that is the immune system? Do we have a little barracks filled with immune soldiers or they just

like everywhere. What I found helpful is to imagine the immune system as an organ system, like like your cardiovascular system. That's basically sure, like you have your heart and you have like all your blood vessels all over and then the tiny tiniest blood vessels going pretty much everywhere. That's sort of how the immune system is. It's like an

incredibly expansive organ system. It's just like completely saturating your body. Basically, do you have like your own immune system highway system, the little the lymphatic system that looks a little bit like your cadivascular system. You have dedicated like a few hundred dedicated immune organs like you asked for, like like a battle stations or something where like the soldiers gather like like your lymph nodes are that basically um, like

spread all over your body. Um, you have like two bigger dedicated organs like the simus above your heart the size of like two chicken wings, which is like a like I call it the murder University because like this is like where immune system cells are trained, but like only two percent of the students survive education. It's kind of like the squid game, but for cells in your body. Yeah,

similar survival, right, I think. And of course there's like an enormous amount of cells of the immune system basically patrolling every border you've got sitting all below the skin, sitting everywhere like just like blow all, um your more cos us just like patrolling your body like um, that's like like billions and billions in your blood right now.

And I think the last aspects of the immune system, um, it's just like like sort of like passive defenses like like sort of like proteins that you can imagine as like mine fields can kill invaders just on their own, are basically in every fluid of your body, so in your blood and are the other disgusting stuff a booby trapped body, And so what is our immune system protecting us against because is I mean, obviously it's protecting us

from getting sick or from getting infections. But those kinds of things like illness and infection comes from many different things, right, It's not just a virus that can make you sick. I mean basically, your immune system protects you from everything that is not you in a really basic way. You can think about immune system as as something that can distinguish between self and other, and everything that is other it wants to kill and destroy. It's like not happy

about other. Like if you enter the body, you need like a very specific ah, what can you say, like like a like a password or a key card? Yeah, okay, perfect, Like if if you if you're like a prop for example, if you're like a healthy bacteria for like your cat microbiome, you need like a special code or password to have to be killed immediately. The immune system basically it wants to make sure, um that nothing that's not the body exists within the body except the few exemptions in our

cut or so. I think a big misconception about commune system in regard to that is that it's like it's it's very it's great if it's very strong and very aggressive and wants to kill everything. But actually, like the the big thing about the immune system is that it seeks balance. So like one way to imagine the immune system would be like rugby players that like just like smash faces. And if your immune system is like that,

that's not great. Like you want immune system to be more like ballet dancers, like like very carefully select where to step and then just like I like, um, not overly aggressive if it's not necessary. Yeah, because if the immune system is overly aggressive, it can actually hurt you,

hurt your body unintentionally. People with autoimmune disorders, your immune system or even something as simple as like an allergy, your immune system is actually hurting you because it's overreacting to something that it doesn't really need to react so strongly to. And in fact, a lot of illnesses the suffering from that illness is from the immune system. And sometimes that's okay because that's just the immune system working

and curing your body of the virus. But sometimes if that immune response is too strong, it can actually be pretty deadly, right, Yeah, Like even going further out, like in the last two years, the papers have come out to suggest that about half of all deadly of like, like, but half the people dying today are dying because of something that was initially caused by immune system overreaction. So basically what But it's like a little bit weird to like I think about is it? Like basically every every

time your immune system gets active, it causes damage. Like an delated immune system is like technically not great, and your body does a lot of stuff to like, um, calm it down once it's activated. But yeah, like whenever you're you're you're sick and the immune system gets active, like damage happens, and that damage is often like the

symptoms we associate with being sick. Yeah, Like one of the dangerous reactions your immune system can have to a pathogen or even something that's not harmful just an allergen is a cytokine storm, which is it's as far as I know, it's as kind of chaotic and frightening as it sounds, because it's you know, it's this chain reaction of an immune response that can cause a lot of inflammation and damage to your body where the immune system

is just trying to basically do its job. And take care of your body and clear out any pathogens that could hurt you. But it in effect, what it does is it started this chain reaction of inflammation that is damaging your own tissues and making it difficult for your own body to function. Yeah, totally look like a cide. The kind storm is definitely one of the more creepy things that can happen to you. Should be briefly explained what cyto kinds are. Yeah, let's do that, and how

about by let's how about you do that? Okay, Like it's okay, let's let's simplify a lot, so like we don't sit here for an hour. But like basically cydeo kinds a little proteins, little chemicals that, like especially mune

cells used to communicate with each other. So for example, like a commune cell that is like agitated and like like aggressive and fighting will release cyto kinds that tell other immune cells, hey guys, get here, get your fast or it will just like generally show like hey, battlefield this direction um or they will like activate other immune cells.

So it's like the all the communication happening within the immune system is like in large parts sales releasing chemicals picking up other chemicals or cyto kinds and then acting

according to the type of cytokinds they picked up. So, for example, like like a cytokind storm, there's too many of those like messengers released at the same time in a in a too large of a scope, and it's basically activating immune cells where they should not get activated at place as where like there is no infection or where they shouldn't activate. And yeahs, as we discussed before,

the immune system causes damage whenever it's activated. So a cytekind storm is a little bit your whole immune system army, and your whole body is like sort of like activated at once. Yeah, everyone's getting scrambled. Yeah, it's it panic that everybody's like everybody's getting their weapons out and shooting around, but like maybe there's nobody to shoot it, so a

bunch of friendly fire. Yeah, that's into sting because the way you described cytokines actually reminds me of pheromones in bee colonies or aunt colonies and these other you social insects where when a bee stings you, it actually releases a chemical that signals to other bees that it has stung you, and it calls other bees sort of to come over, and also sting the thing that it's stung.

So that's why sometimes a bee swarm can be very dangerous, especially for more aggressive b species, because at the more bees that sting you, the more of this pheromone is released that informs other bees, hey we're attacking this intruder right now, come over and you know, get your stings in.

And so that can be very dangerous for you a human being when faced with a bunch of bees, and that can I guess happen in your own body as well with cytokines, so your immune cells are doing a similar thing to bees of like, hey, we're attacking this intruder. Here's it's chemical to tell other cells to come to

my aid and to attack this intruder. And then if that gets out of hand, if you have too many of those cyta kinds, you just have pand ammonium of a bunch of soldiers just shooting at everything in their path, basically inside your own body. Yeah, that's a very good description. I think that's basically how how this works. Like a very stupid things reacting to chemicals and and that's actually isn't that one of the problems with people who get

sick with COVID. Right, So, various infections, especially in the early stages, hugely rely on the cyto kinds of these communication methods to activate the immune system and prepare the battlefield for later fighting. So one thing that that seems to happen in COVID, according to some papers I read, is that like COVID suppresses decide the kind that basically would slow down the virus infection and gives immune system

more time. But while it's the at that time, like at the same time, it's sort of boost the production of cytokinds that cause inflammation. And inflammation is basically just like blood vessels opening up a little bit and letting like fluid into the tissue. So what COVID seems to do is just like while basically avoiding being slowed down by cytokinds, it just like floods the lung swift water. Yeah and yeah, that's not great. And it's like one of one example where like a pathogen has like hacked

the mutism system a little bit. That is one of the creepy things about the arms race between our immune systems and pathogens is that as pathogens evolved, like we are starting our our immune systems will evolve in response to new pathogens, like a new virus. But in the meantime, seeing it when the pathogen has the upper hand against

the immune system, it's it's very frightening. It's it's something that makes you realize, oh yeah, no, we are in a constant arms race with things like viruses and bacteria, and sometimes they actually come out on top, which is kind of a both humbling and frightening kind of thing to witness. And one aspect of that is that, like not all of our immune systems are created equally, so just like like in a population, a certain amount of

people will be extra vulnerable against certain diseases. And so yeah, it's like we as a species need to survive a pathogen, but as an individual, yeah, it's definitely the best, yeah exactly. So yeah, so it is. It is something that's very interesting.

So it's like our immune system, even though sometimes it overreacts and hurts our body, it is absolutely necessary to prevent us from being completely basically devoured from the inside out by things like viruses and unfriendly bacteria and other pathogens. If you think about it, like Basically, if you die, you can like like witness what happens to a body once there's no immune system anymore. It's just like yeah, like it's completely dissolved by micro organisms. Um, so yeah,

that would be our faith without an immune system. Yeah, yeah, exactly. The reason that bodies decay is that you're no longer alive, and so your immune system is no longer around to kill off the bacteria that want to eat you. In fact,

like they're while your life. Some of the most dangerous diseases are things where say bacteria is able to survive your immune system, so like necrotizing fasciitis is something where a bacteria is eating away at you while you're alive, while your immune system tries desperately to stop it, but

it's not fast enough. It is kind of terrifying to think, you know, what life would be like without our immune systems and without modern medicine to help when people are immuno compromised, and it's like the against the vast, vast majority of micro organisms or immune system is perfectly fine. Like most viruses a like have like no capacity to hurt us, like most bacteria don't have that, but like

yet exactly those like those few quitters. I think that's like only like two hundred species of viruses that like can infect humans. I need to like please could not quote me, but like something in this area. Um um. Yeah. So like only once like a like a micro organism gains the ability to like like keep our immune system and check or like like deactivate part of that. Only then it becomes like dangerous to us. Most other things

are basically like no challenge for immune system. In the book Immune, you often describe the immune system as beautiful. What do you mean by this? Because if I think about the lymphatic system or you know, lymph node or some white blood cells, you know, physically speaking, looking at it, it doesn't look that beautiful. I mean, come on, like like the lymphatic system super highway, stretching throughout your whole body, and I think that's magic. It's like so great. I mean,

like the immune system. It's like often called like the second most complex biological system after the human brain. Um. And I think that's like and that's like that's like a description. I really I really like it's like just like unfasom fathomably complex. And I think that's like in that their lives like that immense beauty. I feel at least, how are we even my life? How is it possible like like our body like for for ourselves to defend it,

Like our body is so enormously large. It's like like imagine you had to like defend like central Europe or like like the US. That's like the that's like the scope. If you were one immune cell, you can just like look at the whole US and say like, okay, I need to defend that, and like, um I can I need to be called maybe like too Florida today and to Texas tomorrow. It's like huge distances and the amount of connectivity and communication and like systems that are like

cells and proteins and all that stuff defending you. They're like really like they're stupid, like lovely but stupid, Like like a cell is pretty useless, just like this mini protein robot that does its thing according to the chemicals that picks up and it's like code. But somehow, like like trillions of these stupid paths come together to organize this like incredible defense of of you of yourself, And

I think that's beautiful. I don't know. On the more macro level makes me think about why I find ant colonies or b colonies so beautiful because like an aunt itself, I mean, I mean that's with no disrespect act an individual ant is pretty stupid. But then when you get a whole ant colony together, they have such complex and interesting behaviors like raft building, bridge building, and especially good example. Have that in the book at some point. But like

stupid things doing smart things. Maybe that's why I love my dog so much, because she's a stupid talked out once in a while, that's a smart thing. So we've talked a little bit about human immune systems and why they're so amazing and beautiful, and now I want to talk about some weird exceptions to sort of the immune system rules. I mean, every animal will have a slightly different immune system. In fact, every individual has a slightly different immune system. We don't all come out with carbon

copies of each other's immune systems. That's why some people will get sick more than others. You know, they're not just they're not just complainers that people can literally get more sick than you because their immune system doesn't respond in the same way that yours does. And then on the species level, of course, every species of animals has a different immune system. Some are more similar to ours, some are more different. One of the most interesting mammalian

immune systems out there is that of bats. So I love bats, that's not a secret. They're adorable, misunderstood little cutie's that I want to love and cuddle, but you shouldn't. You shouldn't love and cuddle them, even though they are so cute. But they have really fascinating immune systems. Now, obviously, there are many, many species of bats. They're one of the most diverse groups of mammals with incredibly diverse morphology.

But often they will have somewhat similar immune systems. So when I talk about bat immune system, I'm talking about a range of different species that share these characteristics. Bats get kind of a bad rap, I think. Obviously. There's a lot of the myths, like they nest in your hair, they suck your blood, which are just not really true. There's only one species of vampire bat out of like the three or four total species that has ever even been documented to drink human blood, and it's never enough

to kill anyone. It's like literally less blood than you have to give when you go to the doctor's office. But but one of the things that people are maybe squeamish about bats are that they are seen as being dirty and disease written and that they're always the ones responsible for, say, zoonotic diseases, and which is the actual truth behind that is a little more complex than them just being like dirty and full of disease. So uh,

because bats are actually really a combating disease. They have really incredible immune systems that can fight off pathogens that might kill other mammals. So you know how like you know, everyone's kind of points the fingers at bats for COVID and for other diseases like that sort of your general since from from people's perspectives on bats, I mean, yeah, like they they probably did cause COVID, So that's it's a little bit fair. What what does make the immune

system different? So they it's complicated, right, So like they have this is what I put you through at the first in the first half, But I really want to know, like, like I actually don't know a lot about bats, so I'm really curious to like to learn how they're different. Yeah. So so yeah, so they the reason that they may be anddidates for us finding zoonotic diseases in them. Like, if they do spread zoonotic diseases, it may not be because they're dirty or like more prone to diseases. Actually

could be the opposite. That they have a much more effective immune system than other mammals. So diseases and pathogens actually have to struggle harder to survive inside a bat than they would another mammal because the bat's immune system is so strong but still like similar enough to like ours that if we have bad luck, they can jump

over basically right right right. If these viruses have to mutate a bunch of times to try to even get a foothold in a bat species, these pathogens are just going through many more They have to mutate much more rapidly than if they were infecting another less robust immune system. And so just the that kind of casino of of viruses try to roll the die every time that it mutates to see, you know, whether it can get a

foothold on some sell and some organism. They're just like doing this many more times because it's so much harder to survive inside a bat that I mean, that is a theory. I don't know. This is these are all kind of theoretical things because the we really need to study bad immune systems much more to really get a

good understanding of it. Because the bad immune system is so robust, it doesn't necessarily mean that they're responsible for passing on zoonotic diseases or that this is just like one stop off on the road of like these diseases on their path to humans. But one of the theories is that, like the bad immune system is like a thunderdome for viruses, and so viruses have to basically become really tough to survive the bat. That's that's super interesting,

if that's not too mean. If a question click, do you have maybe an example like like like which sort of which part of the defense, like anti irs defenses of bats are like so efficient. Yeah, absolutely so. One of the theories for why bats are so tough for a virus to survive is that, um, weirdly so, like their immune systems may be less strongly reactive as compared to humans. So remember when earlier you were actually talking about how you don't necessarily want an immune system that

just nukes everything in its site because that kills your body. Um, you want a more gentle immune system. So that it can target pathogens and viruses but not destroy your own body in the meantime. Um. But of course the downside to that is if you have a more gentle immune system, then it's harder for you to combat viruses, so the

virus might be able to replicate more. But one trick that bats have is that, in addition to their immune system, their thermal regulations, so their bod the temperature may play a key role in immune defense. So researchers have studied the immune response of palaces massive bats so that these adorably, very doofy looking bats. They're from Panama, they're insectivores, very

very cute um. When they're infected with a harmless dummy pathogen, their immune system barely reacted, so they didn't have a fever. They didn't have a huge surge in white blood cells, which is really odd because we know bats are pretty good at fighting off pathogens. The researchers did surmise that this bats immune system was engaged because it lost some body mass, which is a sign that their immune system

is consuming or an energy um. So one of the theories that researchers have come up with and have been studying is that bats rely on drastic change in body heat that they go through every day, uh in order to curb the replication of viruses. So basically they are creating a very hostile environment for pathogens by having such severe internal body weather. So like for many species of bats, when they are sleeping during the day, they enter a

kind of miniature hypernation or torpore. So this is where their metabolism slows down and their body temperature drops in for a lot of species it drops down to about seventy seven degrees fahrenheit, which is twenty five degrees celsius, or in some species during the winter, their body temperature can drop to as low as fifty degrees fahrenheit or ten degrees celsius, which for a human, if your body

is that cold, you're dead, so super interesting. So when they go out to hunt, it's body temperature shoots way up to around a hundred and four degrees fahrenheit or about forty degrees celsius, which would be a high fever in humans. So having a fever is really interesting, right because for when we're experiencing a fever, it's really not great, you know, if you have Also, if you have too high of a fever. It can be harmful to your body.

It can um you know, cause like uh damage because you're essentially you're getting too hot for your your own safety. But in general, having a low grade fever or survivable fever, you are destroying whatever pathogen has infected your body. You're like boiling them alive. Right. One of the theories is that basically they turned into fridges during the day when they're sleeping because they're nocturnal, which slows down virus viral replication.

And then during the night when they're active, they heat up to these little furnaces that maybe also is unfriendly towards viruses and pathogens. It seems are not great for us humans because like this way they can like basically breed viruses such like um don't suffer from our fever responses since we are not getting us hot right right.

This is one of the theories is again like the bat is like this thunderdome, this incredibly hostile environment for viruses and pathogens such that they need to mutate to be tougher in order to even survive like a day inside of a bat. It seems like we are propagating, eradicating all bats. No, absolutely not no, no, no. I mean one of the issues obviously with eradicating all bats is that they do a lot more for us in protecting us from diseases than they could ever do harming

us with diseases. Because of the fact that bats are insectivores and so the fact that the bats control populations of things like mosquitoes, flies, other potentially disease carrying insects, they are much much better for humanity than they would ever hurt us. They're also, uh pollinators, so they're responsible for huge amounts of cromp and plant pollination. So without bats we'd be completely doomed. We'd be screwed. Also, they're adorable,

so how dare you? Okay, but it's it's a it seems like we will help hold off on eradicating all bets.

Then good, good, yes. Uh. Some of the evidence suggests that the daily torpor so that many hibernation they do during the day maybe even more important for them to survive than the that kind of fever that they have when they're active, because that body temperature dropping so much really slows the pathogen's rate of reproduction to crawl, and so that may be why they're relatively delicate immune systems are able to be so effective, so they slow down

the athogen with their body temperature, and then their immune system, with their very surgical precision, comes in and takes care of it, which I think is really interesting because in medicine we sometimes use what's it called cryotherapy, or when you lower a patient's body temperature down while they're fighting

off infection or illness. So one of the theories is that the viruses get tougher when they're faced with bat immune cells, so it's more difficult for them to combat immune cells, so they have to learn to spread and

infect cells more efficiently and quickly. But one of the issues is that these studies were done on bat cells outside of the bat's body, so you're they're missing a key component of how the bat's temperature can affect the immune system, so which when you're studying cells in a petri dish, you have to be forgiven for not being

able to completely replicate a bats internal body system. But um, but yeah, it's we don't really have a complete picture of how bat immune systems impact zoonotic diseases, and in fact, one of the there is some controversy about like how responsible bats are for zooonotic diseases. And one of the arguments against them being as bad as they seem is that we will find more antibodies left over in living bats that are captured because they survived these immune system

battles more often. So because they survive battling these diseases more often, we will simply find more of them with these antibodies UH. And so this concept that like, oh a lot of them are disease written and are always responsible for spreading things to humans, it could just be sort of a survivor bias, right, because other animals that

are infected with it, they may die more quickly. And then so we when we're capturing animals and testing them for these antibody UH shapes and stuff, we don't find it because the ones that were in fact it did die,

whereas these bats survive and have these antibodies. I wonder if we will learn how all of that works the next two years, Like, like COVID certainly has to have like given bad researchers more budget, right, Like yeah, maybe like one of the positive side effects of like this pandemic will be like increased budgets for stuff like that, so we can find I mean, these are like super

interesting and crucial problems to sort of. One of the interesting things about the immune system is how it can be you know, obviously it's it's a huge blessing because it keeps us alive, it keeps us from getting eaten from the inside out, but it can also present us with a obstacle in modern medicine, so we have advanced as a species to the point where we can like shove someone else's organs inside another body, which is crazy, and nobody has sent the memo to our immune system

to tell us that we're doing this. It's you know, it's something that our immune system could have never predicted that doctors would someday be like taking someone else's heart and putting it into a different person's body. When you think of it from the immune system's perspective, that's that's not something that it should have seen coming. Right, as we said, it's the very beginning. It's just like it just sees that something that's like not me, that's like

something other, and I need to kill it. Yeah. Yeah, that's what happens when you're trying to transplant something. Yeah, for millions of years of our evolutionary history. It's it's you know, basically been functioning the same way and it's

worked out pretty well. And now we introduce modern medicine and then we get all mad at the immune system when it starts rejecting organs, which I think is kind of unfair, but nevertheless, it is a big medical challenge because when you say do an organ transplant, the immune system doesn't have any way to understand this organ is being transplanted with all its foreign cells to help the body that you you can't communicate that to the immune system.

It's not sentient, even though it is very complex. It can't tell the difference between the foreign tissues of a donated organ and a dangerous pathogen, so it will often attack something like a donated organ. And this has been like one of the biggest challenges to things like being able to do organ transplants. And even today with organ transplants, patients still have to take immuno suppressing drugs, often for their entire life right to cope with an organ transplant.

One of the reasons why the immune system it's like so aggress I like attacks organs that like would save the life of the body is that they're just like they're made to to look for cells a little bit of So for example, like if you're if you have a virus infection, like many like the majority of the viruses at any given point will be in infected cells

and not float around freely. So basically, if you're infected by a virus, your body wants to find the infected cells and kill them, which is like like another not a small thing to do, right, So, like you have cells inside yourself that have like the they have blank check to kill body cells. That's a very very dangerous power. Like you really want to have a few safeguards for that.

So UM, and one of those safeguards, it's basically that the cells have like a little passport, and on that passport it says, hey, I'm you, I'm I'm part of this system, I'm this body. Please don't kill myself. UM. And you have cells in your body that do nothing but like go through your body, go to every cell and just like check their passports and like hey, everything all right, Like how's your day? Please show me your papers?

And if like this cell is infected by a virus for example, um or if it is becoming cancerous like the okay, all the real mechanisms here, like way to complicate it for not but like super interesting, but let's just keep it with the passport. So like like if a cell is sick, the chances that their passport it's a little bit corrupted, is very high. So those cells that patrol your body all the time, if they find a cell where they're like not happy with like what

the passport said, they just kill them immediately. Very authoritarian society and our immune system, the immune system is a police state and it does not care, like it doesn't like and actually like even more gruesome if you want to, because like they won't kill the cell, they will tell the cell to kill itself. Because that's also like another

interesting thing tax in theory. So it is important how our cell dies because of ourselves infected by viruses, and like like the guardian cell, we'll just like rip it open and kill it. Then all the viruses inside the

in fact itself will spread further. Right, So that's bad, you don't want that, But it's that you tell the cell to kill itself, and it's like been selves killed themselves, which like basically I think like every second a million of yourselves commit suicide something like that, like huge numbers, like like yourselves kill themselves all the time, and it's super important that they do. But when they kill themselves, they basically very politely back their remains into little bags

that that can later be picked up by. Funnily enough, also, the immune system microphages just like clean up dead cells apoptos is right, yeah, exactly, And or we're blubbing where they just kind of like disintegrate into little bubbles and then the macrophages come in and then eat all the little bubbles. Yeah, it looks super funny too, if you find a video on the internet about that. Just yeah, like once cell become yeah, turning into little packages that

it can be cleaned up. It'd be like in a zombie apocalypse if like when there's someone infected with the zombie virus and you have someone roaming around testing everyone for the zombie virus. It's like, oh, you've got the zombie virus, and they're like okay, and then like chop themselves up into little pieces and pack themselves up in the little bags for easy disposal. Yeah. It's like like

sadly humans are not that cooperative. Yeah, but like like like like cells, just like they can be ordered to cool themselves. And it's it's great that it's like that. It works like that. Um, we're talking about immune cells,

not don't don't anthropomorphize them to much. I get so excited. Okay, but I can now now I act like now we've talked super super briefly about the natural killer cell, which is like one of the best immune cells just because just because of its name and what it does, Like, the natural killer cell is one of those cells that do nothing but patrol your body and just like ask people, um, like what what's up? Um? And it's it has like

an ingenious strategy. It's just amazing. So as you can imagine um, cancer cells and in fact, like cells infected by viruses. They figured that out the whole thing of the passport, right they think, oh, if we alter the passport, then the immune system and again like nobody's thinking anything. It's just like it's evolution but adaptation. Yes, this is fluff talk. It makes it like nobody is thinking anything here.

But like let's say including like the viruses. Yeah, viruses and cancer cells think okay, wait, like if you corrupt the passport and we will we will we will be killed. That's not great. And so maybe instead we just don't show a passport. We just make sure that like all the cells patrolling don't see the passport and then they will ignore U because they can't find the flaws and

that it is a very effective strategy. Like like like some types of those patrolling cells need to see a passport to like tell us a cell to kill itself, right, otherwise all our selves, which will be bad. Yeah, it's yeah, exactly, Like it's not great. So for example, like red blood cells don't have don't have passports, and there's a lot of them, so it's a it's good in theory, Okay, But here's the other cell comes in, the natural killer cell. What the natural killer cell does. It just goes around

and checks if cells have a passport. Nothing else. It just checks does the seller have a passport? And if the answer is no, it kills the cell. So basically you have like an like the natural killer cell. It's basically a counter strategy to a counter strategy to the immune system. Like their cells that are controlling passports, their enemies that are hiding passports. There are cells that are just looking for cells that are hiding their passports. This

is like a blade runner situation. Yeah, and okay, going back to organ donations, So what what the problem is and what the immune system could not have predicted millions of years ago when it evolved, is that like intelligent apes at some point would like put organs from one

living being to to other living beings. So what happens now if you get transplanted an organ, your immune cells, We'll just check passport and they will see, oh, this passport is a little bit of maybe not even that much of, but it is a little bit of better

kill that cell, tell it to kill itself. And then like another thing that we talked about earlier, like when the immune system gets activated, it usually activates more immune system and gets more immune cells to that place, and they will find so many cells that have like passports that are a little bit off um and so basically your immune system will eat and kill the organ that

is otherwise saving your life. And that's also why it is like way like way better to have like an organ donor that's like closely related to you, because your passports will match or be like not that different. I think like with like one eyed one twins that's a correct way to say that in English. Um, I think with that like you have like the the absolute lowest amount of reject organ rejection. I think, okay, well we'll not please cut that up. I have no idea. That

sounds right to me. It sounds right right if they're identical twins. Even fraternal twins share a lot of genes like siblings, but identical twins share the most gene of any two simultaneous living humans. So I would imagine that their immune systems are probably very similar. I think it is that way, but like, yeah, it's like one of these things where like it's feels logical, but like should you say the things that seems to follow from that, like we we should look that up. Let's put it

this way. Don't practice home surgery on yourselves, twins out there. Don't take our words for it. Yeah, but please please don't. But yeah, that's like the the the amazing magic of the immune system once again, checking passports and ruining your life. It's like without like wanting to do that, right, but yeah, the immune system, it's like it's a it's a dangerous,

dangerous entity. I guess it's good too for your immune system to be so authoritarian when it comes to viruses, but when it comes to friendly cells coming and that are supposed to help you, an authoritarian immune in state

can actually be pretty bad. It's like totally especially if you have like all commune diseases, which is basically um where your body decided that like a type of cell that is part of you is actually an enemy and just like begins to kill it and like whenever and again, like since since the activation cycle works, like like once you activate the immune system, like an immune cell, it calls other immune cells like it's like a self fulfilling prophecy.

You're all like like the immune system. It's like you know, you know the joke about like the okay is it? Okay? Is this called ghost drive in English? If you like go go down the highway on the opposite direction ghost drive? What it just? Is it called in English when you go the highway the opposite way, just driving on the wrong side of their own Okay? So like we have a job what worked for that in German which I

tried to translate, which it didn't work. We don't have a we don't have a many specific words in English for things. Fair enough, enough. So it's like those immune cells that got activated against your own body. They're basically it's like cells going down the wrong side of the highway and they're just like wondering why, Like there are thousands of people going in the wrong way on the highway. What's wrong. It's like like your immune like your autoimmune cells,

it's like the enemies everywhere. Yeah, like like this horrible guys, like we like there's a serious affection going on, like what's happening here? And then that's how you get like inflammatory bow disease and other autoimmune disorders. And yeah, it's horrible, very desperate and like confused and said immune cells that just like thinks they're like like in World War two. Oh boy, a bunch of a bunch of doomsday proper cells that have gone away too extreme in your own body.

That's not a good thing. But yeah, in some cases, the immune system has to be completely revamped in order to work with certain evolutionary traits. So when we're talking about like a fetus or a donated organ, you have this problem of of you have to solve to stop the immune system from attacking that thing. But what if instead of having a donated organ You have a donated boyfriend that is attached to your body. So this is what happens with anglerfish. So anglerfish we kind of the

most famous species of anglerfish. You probably have a pretty good idea of what it looks like. They're those really spooky looking deep sea fish with the big pointy teeth, a bioluminescent lure, and overall very bony, angular, haunted looking bodies. There are many species of anglerfish, but the ones that you're probably thinking of ore in the Sarah Today family,

So they're the creepy, glowing, pointy tooth. Uh. They're actually also called sea devils because they look horrible, like some kind of ghoul that lives at the bottom of the ocean.

They have this fun little quirk where, in order to mate, the male, who is this tiny tadpole like fish compared to the much larger female, actually attaches himself to the female's body so he'll bite down on the underside of her belly, and his mouth actually uses an enzyme to melt their flesh together, so his mouth will melt and that point on the female's belly will melt broken down by this enzyme, and then they're just fused together, and

it's he's like grafted himself onto the female's body, which is, you know, that's a lot of commitment. I got admire, got admire that level of commitment in a relationship. So once the male is attached to the female, he will depend on her for nutrients, for breathing, for the circulatory system, locomotion, everything. He basically becomes like an appendage and and he's an

appendage that will provide her with sperm for reproduction. And this may seem like the perfect romantic story, you know, just a very cozy situation, but there's a big problem, which is the immune response. Because you know, if you try to graft yourself to another person, it's not going

to go well. I mean, first of all, I don't think most people would be cool with that, but also your immune system would not be cool with that, and your immune system would attack this foreign object attached to you. So anglerfish just have decided that they love this uh kind of situation so much where the male attaches it to the female, they've completely ditched a whole part of their immune system in order to make this very close relationship work. Basically is that they don't they did they

skipt T cells and lex the adaptive immune system? Yes, so they they completely scraped the adaptive immune system. They're actually two main categories of immune system, right, There's the adaptive immune system and the innate immune system, right, yeah, the first line defense and like the superweapons if you want, Like what a nice picture. So, like, the innate immune system is less like a supercomputer and more like sort

of a physical fortress. So part of your innate immune system is stuff like your skin, right, like it it protects your your body from invasion or mucasal lining's um. Macrophages are also part of the innate immune system, right yeah, like like all the soldiers cell basically this sold your cells that like when they see an enemy can engage immediately in besson heads. Yeah, heavy the heavy fighting, right exactly. So it's kind of the less technologically advanced part of

the immune system. But the adaptive immune system is that really pretty complex, like a bunch of little computer programs running around. So uh, antibodies and T cells being called into action that are adapting themselves to unique pathogens or viruses or strange new threats. Right, may offer a picture, yes, maybe, like like so as far as I've understood it, Like the like the in an immune system, it's just like already when you're born, it's it's there, it's ready, it's

ready to go, it's happy to fight for you. And the adaptive immune system is like when you're born. It's like it's like a computer. It's like hardware, but it doesn't have software yet, so it's like it's also like one of the reasons why kids get sick so much, they don't like the immunity has not booted up basically, and and what like this hardware without software does it then collects data and gets better and better at defending you.

And it basically is like the I guess in a sense you could say it's like the stronger part of the two immune systems when it's really properly activated. So like, I'm really really curious to learn how it like made sense for the English fish too to drop in like

all of that right right exactly. It's it's really strange because in order for this mating system to work, for the male to be able to attach to the female and not be killed by her immune system, basically that aspect of their immune system doesn't function, so they don't really use you know, antibodies and T cells. They still have the innate immune system, so some of them more or rudimentary kinds of immune responses that they do to

you know, basic basic pathogens. But uh, when that mail will attach to the female, there is no they you know, these cells in that area won't call for an immune response to come over and attack the mail. And so the big question is, Okay, great, but how do they survive? I hate to you know, leave everyone on a cliffhanger. Researchers are still looking into it. There's no definitive answer of like, you know, why this system works for these

weird little fish. Uh, it's possible that they have a stronger innate system to make up for the lack of the adaptive system. So, uh, this is really weird, um, and you you'd probably know more about how weird this is because it doesn't seem like these immune systems should be able to be decoupled, like they kind of work together technically lazy adaptive immune system really technically like the adaptive immune system really super depends on the innate immune

system to activate it. So the the adaptive immune system basically it's on standby always until you're innate immune system decides. Basically, oh, like he's like something dangerous is going on. It's like like too much for for for me to handle. I'll activate my adaptive immune system body. So technically you don't

need too many switches. I mean, like I have no idea, not I'm not pretending anything about angler fish, but at least, like an in humans, if you switch off, like one or two cells from the adaptive immune system have patterned from your innate immune system, your adaptive adaptive immune system should not activate anymore. But that's just like sounds like

such a horrible idea. It's really interesting that like having a little a life sperm bag when your back is basically they should be worth um shouting off like at least half of your immune system and like your defense against any sort of like really serious infection. Unlike you, I'm gonna pretend I know a lot about anglerfish. Um. I wonder if it's because they're deep sea living fish, so they don't have to fight off as many pathogens as they would have to in a more nutrient rich environment.

So you know, in that makes sense, the deep sea, it does. It can host a lot of things. I mean, obviously, bacteria flourishes near deep sea events, these these hot vents that have there, like these little pockets in the deep sea that do have a lot of nutrients, but uh, in certain parts of the deep sea, it's kind of like a nutrient desert, so you have to have all

these clever adaptations to even get a meal. So anglerfish have that wonderful bioluminescent bulb that will draw prey to them, because it's so hard to go and hunt prey when you have these this very like spartan area of the ocean.

So I'm wondering if the only reason that they can just survive on the innate immune system is that there aren't as many pathogens, as many viruses that are able to spread from h from animal to animal or you know, around in this very desolate environment of the deep ocean. So so basically, to never get sick, don't have contact with other living beings. And then, I mean, that's what

we've learned right over the past two years. So every week we do a Mystery animal sound game where I play an animal sound and you all out there try to guess what the heck is talking. Philip, you want to play along this week. That sounds amazing. So first we've got to reveal the mystery animal sound from last week. So the hint from last week was not so fast. This isn't who you think it is, and here is

the sound. So who do you think that is? Philip? Oh, my god, like some kind of bird, but like, yeah, not no idea of beyond that, because it sounds like a baby chick. Right, it sounds like a little little baby chicken or a baby bird, but it is in fact a cheetah. Huh yeah, oh yeah, right, okay, like interesting, right, Like what's wrong with it? It's got it? It swallowed a bird it and it's trying to escape out of the cheetah. No. So cheetahs are really interesting because of

the big cats. They have very cute little vocalizations. So cheetahs don't roar, and they're actually one of the few big cats that purr because the that um the same sort of vocal chord system that allows lions to roar

actually would prevent them from uh purring. So cheetahs don't roar, but they purr, and they make all sorts of adorable vocalizations like chirps, which can be used by a mother to kind of locate it it's young, or let it's young know where it is, or by by siblings to kind of give each other heads up of where they are. And uh, yeah they are. They make adorable little baby bird noises even though they are one of the fastest predators in the world. So definitely shocking to hear that

coming out of a big cat like a cheetah. Congratulations to this week's winners of the animal sound game who wrote me in the fastest, get it fast because you know Jeeta's Abigail m ri Ellen Keegan, y'all guess correctly. I got a lot of correct guesses. The good job everyone, You guys are so smart. So now onto this week's mystery animal sound. So the hint for this week's sound is this may sound like a herd of goats, but if you try to milk these guys, you're gonna have

a bad time. Is that it's some kind of some kind of insect. Well, I can't tell you because I will reveal the answer to this week's guts, Who's talk and game next Wednesday. So Philip, thank you so much for joining me today and taking us on a tour of the wonderful, wacky world of immune systems. So let's tell people about where they can find your book Immune and where they can find some of your other work. Well,

thanks for having me. Yeah, you can get my book, which is called Immune Journey into this mysterious system that keeps you alive. I guess everywhere where you can get books. Um, and I personally don't have social media, so you can't find me anywhere, but you can see my work on our YouTube channel Za Nutshell, which is on YouTube. I highly recommend it if you want to learn about things and really fun and the animate. I'm a little bit of an animation nerd and it's absolutely gorgeous animation and

really clear, really nice explanations for things. It's also weirdly relaxing to learn. So I really love that channel. Um yeah, so check that out. Check out that book Immune if you want to learn more about them. And uh yeah, thanks so much for listening. Uh. If you think you have an answer to this week's mry animal sound game, or you want to write in questions concerns, uh pictures

of your immune system. Wait, don't do that, don't do that, write me at creature feature pod at gmail dot com, Creature feature Pot at Instagram, creat your feet pot on Twitter. That's f e a T, not f e ET. That is something very different. And if you're enjoying the show and you leave a rating or review, that is really wonderful. I appreciate all the reviews. I read them all. I take note of what you guys are saying to help improve the show, and of course it also helps with

the algorithms. We must all obey the algorithms. All hail the algorithms. And thanks so much to the space plas six for their super awesome song x Alumina. Creature features a production of I Heart Radio. For more podcasts like the one you just heard, visit the I heart Radio app, Apple Podcasts, or Hey guess what where have you listen to your favorite shows? See you next Wednesday.