How Your Immune System Functions | Dr. Max Krummel & Dr. Andrew Huberman

How the Immune System Identifies Threats

00:00Sometimes I tend to then think the immune system you want to defend it like you want to defend a nation and you want to defend it from outsiders. And I've just told you a story that's if you want to take a political statement from it's pro- immigration because all these bacteria that live on us are actually bringing us goods and they they do a lot half the audience.

00:15No, I'm just kidding. I'm totally joking. We we're a bipartisan audience. I'm joking. Take it how you want to by analogy. It's the argument for you know why why certain um you know influx of of of u in this case organisms onto us you know create a more robust you know person than we were before.

00:34But I want to give you this story that one a famous um marinologist in the 1970s drew this parallel in wartime and said in you know World War II submarines would be underneath the ocean and they'd be traveling around and they would if they could if they heard another submarine they would scuttle the missiles you know torpedoes because that could be the enemy and the enemy could fire at them.

00:56And so they had two sets of books that they used. Uh, one of them was a book that gave them the sound profile of all, let's say it's a US, of all the US submarines. And so they could listen to the were of the engines. And if they heard a were of the engine that had the certain cycle of a general mo, you know, motors engine, they wouldn't fire.

01:17So that's the sort of like self I know what self is. And then they had another book that was the engine sounds of the known diesel engines of whatever engines of the German uh, you know, submarines. And if they heard that then they absolutely would fire.

01:30And that's a self versus non-self-discrimination problem just like the immune system has to do. But what I bring you with it aging is this concept that as you get weirder and different your body is getting like more complex then that those books you know start to have every possible possibly every possible permutation of every biomolelecule could could could be made by your body at that point.

01:51And then a virus doesn't necessarily have anything unique about it. A virus is also going to make proteins and that's your immune system can see the viral proteins and say oh a new thing has come in and that's you know that's out of range and now I need to mount that a T- cell response against this I need to make the you know bring in the troops but with aging we have this this kind of you know us diverging problem so that this you know this system that's supposed to sense us is just you know has a lot of cosmic background has a lot of noise in it and so I think it I think that's one of the

02:21reasons why we also have issue when we're aging and it's I I think it's also one of the issu reasons why cancer is more prevalent in later life for I mean there's two parts of that one is of course you've accumulated mutations in your cells that could be cancerous but also the immune system has been seeing those and all the various different accumulations of them and ones like them you know over these years to the point where the weird doesn't look that weird anymore you know something like a cancer that is different than you it's not that much different than like another cell

02:48over here that's gone you know like and it's just happily making skin and isn't cancerous but you is it's got some differences. What about the argument that there's so much cellular turnover that um the cells that accumulate these mutations are being eliminated?

03:04You're saying because they're clonal, they're producing different they become different, they produce cells that are also different, then they die. Is this is that the way it works?

How Immune Pruning Prevents Cancer

03:15Yeah. And I think I think you you are bringing something up that's also true, which is that all the time I think the immune system is defending us against, you know, mutations. So, one example that everybody sees when they get to be about 40 or 50 is is little these white spots in your skin.

03:28And we we think that those are places where the immune system has sensed a collection of cells that were precancerous, maybe they were even beginning of cancer, and has wiped them out. And and so the you know, a lot of the origin of cancers in skin is is melanin producing cells like melan you know melanoma is what we call skin cancer.

03:47um those melanocytes that that white area they've been wiped of a whole collection of melanocytes and that's why it's you know like it's white instead of as dark as your as the rest of your skin. So you know to that extent the idea that the immune system is is pruning you all the time is you know there's it looks like there's pretty good evidence for that.

04:06Um and the question is when does something become dangerous? That's that's that's that you know that's fundamentally question with cancer and these sort of things. If you said, "I want to actually have the fittest cells in my skin to uh fill in a gap if I scratch myself.

04:20I would like to have cells that quickly replicate just like maybe in kids. Kids heal so ridiculously quickly, right? Because they have an abundance of these cells that I think I think they're they're their wound healing. I mean, there's a group out of Stanford that studies this, but essentially, you know, wound healing in in in young is quite quite a bit faster and more efficient and and there's many that there's many levels of that.

04:38Yeah. But um yeah, remarkably faster. If you're a parent, you've seen this. You know, you cut yourself on the same day as a kid your kid cut yourself and they're they're three days later they can't even find it on them and you know like four weeks later you're still like got you know scap or something.

04:52But I was just coming to the point that if you do that and you you want this do you want you maybe want that to fill back in because you know certainly out in the wild having an open wound is a bad thing. So you like to heal quickly. Well, if a mutation has happened that fills that cell in quick, more quickly, that is almost by definition a mutation that's let that cell divide faster.

05:14Well, what is cancer? It's cells that divide faster. So, in some sense, all these events in your life where winners win by filling in the space left by cells that die is selecting for cells that get a little out of range with growth. They may be a little bit better at growing.

05:28And then again, the question is like, well, how much better do you want that? You want it to like help you, but at some point you don't want it to basically form a lesion and will grow grow grow and go other places and grow, which is called metastasis in cancer, which is how most people die.

05:41To me,

New Framework for Immunity

05:44that the issue of self and non-self is one of the ones that's been with immunology for a very long time. And again, it's way richer than we thought about, I think, in the 1990s or 2000s, you know. And then at the same time, the idea of what you can do with that information is also I call this kind of a new immunity.

05:59Immunity used to be like a fuel gauge. You'd say it was low for itself. Then it was really high against viruses and it was like a fuel gauge. You know, now it's really hot. And what we originally thought we were doing with cancer imotherapy was making it just hotter in general.

06:12But now you realize that in between like the immune system not caring about something at all and and going and you know like releasing all its fury on something are all these other things it can do with the information it gathers in there. And that's where I was saying you know it can it can like quarantine bacteria.

06:28It's not going to kill them. It's it's in that zone. The bacteria as long as they're in the right zone, there's not too many of them, there's not too few of them, immune system can actually help them be there. It can produce things that like either tighters them out of circulation or keeps them there.

06:39You know, in all these other settings, like I say, in the heart and the can go to almost any organ and uh and the immune system is consistently present and it's consistently measuring you. And the U again is this complex you. It's not just what came from the egg, it's the you that's you right now, including all the mutations that that you might have accred and all the bacteria and and and the viruses.

07:01You know, we have a lot of viruses in our bodies that we tend to think that at the end of a of a illness that we've gone back to our pure state. This may came from religion. You know, we were born pure and if God made us correctly, then we would be pure at the end of things and you know that would be pure immunity would would purify us of things.

07:18But the more we look, the more

Dormant Viruses & Immunopathology

07:21we find that every virus leaves a little evidence of a little bit of itself. And then there's a then there's the goal for the immune system to kind of quarantine that to say this, you know, maybe we don't want to kill every one of our cells to get rid of every virus that's infected one of our cells.

07:32We need to leave some of those alive. We don't like for example herpes virus infection infects the nerves and when people have uh you know emergence they they get nerve pain and worse. A lot of that is caused by the immune system reacting to the virus trying to get out and then killing off neurons.

07:50So the the the it's imopathology. The immune system is c causing as much of the damage and problem as the viruses. And it's the failure of that day taunt. And when certain viruses are just sitting in us, we're perfectly fine. You know, we have viruses sitting around and as long as they're laying dormant, our immune system can say, "Okay, I'm going to just hang out here and if anything bad happens, I'm going to squatchch that."

08:13But it's not like we've been purified. You know, that's a reality that's a little bit too bad. But, you know, it's also one where you say, again, if if the goal of us is to make it to 30, let's say you get a a an early liver infection of a HCV or HPV.

08:25If the immune system can just let that be, you're not going to destroy your own liver and you'll live to produce and your genes will get passed on. On the other hand, if you mounted a massive immune response, you know, you went all the way in the fuel gauge to the right, your immune system can kill you.

08:41It absolutely can. You know, it's can can kill any cell it wants. So, so that that that again that idea that the space in between is the one that we actually are starting to understand that it has all these specialized roles that are not always about getting rid of things at all cost.