r/explainlikeimfive • u/lucindadadada • 17h ago
Biology ELI5: How can our immune system recognize something it has never encountered before?
There are an enormous number of possible viruses, bacteria, and other foreign molecules. If the body hasn't encountered a particular one before, how can immune cells have anything capable of recognizing it in the first place?
•
u/lomina222 17h ago
Our immune system makes a huge variety of detectors before it knows what germs it’ll meet. When a new germ shows up, whichever detector happens to match it gets copied rapidly and used to fight it.
•
u/SuperPimpToast 13h ago
Pretty much this. The immune system has an immense repertoire diversity. In theory there should be a receptor for nearly any antigen available from bacteria, viruses, or even ourselves
To mature an immune cell receptor. It needs to prevent any receptors that can detect "self" so it doesn't end up attacking our bodies.
If the immune system does find a match, it further matures and gets stored into an immune memory cell, so if thats germ attacks again, the body can fight back at a significantly faster rate. This is the key goal for most vaccines.
•
•
u/TheTarragonFarmer 12h ago
The fancy name for this strategy is "generate and test".
What it really means is throwing random shit at the wall and see what sticks.
•
u/AleksyGetTheWings 17h ago edited 17h ago
It's the opposite ! Basically each of your cells has an ID card ( proteins on its surface) which shows it is part of the body. If the police (white blood cells) detects something with another set of proteins, gta-like 2-4 stars immediately, with a chance of a 5th star (cytokine storm. Basically "torch everything, forget collateral damage, we'll repair if we survive") when 4 stars didn't do the job.
It's also why cancers are really hard on your immune system : it's your own cells going full anarchist. Which means your immune system has a hard time differentiating cancerous cells and not cancerous cells, and that's why House MD could explain any weird symptom with "paraneoplastic syndrom", which is "immune system is confused and will hurt some random part of the body in its confusion" (more frequently it's the nervous system, but it's far from 100%)
And autoimmune diseases are when the police becomes retarded and doesn't read the ID cards right. And goes 4 stars on your own body.
•
u/TheJLbjj 16h ago
In autoimmune, more that they do read the ID cards right, but were told bad information about which ID cards to deny because they happened to accidentally arrest someone with one once
•
u/SvenTropics 16h ago
It's actually kind of fascinating. There's an organ in your body that goes through a process where it essentially uses your own DNA and unravels and reforms it to make just about every possible protein that could ever exist. It makes a library of all these different proteins, and then it removes all the ones that it's already seen.
•
u/aecarol1 17h ago
We get antibodies from our mother's breastmilk, which can protect us from some things we've never seen, but it's only designed to get us through until our own immune system gets going, then it fades.
For some people, a small part of their persistent immune system is based on what their mothers saw during her life through microchimerism.
We also have some protection from some of what our ancestors saw. When the plague comes through every few years, the people who survive tended to pass on genes that are resistant to that disease. This is why people from some parts of the world tend to have some protection from diseases that would wipe out entire populations in other parts of the world. Some of the latent protections go back millennia, and some we share with the apes.
Smallpox for example was bad in Europe where it as common for generations, but horrific in the America's where they had no latent immunity. Settlers thought the America's an almost empty paradise, not realizing that in the prior decades, millions of Native American's had died of smallpox as it raced across the continent.
tl;dr before we've seen a disease and learn to fight it, we will have some from our ancestors, and may have some immunity from our mothers.
•
u/ESOTERIC_WALNUT06 17h ago
Explaining like you are 5: It cannot. Immune system just products gazillion of random antibodies by combining random and different parts. Once the suitable one(s) are found, these antibodies and the cells produce these specific antibodies are mass produced.
•
u/AleksyGetTheWings 17h ago
Thats not how it works. The random antibodies testing only happens after a foreign agent has been detected.
•
u/Jkei 7h ago
It is. You generate loads of unique B cell clones first, then they lie in wait for their cognate antigen, and if it does come along and activate them (and they get T cell help), then somatic hypermutation introduces a lot more smaller changes to fine-tune.
The vast, vast majority of random generation happens before & without any antigen challenge.
•
u/7heCulture 17h ago
The question now becomes: how does the immune system know which antibodies worked in that biochemical maelstrom?
•
•
u/FreeGothitelle 16h ago edited 16h ago
The way the immune system attacks foreign entities is fairly standard, it doesnt come up with unique strategies for each pathogen.
Its just recognising where the pathogens are thats tricky, thats the job of T cells (adaptive immune response)
•
•
u/Jkei 7h ago
First you generate lots of B cells with random BCRs/antibodies each. You get rid of the ones that are self-reactive. The rest are released and make their way to lymph nodes, where they just wait (and move to other nodes occasionally). When an antigen passes through / is delivered to the node and bumps into a BCR that can bind &keep hold of it, that B cell realizes its big day has come, and its whole further response kicks off.
It's still a maelstrom. You need the right cells at the right place at the right time, all of which are matters of chance. But you make enough that rolling the dice like this pretty reliably comes up as a win.
•
u/jpb103 17h ago
Recognizing an intruder is easy.
Developing specific antibodies to kill the intruder is not. Viruses have a protein shell around them. Our immune systems need to deliver a payload to kill the generic material, but that shell is strong. Antibodies need to be able to chemically bond with that protein coat in order to deliver the killing blow. That's the hard part.
Our immune systems have incredible imagination. They dream up what protein bonding sites they might encounter and start building variations for their antibody library. Vaccines work by helping your body find the right antibody and make enough copies for it to be fresh and readily available in your antibody library.
•
u/Mammoth-Mud-9609 17h ago
The body "questions" any cells etc. that aren't their own human body cells, some of this questioning takes place in the appendix. https://youtu.be/JeXfPb1jpVU
•
u/FreeGothitelle 16h ago
So theres a specific type of immune cell that only recognizes a specific antigen (foreign molecules basically), these cells remix their DNA to generate essentially random receptors, and while most of them are useless, your body makes a huge number of these so that for any random infection, you will have some of these immune cells that recognize it.
•
u/Esseratecades 16h ago
That's not quite how it works.
Let's say you've never had the flu before.
Your immune system notices the flu microbes but doesn't actually know what it is yet. It knows it's not you, and it knows it's never seen it before, so it forms a response.
It's a bit more complicated than that but ELI5.
•
u/csrobins88 15h ago edited 15h ago
You know how a key has little points and divots that only fit a specific lock? Your body generates antibodies that have random bumps and divots on their arms in billions of combinations so that when a foreign antigen comes in, hopefully they will lock together and start an immune response against that specific antigen.
Also once that initial antigen is detected part of your immune system stations more look-out cells all over your lymphatic system for those specific antigens so that it can mount a quicker, more robust immune response the next time it comes.
This is also how vaccines work. If it sounds like it might take forever for the correct randomly generated antibody to find an antigen - you’re right. So we flood your system with a ton of antigen to help the antibody find it faster and start that process of stationing look-out cells all over your body.
•
u/JJJangles 13h ago
It can’t. When the immune system finds something it has never encountered before it just chooses violence.
•
u/Syresiv 12h ago
You have trillions of cells that are each capable of recognizing something. Each of them has a randomly generated key, and they're tested when created to make sure they don't recognize any part of you that way.
That key can then attach to a specific protein or piece of a protein that may or may not exist. Should that protein exist and be attached to an invader, a secondary immune response ensues.
•
u/bobroberts1954 11h ago
Your DNA has a huge number of target markers that are part of your inheritance. The wbc's are trained from this library and updated as new pathogens are encountered.
•
u/Raiddinn1 9h ago
Think of immune cells as individual soldiers in an army.
If some threat shows up, individual soldiers will go fight with it.
Whatever the result is, your immune system now has more knowledge about what it's fighting and what to do next.
Maybe the immune system will send a slightly different kind of soldier if the first one got its ass kicked. Maybe, instead of one with guns, it will try one with grenades the next battle.
Whatever the result is, the immune system now has more knowledge about what it's fighting and what to do next.
If whatever it's doing is winning, it will do more of it.
If whatever it's doing is losing, it will try something slightly different.
The individual immune cells are worth little and easy to spawn, so it doesn't really matter if some of them die in battle, as long as the threat is eliminated. The immune system isn't above just throwing bodies at the problem en masse.
As for the question of, "How does the immune system even know what a threat is?"... the immune system has its own intelligence division which is tasked with determining what is and isn't a threat.
This division knows generally what kinds of things constitute a threat. Like does this thing have a flower in it's hand or a gun? One of them is going to be way more suspicious than the other. Between the two, the immune system is going to ignore the flower and focus on the gun.
The intelligence division does a pretty good job almost all the time. Autoimmune disease is what happens when it doesn't. When the immune system starts attacking the thing with the flower, bad things happen. This can kill the host if it goes on long enough.
•
u/Temporary-Truth2048 6h ago
They judge a book by its cover.
Most things that are dangerous to us, the things you mentioned, are similarly shaped. The really dangerous ones have the ability to look non-threatening to bypass detection.
It's really very similar to life at human scale. They just don't have other immune cells crying about profiling.
•
u/bremidon 6h ago
As others have said, our immune system has a large number of detectors. Just to give an idea, a single person may very well have billions of different detectors.
Also, how these are created is pretty interesting as well. A B cell deliberately cuts up the DNA for its detector and lets the slightly messy repair process create a new, almost-random version.
•
u/sciguy52 44m ago
Basically you have millions and millions of immune cells that all recognize one particular thing. They hang out always looking for that one thing to show up. If it doesn't they just keep hanging out. But if the thing they recognize does show up they will find it, bind to it and through series of steps grow to enormous numbers to counter it. There are so many that each recognize their own one individual thing that pretty much any virus or bacteria will have several of these that will recognize different parts of it. So just think of the immune cells out there and they all recognize different things and sometimes that thing ends up being useful like with an infection. At a very simplified level you could look at each immune cell and see what it recognizes you would see this one recognizes squares, this one circles, this on ovels, this one hexagons, this one triangles, this one rectangles, this one octagons, this on spiral shapes, and on and on and there would be millions of unique things that a given cell in the body would recognize.
It may seem impossible because how can that be when we have a genome with 20k genes? How could the immune cells have so many unique things they recognize? They would need a gene for each one? Turns out certain parts of some specific genes that are related to immune cells can actually "shuffle the deck" of genetic material to come up with millions and millions of different possibilities of what it could recognize and yet the genome has about 20k genes. If it could not shuffle the deck like this then the immune cells could not recognize that many things. Just another truly remarkable thing about our immune systems.
So there are immune cells in your body that recognize one thing unique to them and it is just waiting for the opportunity when something comes in the body that has that shape so it can attack it. Until then, it will just have to continue hanging out and searching the body and trying to find the one thing it recognizes and it never might.
•
u/PhonicUK 17h ago edited 17h ago
It's the opposite way around, the immune system knows what you look like, so anything that isn't you (or that it otherwise knows is safe) is something it should potentially attack. This is also the basis for allergic reactions, things that are harmless but aren't 'us' creating immune responses that aren't necessary.
There's essentially two main parts to our immune system, the innate and the adaptive. The innate system doesn't target anything specific, that's symptoms like getting a fever and a snotty nose. They're broad and un-targeted.
The adaptive immune system is what responds to specific threats, where our immune system actually collects samples of pathogens to figure out how to identify them and deal with them.
So the body starts off with the "oh shit I don't recognise this" response, and then over time learns to recognise what this thing is specifically, and how to deal with it again in the future.