Lecture 3 - Immunology
Proteins
Our DNA encodes for proteins.
When a gene is transcribed and translated into a protein, we say that the gene is expressed.
Different cells make different proteins.
We call the “choice” to express different proteins gene expression.
Only some of the genes are expressed at any point in time.
Defining Cells
We define cells based on what they make.
We generally focus on what is on the surface of the cell because it's easy to study.
Ex: Antibody+ cell (B cell), CD3+ cell (T cell)
If a cell expresses a protein, we say it is positive for the protein
If a cell does not express a protein, we say it is negative for the protein
PHENOTYPE DEFINES FUNCTION
What the cells make defines what the cells do
These proteins have FUNCTIONS that define what the cell can do
Some markers define an entire “lineage” of cells
Cell types differ greatly in the proteins they make.
We call the collection of everything made by the cell their “cellular program” or “transcriptional program”.
Based on different proteins they make, cell types can often be subdivided further into Subtypes
Molecules
At the simplest level, immunity is a system of cells and molecules.
Immune cells interact with each other and cells in their environment.
Immunity is achieved by cells communicating with one another.
Exchange of signals
Immune cells send and receive signals to non-immune cells in their environment.
Molecular interactions.
Interactions occur through receptors and ligands.
Receptors and Ligands…
“Locks and Keys”
Change in how the cell acts…
Change in gene expression.
Communication and Gene Expression
Direct communication between receptors.
Indirect communication via soluble mediators.
Cells can only respond to a ligand if they express the appropriate receptor!
We call the matching ligand:receptor a “cognate” pair.
This will come back when we talk about “antigen specific” cells in adaptive immune lectures!
How do receptor interactions change gene expression?
Example:
Virus infects cell
Viral DNA is detected by immune receptors inside the cell.
Secondary messengers migrate to nucleus to change transcription
Infected cell changes gene expression to produce interferons
Interferons signal to nearby cells
STOP TRANSCRIBING!!! (limits viral replication)
Receptors
Call them “Clusters of Differentiation” or “Classification Determinant”
And we will provide official designations using numbers.
CD1, CD2, CD3,CD4….
OVER 370 CD MOLECULES.
CYTOKINE
“Signalling molecule that makes a cell move or change
Interleukins
“Molecules that signal between immune cells.”
IL-1, IL-2, IL-3, IL-4…
Approximately50 in total
It turns out that they signal with non-immune cells too!
transcript from lecture:
Alrighty hi everybody. I have been pre-warned that this microphone might be a little bit crappy, so if that uh is happening, uh, just somebody put up your hand and let me know so that I can, uh, find a different one I guess uh oh I just heard it crack just there so. Oh, OK. Yeah, no Hello? No? Hello. Alright, I guess I'm gonna use this instead, which makes me feel like I'm doing stand-up comedy, but it's alright, I'm not not doing stand-up comedy. OK, um, today we're gonna talk about how to talk. Like an immunologist. One of the things that I hear very frequently whenever I'm uh doing, is this good, volume wise by the way? Yeah, OK, perfect. Um, one of the things that I hear all the time from, uh, students who are afraid about taking my course is two things. One, we only ever talk in acronyms, and that is true. And I'm going to apologize ahead of time for that. And number 2, is that there's so much detail in immunology, that it's overwhelming. And I think I tried to convey to you in one of the last lectures, that is also true, but we're gonna do our best in this course to set you up for success. So I have this lecture in here, how to talk like an immunologist, where the objective is to get everybody on the same page. You are very likely to hear things that you already know in this lecture, but for some programs, it may not have been described to them that way. You're also probably gonna hear things before or that you have not heard before, and other people are gonna go, you never heard of that before, and it's just because different programs teach things differently. So. This is kind of how we as immunologists speak, and, and, and I hope it demystifies a few things for all of you. So, we're gonna start back at the beginning, so in the Big Bang, no, that's too far, um, the simplest level, immunity is a system of cells and molecules. And I presume we know the difference between what a cell is and what a molecule is, right? Yes, I'm seeing some nodding. That's, that's ideal. So, remember I showed you this in the last lecture, we have these arms, we have the innate system, the adaptive system. These are all made up of white blood cells. These are immune cells are white blood cells. Who here has heard of white blood cells before? Yeah, OK, many of you. The question is, well, why the heck do we call them white blood cells? And the answer is that if I was to take your blood right now, better if you're sick for this, by the way, and if I was to spin it real, real fast, then what is in your blood will separate by density. The most dense things are the red blood cells, this sits at the bottom, these are your red blood cells. And at the top, you have the liquid, we call that the plasma. And in between, you'll see this very small little line, a little white fluffy line, and it's very, very white, if you've ever done one of these preps before. And what we have found in research, many, many moons ago, is that inside this white coat here are immune cells, and when they didn't know that, they called them the white blood cells because they are part of the buffy coat layer of the blood. What those cells actually are, are a collection of cells, and there's all kinds of details on this slide. And that is scary, and you will know all these details by the end of the course, don't you worry. These cells are different cells, we have macrophages, we have NK cells, eosinophils, all these different cells together make up your white blood cells, your immune cells. It's a cast of characters, and when I was in 303, which I took 3IO3 by the way. Um, I remember thinking, wow, this is really cool, it's a cast, and around the same time, not to date myself, the first Avengers movie was coming out, and I was like, oh cool, every single one of them is like a different superhero, this one's green, it's the Hulk obviously. And each superhero has a specialized function. Does something different. Ant-Man is gonna solve a situation differently than the Hulk is gonna solve a situation, and that's kind of how the immune system works. We have all these cells, so that we can specialize, there's so many of them, and you will know which ones you need to know and, and how they operate, uh, because we'll tell you. So, one of the names that we give for this is a leukocyte, and that is just the fancy way of saying white blood cell, because leuko is Greek for white, and cyte is Greek for cell, which is basically a container, or receptacle, so it's a white container. Why do they do all these different names for things? Well, not everyone speaks English, to start. And secondly, because it just sounds fancier. Why would I say white blood cell when I could say leukocyte, right? And for a long time that was science. Let's make it sound fancy. Nowadays, I'm not a big fan of making it sound fancy because that just makes it confusing. But you will see leukocyte a lot, and you'll often find that I'm going to break up words like this for you into what its components are, and those are most often based in Latin or Greek for historical reasons. So Another one you're gonna hear is lymphocyte. Why do we call it a lymphocyte? Well, lympho comes from lymphatic tissue, which is another word for lymph nodes, which are those big balls that you get underneath your chin when you're sick, and then you go. Like this, and you're like, why is it suddenly hard there? And then like a week later, it's not like that anymore. And if you haven't noticed that about your body, I implore you to go and get sick, and then try. No, I'm kidding, don't get sick. But when next time you're sick, remember to palpate under here and see if you can find your lymph nodes. So, all leukocytes, sorry, all lymphocytes are leukocytes. But not all leukocytes are lymphocytes. So, all of the lymphocytes are white blood cells, but not all of the immune cells come from your lymphatic tissues. OK, a little bit of a differentiation. It's, it's like, you know, you know, the whole thing like all squares are rectangles, but rectangles are not squares, that, that whole thing, that's that, that concept. OK, so, these immune cells, where do we get these things from? By and large, they come from our bone marrow. It's not universally true, but for the vast majority, and especially for this course, our immune cells are all come from stem cells that live in our bone marrow. So here this is bone, and then the marrow's the part inside the bone. We have stem cells, and these stem cells are what we call multipotent. They can differentiate into multiple different things. And what that means is that you'll get white blood cells, but the same cells will also make red blood cells, and they'll also make platelets. And part of understanding immunology is understanding how we get these cells. Where do they come from, how are they related to one another, and these can be very helpful things, and we're gonna talk about all of it in the course. When these cells turn into one another, we use the word differentiation. They differentiate from one to another. And you're gonna hear that a lot, because a naive T cell will differentiate into an activated T cell, or a B cell will differentiate into a plasma cell. And if you didn't know that word, it, that would be very confusing for you. But now you do. Another word that you're likely to hear me say is self fate. Now this is not universal for every immunologist who uses this word, but it's a very common thing in my specific subfields, and the reason I put it on here is because I accidentally say it a lot. And so I want you to know what I'm talking about when I say this. A cell fate is basically the end type of cell. So this stem cell might differentiate into the white blood cell state, or cell fate. OK? Can you appreciate how we're already talking a different language? Every single thing I just said there just like sounds like jargon, right? This is how immunologists talk. There are different cell fates, these different end states, it could follow the red blood cell fate, it could follow the white blood cell fate, it could go to any of these fates down the line. Once these things, these immune cells differentiate out of the bone marrow, they tend to go out throughout your whole body. We have a lot of names that people use for that process. Some might say they migrate, another might say they home. Another might say chemotaxis, which I don't think I put up on there. Chemotaxis is taxis, taxis is literally taxi, essentially, which means movement, so it's moving based on where the chemicals tell you where to go, chemotaxis. You will hear all of these different words, but migration or homing is generally how I'm going to refer to that, OK? So Because our immune cells come out of our bone marrow, and then they go into these different tissues, it makes the immune system overwhelmingly complex. You can think about the brain, the brain is very soft, right? I don't know, I mean, no, I don't imagine many of you have touched brains or seen brains, but if anybody here has done research on brains, it's very, very soft. Whereas the liver, or a kidney, is very, very hard. It's a very dense and collagenous tissue. And the immune system lives inside of both of them. In fact, the same cells will live inside of both. And the cells have to be able to do that, they have to be able to live in those environments, very, very different environments. And then they will specialize inside of those environments and do different things, so it makes the system very complicated. So what you're gonna get in 303 is the bigger picture ideas of how these different systems and how these different cells actually work. If you go and do research in a lab, which I know multiple of you in here are actually in labs in immunology, you will go, oh yeah, that's true, this is very complicated, because the macrophage that you find in here is called a Cuper cell, and then the macrophage that you find inside the brain is called a microglial cell, and that is crazy. And that's what we have to deal with. But don't worry, we're gonna teach you all those things. So, immune cells will will be looking in all of these tissues for all kinds of things, they'll be looking for invaders, pathogens, but they'll also be looking for damage, they'll be looking to repair, there's many functions that these cells will do in these different tissues. So, uh, the important word here is homeostatic, and I'm reworking some of the lectures that are gonna come up, but we're gonna hit homeostasis a lot in this course. I presume we all know what homeostasis is. Hands up. That's ideal. Also, you're still listening. Good. The immune system's job can be understood as maintaining homeostasis. Something external to us is trying to throw us off course, like an infection. Sometimes things within ourselves are trying to throw us off course, like cancer, and it's the immune system's job to correct that course and put us back to homeostasis. OK. Cool, so I've been throwing around the word sell a whole lot. I know grade 9 covered this, but what is a cell? What is the university definition of what a cell is? A cell is the individual unit of an organism. Surprise, you're not a person, you're many people, by which I mean a lot of cells. OK? And they all have their own wants and needs, so good luck. Except for red blood cells, every cell has a nucleus. And inside that nucleus we have DNA. You guys know all this, you're pros. So then here's the question, if every single cell contains a copy of all of our genetic material, how is it possible that these two cells are different cells? Epigenetics. Ah, they have the same DNA but they express the DNA differently. My favorite word, gene expression, correct, the genes are expressed differently, and when we say the word expressed as immunologists, which we say a lot, OK, what we mean is DNA becoming RNA becoming a protein. You know all the process of this already. But what gene is expressed will determine what that cell is. So, for example, this is an eosinophil, it expresses a protein that's pretty specific to the eosinophil, it's called eosinophil peroxidase. It expresses it, but the macrophage does not express eosinophil peroxidase. So that's what makes these things different, and the choice to express these things, that's gene expression. And an important point is that some genes are expressed sometimes. Gene expression is fluid, it changes. And so if we take this one idea further, I've already told you differentiation, right? So what differentiation really is, is a cell choosing to make different proteins, and now it's doing something different. OK? Cool. So. We as immunologists, we er take this to the extreme. In fact, we define cells based on what they make. This is how we talk. So, this year. Is a cell that has an antibody on its surface, OK, and this here is one that has this molecule called CD3. Don't worry about CD we're gonna get there in a minute. We focus on what these cells make to define what those cells are, and oftentimes we do that based on their surface phenotype, so the proteins they have on their surface. And there's a pretty easy reason for that, it's actually a very technical one. It's easier to look at things that are on the surface of a, a cell, by comparison to inside the cell. Just technically from a research standpoint. So we tend to look at things that are on the surface of the cell. So, in immunology, if a cell expresses a protein, we put this little plus sign here, OK? This is very important because this will be on your test. You'll say, hey, this is a CD3+ cell. And if you say it like that to me, CD3+. Then you're a noob. That's not how we as immunologists say it. We would call this a CD3 positive cell, but we wouldn't call it a CD3+ cell, OK, and we wouldn't call, you know, when they don't express things, we put a little negative sign, but we don't call it a CD3 minus cell, we call it a CD3 negative cell. It is positive or negative for those markers, OK? So if you wanna sound cool to your immunology friends, just be like, yeah, CD3 positive cells, and they'll be like, I see you. I got it. So, this cell does not express CD3, so it's CD3 negative. This one does not express an antibody, so it's antibody negative. And obviously. That's a B cell and a T cell, right? That's what you guys look like right now. It's not obvious what they are. So you're supposed to say no there, I forgot that part, I'm sorry. I've had a long day. So, don't worry about it. You're gonna learn what all these different cells are, but part of our job as immunologists is to explain what these cells are accurately, and by explaining them, by what I mean by that is that they make something, and we have it on their surface, we can detect that thing and we can define what that cell is. So this brings up a really important. Set of a piece of information that I don't know if everybody's heard before. Oftentimes it's about fifty-fifty in the class. Somebody heard this before, phenotype defines function. Yeah, see, it's about fifty-fifty. This is why it's important. Phenotype, what's a phenotype? Any takers? The way something looks, the way it presents physically, one might say. What it expresses. Exactly, so that's how we define phenotype immunologically, gene expression. So it expresses this, that's its phenotype. The phenotype defines function. What do you think I mean by function, in this standpoint, uh in this context? What a cell does, exactly. So, what the cell make, what the cells make, yeah, I'm really tired, I can get the plurals right there. What the cells make defines what the cells do. So, in this case, these proteins. Proteins that are on the surface, this antibody that's on the surface of a B cell, or this CD3 that's on the surface of a T cell, that defines what these cells actually do. B cells are antibody producing cells. They are the reason we have those antibodies that Paul Ehrlich, time traveler, described. They're the ones that make them. CD3. Is necessary for a T cell to bind to its target, it's actually called the T cell co-receptor. So this is a critical requirement for this cell to actually be a T cell. So the phenotype defines the function, and you can take this one step further. These are two different cell types, like I had said, or cell fates. Cell types will differ greatly in their phenotypes. So, this one and this one are two very, very different cells, these are two different cell types, OK? Everything that this cell makes, antibody is one thing, but, these cells differ by tons and tons, in fact, thousands of genes. OK? And the whole collection of all of those genes, or all of those proteins that they make, we generally call that their program. It could be their transcriptional program, their cellular program. That's generally the wording we use for that. But, what you'll also hear us say a lot is subtype. Or subclass, these types of words. A subtype is a cell type, is more specific than a cell type. So if these are all B cells, then these are subtypes of B cell, and in fact, we can further define them based on what they make. So you can think of this kind of like a tree. If I find a cell that is positive for antibody, then I can say, alright, then if it's positive for this molecule CD5, then it's a B1 cell, don't worry about it, we'll tell you what that does later. And if it's not, then we would call that a B2 cell. Or if this CD3 positive cell is positive for CD4, we would call that a helper T cell. I fixed that. No. I swear I aligned that cos it was bothering me. Oh, no. My heart, OK, anyway. If it expresses CD4, it's a helper T cell. If it expresses CD8, it's a killer T cell. And these sound like cool words, and you're gonna know what they mean, don't worry about it. So we have types within types, we call those subtypes. So I've told you, at the simplest level, we have the cells, we have the molecules. We're gonna talk a little bit about the molecules now, OK, those were the cells of the immune system, what makes these cells different from one another. Molecules. Well, the way that immune cells function is because of their phenotype, it's because of the things they make. So we talk a lot in immunology about the molecules that these cells make. And the reason that this matters is because immune cells interact with one another through these molecules. So. This is, here's an example, this is a generic tissue cell. If you have your immune cells, they will live within your generic tissue, so you can say that this is like a kidney cell, it's not, cause they're not columnar, don't get at me, but um this is a generic tissue, and then your mac uh your macrophages or your immune cells will live kind of within that tissue. And they're constantly exchanging signals back and forth, communicating to each other about what's going on in the tissue. They're also, so for example, if this was Dune, you know, are they talking to one another? Is that how they're doing it? Is that they have little mouths and that they speak? No, of course not, that's not how that works. So The question is, how do they talk to one another? And we'll get there in just one second, here. Immune cells can also talk to non-immune cells. So, immune cells are kind of like a hub, they're constantly listening. They're listening to other immune cells, they're listening to the cells of the tissue, and they're deciding, based on what they're getting from the other immune cells and what they're getting from the tissue, what they're supposed to do, how they're supposed to act. And all of that communication, it's not through conversation, so Zendaya's not telling Timothy Chalamet what to do. It's through these molecular interactions, and what we mean by that is that cells will communicate with these proteins, and these proteins, by and large, are receptors and ligands. You've all probably heard receptors and ligands by now. But in case you haven't. You can have two proteins that connect kind of like a lock and key. They connect like that, click. And when that happens, it will change how the cell acts. How does it do so? It changes that cell's gene expression. So if you want a cell to act differently. You need to give it a signal. And then that cell will change what it does in response to that signal, and to change what it does, it needs to change what it makes. OK? So. Cells will communicate, either by direct communication, where this one has a receptor, this one has a receptor, they talk to one another, they make what we call a synapse, and then they communicate. But another way that they talk, and if you're from uh the Honorsal science program, then you know, as I was, Doctor Rangachari talks about histamine, and histamine acts through receptors, and you know all the receptors, and you know all the signaling pathways, cause he forces you to memorize them all. And then I always explain to people, because he discovered a lot of them, so that's the reason why. But he, very instrumental researcher in doing that. But the cells can communicate not just by direct interaction, but also by soluble mediators, ones that they release, and then some cells have receptors for. So Remember how I said all the cells are different, right? So not every cell has every receptor. That means that not every cell can listen to every signal. In order for a cell to respond, they have to have the receptor for that signal. This one can react, this one cannot. This one can react, this one cannot. So, they have to express the receptor. Here's a piece of language that you probably don't know. So I've just told you the thing that you all probably know, the thing that you don't know is that people call these cognate pairs. OK, when a receptor, and it's matching ligand, connect with one another, those receptors are cognate for one another. They like to bind each other. Non-cognate means that they are interacting, but they're not specific to one another. We don't usually have molecular interactions that are non-cognate, but you will hear us talk about cellular interactions that are non-cognate, and you will hear that later on in the course. So the word cognate, if you hear, it just means like matching with like. OK, this is the proper pairing for that receptor. This is gonna come up a lot when we talk about antigen specific cells, like T cells and B cells later on in the course. And I am very guilty of this, because I say this word a lot when we do that, uh, part of the course. So, how does a receptor actually change gene expression? You have a receptor here, you have a ligand here, and when these two things come together, what happens is you have these messengers that are inside the cell. These things, by and large, can't actually change gene expression. Simple reason why, that's the cell membrane. That's the nucleus. So in order for this to change that, this would have to be there, and it's not, it's there. So instead, what happens is that these recruit other messengers, secondary messengers that are inside the cell, and these ones will create often something called a cascade, which will result in something going into the nucleus, a transcription factor most frequently. And what that transcription factor will do is it will make that, it'll transcribe a new gene, that'll make a new product, which means that the cell is acting differently now. This is the fundament of what immunology is based on. It is signaling. A transduction or a cascade, and then a change in gene expression because of these transcription factors. So, here's a real life example, to give you some actual immunology in uh today, not just all language. So, here's what happens if a, if a cell gets infected by a virus. Not everything we're gonna talk about is viruses and infections, by the way, because the immune system does a lot more than that, but it is a prototypical example. So, this cell here is the target of this funky looking virus. And what happens when a cell, or when a virus infects a cell, is that it'll put its DNA inside that cell. The idea, or RNA if it's an RNA virus. The idea here is that this virus can only replicate if it uses the machinery of this cell. But guess what? We evolved alongside viruses, so. We actually have receptors. Inside the cell that look for virus DNA. So that receptor is specific for the virus of the DNA. The the DNA of the virus, wow. Oh my gosh, I'm sorry guys. What happens is, now that this um receptor has bound to its target, it goes into the nucleus, and it causes the transcription of a new molecule, a soluble molecule. This soluble molecule is called an interferon. OK, I know that there's some people who I think are in Doctor Ashkar's lab in this uh here, so if you're in Doctor Ashkar's lab, he loves interferons. Interferons are soluble mediators, they're not receptor ligand mediators. You're gonna learn about a lot about interferons, don't worry about it. Interferons have receptors, and these cells over here express the receptor for the interferon. And what happens here is when this interferon binds to the receptor, it signals, and it tells the cells, stop transcribing. Why? Any ideas? Cheater, sorry, it's fine. Exactly, so what was just said by somebody who I believe works in a research lab, am I right about that? Yeah, there we go. So just uh, just, I, I, I only say that not, not to out people, but more so to say if you don't know the answer to that, it's probably because this person works with that stuff, so don't, don't, you know, don't worry about it too much. But what, why it says stop transcribing is because this can't make new viruses. If it doesn't transcribe those viral proteins. So this is a way that we restrict the virus from spreading across our tissues and infecting everything. None of the cells there can make new viruses, and it gives time. It gives time for the immune system to come in and destroy the viruses. OK, this happens because of evolution. We've evolved alongside viruses, and somewhere along the way, having a mechanism like this has helped an organism survive, and then that gets passed forward and forward and forward, and now we have many of these mechanisms to help protect us. Hand. So So it's a very good question. The question was, does this interferon act by autocrine signaling, which means it signals on itself. Um, I'm gonna guess the answer to that is yes. Um, but I'm also, as, OK, here's the part where I tell you where I'm coming from. I don't study viruses. I don't study bacteria, I study allergies. So like, people are asking me all the time about these infectious things, and I'm like, I know the answer, but if I'm really off base, you can totally call me on that because this is just not what I study. However, in this circumstance, I think I do know the answer to this, which is. You will, I will explain this to you more down the line, but in order for any pathogen to actually infect us. It actually by definition, needs a way to evade the immune system. That's why when I take my hand. And I run it across here. Everybody just went, oh My hand's not gonna fall off, and I'm not gonna run out and wash my hand right away. You will see my hand next week, it's gonna be so funny if I don't have a hand next week. Sorry, I don't hope, I don't hope that for myself, but imagine I go, hey guys, guess what? My hand isn't gonna fall off, because none of the stuff that's on there can actually, I mean, unless somebody literally just went and coughed right on it before I did that, of course, but most bacteria don't have a way to evade our immune system. And our immune system is essentially perfect at protecting us in that context. So, why would, why am I telling you that? Because the number one way that pathogens evade the immune system is by interrupting the interferon response. So likely what's happened here is this cell is now starting to produce some viral proteins, and those viral proteins will be inhibitors to the interferon response, which means that this cell will not respond to interferons anymore, because if it did, then it wouldn't make more viruses. Cool. Awesome. So That's actually a perfect moment. Look at you. Do you have ESPN or something? No, that's a bad joke for Mean Girls. Anyway, um, any questions so far? About this, yeah. Can you prescribe interferons? We thought so. We tried Not me, of course, but other people. Guess what? If you provide interferons before someone gets sick. Very, very good. Helps protect them. If you provide interference after someone gets sick, they die. The reason is because of something called a cytokine storm. Once the immune system's already kicking off, by adding the interferon, all you're doing is making the immune system kick off more. And as you're gonna learn in this course, it's a big pillar of immunology, the thing that tends to kill you from an infection is more frequently the immune system than it is the infection. It's your immune system going too far, fighting too hard, and then destroying you. So We're actually gonna talk about that in the course, very good question. Next question. What's up? So, can this interferon act on this cell to tell it to up its immune system? So you know what my, well, OK, so. I'm gonna take those separately, can it induce apoptosis? If you start killing all these cells, then you're not gonna have a tissue anymore. So the reason that we don't just kill them all for fun, is to say, hey, how about we try and preserve some of these things, because this virus is already tearing through and killing a whole bunch of these cells, right? So we don't wanna just kill them all. Good idea. I'm sure in some organism that's been the solution and they're not here anymore. But, um. Now, you said, does it boost that cell's immune system? And this is one of the really fun parts about being in this course, that's a good question. In a sense And what I mean by that is, why wouldn't a cell have an immune system? We have immune systems. Right? And to a certain extent, the cells kind of do have immune systems, but it's not something that you're gonna talk about in this course. The immune system is a system outside of these cells. Right? So it's other cells. Like This, that are sitting there, right where the virally infected cell is, right? And guess who listens to interferons very, very potently. Those immune cells, so your, your idea is 100% right. You don't need it to be those other cells, those other cells have jobs to do. OK? They're unionized. And they're not gonna go and, and mess around with the immune system union, they're gonna leave that to the immune cells. So the immune cells are sitting there waiting for the interferon so that they can kick into action and do more immune stuff. So very, very good instinct and very good idea. Cool. Another question? Sorry, I'm just trying to, yeah, what's up? What characteristic of the viral DNA do the interferons bind to? You know, I think a lot of lecturers would be terrified by that question, because they'd go, oh, I don't know. Uh, but it turns out I do know in this context, um. Uh this might get a little deep and maybe the molecular biology students will know this more, but who here has heard of a CPG island? Yeah, what, so CPG Islands, what are they involved in? You said the thing before. I know you're very involved in. Yeah, exactly, epigenetics. It's like Like a lot of studies. Yeah, so they're GC rich regions, basically, these are places where transcriptional regulation happens. Very dense CPG islands change whether or not a gene is going to be transcribed. It turns out that those CPG islands are very different species to species to species. So we have receptors that are looking for the CPG islands in viruses. Which is crazy, if you think about it, cause we have those. But the, that protein has adapted in such a way that our immune system goes, yeah, yeah, yeah, those aren't my CPG islands, those are bad CPG islands, and we're gonna get rid of those. And that's how this stuff works. I mean, these proteins have evolved alongside these viruses, such that now they're able to bind to those uh DNA elements very, very well, for example. So that's, that's one example, and then there are many, many more. Cool. Oh, back there. What's up? Yeah. So buy some time. So why did I say buy some time is kind of the question, is that what I'm getting? It buys time because the cells can't stop making proteins forever, right? Think about it, the cell has actin that it needs for keeping the cell a cell shape, right? So it can do it for a while, but it can't do it forever. It's slowing down the replication of the virus enough that the immune system can really kick off, and I just told you, the immune cells are sitting there listening for the interferons. It gives them time for the immune cells to hear the interferons, and what they're really waiting, trying to buy time for is the adaptive immune system. Which is our very, very strong immune system, it's the reason why when you get sick, it takes about 7 days for you to feel better, because that's how long it takes for the adaptive immune system to kick in. And once it kicks in, it's pretty good at getting rid of the problem. I have to move on because I have more lecture, but I, we can, we can talk after, OK? Or, or at the end potentially. So, we have receptors for like. All kinds of stuff, like stuff that we don't even know about yet, we're still discovering receptors that bind to stuff, OK? We have receptors that help you move around, that help you attach to things. This is all gonna be gibberish to you, that's on the slide, but I wanna give you a sense of the. Number of different types of receptors that we have and the different stimuli that our system is constantly looking for, measuring and monitoring to see if there's a problem. PH, if pH goes off, maybe that's because something's gobbling up and creating CO2, and, uh, that's not allowed, because that means it's not us that's doing that, right? So we regulate pH very, very carefully, we regulate lipids, osmotic pressure, all of these things are sensed by our immune system, it's incredible, and by our whole body, actually. So, here's how immunologists talk about receptors. Uh, we have a lot of receptors, and what was happening back in the day, is that people, researchers, were discovering these receptors, basically, monthly. It's like, hey, cool, we now have the biochemical techniques to find receptors. I purified a new thing and I found it might be a receptor, and look what it does, it activates B cells, so I'm gonna call this B cell stimulating factor. And it's the 2nd 1, so #2. And then this guy is like, without knowing it, he's discovered the same receptor. But he doesn't know, because he doesn't study B cells. What he's doing is working with hepatocytes, and he goes, no, no, no, this is hepatocyte growth factor. But there's no Google These people have no idea, they're discovering the exact same thing. And so They had, they, they, I mean, without knowing it, they're creating all this confusion, so what happens in 1982, is a bunch of immunologists came up with a plan. They said, we're gonna start naming these things. Because 4 people have discovered the same molecule, and when we find out it's the same molecule, all that's gonna happen is we're gonna make someone angry when we pick 1 of the 4 names. So instead, we're just gonna go with a naming convention, a system. They call this the cluster of differentiation, or, so, clusters that differentiate different molecules. So all these molecules are one cluster, they're the same cluster, and all those molecules are a different cluster, right? And if you wanna know why that's the case, uh, basically it has to do with how receptors were discovered, people were making antibodies about, uh, against these receptors, and they were grouping antibodies that bind the same thing together. That's essentially what they were doing. And what they did was, they said, well, let's not just use 1000 names, let's use one naming convention so we can increase the rate of discovery. That's a really good idea, right? Open science, let's work together. So then they start going, cool, well we're gonna name the first one that we find, CD1. And then we'll name the second one that we find, CD2 and then CD3. We've already spoken about CD3. CD4, same. And what could go wrong? How many could there be? There's more than 370 of them now. Not the plan. They were like, there might be a dozen. There's too many So, this is how many of you feel, cause you're gonna, what's the difference between CD3 and CD4 and CD5 and CD6 and CD7, CD8, and that's hard, and I know. Why? Because I'm an immunologist too. So I also hear these things, and I know what some of them are, but like CD1, actually I know what that is, but for a long time I had no idea what CD1 was, and that's the first one, which is kind of crazy. Before you go and find a chart that has all of them. You don't need to memorize what they all do, OK, but there are some that you're gonna have to know, and you, and, and we'll let you know what those are. So That's, those are the receptors. What about the molecules, the secreted molecules? Well, we actually use a word called cytokine for this. And cyto is that same cell, and kine or or I think it's kina, is movement, like kinetic, right? And these are molecules that make cells move, and it's not literally move, it's, it's change. So it's not literally just making them move around, it's that push cells to do something different. It's essentially just signaling molecule, when we use the word cytokine, a soluble signaling molecule. And of course, at the same time that they're discovering all these receptors, they're also discovering all these cytokines. And they all have different names for them. So what do they do? A little earlier than the receptors, they say. Let's go and make a naming convention for these things. Here's what it's gonna be, it's gonna be the interleukin system. Why? Well, inter means between. And leukin refers to leukocytes, so these are molecules that signal between leukocytes, between immune cells. And rather than having 1000 different names, we're gonna make a unified convention. Aisle 1, aisle 2, aisle 3, aisle 4. Luckily for these people, there's only about 50, which is still too many, but that's how we name them, that's why it's aisle 1, aisle 2, aisle 3, aisle 4. But there is a problem with this name that persists to today, which is that the vast majority of cytokines do not only signal between immune cells. They actually signal all kinds of cells. So, I'd hate for you to walk away going, no, no, no, this can only be something that signals between immune cells, no, of course not. It's, they signal everywhere. So, for now, If you wanna walk around saying CD3 and IL 4 in a random order, you're pretty much talking like an immunologist, cause that's how we all sound. Over the rest of the course, you're gonna learn what all these cells and molecules do, and I hope by setting this baseline for you all, that I've given you some context. So does anybody have any more questions that I can try and answer while we still have everybody? Anymore. No? Alrighty, well, Next class, I'm gonna tell you how the Lord of the Rings actually plagiarized the immune system, and uh that I act, I mean JR Tolkien's gone now, but if I had known at the time, I would have sued him into oblivion. All right, thanks everybody.