The Science of Everything Podcast - Episode 73: Introduction to the Immune System Part 2

Episode Date: June 29, 2015

Continuing on from the previous episode, I discuss the role of antibodies and antigens in mediating adaptive immunity, and follow with a discussion of the functions and roles of B-cells and T-cells. I conclude the episode with an overview of the many components of the immune system and a discussion of how they interact to protect the body from pathogens. Recommended prelistening is Episode 72: Introduction to the Immune System Part I.

You're listening to The Science of Everything podcast, episode 73. Introduction to the immune system, part two. So this episode continues on directly from episode 73, Introduction to the Immune System Part 1, funnily enough. And I'd strongly recommend listening to that first, because much of this episode won't make very much sense without that background. But in this episode, we're basically just going to continue straight from where we left off last time, and I'm going to talk in particular about the adaptive immune system

and antibodies, B cells, T cells, a bit about agglutination, and then I'll try and sort of summarize and put it all together and give an overall framework of how the immune system works. Just before we start, a brief note, I wanted to apologize for the very long delay between the previous episode and this one. I unfortunately undertaken rather too many obligations of late, and my time has been quite limited. I'm hoping, fingers crossed, that in the relatively near future, I'll be able to restructure my schedule so that I have a little bit more. more time for the podcast. The podcast is important, and I certainly want to keep it going, so I don't have any immediate plans to stop making episodes. It's more just a question of time. I thank my loyal listeners for sticking in there and continuing to subscribe to the podcast,

even if there aren't any episodes for a little while. Okay, so that being said, let's jump back into the immune system, and to remind you of where we were, we had talked about the different types of leukocytes, so white blood cells in the immune system, basically, that fulfill different functions. We talked about the difference between the innate and the adaptive immune system, and mostly in the previous episode we talked about the innate immune system, which includes non-specific responses, which are mediated by both cell and humoral components, and that does not have an immunological memory versus the adaptive immune system, which is much more specific, and we'll get to that momentarily. We talked about surface barriers and inflammation,

And we also talked about phagocototic cells. So these are cells that basically engulf viruses or other invasive organisms and, well, eat them essentially, digest them in a vesicle. And these include things like macrophages, neutrophils, and dendritic cells. So we talked about those. And that led us up to a discussion of the complement system. So the complement system consists of a number of proteins found in the blood, which, made mostly by the liver, and have a number of important roles to play in the immune system, and there are also a number of different ways that the complement system is activated.

And so last time we talked about how the complement system can be activated by phagocytosis, so the interaction between particularly macrophages and the complement system. What I want to talk about in particular this time are antibodies, which are responsible for what is called the classical pathway of activation of the complement system. And so in order to talk about that, we'll have to, of course, introduce what antibodies are. And so let's make that our point of departure for this Part 2 episode. But that's where we're sitting in relation to the previous episode. We're talking about the complement system, and we're talking about how it's activated and also the functions it fulfills.

And in order to do that, we need to understand what antibodies are. Okay, so antibodies. What is an antibody? Antibodies are also called immunoglobulins. Basically, they're just big proteins. They're shaped kind of like a Y, like a capital Y. So there's so-called heavy chain and light chain. The heavy chain sort of makes up the inside, and the light chain is kind of like the outside, which is smaller, but we don't really care about the structure very much.

Just remember that it's a protein that looks kind of like a Y, and the tip bits of the Y, that the top two edge parts, if you like, of the Y, these are important. These tip regions of the antibody are called paratopes, which act kind of like locks. And, of course, a lock has a key. the key that is specific to a particular paratope is called an epitope. So epitope and paratope, they bind together.

This is at the top ends of the Y structure which forms the antibody. What is the point of this? Antibodies detect antigens. Antigens have particular epitopes, which are locks, which fit into particular keys on the paratopes. So there's a direct sort of correspondence between paratopes and the epitopes. Paratope recognizes an epitope. Lock, key, go together.

So, this is the way that a particular antibody recognizes a particular antigen. But what's an antigen? I haven't defined an antigen. Let's talk about that. An antigen is really sort of circularly anything that elicits a response or binding by antibodies. That might not be very helpful. Let's state it another way. Antigens are usually proteins or things that are, you know, glycoproteins or other things like that. They are just molecules that are recognized by antibodies. Here's how it fits together. got an antigen. It's just some molecule, probably a protein. Parts of that molecule, part of the antigen are called the epitope or epitopes. They act like keys. A particular epitope interacts

with a particular parotope, the lock, the lock and key fit together just precisely. A different key and a different lock won't work. You need just the right ones to fit together. When they do, you have an interaction. You have a binding between the antibody, which is the Y-shaped thing, and the antigen, which is the other protein, which connects up to the epitope sites on the top of the antibody. Why on earth do we care about this? How does this relate to the immune system? Well, it's very important to the immune system because, and this is a key point here,

infectious agents, so this includes viruses, particularly bacteria, carry antigens. They have them on their cell surfaces, and they also often excrete them into the, through various ways, into the bloodstream or the intercellular fluid. So when you have infection, when you have an infection, you will have antigens from that infection. and the antigens will be specific, or at least some of them will be specific to that particular type infection, that particular strain of the virus or species of bacteria or whatever it be, because there are many different variations you can have on these antigens and epitopes and so on, and the exact structure of the matters.

If it's just a little bit different, it won't bind properly with the antibody. And so the antibodies and antigens are specially designed for each other in some sense, or especially fit together with each other. Now that's very important, and that's how the memory part of the, adaptive immune system works. It recognizes specific antigens which come from specific infectious agents. And that's how your immune system can respond to very specific things. Or the adaptive part of it can respond to very specific things, very specific infections. Now, as I mentioned, antibodies can occur in two ways. They can either be in the soluble form.

They're secreted from the cell and they're just sort of floating around in the bloodstream or in the solution, in the fluid between cells wherever. The other form is attached to the of the surface of cells, so bacterial cell or whatever. So these two different forms of antigens, I mean the antigens are basically the same, but the two ways they can exist in solution or attach to the membranes, are recognized by different types of cells. Free antigens that are in solution are detected by B cells, whereas the membrane-bound antigens are detected by T-cells.

That's not the only difference between B-cells and T-cells, but that's an important difference between them. So, hopefully you recall, B cells are a type of leukocyte, specifically they're a type of lymphocyte, which are part of the adaptive immune system. Their job is basically to recognize these extracellular antigens, the ones that float around in solution, bind to them, gobble them up, essentially, and I'll explain what I mean by that, and present them to T cells, to show them to T cells. thence they become activated by T cells and produce antibodies. So B cells are also called plasma factors, or plasma B cells specifically, are called antibody factories. This is where antibodies ultimately come from. They're produced by B cells.

So B cells have a role of, one, recognizing extracellular antigens, and two, churning out antibodies, and the right type of antibodies, obviously, that correspond to the antigens that the body needs to respond to. Now, they need T cells to help them out for this, specifically the T helper cells. We'll get to how that works later. But, first to explain how B cells recognize the extracellular antigens. Well, each B cell has a unique special receptor protein on its surface called a B-cell receptor, or B-CR, on its surface on this membrane, that will bind to one particular antigen. So this is the lock and key thing.

Basically, each B-cell has its own unique lock, and that's stuck on the membrane. this lock will come into contact with a lot of extracellular antigens. A lot of different keys. So you can think of a lot of keys are floating into the lock, and a lot of them, most of them don't fit, because they're the wrong type, and so they just sort of bump out and diffuse off wherever. But occasionally, by chance, the right one will come in. You'll get the right antigen hitting, finding the right B-cell that has the exact key,

sorry, exact lock that corresponds to that key. In other words, you'll have a match between the epitope and the parotope, epitope of the antigen, paratope of the antibody on the surface of the B cell. When that happens, essentially the antigen and antibody complex, you know, the binding of these two things together, is ingested into the cell. It's sort of pulled in, if you like. It's internalized and processed, a bunch of reactions happen inside the cell, and then the B cell starts displaying the antigen on the surface of the cell. This is called the MHC Class 2. complex. So if you remember the major

histocompatibility complex, the MHC1 that we talked about for natural killer cells, this is a different type of that, MHC2. Basically, it's this class, this bunch of proteins on the surface of the B cell, says, it doesn't say that I'm an enemy cell, kill me, that would be bad because we don't want to kill the B cells. Rather, what it says is, hey, look at what I've found.

I've found this type of bad guy, and then it just waves the appropriate flap. In other words, it displays the appropriate protein. It displays the antigens. Literally, the antigen sits on the surface of the cell membrane of the B-cell. It's displayed so that other cells can come and bind to it. Examine it. Look at it, essentially. Particularly the T-helper cells. So the T-helper cells come along, bind to the antigen that's been displayed on the surface of the B-cell,

MHC-2 complex, and that then activates the B-cell. If the B cells displaying an antigen and it comes along, then it's recognized by the helper T cell, that activates the B cell. Activates the B cell to do what? Activates the B cell to pump out antibodies that correspond to that particular antigen. So basically, what the B cell is doing is it saying, hey, look, I found this. Look at this key that I found. I found this key, and it fits with this lock.

And it shows it to the T helper cell, and the T helper cell binds to the surface of the complex, effectively saying, yes, I recognize that, I give you permission, go ahead. And the B cell transforms into what we call a plasma B cell and starts pumping out those locks. It starts producing a bunch of those locks, the antibodies, that correspond to the antigen

that it's just found. And these antibodies are released into the bloodstream, generally, or into the intercellular fluid. These antibodies will be specific to the exact type of antigen, the precise type of pathogen, whatever it was, that the B cell found in the first place.

Now, why would we want the plasma cell to produce a bunch of these antibodies? We haven't killed anything yet, all we've done is recognize an antigen. Now, this is where we come back to what I was talking about before. The complement system, remember the complement system? In order to activate the complement system, which in turn is really useful for helping out with the inflammatory response and macrophages and so on, you needed antibodies. That was the classical mode of activation. You needed antibodies to activate the complement system, which in turn activates these other things.

Well, this is where the antibodies come from, or at least this is one place they can come from. They come from the B cells that are activated by the T-helper cells in response to the extracellular antigen, which they detect. So, we've traced the process all the way back to these extracellular antigens, activating the B-cells, well, being detected by the B-cells, presented in the form of the MHC Class 2 complex on the surface of the B-cell, which then is detected and activated by a T-helper-cell, which then turns the B-cell into a plasma cell, which pumps out the antibodies, which goes on to activate the complement system, which helps with, with inflammation, which draws up all of the macrophages and other phagocytic cells, and which then starts chomping up and killing and eating and destroying the pathogens that produce

the antigen in the first place. And the beauty of this system is that it's specific to just that type of antigen, just that type of organism. So you get much stronger binding affinities, a much more robust, more specific, quicker response. So it's much more effective in that sense than the innate immune system, which reacts in a general way. This is able to be much more targeted, much more specific, and therefore much more effective. If you recall,

when I talked about the difference between the innate and the adaptive immune system, I mentioned that the adaptive immune system has an ability to remember what it's been exposed to in the past. This is possible thanks to memory B cells, and they're also a form of T cells, memory T cells, which effectively have a similar purpose, but they

are formed and then just sit around. They can last for years, many years. And basically, they're just there to remember to, that they hold on to that MHC Class 2 complex or something like it, so that in the future, if we ever see this, if the body ever comes across this same pathogen again, we're ready. We've already found the lock that corresponds to the key of the antigen. We've got it in reserve, in a sense.

We just have to do and start pumping it out with the plasma cells. So these memory B cells then allow for a much quicker response, a much more robust, dramatic response to this infection if we see it again in the future. future. It's basically the same thing. You'll pump out antibodies. It's just that you'll pump them out much more quickly and a lot more of them if you meet the same infection in the future, thanks to these B cells, which quietly carry this record along with you for many years. And this is how vaccinations work. Vaccinations work by presenting antigens in various ways, often through an inactivated form of

the pathogen, or you just by chopping off parts of the proteins on the surface and presenting them to the body or you can present very similar organism which is not pathogenic but has similar enough antigens to elicit an immune response. There's different ways of doing it. But basically, you get the antigens of the pathogen into your system without actually getting the disease organism or the pathogen itself into your system. That way you can get these B memory cells all ready to go in case you ever do come across the actual pathogenic organism.

Then you've got the type of lock that you need already in storage all you have to do is pump out all those antibodies. and you get a much more rapid, much more robust immune response, and therefore you're able to beat off infection with relative ease. And that's B cells. Let's now talk about T cells. I've already mentioned one type of T cell, T helper cells. Remember these ones that basically,

this is the one that recognize the MHC2 complex on the surface of the B cells and basically activate the B cells, sort of giving them permission to start pumping out the antibodies. But that's not all T cells do. That's what helper T cells do, but there are some other types of T cells as well. I mentioned memory T cells, sort of similar to memory B cells,

but there's another type of T-cell that are called killer T-cells. They're a little bit similar to the natural killer cells, which I mentioned earlier. So these killer T-cells go around looking for the MHC-1 complex that I mentioned earlier with respect to the natural killer cells. So they really do a very similar thing, except in a bit more specific way.

They go around looking for cells that don't have this. Remember, this MHC1 complex is the white flag that says don't attack me, I'm self. Well, the killer T cells go around looking for cells that don't have this, which means they're not self, which means, boom, kill them. Cytotoxins, which poke holes in the membrane and apoptosis, all that stuff. So it's very similar to the natural killer cells, what the killer T cells do. But there is an important difference between how the T cells work and how the B cells work, particularly how they're activated. Remember I said that you have an antigen Antigens come along when pathogens enter the body

Antigens can exist free sort of in solution B cells take care of those, recognize those They can also exist on the surface of other cells T cells take care of the latter case So T cells cannot respond to Bear lone antigens that are just sort of sitting around in solution They need antigens to be expressed or displayed Presented is the term that's often used

presented on the surface of other cells. These are called antigen presenting cells. An antigen presenting cell is a cell that has found an antigen somewhere, displays it on the surface of its membrane, and basically is sending a message through the displaying of the correct protein structure, obviously. This is not verbal communication, but often helps to think of it in that way. So it's sending a message to the T-cell saying, hey, look what I found. Look at this.

I found this particular type of enemy. this is what an antigen-presenting cell does. Now, B-cells are a type of antigen-presenting cells. I just explained about how they recognize the antigen and then display it on its surface, and then the T-helper cell comes along and activates the B-cell, and then they form plasma cells which pump out the antibody. So B-cells are antigen-presenting cells,

but they're not the only type of antigen-presenting cells. Excuse me, macrophages and dendritic cells, as well as B-cells can also act as antigen-presenting cells. So they all conform this MHC Class 2 complex on their surfaces, which, remember, is the protein structures which say, hey, look what I found. I found this type of bad guy. So the major function of the helper T cells

is to be able to recognize antigen bound to these Class 2 MHC complexes, again, not just on B cells, but also on macrophages and dendritic cells, which once activated, then the Helper T cells divide rapidly, and they secrete cytokines. Do you remember cytokines? these are molecules which help to regulate and assist in activating the immune response. So cytokines will send messages, for example, potentially triggering the inflammatory response, or triggering natural killer cells to go around killing cells,

or they might trigger macrophages to come, or they might produce one of these chemotaxis that we talked about before, the chemical gradients that help attract cells to come in. So cytokines can perform all of these sorts of functions, and those are produced by helper T cells once they have recognized the antigen in the appropriate presentation, complex on the cell membrane of one of your macrophages or your dendritic cells or B cells. Now, there's another type of T cells, in addition to the helper cells, the killer T cells,

and the memory T cells. There's also regulatory T cells. These are also called suppressor T cells, and they're important for maintaining an immunological balance, basically, which helps to shut down the immune system before it goes too far, and it starts to attack things that shouldn't. So when the regulatory T cells go a bit haywire, that can lead to an autoimmune disease. where effectively you're attacking, your immune system's attacking yourself, and that's not good. But we won't talk too much about those, just be aware that they exist, a regulatory T cells.

That's antibodies, B cells and T cells. That's the acquired immune system. There's one more concept that I want to discuss before we go and have a big recap and try and put everything in focus and hopefully bring things together, because we've gone through a lot of stuff, and it's kind of complicated. This last thing that I want to talk about is called agglutination. Now, it's a concept in linguistics, but that's not what we're going to. talking about here, we're talking about agglutination as it applies to biology. It refers to the clumping together of particles, and particularly in an immunological context, agglutination occurs when an antigen is mixed with its corresponding antibody. Do you remember the lock and the key thing?

So when you put a lock together with this appropriate key, that produces, and you have enough of them, then that produces agglutination. Basically, they all clumped together, forming a precipitate, so you can actually see them come out of solution. This is very useful. This is very useful. useful because we can use it for testing. So, for example, this is a way that you can test a person's blood type. The person's blood type refers to the types of antigens that are displayed on erythrocytes, the red blood cells. If you have, say, type A blood, that means you have A antigens on your red blood cells. So if I add a type antibodies to a type A blood, then I will see agglutination because I'll see that the lock and the key connect to each other, form this precipitate, and I can see that visually. You can literally see it as little sort of dots

in the fluid. And I can see, okay, this person has type A antigens, and I can do the same for type B. And if you have reaction for both A and B, then you're A-B. If you don't have a reaction for either, then you're type O. And that's how people, that's how basically we test blood types, or ABO blood type anyway. So that's an example of how we can use a glutenation, and it's a very, very useful test, because we can use it to figure out what type of, whether someone's been exposed to a particular pathogen. You know, suppose that we're concerned about, I don't know, the Ebola virus or something like that, has the person been exposed to this pathogen?

Well, if they have, their blood should contain antibodies to the antigens that are specific to this particular type of pathogen. So we take a sample of their blood. We perform an agglutination test, and see, does their blood clump form this agglutination reaction in response to reaction with the antibodies? If it does, then it shows, ah, they've been exposed to. to this antigen before, and they've got the antibodies flirting around in their blood serum. If not, well, then they haven't. Or maybe that they have some very severe immune deficiency,

but I guess that's another issue. Now, you might wonder why this happens. What's the deal with the glutenation? Surely, it didn't evolve just for our convenience for detecting infections or determining blood type. No, it certainly did not. That's just a useful side effect. The reason it evolved is because this clumping makes it much easier to get rid of the pathogenic organism. Basically, I mean, it's Just think about this, it's much easier to clean up a mess when it's all in one place than when it's all spread out and mixed up with other things. And this is basically the same idea. If we can clump all of the pathogens together, it's much, much easier to clue them out of the system than if they're all dispersed and mixed up with healthy cells.

So that's how glitonation works, basically. You have the appropriate antibodies, which bind to the, whatever the pathogen is. This is very hard to explain without a diagram, but basically what can happen is the antigens sort of surround the pathogen, and then bind to either each other or other pathogens in a way so that it's sort of all, forms a big matrix. It all connects up together. Antibody binds to antigen, binds to another antibody, bites to another antigen, and so on. It all connects together up into a big mass, which can precipitate out of solution, and then we just get rid of it. So it's a very convenient way of getting pathogens out of the body. So this is an agglutination reaction. So that's a

glutenation. Let's now go through and try and put everything in place, put everything in perspective of what I've talked about. The immune system is the system of our body that is responsible for keeping out pathogens and for destroying pathogenic organisms that do make it in. We have a number of layers of defences in the immune system. The first layers that we talked about are the skin and the mucus membranes, which help to keep things out or physically push organisms out or particles that have entered the body. Those are fairly easy to understand.

It gets a bit harder when we start talking about the leukocytes, the different types of white blood cells which circulate around the lymphatic system and also the circulatory system and help mediate the particularly killing of cells and help mediating the immune responses specifically. Leucococytes, white blood cells, are divided up into two types,

those that are part of the innate immune system and those that are part of the adaptive immune system. Anate immune system has always the same response. It doesn't have any memory. It's sort of always reacting the same way, immediately in the same way to each different type of infection. Whereas the adaptive immune system has a memory, it's able to know what's happened in the past,

and so it has differential responses. It can respond very specifically to very specific types of infections, but that takes a little time, so there's a lag involved to it. It's not as immediate as the innate immune system. There is, of course, a lot of interaction between the innate and adaptive immune systems. So the adaptive immune system includes the natural killer cells, and also lymphocytes, which include the T cells and the B cells. Everything else, essentially, is part of the innate immune system.

This includes mast cells, basophils, neutrophils, eocinophiles, monocytes, and macrophages. And I think I also mentioned dendritic cells. There are actually some dendritic cells in both the inase and adaptive immune systems, but don't worry too much about those. What do all these different types of leukocytes do? Well, basically, the purpose of leukocytes is to first find and then destroy pathogenic organisms, or also cells that have become cancerous or infected by viruses. How do they do that?

Well, there's two broad categories. There's phacocytotic cells and non-facocytotic cells. Phacocytotic cells work by going and eating things. So they find the pathogenic cell, often bacteria, and literally eat it. Digest it with enzymes and spit out the remains from the other side. There are a bunch of different types of phacocytocytes, so monocytes, macrophages, neutrophils, and dendritic cells, all work in similar ways by eating up.

the pathogen. But phagocytotic cells need to be activated. They need to have a way of finding where the pathogen is. That's where the complement system and antibodies come in. So the complement system is a set of proteins, as we discussed. A bunch of different types of proteins and different groups of them have slightly different functions. But it's responsible for helping out the phacocytotic cells, and also the non-facocytotic cells, but particularly the phagocytotic cells in knowing what they should eat. And one of the most important ways that they do this is,

is by opsonization. The proteins in the complement system coat the surface of the microbes, marking them as, hey, I'm an enemy, kill me, and then the macrophages and other phagocytes come along and can bind much more readily to these obsonized microbes, and then they can eat them up and phagocotized them more easily. The complement system also helps the phagocytoters to find the microbes in the first place by the chemotaxis, by which they release chemicals, which then diffuse and you have this chemical gradient where if you follow the concentration along the phagocotic cells are able to locate the center of the infection and thereby get to where they need. Compliment cells also can, as I mentioned earlier, directly kill cells by rupturing their

membranes, and they also help out with the inflammatory response, which I'll go over again in a moment. But how do we activate the complement system? Well, the complement system, one of the big ways that it's activated is the classical path of activation which requires antibodies. What are these antibody things? Remember, these are the Y-shaped molecules, which on their ends have what are called paratopes, which act like locks, and each lock binds to a specific type of part of a molecule called an epitope. So one antibody, one particular type of antibody, reacts with one particular type of antigen, which is just some particle or protein or something like that that comes in with with pathogens,

with pathogens. Often it sits on their membrane surface or is excreted from those waste or something like that. So one antibody, one antigen, they bind together, parotope to epitope, recognized in a very specific type way.

We have what are called B cells, which circulate throughout the body, basically looking for antigens to bind to. Antigents can exist either bound to the surface membrane of cells or they can exist free in solution. B cells focus on the ones that are free in solution. when a B-cell with the correct receptor on its surface finds the matching antigen, it binds with it, ingests it, displays it on its surface,

and that acts as a signal to the T-helper cells, and basically it says to the T-helper cells, hey, look what I found. I found this type of bad guy. The T-helper cell then activates the B-cell, which becomes a plasma B-cell, and then pumps out antibodies. So now we've got a whole bunch of antibodies just specific to this antigen. These antigens then are able to activate the proteins in the complement system. The proteins in the complement system can also be activated sometimes directly by the antigens,

so they can sometimes go through antibodies. Sometimes they can just directly activate the complement system. And also you can activate the complement system through chemicals released by the macrophages directly. So when they eat something, this is the lectin pathway. They release chemicals which directly activates the complex system. So there's different ways of doing it. But the classical way is through antibodies, which activate the complement system, which then does all of the nice things that I mentioned before,

opsonization and the punching hole in the membrane thing and helping in the inflammatory response and the chemotaxis, helping the cells to know where to go. All of that, thanks to the antibodies produced by the B cells in response to finding the right type of antigen that corresponds to the lock that they have on their surface. But in order for that to happen, you need the T-helper cells. And you also need antigen-presenting cells.

B-cells, remember, antigen-presenting cells are the cells that say, hey, look what I have. found, I found this particular type of pathogen. You should go and start killing this. The T-helper cells go and bind to the proteins on the service of these antigen-presenting cells and then activate, well, activate macrophages, activate the complement system, and activate plasma cells and plasma B cells and so on. But it's not just B cells that can serve as antigen-presenting cells. It's also macrophages themselves and dendritic cells that can serve as antigen-presenting cells. So T-helper cells combine to all of these types, not just the B cells, but macrophages

and the dendritic cells. So there's a multiplicity of ways that you can activate all of these processes. And they're all occurring together in sync with each other. So there's never just sort of one way to do something in the immune system. There's always different ways to get to the same results. And that's, I think, very important because it means that the system is fairly robust. If one thing doesn't work, if one cell line has a malfunction in it or something like that, you're not just going to automatically die. Your system might be, we can a little bit, or maybe you're lacking a nutrient or something, that might weaken your immune system, but there are potentially other ways around it. So it's not sensitively dependent on a single pathway.

If you don't have this, then you're not, you know, you're bam. Your entire immune system doesn't work. There are multiple ways of getting to the same end. So, for example, as I said before, the complement cells can be activated by antibodies, or it can be activated by antigens and endotoxins and other things directly, or it can be activated by macrophages directly. or the macrophages can display antigens to T cells, which in turn signal then to B cells to produce the antibodies, which interact with a complement, or those same B cells can detect the antigen-free in solution,

then displayed on its surface and then interact with the T-helper cells, which then signal to plasma cells to produce the antibodies. So there's a whole bunch of ways that you can do it. End of the day, though, the result is the same. You activate the complement system, which then does all these helper things, with the chemotaxis and the cell lysis and the obstinization and so on. In addition to the phagocytotic cells, which are sort of the main focus, there's also several non-phagocytotic cells,

which also perform important functions for the immune system. So if you recall, there are natural killer cells, and also killer T cells, which are quite similar. These go around looking for the so-called MHC-1 complexes. MHC-2 complexes, if you recall, these are the protein complexes on the membrane which say, hey, look what I found. this type of pathogen, you should kill this guy. MHC1 cells, rather,

are the ones that they're self-markers. They say, hey, don't shoot, I'm friendly. Well, natural killer cells and also killer T cells go around looking for these MH1 complexes, and they should find them on all cells in the body. They want to always see them. It's like a passport. Everyone should have one. But sometimes cells don't have them.

And if they don't have them, that means probably it's a pathogen, or it's a tumor cell, or it's been infected by a virus. And when natural killer cells come across the cell that doesn't have this the right passport, it doesn't have the MH1, then they get mad, and they shoot out toxins and enzymes which can punch holes in the membrane and trigger apoptosis, pre-programmed cell death, and they just eviscerate their enemies, or at least they try to. So very important for the immune system, but non-facocytotic. Also, the other two types of leukocytes, white blood cells, which are important for non-facytocytes functions are basophils and the eocinophils and mast cells as well.

These cells are all important for mediating the inflammatory response. Remember, the inflammatory response is when your blood cells get leaky, basically, and the leukocytes and other cells are able to sneak out through the gaps between the cells in the wall of the blood vessel and get to the site that they need to, where the pathogen or infection site is. So basophils, eocinidyls, and mast cells all help out with that. And they also do other things as well. So they release cytokines, you know, chemicals that help to tell other cells where to go. Eocinophils also have a special purpose of attacking multicellular parasites,

like parasitic worms, for example, which aren't very susceptible to natural killer cells or phagocytes. Another thing that can happen is that when we have the right antibodies, which bind to the antigens of some organism that's pathogenic, that we can have agglusionation, basically. The bad cells all clumped together, which makes it a lot easier to clear them out, and antibodies are very useful for doing that as well. So, to sum up, the immune system consists of this very, very diverse

array of cells and also proteins. So there's a complement system with all of these different proteins which help out the macrophages and the leukocytes and other things so that they know where to go. They're releasing these chemicals, cytokines and other things, sending off signals to produce the right proteins or activate the right type of cell division to get the right cells that it needs, also to tell the cells where to go, so the chemo-tachsy is following down the gradients. You've got the natural killer cells, making sure everyone's got the right passport and killing any cells that don't show their credentials. You've got the B cells and T cells going around looking for antigens, either in the solution or on the surface of other cells, and when they find the right

antigens, pumping out the antibodies, which then go and bind to the antigens on the surface of cells or elsewhere, marking them for destruction or attracting macrophages and other things to the right spot. Of course, antigens also help in activating the complements, which then, as we said before, help out with all of the attracting of cells and the killing of cells directly through punching holes in the membrane and helping out with activating the inflammatory response which helps to get the cells in the right spot.

All of this stuff is all happening in concert together. It's all interacting, it's all interchanging together. That's why there is no real there is no hard and clear separation between the innate and the adaptive immune systems. The cells are separate.

They're different types of cells, but the functions they perform are linked. If you just had an adaptive immune system, you wouldn't be very effective because you need the, particularly the neutrophils, the monocytes, and the macrophages to perform the phagocytosis. That's one of the major purposes of having antibodies produced by your B cells. If you didn't have the innate immune system to complement that adaptive immune system, then the antibodies wouldn't be that much use. That would be some use, but much less.

Likewise, if you just had the innate immune system, your reactions to pathogens would be much less robust, particularly after seeing them for the second time, because when you have the immunity stored away, the record of what lock worked in the past, what particular type of antibody worked in the past, when you've got that stored away in your memory B and memory T cells, that can produce a much more robust, much more rapid immune response the second time you're exposed to the same pathogen.

And so that really helps out the innate immune system, making it a lot more effective, allowing much more specific binding and much more rapid response. So, these two systems work together, and they complement each other. And really, that's all I have to say about the immune system. There are a lot more aspects of it that I haven't gone into, and a lot of complexities and details that we haven't discussed, but hopefully that has been a reasonably comprehensible introduction to the subject.

Hopefully, you found that interesting and enjoyable. If so, I would be very grateful if you could log on to iTunes or whatever other podcast aggregator you'd like to use, and give the podcast a favorable review. It really helps to keep up the ratings and interest in the exposure of the show. We also have a Facebook page where I post up occasional updates and also a visual material to complement the shows. You can go to Facebook and just type in The Science of Everything podcast.

You should be able to find us and give us a like. If you'd like to send me an email and make a suggestion about how to improve the show or what topic to talk about or just say hi, I like to hear from listeners. My email address is Fods12 at gmail.com. That's FODS12 at gmail.com. Thanks a lot for listening, and I'll talk to you next time.