Immune System

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Imagine if I ask you to visualize a steak, a nice piece of meat. If I asked you to touch it, would you? Yeah it’s a bit uh, but you can handle it, not a problem. What if we left it lying out for a couple of days or even a good month and it got all nasty? That’s disgusting. Now what if it had been left out for decades? You’d think that’s utterly gross. But if you pay attention to the tabloids, people are more than willing to buy pictures of decades old hunks of meat that had been exposed to the environment forever like Angelina Jolie and Brad Pitt. Why aren’t they so gross and nasty?

Well, despite those occasional rumors of digital editing and plastic surgery, it’s because they have an immune system that’s constantly battling the things that would cause them to get all rotten. Take a deep breath. You’ve just sucked in hundreds of mould spores, and bacteria and viruses that are eager to go to town eating you, using you as a source of nutrition. Why aren’t you rotting? That’s because your immune system, a subdivision of the lymphatic system ,is in constant battle fighting them off. Ready to take them out.

So it’s a really interesting system to study. Not only to find out why Angelina Jolie doesn’t have green fuzzy mould spores, pouring out of her cheeks, but also because if we can learn all about it, we can use out knowledge to help fight off diseases like HIV. And also figure out ways to deal with the malfunctions of it that can cause things such as asthma or other allergies.

Now, to make sure that you can understand everything I’m going to go through, I’m going to begin by touching on what are the components, the parts of the immune system. Then, I’ll get into the non-specific defenses. These are the parts of your immune system, that are ready to fight pretty much anything that comes at you. They’re kind of like the police force of your immune system.

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Now just like the police, they’re pretty good at fighting things. Sometimes there’s threats that are beyond what the police can handle. That’s what the specific defenses are for. Those are like the military or the FBI, the federal forces, that are ready when alerted to assemble a vast army to target just a specific invader.

I started by comparing your immune system to the military, to the police officers which is a common analogy used in textbooks. But just like the military isn’t made of a bunch of guys just carrying out M16s, your immune system has a whole bunch of different weapons in its arsenal, just like the military has submarines, airplanes and those guys with the M-16. So let’s take a look at some of the components of the immune system.

Now, there is the barrier methods. Now those are unique to the non-specific defenses. These include things like your skin or mucus, because they just physically block their barriers that prevent the foreign invaders from getting into your body. Whether it’s some bacteria lands on your skins, there’s layers upon layers of dead cells and other things produced by your skin, that just keep them from being able to get into your blood stream and eat you.

But imagine you’re a fungal spore, you get inhaled. Now you’re past the skin. You’re ready to get in and you get inside the lung. Nice warm, moist, humid. It’s perfect. It’s full of food, but you’re screwed, because you just get trapped in that sticky mucus. And there’s cilia in your lungs that help flood that mucus up, and then you swallow. And those fungal spores die a horrible screaming death in your stomach.

Now, next up are the chemicals. Now the chemicals have a wide variety. Some of the most common of them are the antibodies, a weapon of the specific defenses. Proteins that stick to specific foreign invaders. Then there is a series of proteins called the complement. That is a group of proteins that help or complement the effects of both the specific and non specific defenses. There’s other chemicals like Histamine which can trigger off things like inflammation.

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Now the cells, these are the white blood cells that everybody is familiar with. The proper name for those is Leukocytes. Let’s take a closer look at some of the combinations or a variety of leukocytes. Here you can see, while those are red blood cells, the other guys around them are some of the different kinds of Leukocytes. These can range from the macrophages, or phagocytes, which are the cells that eat other cells that everybody thinks of as white blood cells. But they can also include a subdivision called lymphocytes, which include the B-cells that pump out thousands of antibodies per second, when you’re infected with a foreign invader, to the Helper T-cells inside of toxic T cells that some of you may have heard of. But they are a little less commonly known.

All of the white blood cells are made in the bone marrow, just like the red blood cells are. But some of them will go to a special part of your body, called the thymus gland to mature. That’s called the T-Cell. That’s what the T stands for.

The last components of the immune system, are the lymph nodes and the lymph vessels. I think I mentioned before that the immune system is actually a part of what’s called the Lymphatic system. This is the loser in the whole popularity contest of the organ systems. Everybody has heard of the circulatory with your blood vessels pumping out blood everywhere. It’s great. It’s wonderful. But remember, what’s the job of the circulatory system? It’s to allow the oxygen and glucose, that’s in your blood vessels to leak out and feed your muscles and the rest of your body. But if they’re allowing oxygen, which is a very small molecule to leak out, and glucose which is a bigger molecule to leak out, how come everything else isn’t leaking out? It turns out it is.

When the fluid that’s in your blood supply starts to leak out, then it’s no longer called blood. It instead becomes a fluid called lymph. Much like the storm drains collect the water that comes into the roads, you have these lymph vessels which collect all of the various fluids that are leaking out of your circulatory system.

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These lymph vessels collect and they start to form things called lymph nodes. If you take a look at the structure of lymph node, you can see here these lymph vessels are allowing this fluid to come in. Now it’s under much lower pressure than the blood is. The blood stuff is rushing through, because you need to get that oxygen to your muscles really quickly. In the lymph however, things are going much slower. It’s much more sedate. That’s why you have a bunch of white blood cells hanging out in these lymph nodes, because that slow pressure gives them more opportunities to inspect the things that are coming through your body. This is also where you’ll have your B-cells starting to multiply when you’re getting infected. That’s why you have a bunch of lymph nodes right here. When you’re sick and you go to the doctor, and they start poking you, it’s not just, because it’s kind of fun to see your face when you go 'ouch stop it'. It’s because, they’re swollen up with this vast army of defenders against that specific invader. So there you go. That’s the four major components of the immune system.

All those components work together to fight off germs and keep you safe. While both the specific and non-specific have cells and chemicals. Like I said before the barriers are unique to that non-specific set of defenses. So the non-specific defenses, with those barrier, those barriers personify the whole thing that makes the non-specific defenses called that. They fight off not a particular kind of pathogen, or thing that causes the disease, but instead they fight off a whole broad range of pathogens.

Your skin doesn’t just block the polio virus, or just block the E. Coli. It blocks anything that can eat its way in through your skin. Plus the skin is constantly pumping out certain chemicals like in your sweat, that actually can help fight off some bacteria. That’s kind of analogous what’s going on with the barriers of your lining of your digestive tract. The lining of your stomach, not only pumps out the mucus that I’ve mentioned before, but it also pumps out like the Hydrochloric acid that we talked about. That can destroy any bacterial virus that happens to make its way into your body by way of being on your food.

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Now let’s imagine something does manage to penetrate your skin and poke you. Well, that’s when a process known as inflammation will kick in. Take a look at this. You can see what’s going on with the inflammation. Inflammation is triggered off by the chemical called Histamine and other similar chemicals. The damaged area of your skin, those cells which are released, these chemicals, and a specialized cell called mast cells will also release the histamine. What histamine does is, it tends to open up the blood vessels that feed that area. That’s why it’s turned all red, because there’s more blood getting to that area. That brings the white blood cells, the street-cops of your immune system to that area as well as any specific defenders that you happen to have.

Now, not only does it bring in those white blood cells, it's also bringing in the nutrients that those white blood cells will need to go town against the invaders. The histamine not only brings more blood vessels by relaxing the arteries that feed that area. The capillaries, the tiny little blood vessels that are in that immediate area, their cells start to become leakier, to allow the white blood cells to actually squeeze their way out of your bloodstream. So that they can get into the tissue and start eating the bacteria that are causing the problem.

Now, the next kind of chemical defense is something called complement. You can see here it looks like a little ring has been poked into this layer of blue things. What that is, is a pore, a channel that’s been tunnelled into the membrane of an infected cell, or of a pathogen. Any cell that is a foreign invader, or an infected cell, that’s been labelled with antibodies by your specific defenses. This complement system, it's a group of like I said, roughly 20 different proteins. They’ll combine and they’ll start poking these holes, which causes obviously the interior of the cell to be exposed to the exterior. And depending on stuff, will swell in to pop the cell. Or depending on the osmotic pressure, it may cause the infected cell to just leak and die.

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The last thing I’ll talk about are those cells of the non-specific defenses. Those are the phagocytes. Which means literally the phag- is a root where that means to eat, -cyte means cell. These are the cells that eat other cells. The stereotypical white blood cells that you guys all know. There’s two major phagocytes of the non-specific defenses; neutrophils and macrophages. Let’s go ahead and we’ll take a look at a YouTube video that shows a neutrophil hunting down its prey.

Here is that YouTube video. Now let’s go ahead and let’s make it bigger so it’s easier to see. Before I get started, I want make sure you understand what’s going on here. Here we see this large thing there, that’s a neutrophil, one of those phagocytes I mentioned. All these little round guys around it, those are red blood cells. See this little guy down there, next to those two red blood cells, that’s a bacteria. That bacteria is going to try to escape, but it’s not going to get lucky. So let’s go ahead and watch it hunt.

You can see that neutrophil is just chasing it. And when it finally manages to corner it, it eats it. Now that bacteria stuck inside of that neutrophil unable to escape. White blood cells don’t just do that to one bacteria, they can take in hundreds, dozens, doing that endocytosis process that I’ve covered before in my cellular transport video. Once it’s inside, it then sends lysosomes; specialized cell organelles that are filled with digestive enzymes, to kill that bacteria.

You can see the effects of this. Because occasionally the white blood cells will lose the fight, and then they die. That’s what pus is. Pus is the dead bodies of white blood cells caused by the death of them as they’re fighting off the hundreds and thousands of bacteria they've eaten. That’s why it’s all kind of sticky and gooey. It’s because all the DNA of the white blood cells is starting to get tangled up. Fun isn’t it?

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The macrophages of the non-specific defenses are also a key component of the immune system, because they also are the ones that help activate the specific defenses. Now again, the non-specifics are like the police force of your body. The specific defenses are like the forces that the federal government can bring to pair up. Like the Elite SWAT Teams of the FBI or the armed forces. So what happens is that, those specific defenses, what gives them their special ability is that, they can attack only one particular kind of antigen or pathogen.

Now how do they get to be so specific? Well, that’s because, each one of these cells has a special region of their DNA that controls the creation of a special protein on the surface of these cells called a receptor protein. It turns out that this region of the DNA, can undergo a lot of genetic reshuffling during development. So what happens is that, each cell as it's being created randomly shuffles its genes and thus creates a random receptor protein. This is how your cells are able to recognize so many different kinds of foreign invaders. Each of these specific cells will create a different kind of receptor protein. It’s not that your body has the ability to know tuberculosis bacteria. They must have this particular protein on their surface, or make a receptor that can dock with that.

Now instead, your body makes a gazillion different kinds of cells, each of them with a slightly different receptor protein. Just by sheer probability, you’re bound to have a few receptors all bind to something, that a tuberculosis bacteria has on its surface. It’s these receptors that make it so highly specific.

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So how does this all begin? Well, the first cell that’s very vital for this, are the ones called the Helper T-cells.

Now if you take a look here we see a macrophage. What a macrophage does is again it goes around and eats anything it doesn’t recognize. That’s what we see here, this little orange circle thing. That’s a foreign invader say a bacteria. It goes ahead and because it doesn’t recognize it, it eats it. This is like a cop going along the street going well, there’s some guy over there planting bombs. He yells, freeze, the guy says, "No I ain’t coming cop," and so the cop shoots him. Now he drags the corpse back to the police station and starts trying to find who recognizes this bad guy, because maybe he’s part of a gang.

Well, that’s what you see happening here with the macrophage. What it does, it takes in the bacteria, eats it, and chops it up. Now what it does, it take a part of the components that made up the bacteria, and sticks those pieces which are called antigens, because they can generate an immune response. It takes these antigens and puts them up on special proteins called NHC2s. That’s what this little white guy here is moving up to the surface of the cell.

Now that the macrophage has eaten some kind of foreign invader, and it’s putting antigens on its surface, it's called APC or antigen presenting cell. What it starts doing is it starts roaming through your body, going through your lymph nodes etcetera, looking for a kind of specific defender called a helper T-Cell. The Helper T-Cells are the generals of your immune system army.

Now, each of these generals, these Helper T-cells, is like I said specific in what it can attack. What happens is that the APC goes up to each of these Helper T-Cells and says, "Do you recognize this bad guy? Do you recognize this bad guy?" Ultimately, you’ll find a Helper T-Cell that does. When that happens, when the receptor, sometimes it’s called a CD4 molecule here, that helps guide it in.

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When the receptor of the helper T-Cell binds to the correct antigen, something starts happening. The macrophage will release some chemical saying, "Go, these are bad guys." The helper T-Cell then becomes what’s known as a mature Helper T-Cell. A mature Helper T-Cell starts dumping out a vast stew of chemicals. The major one of these is called Interleukin-2 and other chemicals called cytokines.

You can probably figure out what Interlukin-2 does, because inter means between, -leuk refers to leukocytes, those white blood cells. So it’s a chemical used to communicate between different white blood cells.

The effect of the Interleukin-2 is to make more macrophages come to fight the invaders. And it stimulates the helper T-Cell to start rapidly dividing. So instead of having a few of these generals, who can recognize the foreign invader, you start having a much larger army of them. But the thing is, much like generals, do generals actually fight bad guys? No. They’re the ones who sit from behind and they direct their troops to attack. So let’s take a look at one of their first troops.

There are these things called B-Cells. Now the T-Cells, the Helper T-cells, and later on I’ll talk about the cytotoxic T-Cells. These are white blood cells that mature in your thymus gland, which is a gland right above your heart. That also releases a hormone called thymus and which helps do the programming of your specific defenses. The B-Cells on the other hand, they actually mature in your bone marrow. Now the amateur B-Cells have those receptor proteins as we can see on their surface of their cells. They’re like the macrophages in that, when they bump into a foreign invader. If it’s the right foreign invader, it’ll stick to that receptor. Because remember the receptor protein has been randomly generated to match up and bind to a particular antigen.

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What will happen is that the B-Cell will pull that in, and they’ll stick it up on its MHC2, and say look what I found? Like let’s suppose the B-Cells are like bombers. And suppose there is some bombers circling overhead and all of a sudden they look down and they go, "Wow that’s the guy that I’ve been told to keep an eye out for." They’ve spotted it, but they don’t start attacking until the helper T-Cell gives them the order. Because just like with our military, you don’t want the air force guys to accidentally mistake some Canadian forces for some Taliban. That would be bad.

But when an activated mature helper T-Cell, does bind to the activated amateur B-Cell that’s got that orange surface, the helper T-Cell starts releasing that Interleukin2 and other Cytokines. You start having those B-Cells start dividing. They start making a vast army of identical B-Cells that are getting ready. This is called Clonal Selection, because we’re making this clone army of B-Cells, specific to that particular antigen. That’s one of those things to toss out if you have to write an essay about the immune system. You’ve got yourself a point if you mention Clonal Selection.

Now, a B-Cell when it matures, it starts pumping out these receptor proteins called antibodies. Taking a look here at this antibody, you can see it has at least two sites that can bind to its specific antigen. Notice there’s all these different antigens, only the yellow one would match up to it.

Now this is a simple diagram. This is what they really look like. You can see it’s made out of several different chains of proteins. So it has a fairly complicated structure. This is why we always draw it like that, because that’s too hard to take down in your notes when you’re frantically taking notes from a lecture.

So by binding to those antigens, the antibodies they’re being pumped up by mature B-Cells called plasma cells. A plasma cell will actually work itself to death, because it pumps out these proteins so fast. It can pump them out. I read once about a 1,000 antibodies per second. That gives them a very short life span, because they literally work themselves to death.

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But these antibodies, by binding to the antigen, they can do all sorts of things. First, by binding to the antigen, notice those two binding sites? It can lock two different bacteria together. Then other antibodies will start clumping them together into larger and larger groups of bacteria, and they’re stuck. It’s kind of like when Spiderman starts spraying his webs to stick bad guys together.

Other things they can do, they can bind to toxins and make those toxins unable to work. When they bind to a protein, remember that complement chemical from the non-specific defenses? That’s attracted to any cell that has an antibody stuck to it. It also attracts the attention of the macrophages and other cells of the immune system. So let’s go ahead and take a look at a YouTube video that shows some of the ways that antibodies can work.

Let’s go ahead and make it bigger and take a look at what’s going on. Here we are inside of a capillary. You can see the red blood cells and these white guys are the white blood cells. You can see things are rushing through. Well, it’s hard to see at this frame rate, but you can see there’s also tiny little particles; the antibodies. Now here comes one of those evil bacteria. Notice on its surface, it’s got these receptor proteins, that’s what it uses to attack its targets. It’s attacked one of its targets and then it’s going to start infecting and attacking that cell. Here comes more bacteria. It’s a bacterial infection and they’re attacking.

Here comes our antibodies. They’re gumming up the receptors of the bacteria. Now it can no longer affect it. Now it doesn’t stick to your cell, but it does block them. Now here comes a macrophage. So now that you’ve seen how the antibodies work, and again the B-Cells are like bombers. The bombs that they drop are guided missiles that come in and they start bombing the guys from far away. But for close up work, that’s where the cytotoxic T-Cells come in, sometimes called killer cells.

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They’re like the B-Cells in that, they first encounter the antigen, before they’re activated. So they’re like a marine. He’s on leave, he’s walking down the street. Now what cytotoxic B-Cells do is, they’re always inspecting cells, your body cells. What they’re doing is they’re walking up to them, and there’s another one of those MHC things, only this one is called MHC1.

Every cell in your body that’s got a nucleus, has MHC1 particles on it. What these proteins are, is essentially like a window that gives a sample to any cell on the outside of what is your cell doing? Well, if your cell has been infected by a virus, or if your cell has become cancerous, it’ll stick up on its MHC1 complex. It’ll stick up proteins made by that virus, or proteins that are commonly found in cancer cells.

Just like the marine, he’s strolling along the side walk looking in to the windows of the various stores that he’s walking past. If he sees the guy he spent the last 10 years of his life training to get ready to attack. If he sees one of those bad guys sitting there assembling a bomb inside of a store, he will go and become activated. But again, he is not given the go signal until a general, one of the Helper T-cells, gives him the right to attack. This is one of the ways that your immune system helps protect itself against accidental activations. Because, you don’t want to have a massive immune response to something that was just a tiny pathogen. If you only inhaled one mould spore, you don’t want your entire immune system to go to alert, just to deal with one guy.

So once it’s been activated by the helper T-Cell, how does the killer T-Cell work? Well, what happens is that using its receptors, it’ll nudge up against and infect its cells. This is sometimes called the Kiss of Death. It uses its receptors to hold on to the MHC1, that has the proteins, that the receptor matches to. Then it starts releasing.

See those purple spheres? Those are little tiny vesicles. Little sacs of membranes filled with a chemical Poriferan. You think Poriferan that doesn’t sound do bad.

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Well, it comes means a chemical with Nitrogen it's protein. What does it do? It makes pores.

Pores are holes. It’s like Jack Bauer from 24 walking up to a terrorist and go stabbing it with ice pick, and dead bad guy. That’s what the cytotoxic T-Cells are called. That’s why they’re named cytotoxic cell poisonous. They start releasing all these chemicals. They can even release chemicals that will cause the cell to commit suicide like 'you suck, you die'. They do.

So the cytotoxic T-Cells start rapidly dividing and you get a whole bunch of these. So let’s take a quick look at this again.

So in the immune response, you see here are our energy presenting cell, our macrophage that eats a bad guy. It goes up to a helper T-cell and says, "Hey time for you to make more." So we see that Clonal Selection of our Helper T-cells.

The Helper T-cells go to B-Cells that have bumped into the correct antigen, and make those B-Cells become the plasma cells that are pumping out all those antibodies. The Helper T-Cell can attract the attention of the specific defenses, the macrophages etcetera. And alternately they can also tell the killer T-Cells to start rapidly diving again making a vast clone army of your knife wielding maniacs. So you have an army of killer T-Cells attacking. You’ve got an army of your B-Cells attacking, plus the non-specific defenses are being summoned to attack.

This will increase and increase. This is why, usually when you get sick, you feel kind of crappy. It’s not because the bacteria is causing you to feel crappy, or the virus is causing you to feel crappy, it’s because you’re using so many of your resources to make these swollen lymph nodes. Swollen with the millions and millions of new cells. And that takes a lot of energy to build all those new cells. And it's your body is diverting resources from doing exercise or things like that, to make these new immune system cells.

Now how long does this process take? Well, it depends on how often have you been exposed to those cells. Let’s take a look at this graph.

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The first time you get exposed to a new antigen and new pathogen, you’ve only got a few of the Helper T-cells that recognize it. A few of the cytotoxic T-Cells, and a few of the B-Cells that might recognize it. It may take 4 to 10 days before you’ve got enough of that army, where you actually start seeing the massive response. So now you’ve got tons and tons of antibodies pouring out, tons and tons of the cytotoxic T-Cells, which they call effectors cells, because they’re having effect on the antigen. Eventually though, why doesn’t this keep going? Once you start winning the war, some of your Helper T-cells they start saying, "Oh come on can’t we all just get along?" They become what are known as Suppressor T-Cells.

They’re a subdivision of the CD4, or helper T-Cell types. They suppress the immune response. This response here, this rapid response. This is one of those examples of what’s called positive feedback. If you’re ever asked about negative and positive feedback in an essay question, immune response is a primary example of positive feedback.

Now what happens? I didn’t go over that much when I was describing it. But of the vast Clone army of B-Cells and vast army of cytotoxic T-cells, and in fact of the vast clone army of Helper T-cells, some of them are specialized cells called memory B-Cells.

Remember, I start off with only a few Helper T-cells that recognize the invader. But after the invader has come in, rather than having a few remaining afterwards, I instead leave several thousand distributed throughout my body. They’re on alert.

If I’ve encountered say a particular co-virus once before, now my specific defenses are ready. The memories B-Cells are occasionally releasing some antibodies. My cytotoxic T-Cells are now roaming around. In this small subdivision of the cloned army, that is left after the primary response is gone, is why next time I get infected, rather than taking weeks for me to get an appropriate response, within a day, I’ve got a massive army.

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Now this protection can last weeks or months, and in some cases years. That’s the whole idea behind vaccination. What a vaccination is, you basically take a virus or you take a bacteria and you boil it. That’s the basic idea. You boil it until it’s just a bunch of pieces of bacteria, a bunch of pieces of virus. Remember, it’s those pieces that are the antigen.

Inject that into your body, and a macrophage comes along and says I don’t recognize this, puts it on enzymatic C2s and starts activating your Helper T-cells etcetera. Your immune system is like, "They’re attacking." Get the specific defenses, but it’s just pieces of a virus. Pieces can’t do anything. But now they’re on the alert and that’s how the vaccination defense works. So that’s your specific defenses.

Now, while that specific response may seem kind of complicated, outside some of the technical details like what’s the difference between MHC1 and MHC2, it’s not all that hard. Remember, with the immune system there’s the barriers, the chemicals, the cells, and then the lymph nodes. There is this non-specific, which can attack pretty much anything you want, and the specific.

Now one last time I’ll go through the specific response, just to help highlight it in your memory and help you get your way through it. But using this slide, or a similar picture from your textbook, this is a great way to review. Remember, antigens are things that trigger off responses by your specific immune system. It’s very often a common mistake for kids to mistake antigen for the word antibody. Don’t make that mistake.

So an antigen comes in, gets eaten by one of those non-specific macrophages. That non-specific macrophage finds a Helper T-Cell, and stimulates it to start dividing and form lots of helper T-.Cells. An antigen also bumps into a B-Cell getting it ready. Now a Helper T-Cell that’s been activated releases its Interleukin 2 and Cytokines or chemical signals, and we wind up having a vast army of B-Cells, Clonal Selection, point.

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The antigen bumps into a Cytotoxic T-Cell getting it ready. The immune system Helper T-Cell here gives it the Interleukin 2 or Cytokines, activating it forming our vast Clonal army there. The Plasma cells are the mature B-Cells. They pump out the antibodies. They also create some memory B-Cells that stay behind in your lymph nodes or stay behind going through your circulatory system. Just to be on the look out for this pathogen, this disease causing germ or whatever, that you’ve bumped into before.

Similarly, the cytotoxic T-Cells, they’re active. Ones that are constantly killing any of the infected cells, but there's also memory T-cells. Last the memory Helper T-cells also stick around. And that means the second time that you get exposed, the response is much faster, much more deliberate and you probably never even know you encountered them. That’s it. That’s immune response.

I would through, watch this video maybe one more time, really spend some time with this picture here to make sure you understand it. Just be able to rattle off a couple of the non-specific defenses, and you’ll be fine with any multiple choice question. You should be able to ace any of the essay questions that could be on the immune system.