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Clonal selection

Clonal selection is a process by which the body produces B and T cells to respond to infections. These cells each have unique receptors that allow them to identify specific pathogens. When the body encounters an infection, the B and T cells that can recognize the invader multiply rapidly to create an army of cells to fight it. Created by Patrick van Nieuwenhuizen.

Video transcript

In this video, I'd like to give an overview of how the B and T cells in your body are prepared to fight infections. And so, let's start with where B cells come from. So where do B cells come from? They come from the bone marrow. So, here's a bone and inside it we have some bone marrow, and it's from there that B cells come from. But the process by which the B cells are prepared in the bone marrow is actually very interesting and unique in terms of the human body. Because well, like many other places in the body, the B cells divide and form millions of descendants and that is how your whole body grows and comes to be as big as it is. But, for B cells there's something very different from other parts of your body, and that is that each daughter cell that grows up in the bone marrow is different from its parent and is also different from all of its siblings. So, just to remind you, B cells have these receptors that later on will be their antibodies. But each daughter cell of this original B cell will have a different receptor. And that's because, in the process of being made, these daughter B cells will have a slight shuffling, a slight changing in their DNA, but specifically for this receptor, and so by the time they're created, they have a unique receptor that will identify a unique criminal, a unique bacterium or virus or something in the body. That receptor will be useless for all the other criminals in the body. So, it's very specific but very powerful if it finds the thing that it wants to kill. So, this is happening in the bone marrow. And, basically the same exact thing is happening for T cells, except it's not happening in the bone marrow, that's happening here. You know what this is called? This is called the thymus and I'm drawing it a little bit bigger than I should, maybe, but that way you can see it clearly. The thymus has two lobes or two parts, and it's located right behind your sternum. So, T cells come from the thymus. And, very similar to B cells, they have a unique receptor. It's not quite the same and it doesn't become an antibody later on. They have a unique receptor and, while these T cells are dividing and creating millions of daughter T cells, each of these daughter T cells will have its own unique receptor that will also identify a unique criminal or bacterium in the human body. And we remember that these receptors actually find antigens, so pieces of these criminals that are presented to them by antigen presenting cells and we'll revisit that in a second. So, all this is occurring in the thymus. And so, this is step one of the process and it's unique to the human body because we end up with all these actually, literally genetically different B and T cells that are very specific to things which may or may not even exist out there because they're really created at random. Now, the next thing that happens is that these B cells and T cells, once they're ready, are going to migrate to a lymph node, and you have lymph nodes all over your body, about 600 of them. But, let's say that they go to one here, in your armpit. They're going to migrate to that lymph node, for example, and that is where they're going to wait for their special criminal that they can react to. So, they're going to go over there to that lymph node. And let's draw that down here, maybe significantly bigger. So here's the lymph node, and you're going to have your B and T cells, all the different kinds of them, lying in wait there. And they have their special receptors. Each one is specific to something else. So, these guys have migrated here to all the different lymph nodes of the body. And now these guys are ready, and so the next step is really infection, so let's look at a tissue in your body with some cells. These are cells, let's say it's over there. So it's not too far from that lymph node there. And let's say it gets infected. So here are some bacteria which are causing damage. And one of the things we have out here is these cells, which are part of the immune system, which are called dendritic cells, dendritic cells. And these cells can eat some of these bacteria, so they can actually kill some of those bacteria, they can ingest them. But, it's actually not quite to the point that they can defeat this infection and that's not really their purpose. And their purpose is actually more to present these bacteria to the B and T cells that we've been talking about. And so, the way that they do that is that they come here into these lymphatic vessels, which start here in the tissue, and they go up to the lymph node where they're going to present these bacteria to these cells. And at the same time, some of the bacteria might also get swept in there and might go into the lymph node. And so, you get some of them out here. You get some bacteria and maybe just some pieces of bacteria that got broken down. And you also have your dendritic cells here, which are antigen presenting cells, which means that they have this protein that we've talked about called MHC, MHC, on which they present pieces of those bacteria that they've ingested. Now these T cells here are unable to identify these bacteria when they're just freely floating. They need this antigen presenting cell to show this piece of bacteria to them. And only the T cells, which can recognise this very specific pathogen, are going to see it and bind to it and react to it. So in this case, it's this guy. He's going to bind to that little piece and recognize that his invader, the one guy he's been created to kill is somewhere in the body. Meanwhile, these B cells are made to react directly to these bacteria without this antigen presenting cell. And so, the specific one that is specific to this bacterium is going to see it, bind to it and also be alerted. However, all these other guys? They're not going to know that anything's going on. Because, they can't bind to any of these pathogens that were brought into the lymph node. And so, this right here is step two. When the infection occurs, and the right B and T cells are alerted. And what are they going to do now? Well now, they're going to activate. They're going to jump into action because finally they're needed. Now these B and T cells are going to start replicating like crazy. So here are the two lucky winners who got selected. And they're going to say, "well, "now that we know we are useful for fighting "this infection, we better replicate like crazy "because right now there's only two of us "and that's not nearly enough." So, they're going to start replicating, and each of their descendants, unlike this kind of replication, now each of their descendants is going to have the same receptor. It's going to have the same receptor. If it had a different receptor, this whole process would be useless because it wouldn't be able to fight the specific infection that we've just identified. And I should mention that not all of these guys are going to do the same thing. So, most of them will become effector cells, which means that they're going to be ready to fight this infection right now. But some of them are going to become memory cells, which means that they're not going to actually fight right now. They're going to wait until the next time that this pathogen comes around. And the reason why we create these guys is because if we get this bacteria once, there's a high chance that we're going to get it again. Because, really, you create billions and billions of these different receptors, but only a very small subset of them will actually end up being pathogens that you see. And so, this is step 3 of our process, which has finally resulted in an army of B and T cells, ready to fight this specific invader. So that's what they're going to do now. The B cells are going to pump out antibodies to attack this bacterium and the T cells, some of them are going to stay in the lymph node and some of them are going to travel out to this site to join the battle. And so, this whole process can actually be called clonal selection, clonal selection. Which is a name for the theory of this process when it first came out. So this is clonal selection and the reason it's called clonal selection is because you're going to select B and T cells that you need and then you're going to start cloning them like crazy into this army. And the process involves all these very unique, specific B and T cells coming from the bone marrow and thymus to the lymph node, where they're going to be met by these bacteria that are infecting your skin, that are going to travel through the lymphatic vessels to the lymph node. And so, they'll meet there and then the armies will be prepared.