In this next section, we're going to look at some specific types of lymphocytes. Those cells that tend to concentrate in the lymphoid tissues. If you will recall, the lymphoid lineage of the common lymphoid progenitor produces a variety of different cells including the B cells and the T cells which are adapted and rearrange their genes. The NK cells are innate and do not, but they're part of this lineage, and there are some other cells that we will discuss later on, including gamma-delta T cells, and invariant IKT cells. So here is the cells basically that we're just going to kind of introduce today, and we'll study in detail much later on. The B cells, that's where we're going to start, are so named because they develop in the bursa of Fabricius, which is the dorsal wall of the cloaca or common exit of both the digestive and urogenital system of the bird. Birds also have a thymus. But the B cells were first kind of studied in them and are named for the bursa. But they're also in mammals, will develop in the bone marrow and so you can use B for either one. I think it's interesting that the B cells started out in the bursa, because B cells still also develop around the digestive tracts of many other organisms. And we believe that the adaptive immune system, again, got started in part to protect you from what you eat. So here is a picture of the location of the bursa in a bird. Now, here is our representation of a B cell and this is really I think one of the most sophisticated cells in the immune system. So here we have a James Bond B cell, and this cell has a variety of disguises, fakes, and strategies that it uses to protect you from the pathogens that threaten you. So in this particular B cell we see that it has membrane-bound antibodies in the surface. So I'm going to look at them in much more detail later on. But these are its sensing receptors and so there they are. This represents a membrane-bound antibody. They also have, not shown here, class II MHC molecules, which would be part of their way of communicating with TH cells. That is, James will come back and let the British Secret Service know what is going on in the outside world. Now, it turns out that it's really not very interesting to show you a B cell in a micrograph because they're relatively small and they look a lot like T cells. And frankly, you can't really, most people can't tell them apart just by looking at them. However, when this B cell is stimulated to divide and develop, and more importantly to secrete antibodies, it's going to become much, much larger. And its protein synthesis apparatus will be up regulated. So here is a picture of a plasma cell. And that's a plasma cell that you can see is secreting antibody. It has the endoplasmic reticulum here, which is actually rough endoplasmic reticulum upon which these are made. And passed through the endomembrane system, and eventually secreted to help save you from various pathogens. This is a type of effector cell. Another thing that a B cell can develop into is a memory cell. These are smaller and still have the antibodies embedded in the surface. But they'll sit around and wait for this antibody to be needed again in the future when a similar pathogen shows up. So in the B lineage then, we have the small circulating circulating lymphocytes, the enlarged plasma cells secreting antibodies, and memory cells held in reserve. Now, the T cells will develop in the thymus and again, they start out looking pretty anonymous. They're not particularly exciting to look at and these initial cells will have a large number of important developmental. If took that part of the previous flow chart out and just to remind you one of the first decisions they make is whether or not to be a cytotoxic T cell or a helper T cell. So here we have the TC and the TH, and again that's going to be determined by what co-receptor they will eventually select. And here I have a reminder that the TH cells, which use the CD4, have at least four different fakes that we haven't really discussed much yet. And there will be other ones as well, so that there is again, as with the B cell, a lot of variability in the development phase of a T cell. And so that these cells then together work to recognize and respond to specific pathogens. This electron micrograph shows you a red blood cell, a platelet, and what looks like probably a small lymphocyte, maybe a TH cell, small one, maybe a TC cell, maybe even a B cell. And you can see they're not very big. They're approximately the same size as a red blood cell. When they become activated and begin to divide, they will enlarge and particularly in the case of the B cell, they'll get a whole lot larger in order to make antibodies. But here we have a cell and notice the surface of this thing is anything but smooth. It's ready to gather and disseminate information as part of its function. And so here, again, is a reminder of the difference between a TC and a TH cell. The TCs have the CD8. The THs have the CD4. And again, the TCs will be involved in killing rogue self-cells. So a lot of the details in this are things that we're going to look at later. But just remember that we're going to make some important distinctions between TC or CD8+ and Th or CD4+. In addition to that, the TH cells can, again, be either TH1 or TH2. We discussed that in the first lecture. The TH1 is an all-out war response, and a TH2 is a more constrained, restrained containment response. And, in addition to that, not shown here, is the T regulatory response, which is also a T CD4+ cell. That is, essentially, the down regulating response that's critically important to keep all of these cells from going overboard and killing your own self by friendly fire. We'll also see there's another version of TH17 and that's a little bit in between a TH1 and TH2 in terms of inflammatory destruction. So a reminder is that the TH cells have a variety of strategic ways of instructing the immune system into how vicious and how strong a response it should make to a particular threat. The last one we're going to look at in this clip is the NK cell. And electron micrographs of the NK cells show a fairly big cell with a pretty ordinary round nucleus and a lot of granular inclusions. And so I thought this way of representing it would be a lot more fun. I consider the NK cells to be the Seals or Green Berets of your immune attack. That is, they're highly trained. They come out ready to defend you. They don't require T cell instruction and they are armed and dangerous. This one has a trident of Fas ligand and that will again up regulate apoptosis of the cell it sticks into. In addition to that if it synapses with a rogue cell for viral infected or cancerous cell. It has a lot of ammunition in the form of granzymes and perforin that will, again, help to break up the cell and send it into asbestosis. It has an MHC1 regulator, which you can see here down regulates, it's in red, it's going to stop it from attacking. And that, we'll see, is part of its coordination with the TC cells. And on the other side, it has a green up regulating FC receptor, so that if it finds antibodies stuck in the surface of a cell, it will, again, attack that cell. The most interesting part of the cell is the way the MHC receptor works. In a TC cell, if you'll recall from some of our little skits, the receptor will recognize foreign antigen on MHC1 and attack the cell. Well, a virus is not your friend, so what the virus sometimes does is it down regulates the production of MHC so that a TC cell can't be alerted to the presence of foreign antigen. But these guys are looking out for you. And if they find a cell without the MHC stuck out, they will attack it. So this is a general response, it's a innate response. It doesn't really have anything to do with exactly what's on that MHC1 molecule. But what this cell is doing is checking to make sure that a cell is not hiding its MHC1s, and attempting to keep the TC cells from finding out there's foreign antigen inside. Now, of course, there are viruses that are not your friends even worse. And we will see that some viruses can even put out a fake MHC1 and use that to get rid of the NK cells. And we'll see that there are some mice that have evolved and K cells that can tell the difference. So we had this sort of constant evolutionary tug of war between these guys and the technology they use to recognize the enemy and the technology that the enemy uses to hide from them. This is classically described by the metaphor, The Race of the Red Queen, taken from Lewis Carroll's Alice in Wonderland. And it refers to the episode where the Red Queen drags Alice at a furious pace, running and running only to wind up exactly where they started. The queen observes that it takes all the running you can do to keep in the same place. And this is used as a metaphor for many evolutionary arms races. You keep upping your game only to find the opposition has and you're really kind of where you were to begin with. And so next, we're going to look at the primary lymphoid organs, the sites where gene rearrangement and the initial production of adaptive immune cells takes place.
