The lymph nodes are not the only place important in activation and instruction of B cells. We find follicles of the same type in the spleen, we find them in regions of the gut mucosa as well. So all three of these sites are for that reason termed secondary lymphoid organs. We're going to begin with the spleen. We're going to start here with the spleen. And this is an artist conception. It's a bit kidney shaped, but the real spleen lies higher in your abdomen. And you can see that it's got a good blood supply going in and out because its purpose is to filter and monitor your blood, not your lymph. It has red pulp tissue where the macra fascias recycle old red blood cells. It has white pulp tissue where T cells participate in immune surveillance. And there is a marginal zone that has B cells and those B cells are in follicles as you can see here. And this ought to look a little bit familiar to you, because it ought to look like the follicles we've seen in the lymph nodes. And so here we have two, and you can see you've got the dark region outside, light region inside, and this is where B cells will be maturing. Now you can remove the spleen from a person, and you raise that person's risk for bacterial infections. But there does seem to be a fair amount of redundancy in this situation. Because of course anything that's a general infection of the blood is likely to be filtered out in the lymph by the lymph node follicles and will get caught in the act in that location. We also have a whole collection of tissue that's collectively know as the MALT. That is the mucosal associated lymphoid tissue. And this is includes a number of different related types like the bronchial associated, or BALT. And the NALT, the nasal associated. And we're about to get to the biggie, the GALT and it does kind of feel like we're in Dr. Seuss land. Where we're going in the MALT and the BALT and the NALT and the super related GALT and that's what we're going to look at next. Also, but before we go a reminder that the tonsils, the appendix, Peyer's patches in the intestine of some animals will also participate in the activation of B cells. And be part of this secondary lymphoid tissue. So here we are in the gut mucosa, also called the GALT, and we can see we've got an intestinal bolus here that is one of the projections in the epithelia that increases its surface area. And we've got places where we're defending you, so I think people don't really appreciate their guts enough. Your gut has a whole bunch of neural tissue that's involved with mood and depression. You have a whole bunch of different immune cells there that are surveilling what's going on in your gut and responding to it. So it's not just about food. In this case we're going to see that this tissue has many, many folds, called villae. And I'm just showing one of them here. The outer layer of tissues, the epithelial cells here, also have something called micro villae, and those are the extensions that extend out from the individual cells, and this whole system vastly increases the surface area of the gut. The gut will be using this surface area to absorb food, but it will also be using this surface area to monitor what is going on inside the lumen or the food that you eat. So you've got defensive lymphoid tissues here, and sometimes they also produce follicles, and here we have a follicle down here. In this case we have a virus that's crossing over, and usually what we have in the gut is a lot of bacteria. But if you've ever had a viral infection in the gut, you'll be very happy to know that we can fight these off as well. Here we've got the antigens being picked up and transported into a developing follicle. And you can find organized structures like this in your tonsils, your appendix, and what we're getting in here is B cells and T cells coming together. If I have a bunch of these things organized together, a bunch of follicles, then I have something called a Peyer's patch, and that's actually more common in animals outside of us. So who do we have? The epithelial cells, they're delivering antigen samples to this follicle. We got the T cells in green, the B cells that are sort of purple, and you can see that after activation these B cells are going out, and they're secreting antibodies. When we get into antibodies we'll see that what they're really secreting are A class antibodies, which is really two or three of these guys held together by something that allows them to escape into the mucosa. But, we'll cover that more as we do a later lecture. Now, I want to take a closer look at what's going on. So, I'm going to take one of these little cell places and blow it up. And take a closer look, and you can see that one of them is something we called an M cell. And an M cell is a very interesting cell, because basically, it's functions as a pocket or a meeting place. And in this area here, it's essentially sequestering a bunch of immune functions cells. So the whole big this, the yellowish thing, is an epithelial cell. And in the epithelial cell, which is clearly much bigger than these immune cells We have here a macrophage, probably presenting antigen from that old virus to the T cell. We have the T cell here in green activating the B cell, which is shown here. And the B cell has the immunoglobulin receptors on the surface. It's going to activate and eventually it will start secreting some form of antibody, so here you have this M cell and it's actually serving as a walk in closet or maybe a singles bar. Or something like that to keep everybody meeting up and interacting together in a nice locale where they can monitor what's going on in the inside of the gut. So, here we have finally what looks like a little cube of skin. Now, skin is the largest organ in the body. It's technically not a secondary lymphoid organ, but rather something called tertiary. The reason you don't call it secondary, despite its importance, is that it doesn't produce follicles where B cells will mature a class switch. None the less it's critically important to innate defenses, it's made up of the dermis and epidermis, so there is the epidermis is from the top layer, here is the dermis and the epidermis is the epithelial tissue that sits on a basement membrane and a basement membrane will separate the epidermis from the dermis. The epidermis derives from embryonic ectoderm. The dermis derives from embryonic mesoderm. So the skin is an organ that's produced by combining cells from two different tissue layers and it has a highly complex function. Look at this hair follicle here. Do you see that it is actually part of the epidermis? Those cells get way down in around it. Now look at this gland here. This is probably a sweat gland, or maybe an oil gland. You can see, however, that this one is actually part of the dermis, and its duct extends up through the epidermis. And this collection of cells down here can also be secreting in addition to water a variety of defensive compounds that will also protect you from bacteria at the surface of your skin. Again, we have the epithelial cells here, which are keratinocytes, and these guys when they die will form a layer of dead cells and those dead cells will still retain the keratin and they'll help to make the skin waterproof. From the basal lamina up you have the epidermis, from the basal lamina down, you have the dermis and they again have different origins and together cooperate to form this tertiary structure. The keratinocytes also express MHC2 and can actually present antigen to T cells assuming the T cells are wandering around in this particular tissue. Not shown here are some or setenal dendridic cells that antigen here and then can leave the epidermis and go off and look for T cells someplace else. There is also a special class of T cells that reside in the epidermis and other mucosal tissues. That have special receptors and these T cells will do some patrolling and have, basically, built-in, quasi-innate recognition for the kinds of organisms that are likely to cause you trouble. Your skin is not just a form of boring shrink wrap. Your skin is very active. It's a two part organ with both mechanical and defensive immunological decorative functions in the human body. And they work together with the other cells to keep you and your organs healthy.
