The previous clips in this lecture have contained a lot of miscellaneous information. Many immunology courses and text will begin with signalling, which is logical, if you consider how fundamentally important information transfer is to the whole response. But, I always felt that hitting a beginner with this information before they've developed any context is a huge mistake. So what I want to do in this clip, is review some of the earlier material, and add some new material that will allow you to start knitting the different concepts together. Welcome to the cytokine lecture. Cytokines are basically informational molecules, and we're going to use that to signal from one cell to another. One insight we've had from biology of late, is that signalling is critical to any biological function. Bacteria do it to each other. It's part of development. It's part of any basic physiology, and it's certainly central to managing the immune response. Now, you might have noticed that at the beginning of this outline, I put in a quote that's a hundred years old, and it refers to the distribution of nematodes throughout the environment. They're not only ubiquitous, they're tailored to essentially parasitize off of everything they can find, and that is a challenge that we have faced since before we were even human. So when we're looking at the immune system, one of the things that we're going to be looking at in terms of signaling, is how you adapt your response to the particular pathogen challenges that you face. In the case of worms, we're going to use a somewhat different strategy than we would use in the case of a flu infection. And I mentioned that I think the first week of the first course, we have an all out war response against serious bacterial and flu infections. because if we don't, they'll kill us. On the other hand, we have a much more restrained response that we do, if it's certain kinds of chronic infections, particularly, certain kinds of worm parasites. We use a more containment approach that is less likely to damage our own tissues, and to basically claim too many of our resources. So what we're going to look at, among other things in the cytokine lecture, is how we decide how much of an effort to put into fighting off a particular threat. And to do that, the TH cells, in particular, will gather in a lot of information from a variety of sources, and then, will distribute that information in terms of organizing how to fight the response. One other thing that's come out of this, is that when you look at the human Genome Project, and you look at the genes that you find in humans, I would refer to our genome as administratively top heavy. If I look at a bacterium, I will see that it has lots of genes for enzymes that chew things up, for proteins that make up its structure, and indeed, it has some enzymes that are in there to control things, or rather proteins. It has operon proteins, it has transcription factors, and it has that. But they're not the majority of proteins. If I look at the human genome, the majority of proteins are things like transcription factors, signaling molecules, the receptors for those signaling molecules, and the genes for the enzyme sequences that essentially pass that information on. Now, you can get that information in a variety of ways. One of the biggies is cell to cell contact. If we look at presentation of antigens to a TH cell, we were looking at one cell contacting another. If we look at the recognition of pathogens, by say a macrophage, that happens when the pathogen contacts its toll-like receptor. And there are other examples of this, and I think I put a few more in the outline, okay? In addition to that, there are specifics signaling molecules that are present on the surface of the cell, and we call these things juxtacrine signals. It's essentially, in most cases, a little protein that will reach out and touch another protein receptor on another cell, and transfer a piece of information. One of the nastier pieces of information you can get, is the signal that says, basically, die sucker. So in the next course, we're going to look at something called fast lygant on a cell that reaches out and touches a target cell that maybe has gone malignant, and says I want you to kill yourself right now by programmed cell death. Okay, juxtacrine connection, you clearly don't want a signal like that running around your whole body. Now, another type of signal, and this is really more of the kinds of signals we're going to look at in this lecture, is a paracrine signal, the immune system uses a lot of chemical signals that go back and forth from cells, but they don't usually travel a huge distance. Typically, four cell diameters at the most. So these are local signals from one cell to another cell that help to coordinate an immune response, maybe up regulate some things, or down regulate others, or tell a cell to do a specific form of development. Okay, that's a paracrine factor. This is distinct from what you might have studied in other courses is hormones. Hormones are secreted into the blood supply, and will travel throughout the whole body. And generally, exert their effects, or at least are capable of doing that a long way away from the secreting cell. Paracrine factors are much more local. So when we're looking at most of the things we're looking at now, they're going to be in the general category of paracrine factors. But of course, they don't have that name. When you get into the immune system, the immune system likes to put its names on everything. And so, most of the paracrine factors are referred to generally, as interleukins, which means, it goes from one white cell to another white cell. And you remember the stuff we had with compliment? You remember the stuff we had with CD's? It's that same awful thing all over again, they are numbered IL1 to on up to, I think, there were 29 in the old text. There are probably 50 or 60 of them by now. And again, the numbers tell the order in which it was discovered, they don't tell you anything about it. And I want to apologize for this in advance, because here it is all over again. I'm going to be using a lot of really confusing IL whatevers for the names of some of these factors. And there's more, okay. Some of them have also names that were named before they began numbering them. Just like the compliment proteins. There are some strange idiosyncratic names, TNF for Tumor Necrosis Factor. Somebody found a signal that caused tumors to decay. And later on, they realize that this was really an immune signal that was a general inflammatory signal. We've got interferons, we've got of a number of things, and we'll look at them, and all name them as we go along. I will try to make these name something you can remember. But all I can do is apologize in advance for immunologist complete refusable to make their naming system accessible to the average person. This is just something we live with. The other name that you're going to get is something called, a Chemokine, okay? Chemo means chemical, kine means motion. This is going to be an interleukin, or paracrine factor that's specifically involved in making leukocytes, specifically, many neutrophils, sometimes T cells, but some white cell go from one place to another. So a chemokine is something that redirects an immune cell, often neutrophils and macrophages, but also lymphocytes as well, to the site where it is needed. Now, the nice thing about that, when we look at them, is we will see that they're all in the same general category. At least most of them are. It's a seven span protein that, again, triggers a G protein. That may sound bad, but you learn it for one of them. You learn it for all of them. And we'll see that when they're represented in the diagrams, they're typically represented as something that looks like a bicycle rack. And it actually is, you can see one, two, three, four, five, whoops. One, two, three, four, five, six, seven places where this crosses the membrane. It curves in around to form a site for things to bind, and we will be looking at that specific one, a great deal, when we look at the inflammatory response. So again, get ready for a really nasty load on your memory. I will try to make it clear, if not interesting. And here we go.
