字幕表 動画を再生する 英語字幕をプリント >>Dr. Ketchum: So we are going to go ahead and continue our discussion of the immune system, and we’ll be discussing innate immunity. Now before we discuss innate immunity, you need to understand that there’s actually two different types of immunity—one of those being innate immunity, which is also called nonspecific immunity, and the other is called acquired or adaptive immunity, which is also known as specific immunity. But just to give you a quick overview of both of these, when you first think about the nonspecific or the innate immunity, it’s a very rapid response. This is your first line of defense. And what this does is it gives your body time for the specific immunity to kick in. So innate immunity is always there. It’s present; it’s going to happen as soon as your body is invaded by a foreign object, and then the specific immunity will take over after that. It’s rapid, and it’s also not selective. So it’s not targeting specific species of invaders, for example. It’s not specific. It just wants to kill foreign invaders, and that’s the end of it. The innate immunity involves physical and chemical barriers, and it also includes cellular defenses. Now once the innate immunity has occurred, then the next type of immunity that will occur or kick in is the acquired immunity. It’s a slow response. And so because it’s a slow response, it’s very selective in what it’s killing. It may kill a specific bacterial cell or a specific virus, and specific immunity includes two different types of responses—humoral responses, which are also called antibody-mediated responses, and cell-mediated responses, which are also called cytotoxic lymphocytes. Here’s our analogy. When you think about an innate response, the castle is the body. And the first thing that this innate response wants to do is it wants to prevent that invader from entering the body. And once that invader invades the body, then the innate response will have some other methods for killing the invaders as well. These things are all taking place as the acquired response is just getting started—but remember it’s slow, so it takes a while to get the acquired response going. So neutrophils, the eosinophils, basophils and monocytes are all cells that are important in an innate response. The lymphocytes, on the other hand, are the type of white blood cell that are important in the acquired response. You don’t have to memorize the amount of each of these cells in a microliter or their diameters or any of that. You need to understand their anatomical features and their functions. So these are important columns here, but you do also have to know their abundance—their relative abundance. So again, if you remember “Never Let Monkeys Eat Bananas,” that tells you the most abundant leukocyte all the way to the least abundant leukocyte, which are your “bananas” or your basophils, so that way you don’t have to memorize the amount per microliter. The reason this is important is because if you’re looking at a slide—let’s say you take a blood smear on a microscope slide—and, and this is a healthy person, and you’re going through and you’re identifying all the various white blood cells. Well if you’re finding more basophils than you are neutrophils, then you’re probably not correctly identifying those cells. Okay, so here’s a flow chart that I put together to help organize the innate versus the adaptive response. So you’re definitely going to want to use this as your road map. We’re discussing the innate responses in this part, in part two. First let’s start with the physical and the chemical barriers; you think about these as being the wall of the castle. So the first thing I’d like to discuss are the lysozymes. So you have lysozymes that are in your tears and other secretions. These are not lysosomes; lysosomes are different. Lysozymes are antibacterial. So when you cry, it’s actually a good thing because you’re killing any kind of bacteria that’s on your skin. You also have the skin, then, and the skin is a physical barrier. The skin also has fatty acids and normal flora as well that’ll affect the pH and some foreign invaders cannot survive on the skin just because of the normal flora on our skin. Then you have the mucus and the cilia that line the trachea. The mucus traps any formed particles, and then the cilia works that debris up the respiratory tract and into your mouth so that you can either swallow it or spit it out. If you swallow it, it goes down into your stomach. And remember, the stomach has a pH of two; it’s very acidic. So it’s likely to kill most invaders, but not all. Now taking a closer look at the skin, we’re not going to spend time on the skin. This isn’t anatomy, but you should realize in this course that you do have two major skin layers: the epidermis and the dermis. So pay attention to those two layers and know where those two layers are located—which one’s on the outermost which ones on the innermost. The dermis, then, the only thing that you need to know about the dermis are the sebaceous glands, and I want you to use your textbook to figure out what’s the function of those sebaceous glands? Why are they important in the immune response? Then we have inflammation. So inflammation is part of the innate immunity as well. When you think about inflammation, it’s your body’s response to tissue damage or microbial invasion. So you’ve sprained your ankle and your ankle is now inflamed. You stepped on a nail, and—so now you have tissue damage and microbial invasion by stepping on a nail. So the goals of inflammation are listed here for you. You want to bring phagocytes to the injured area, because if you can control those invaders at the area that they’ve invaded, then they can’t spread throughout the body. You want to stop them there. So if you can bring those phagocytes to the injured area, you can destroy, inactivate invaders, you can remove any kind of cellular debris, and you can start preparing for healing. So let’s take a look at this flow chart. The leukocyte that automatically will start phagocytizing as soon as invaders enter into that wound are your macrophages. So those macrophages are there, and they immediately start attacking foreign invaders that enter the wound. The bacterial invasion itself and the tissue damage as well can cause the mast cells to release histamine. Histamine then, we know, causes vasodialation. So when an arterial vasodialates that means you have less resistance, right, and therefore more blood flow to the injured area. So because there’s more blood flow to the injured area—that’s why it becomes red and that’s why it gets hot. So because there’s more blood there, that means that you have an increase in certain plasma proteins that may be important in the healing process. So these may be clotting factors, for example, that would prevent you from bleeding out. The release of histamine by the mast cells also increases the capillary permeability. So what I want you to do is think about a capillary here, and I’m just going to draw three endothelial cells that are forming the walls of this capillary. And when you have histamine release, the pore size has increased significantly. So if you increase the pore size, that means more fluid can flow through those pores. So that means you’re going to get a local accumulation of fluid, some of that fluid being in the interstitial fluid. Remember that we’ve talked about swelling or what we call edema, an excess of interstitial fluid. It can also cause pain, because you have excess fluid in an area and the skin can only stretch so much—that causes pain. Pain is a good thing, because pain actually forces you to rest whatever part of your body is injured, and that way it can repair itself if it’s resting. Because you have this increased capillary permeability, then that’s going to increase the number of phagocytes that can make it to the tissue, like your macrophages. If you have more phagocytes, that’s going to increase their secretions. And their secretions can cause systematic responses like fever, for example. All in all, then, this is an inflammatory response and all of the information in red here—these are all cardinal signs of inflammation. And all of these cardinal signs of inflammation are because you had changes in blood vessel function—the blood vessel vasodialated. When we talk about phagocytosis—this is a form of endocytosis, but specifically, how is it achieved? So it’s going to be your job to fill in the steps. Don’t go into more—any more detail than what these four steps are asking for here. Opsonins, I do want you to look at opsonins and, and, why do we need opsonins? Why are opsonins important in phagocytosis? Then we have interferon. This is another type of innate immunity, and the goal of interferon is to interfere with viral replication. Now many of you have had Intro Zoology and so you know that when a virus gets inside of a cell, the virus takes over the machinery of that cell. And so it starts producing it’s own viral RNA and it’s own proteins. So there are some other functions of interferon that are listed here, and go ahead and read them and at this point realize that there are other functions for interferon besides interfering with viral replication. So let’s take a look at how this will work. We’re going to take a cell, and it’s been invaded by a virus. So what the cell does— once the cell is invaded by the virus—the cell is going to be releasing interferon. So the interferon is going to enter the extracellular fluid, and it’s going to travel to healthy cells, cells that have not been invaded by the virus. And when it binds to these receptors on an un-invaded cell, this un-invaded cell now will produce inactive enzymes. So basically this cell is just waiting, it’s waiting to be invaded by a virus. Because what these enzymes will do once they become activated is they will break down viral messenger RNA and they’ll inhibit protein synthesis. Now here comes our virus; it invades this cell. So those inactive enzymes are now active enzymes. We’re going to stop protein synthesis of the virus. So if a virus cannot multiply inside of a cell, the virus is dead. Viruses rely on cells in order to make their own proteins, and they, again, take over the machinery of the cell. So if they can’t do that they have nothing to survive on. This is why we call it interferon. Interferon is interfering with a virus; it’s interfering with its replication. So next we have the natural killer cells. Natural killer cells are kind of like lymphocytes. They’re important in the innate response, and they’re going to release some chemicals called perforins that we’ll discuss here in a second. They’re going to target cancer cells and they target virally infected cells, and they’re going to lyse the membranes of those cells. So let’s look at how natural killer cells work. This killer cell here is a natural; so it binds to the target cell. Once they come into contact, the natural killer cell releases perforins. What perforins do is they create a pore in the membrane of the invader. So if we do that then water and ions can rush in. We increase the permeability. So if you increase the permeability for water and ions into the cell, the cell will swell and burst. It’s going to lyse. Then we have the compliment system. The compliment system is activated by two different means. The only one we’ll discuss here is listed here at number one. We will discuss number two here later, but first, let’s focus on number one when we activate a compliment system. So here you have a bacterial cell, and on the surface of it is some carbohydrate. That carbohydrate is recognized by a compliment protein. So these compliment proteins are floating around in your plasma. That’s where they’re located; they’re in the plasma cruising around. And when the compliment protein recognizes this carbohydrate chain, the compliment protein will bind to the plasma membrane of this bacterial cell. And once it binds to the plasma membrane that creates a whole cascade of events that end up developing what’s called a membrane attack complex, a MAC. So this membrane attack complex is essentially a pore. So once you develop the pore, fluid can rush into the cell, and then the cell will burst and it will lyse. So that kills that target cell as well. So compliments really good in killing bacterial invaders. So innate responses are really good. They’re quick, but they have their limitations. They’re not specific; they’re not going to kill specific bacterial species, for example. And they’re also short-term—they don’t last very long. So the problem with it is that because they’re short term and they’re not specific, then you have to have a smart system, and that’s what adaptive immunity is all about. So in the next part we’re going to start discussing adaptive immunity, and specifically, we’re going to look at characteristics of your B and your T cells.