Biology: The Immune Response: Nonspecific Defenses

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09/18/2010

~ Kim11

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You would think you and I had enough to worry about trying to maintain homeostasis by our own generated dilemmas. Here we are producing wastes, we've got to get them out of our body; here we are, we need to - we see something, we need to convey an impulse - and on and on it goes. It's a tough life having to constantly maintain homeostasis; and now, on top of it all, I'm going to tell you that there are things out there looking to disrupt your system, parasitize you, use your DNA, grow on you, grow inside of you, and literally make you into just one bucket of germs. And, yes, these things are called pathogens; and life is tough, because the pathogens are out there, looking to disrupt your homeostatic relationships.
The good news is, you have an immune system, and the immune system is what is used when you have a challenge to homeostasis from an external source, and sometimes from an internal source, like cancer. So we talk about the immune system, or immunity, and I just want to - oh, we could spend weeks on the immune system, trust me. We're going to do the highlights of the immune system, though.
Now let's think about why you need an immune system. If you think about it, pretty much, our bodies are very well protected. There are only about five or six places germs can get in - your eyes, your nose, your ears, your mouth - these are openings into our internal systems - your urogenital openings, and your anus. And after that, you're pretty much as tight as a drum; you don't have many places germs can penetrate.
Well, then, how come we get sick so much? Well, what does "so much" mean? You've got 80 or so good years, most of us. So let's take a look at how we manage to fight these bugs. And the thing of it is, is that even those places that I just mentioned are protected, because we have a group of what we're going to call "nonspecific defenses," meaning that anything in their way is in trouble. Well, let's see what I mean, and let's talk about the first line of nonspecific defense. In other words, what - you know, like you have lines of defense in an army - I mean, we're going to use a lot of paramilitary talk here, we're going to be talking about the first line of defense, and the second line of defense, and the artillery. I mean, this is - for those of you into this military stuff, you're going to love this unit.
So the first line of defense is those things that protect you from exterior invasion. Obviously, the first thing you would think about, if I said to you, "Name your first line of defense," most of you would say your skin; and you're right. And besides the fact that most germs can't get through skin, the skin is pretty resistant to bacterial and fungal growth. The pH of the skin, even though it's pretty much keratinized, non-living tissue, the sebaceous glands - the oil-producing glands, and the sweat glands - keep the skin at a pH of about 3 to 5, and that's acidic enough that most bacteria and fungi can't grow on that.
Now, yes, every once in a while you get some fungus that takes advantage of nice warm, moist places like the area between your toes, and grows there, and that parasitic fungus basically eats your tissue - that's called athlete's foot. And some fungi, like yeast infections, can get in through urogenital openings, and cause dilemmas there. But, generally speaking, our skin protects us from fungal growth like ringworm, and bacterial growth.
There are other ones too. We also have a group of membranes called mucous membranes that line most of the organs I told you about - mucous membranes. Mucous membranes - for example, in the digestive tract - contain - particularly early, and also in like the trachea - contain ciliated epithelium. And if you think about - besides containing mucous, they contain ciliated epithelium, which you know is an epithelium with cilia that beats and pushes stuff out before they can get a root on, or grab hold, and live in there.
Secretions - we make all sorts of secretions that are just generic defense mechanisms. What's a good example of that? Hydrochloric acid in your stomach - tough to live in there. Some can, like the Heliobactor, which can grow in your stomach and cause ulcers. Tears - tears actually produce an enzyme called lysozyme, and that has antibiotic effects, it kills bacteria - "ly-so-zyme."
That being said, suppose things get in. Well, now you call up your backup, your second line. Sometimes bad things happen. You might get a sliver. Hey, you can't spend your life worrying about getting a sliver. So we're going to have some other things that are going to take effect there. One of those things is a group of white blood cells called phagocytes, and like amoebas, they eat things. It's very cool. You can almost picture your body as an ecosystem with these amoebas living in there, looking for things - they're amoebas, they're your own cells - genetically, they're you, okay? But you get it - phagocytes.
There's also a group of proteins - antimicrobial proteins - in your plasma. Generic - we're not talking about antibodies here, they come later. Then still another is something I want to tell you about in a few minutes here - or for a few minutes - and that's this unbelievably cool thing called inflammation. Let's talk about those, and then we'll talk about how antimicrobial proteins might work, and we're going to see that phagocytes and inflammation go together.
A sliver - there's you innocently walking along, you go to pick up a piece of wood, and it gets into your finger. The wood sliver ruptures the skin, and with it come bacteria; there are bacteria everywhere, and that's the red and blue guys here. Your blood is just kind of like, "Yeah, no problem," and going along and - boom - all of a sudden, things start to happen. What's the first thing that happens when you get a sliver? Well, because of the mechanical rupture of the tissue - you know about blood clotting, let's not worry about that yet, let's talk about the immune response - well, as soon as you get a sliver, the first thing that's going to happen is two cells - one is a white blood cell called the "basophil," and another is a cell called a "mast cell" - start to produce a compound that you've heard of in a negative way. They produce a compound called histamines.
Now you're saying, "Wait a minute, I take antihistamines. Why?" Well, when do you take antihistamines? You take antihistamines when you have a cold. Why? Because your nose is leaking, and it takes away that symptom. Well, guess what histamines do? Histamines make vessels leaky. They make blood vessels leaky, they make mucous membranes leaky. Why? If I get an inflammation, I'm going to want my white blood cells to be able to migrate to this thing, so I'm going to want my capillary pores to open, and I'm going to want mucous membranes. And literally histamines affect membrane permeability.
So when you have a cold, one of the first things that your body does is it makes histamines. Now a cold is not the same thing as this localized inflammation. But you get the idea, and it's very uncomfortable, because we don't like things dripping out of our nose; so we take an antihistamine, hoping that our body is going to take care of the problem on its own. And the good news is, it usually does. Most people don't die from colds.
So now that we're making histamines, and what is that going to do? Well, the histamines are going to increase the membrane permeability - the capillary permeability, and what that is going to do is, it's going to send a signal. And in addition, you're going to get an increased blood flow. So a second thing that's going to happen is you get an increased blood flow, because another chemical is produced - a kind of a modified lipid. And that's due to a chemical called prostaglandin. We're going to talk a lot about prostaglandins in the course of our discussion of chemical feedback mechanisms.
So prostaglandin - and now the big stuff starts to happen. You've got bacteria you've got to eat, and along come your phagocytes, and the first phagocyte that comes along is one called a neutrophil. There are not a lot of these, but they do the job. They come over, and they start to eat your - actually, I shouldn't say there are not a lot of them; there are a lot of them, but they have a fairly short life span - a few days. Actually, probably about 60-70% of your white blood cells are neutrophils, but they don't last very long. But they come over and start eating the bacteria, and then the big boy comes over - macrophages.
Actually, macrophages are a derivative of a cell called a "monocyte," but macrophages means "big eater." I've been called a macrophage in my day. Macrophages are big eaters. These things come over and they start eating the bacteria, and eating the neutrophils, and eating - and they form - they eat everything, including the bacteria. In fact, so many of these come over, you get a buildup of them. Do you know what it's called? Pus - that's what pus is, it's a buildup of all these dead white blood cells in this horrible battle for your life. It doesn't sound horrible to get a sliver, but it could be.
So along come these things, they come in, and they eat, and they start to digest. Those are the neutrophils. Here come the macrophages. The macrophages come in there, they start chowing down, and life is good. You heal the wound, and it's all over. Sometimes, if your information is bad enough, you might even produce in this nonspecific device a chemical called a pyrogen - fever. Yes. Why? Yes, we think it helps the immune system; we think it might slow down the bacteria - but we're not sure. And then last but not least, you might have some antimicrobial proteins - I mentioned those before. I just want to say - we'll get back to those - but there are 20 proteins that do this unbelievably complex series of reactions all together, and this is called your "protein complement." Not like, "Oh, you look good today" kind of compliment, but it's called the protein complement. They cause invading cells to explode, and then one other nonspecific protein that can help - one called "interferon," which is a - it's very interesting. This is one that - here's what happens: When a cell gets infected, the infected cell - by a virus, when it gets infected by a virus - the infected cell produces interferon in almost this - it's like signaling to other cells that, "Yo, boys, there's a virus. Watch out." Then they end up enhancing their immune - or getting ready for an immune response. That's nonspecific immunity, and that's only a tenth of the story. Wait till we get to see what happens when you really start getting germs - that's fun.
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The Immune Response: Nonspecific Defenses Page [3 of 3]