In the beginning of this lecture set, we talked about some of the chemicals and enzymes in the body that actually protect you as part of that first line of defense. So we talked about lysozyme in your tears, breaking down the peptidoglycan and bacteria. We talked about sebum in your body secretions, this waxy substance that helps prevent bacteria from getting inside you. There are molecules we didn't talk about called lactoferrin, and there's other ones as well, but...
they have the role of binding up free iron so that bacteria don't have the iron they need to survive. And there are also antimicrobial peptides. I had a link to the one that we find in sperm, but there are other antimicrobial peptides. We're learning about these all the time.
They have lots of different names, defensins, germicide, and there's a ton of them. Many of them have the ability to poke holes in the bacterial plasma membrane. So these are all part of that first line of defense, preventing bacteria from getting in you and successfully initiating an infection. Now in the second line of defense, we also have chemicals that help protect us. So we have inflammatory mediators.
Some of these are chemicals that stimulate inflammation, recruit cells to the site of injury. We have molecules like cytokines, which also can recruit cells to the site of injury. And then we have plasma proteins, which include the complement system. So that's what we want to talk about in this final video. Inflammatory mediators are molecules like histamine.
We just talked about inflammation, and we said that one of the hallmarks of inflammation is this swelling, that you have fluid rushing to the area. That occurs because when histamine is released by those mast cells, it results in vasodilation. So you have a...
widening of those capillaries where the injury has occurred and that's going to allow them to bring more fluid to the area, more white blood cells to the area. The cells are going to become leaky so we also see for example in a molecule called bradykinin which is also released during inflammation we have more vascular permeability those vessels get leaky resulting in tissue swelling or edema. The histamine has another effect on your bronchioles. So it actually causes smooth muscle contraction. So for example, if someone has allergies and they have a histamine is released as a result of pollen, one of the things that can trigger is asthma.
And that's because it results in the constriction of the bronchioles. And so they have less, the tubes going into the airway are smaller as a result of that contraction. So they have a little bit of a harder time breathing.
It can result in increased mucus secretion as well. So these are great if you're fighting an bacteria, but they're not so good if it's just an overreaction to pollen. If you've ever taken an antihistamine because you're having an allergic reaction, that's what you're doing.
You're trying to block this histamine response and help over time get those airways opened up and stop the drippy nose that you might be having because you have all of this edema and vascular permeability resulting in leakiness from your nose. Histamine is present in the nose. initially in these mast cells, but there are also molecules like leukotrienes and prostaglandins that we associate with inflammation, but they're produced as a result of the injury.
So the synthesis of these molecules happens in response to the infection or the injury. Prostaglandins not only promote inflammation, but they also are one of those pyrogens that cause fevers to occur as well. And so when you take something like aspirin, that reduces fever, we believe that the action is on prostaglandins that results in that the reduction in fever. Cytokines include molecules like interleukins, which are molecules that white blood cells make to communicate with each other and they include chemokines, which are molecules that recruit white blood cells to infected sites.
Cytokines are also They also include a group of molecules called interferons, which help us fight viral infections as well. So we'll talk a little bit more about them separately. You probably learned this in another class, but I'll just remind you really quickly about the different kinds of ways cells can signal to each other in a larger organism like a human.
So sometimes a cell will make a molecule and then that molecule will then act on itself. So here you see this cell is producing these cytokines, and then they are binding to a receptor on the same cell. So this would be called an autocrine response. or autocrine signaling. And then we have paracrine signaling is when the secreting cell is sending a message just in its neighborhood.
So it's these particular molecules are being responded to by a nearby cell. And then we have endocrine messaging, which is when the cytokine is released, it goes into the blood vessel, and then the blood vessel sends it to the rest of the body. And so this message would be received by some distant cell in the body.
The point here is that your immune system has lots of tools to communicate not just with cells nearby and itself, but also to send messages throughout your body to respond to an infection. One of the systems that we talk about a lot in the innate immune system is the complement system. And complement is incredibly complicated.
We could probably spend two lectures just describing all of the parts of complement, and we don't have time to spend that much on complement. But... I'll try to get through some of the basics here in a couple of slides.
The complement system is a series of 30 proteins, 30 plus proteins that are actually synthesized by your liver, and they're always in your bloodstream circulating. Most of the time, they're doing nothing but goofing off. They're twittering and Instagramming and Facebooking.
But if a pathogen gets into your body, they're actually... able to respond even before your immune cells become activated because they're always there patrolling in your bloodstream. So we talk about the complement system, it complements, so in quotes, right? It's complementing the cells of your immune system. And because it doesn't change over your lifetime, it's innate, it's not adaptive.
However, like many branches of the immune system or many parts of the immune system, it can handshake with the adaptive immune system. So we'll talk a little bit about how that works in a moment. Your complement system has three different ways that it can destroy pathogens.
It can break them down by lysing them. It can stimulate inflammation. And it can stimulate phagocytosis.
There is a critical thinking question that says, summarize the three outcomes of complement activation. That's what I'm looking for. I'm looking for you to identify these three mechanisms and at least describe minimally how they work.
So let's look at the next slide and talk about that a little bit more. There are different ways the complement system can be activated. We're not going to talk about all of the different ways, but I do want to point out that one of the ways is actually by responding to the presence of antibodies binding to the surface of bacteria.
And when this occurs, the antibodies are actually produced by your adaptive immune system. So this is a way for the complement system to continue to help fight off an infection, even after the adaptive immune system has become engaged in the process. However, there are other pathways that allow the complement system to get triggered even before you begin to launch an adaptive immune response. There are over 30 proteins we said that are part of the complement pathways, but C3 is one of the...
major proteins and when it is stimulated by one of these pathways, it can lyse into two separate proteins, C3A and C3B. C3B can actually coat a bacteria. That's what we're looking at here. So these are little C3B molecules bound to the surface. And when they do that, they actually cause there to be a greater amount of phagocytosis.
So I mentioned when we talked about phagocytosis, this idea of opsonization. And I said that there are some molecules that can bind to bacteria that make them seem even more delicious to a phagocyte. And I said it's kind of like dipping a tortilla chip into guacamole or salsa.
So this complement protein stimulates phagocytosis by coating the surface of pathogens, and then it causes, it enhances phagocytosis. So The word opsonization, opsonin means prepare for eating. I think that comes from the Greek.
And so the idea here is that you're going to make this process of phagocytosis more efficient and enhance it. So that's one of the mechanisms by which the complement cascade results in stimulation of or helps bacteria be killed by your immune system. We call it the complement cascade because once C3A begins to break down it. all these other pathways also occur. So after C3b can result in phagocytosis, it can further break down into molecules C5 and then C5 can break into C5a and C5b.
I said it was complicated. C3a, which was created here, and C5a, both of these can bind to mast cells. which is what you're seeing here, stimulating them to release histamine. We know that histamine is really important in that inflammatory response.
So this is the second way that the complement pathways can help your body fight off an infection by enhancing phagocytosis and then also by stimulating inflammation. A C5B can then get together with other complement proteins, and it forms, it's trying to show this here, you can see this. hole that's been produced.
These complement proteins poke a hole in the surface of bacterial plasma membranes, allowing fluids to rush in. And this is going to cause lysis or cytolysis. So this is going to cause these bacterial cells to break apart as fluid rushes in. Okay, so one of the critical thinking questions says, what does MAC stand for?
And it stands for membrane attack complex. And it's the result of this cascade. that occurs from these different complement pathways and the effect it has on bacterial cells is to it results in cytolysis the lysis of bacterial cells by poking holes in them. The last set of chemicals we want to spend a little bit of time on are interferons.
So we associate interferons with significant antiviral activity and this is just three different ways interferon can help. Here's our infected cell. This cell is doomed.
It is not going to survive the viral infection, but it has one last trick up its dying sleeve, and that is it's going to produce interferon. And interferon can do a few different things. It can activate immune cells to begin help fighting the infection. It can trigger apoptosis in other infected cells, and it can signal uninfected cells that there's a invader in the neighborhood and cause them to protect themselves.
So let's talk about how that works here. Here we have our infected cell. This is our doomed cell.
The virus has gotten in, the cell is already making new virus, but it's also synthesizing interferon. And when that interferon leaves, it's going to stimulate cells that are nearby. It's going to bind to the surface. And basically when it does this, that tells the cells that are nearby that are not infected, that there's a danger in the neighborhood.
And it's going to result in these cells synthesizing antiviral proteins. And these antiviral proteins might be able to break down viral nucleic acid. They might be able to block viral replication. And so when a virus tries to infect this cell, this cell is able to destroy it before it becomes a virus production factory. It doesn't solve all viral infections, it doesn't work for every cell, but it is one of the tools in the toolkit that your body has to fight viral infections.
Okay, this is my last slide. If you have questions, make sure you email me through the Canvas inbox, make an appointment to talk with me on ConferZoom, or post a question in the Q&A forum.