Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Turn red. OK, everyone should be in now. OK, good evening, everyone. Um Welcome to uh the third lecture in this pathology method lecture series. We've got Sar who will be delivering immunology one which is quite um a complex and probably the most difficult domain in pathology in my opinion. So hopefully you guys are in for some really good teaching. Now. Um Sneha is a path VRE recipient and she's also been a co-author for one of the sections in the path um uh guide for me. So I'll just introduce her and um she can uh deliver the lecture. Thank you. Cool. Um Thanks Dennis. Yes. Hi, everyone. Um Today, I'm gonna be taking you through immuno one. Um So I'm gonna be covering sort of the basics um and kind of explain, I guess all the really tricky bits that, that do tend to kind of come up. Um Before we start, I just wanna do a bit of housekeeping, so feel free to kind of unmute yourselves and shout out, I can't actually see the chart. So I think Dennis is just gonna be monitoring it um and he'll kind of interrupt with any questions or, and things that are coming up in the chat. Um And of course, I've got my email at the start. So if you have any specific questions or you want kind of any more explanation for anything, um then by all means, just feel free to email me. Um Yes, as I said, immuno is a really, really tricky part of the path course. And it can seem really daunting, I think, especially in that first lecture. I remember watching it and having absolutely no idea what was going on. Um So I'm just going to explain immunology and kind of desert down to the basics and then we'll go from there and you'll kind of see that things will slowly start to make sense as we go through. Um And yeah, any questions or anything and you need me to explain anything just on me. Um I'm more than happy to be interrupted. Um So, yeah, we'll start off with basic immunology. Move on to immunodeficiencies then talk about autoinflammation and hypersensitivity. So with basic immunology, so essentially the immune system can be broken down kind of into three main parts. You've got your first line of defense, which is your anatomical barriers, second line, which is the innate immune system and your third line of defense, which is adaptive immunity. So with regards to your first line of defense, which is your anatomical barriers, you can think of it almost like a brick wall. Um that includes stuff like your skin or your mucosal epithelium and they basically just act sort of as a physical barrier to anything foreign. Um, but if you think of, if you do think of a brick wall, sometimes there are some small gaps in it, right? Um, so we then need another line of defense, which is your second line of defense, which is your innate immune system. So, your anatomical barriers and your innate immune system are nonspecific. So regardless of what the pathogen is or regardless of what is trying to enter your body, um these, these kind of defense lines are going to be nonspecific. And then with your third line of defense, that's your adaptive immunity. So that is kind of your B cells and your T cells and they sort of mount a specific immune response. So they are specific to a particular pathogen and its antigens and they kind of provide us with the long term immunity that the 1st and 2nd line defense can't achieve because they're not specific. Um So kind of touching on sort of the innate system a little bit more. Um We've got the anatomical barriers which I said your skin and your and your mucosal. So essentially the reason for the mucosal surfaces, the protection of the mucosal surfaces is basically anywhere you have a hole in your skin. So for example, your nose, um or your mouth, you need another special lining. Um And that is essentially what a mucosal surface is, um, and then our second line defense, as we said was our innate immunity consisting of macrophages, granulocytes and natural killer cells. And then finally, we've got adaptive immunity, which are our B and T cells. So one thing to note is as we're moving from, um sort of the first line to the third line in advance, we're getting more specific. Um We're getting memory and we're prolonging the time that it takes to achieve that part of the immune response. So if you think about it, your anatomical barrier, your skin is instantaneous, it's always there. It's always just going to block anything coming in. Whereas the formation of B cells, T cells and antibodies that takes a lot more time because it is more specific. Um So that's kind of the difference as you progress through the different lines of defense. Um And one thing to note as well, that's very, very important is complement. So complement is you can kind of think of it as an adjunct to the immune defense. Um And it essentially it's in its name, right? It complements the immune response. So we'll talk, we'll touch on kind of exactly what complement does in a little bit of time. So with our innate immune system, we've obviously got our anatomical barriers which we talked about and then we have ourselves and our soluble components to. So with regards to path and immunology, it's really important. Memory is really really important. So it's important to know exactly which cell types are, which cell types are part of which of the immune responses. So, for our immune system, we've got our polymorphonuclear cells which are neutrophils, eosinophils and basophils. We've got our monocytes and macrophages and we've got our natural killer cells and our dendritic cells that of course, the soluble components, we've got a complement which we talked about acute based proteins and cytokines and chemokines. Um If you guys aren't familiar with cytokines and chemokines, cytokines and chemokines are just chemicals produced by basically immune cells that aid in communication between different parts of the immune system. Um And chemokines are um a type of cytokine that essentially acts to attract cells to um a site of injury. Basically. So essentially, um this diagram looks really, really complicated and I do think it is a diagram that's used in that fast immuno lecture that you do have immune deficiencies. And I don't think it's too well explained, but once you sort of understand the slide, it's going to form the basis of sort of most of what we cover today. So I'm going to go through it and if there's any questions or anything and then if you could just read them out to me and I'm happy to answer them. OK. Um So yeah, essentially, this is kind of explaining what happens in the innate immune response. So first and foremost, we're gonna start also, can you see my mouse. I can, I'm just gonna scroll across. Yeah. Yeah. I don't think I can see your mouth. Sorry. Right. OK. That's fine. So we're gonna start at the box in the top left. Um Essentially, the first thing that happens is um when a pathogen sort of enters our body, our bone marrow is consistently producing phagocytes. Um So these phagocytes are gonna be released into the blood stream and essentially you want a pathogen enters our body. It's gonna sort of be residing in our tissues. So we need basically a mechanism for these phagocytes to enter the tissues um from the bloodstream. So what happens is that um endothelial cells which line up blood vessels express adhesion molecules, which are literally just um you can think of them as chemicals or sort of structures that they present on their cell surface. Um So our macrophages circulating in our bloods. And when there's an up regulation of these adhesion molecules, it makes the blood vessels a lot more sticky um enabling our macrophages to bind to these adhesion molecules and then sort of roll around and basically um migrate into the tissues, which is where the site of inflammation is. Um And then the one thing that everyone does know about macrophages is that they basically do phagocytosis. So they go to the site of inflammation in the tissues after kind of migrating through um the endothelial cells. And they then phagocytose the organism. And once they phagocytose the organism. Um, it basically kills them, they kill the organism in two ways. First way is oxidative killing and the second way is non oxidative killing. Um One thing that's really important to note is that the bone marrow produces both macrophages and neutrophils and they essentially do the exact same thing. The only difference is that when macrophages go to migrate through the endothelial cells and they phagocytose organisms, they don't die, they're able to phagocytose organisms and they then go on to activate t cells. Whereas neutrophils when they migrate into the tissues and they kind of phagocytose organisms, they die instantaneously. It's almost like a bee in a wasp. So we know that one bee kind of sting something, they die instantly. That's sort of your neutrophil equivalent. Um Whereas your macrophages, those are like wasps, they can continually phagocytose and they're not going to die almost like a wasp just can continually sting things and.