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end of it have helped so many students get top marks for the for the examinations. If you just used the discount coat off skis E 20 and you get 20% off your request. Mint subscription We've created a community. It's it's been posted in the chat. And so, um, it's it's It's a free space where you can ask any questions, whether it's career related or education. This session related and we're all there to help you answer. Answer those questions We post a regular SBS. They're two s o keep a look out and try to engage a much as possible. I'm not just a few quick, um, rules and regulations. Please engage in the ports because this is a SP a session. Also, the session is gonna be recorded. And if any sort of interaction is present in the recording by attending the sessions, you're giving us the permission to upload it. If you do have a problem, please email us at our skis yet outlook dot com or gmail dot com, and we'd be more than happy to edit it out. Um, please be respectful. And if you have any questions, please please. Um, email us. We've also posted a, um, a link for the link for the mailing list that to keep updated with our session. So if if you're interested, if you want regular emails and when our sessions are we due sessions almost every week. Um, if you want regular updates on those sessions, feel free to join the mailing link. Um, but then, yeah, So without further ado, a pass it over to Sana is our first presented today is sorry. I meet it. Um, thank you. Um, onthe, um, skin to something with screen. Okay. Okay. Keys. You up? Yeah. Okay. Great. Hi, everyone. My name is on a, um on, but I'm a third year medical students on day to day one of going over three immuno immunological response to viral infection on D. Well, like, you know, detail. So I'm not gonna be good covering every single thing you probably learned. But I'm going to cover like, the main things. You should know. The main, like receptor names. The main mechanisms by which the body responds to a viral infection. Um, I think the best way to start this would be to discuss what the virus looks like What is the structure of a virus? Um, bars. It was really weird, never quite different to human cells or other animals. Ldv bacteria. So their genome is usually either it could be DNA or or any it could be single, stranded or double stranded. Or it can be circular or lena as opposed, for example, human DNA that is, double stranded DNA on. It's always double standard DNA, so viruses have a large variety of genomes and can be anything, really. And this effects the way they replicate inside other cells and inside whole cells and infect other organisms. So this DNA, this genome is protected within a capsule coat a capsule coat, essentially a protein coat made of many capsule meals, which is many like proteins. Lots of little protein molecules that add up to make a cap, said protein coat. And this protects the nuclear Cassidy inside. This new like acid is the most important part of this virus because it's what helps the virus replicates, and in fact, as many cells can. Steph only to be protected and therefore has another layer of protection, usually which is called the envelope. So some viruses have envelopes, but some don't on. This also affects the ability to infect other cells. So the way of virus infects cells is that it finds a whole cell. It attaches to it. And then what it's going to do is it's going to penetrate the whole cell. Then it's going to unquote it's captured. Release its nuclear acid. Then I replicated nuclear Casodex multiple copies. Now, once it replicates nuclear acid, if you remember DNA RNA transcription in translation, it's going to create a viral proteins, so it's basically going to clone itself inside the host. So it's going to use all the resources and whole cell to clone itself and therefore make more off itself. And then once it once it's made more vial proteins, the's vial proteins are released into the in the body or in the what of organism is infecting to create more viruses, viral cells and, therefore to spread the infection. So that's how viruses work in his, in essence, as a very simplified explanation, Um, but I hope that makes sense. So now let's say a virus attacks your body or not in a virus, even a bacteria. Your body has three ways of responding to an infection. The first line is called the Immediate in eight Response, and this is what happens the second it a very uncomplicated organism or a very complicated organism. You always have an immediate response. Um, and this says, and immediately, if this response is not sufficient enough to tackle this organism, you then move onto the induced in it response that it's slightly more complicated. Um, but although isn't as strong and does not provide the memory response that a adaptive response would provide, which is like your last result and is usually the basis of how, UM, you don't usually develop until NISP more than once is because your body remembers and in addition, the last time and it's adapted to the illness and therefore you don't develop it a second time. So these are three kinds of immune responses to infection, and we'll cover each of them today. So is that with the immediate immune response, you have two types off chemicals involved. You have cells, different kinds of immune cells, and you have a bunch off immune molecules. So we talked about the immune cells involved in the immediate immune response reversed, have neutrophils a bit of revision. Anyone Tell me on the chat, um, the function of neutrophils, that primary function. What is the primary function of neutrophils? Yeah. Perfect. Tiger side doses. So neutrophils basically license to kill. That is their primary function. They kind of they have very short lives. They barely exist there later. Most the time. Any time they see something, they want to kill the just go for it and the dye. So they kind of are like suicide bombers, and they kind of they don't. That's That's literally the only thing for them we want to macrophages. Can anyone tell me the functions of macrophages? Macrophage is and I'm transit. It's more than one. There are three functions of macrophage is because I just this Okay, Something added in presenting inflammation. Yeah. Amazing. Yeah. Perfect. So first is the garbage collectors. Any time. So because your body's are under always under attack. When your body is just resting, your mark fridge is still alive. They're still around. And what they do is they collect debris like random. If a set of there's like a cell, some skin cells dying, or random turnover of red blood cells, anything macrophage is collected random debris around your body. They're androgen presenting cells. We'll talk about this more detail that is involved in the adaptive immune response on. They also really good if I go side doses and therefore they're vicious killers. Natural killer cells. Anyone tell me the function of natural killer cells. Yeah, someone's in April Tosis that that's correct. So unlike new troubles and macrophages, national care cells do not do fibrose I. Josephs. Instead, they approached the cell that they want to kill, and then they force the cell to kill themselves. If that makes sense so they don't. They induce the killing off the other cells of the other. Cell is forced to commit April Tosis and die on its own, so it's quite clever. Um, it's complicated the way it works, but that's all you need to know. Basically, it forces ourselves commit suicide. Must cells the function of mosques, cells and what they're involved in induced information. Let's go vague, Really System mean? Yeah, perfect. So Marcel's are involved in allergic reactions. The way I like to think of them is that they're a average in bombs waiting to explodes. Seven in allergic reaction. The reason is allergic reactions is because that person is hypersensitized to allergen. When I say hypersensitized, it means that they have, ah, high amount of IgE antibodies to that allergen on must still have receptors for I G antibodies on there plaza membranes. And therefore, if you're exposed to this allergy in ah, Marcelo is going to bind all these anti IgE antibodies and then explode and release all the system mean. And that's what leads down of lactic shock. That's what my cells do and and excels. I'm not gonna ask you what they do, because this entire lecture is basically about 100 XL's. So I'll get Let's just cut to the chase and get that and of it in the immediate in a dress. Immediate in a response. You also have some chemicals involved in fighting off unorganised. Um, these includes defense and lactoferrin and lysozyme. So, and basically, these have properties that allow them to stop the metabolic SSM in organism or interrupt the metabolic SSM or to penetrate that plasma membrane and stop them from being able to grow. Or, in fact, and there's also includes the complement system. Let's go to the real meat of this lecture. And that's our the induced immune response. If your immediate in a response fails to work, then you move on to the induced immune response, which is a bit more complicated. So let's say you have this virus in your blood. This is your blood vessel, and you have a virus there now and the immediate immune response has failed on the virus is still there, and the virus is still replicating on D. Yeah, So what's gonna happen now is that your two main cells that we care about Ah, your sentence cells that include your dendritic cell is a conventional dendritic. So and this is a macrophage. Okay, so these are the most important cells in the immune response, in my opinion. So this is a conventional did excel. And so let's talk. Let's use this as an example. Okay, so all the sentinel cells have proteins on them called pattern recognition receptors. That's what they are. Are stands for the's pattern. Recognition receptors will identify pathogen associative molecular patterns on pathogens. That is a complicated way of saying that in the context of a viral infection, these PR ours can recognize our competence of a virus that is, it's able to identify parts of a virus or a pathogen that are unique to that species. So in our case, um, these dendritic cells are going to use that p R O. Z to recognize that a virus is present for recognizing the RNA competence in that virus. Okay, some viruses that have a DNA genome it probably wondering, How does that work? Well, lot most viruses that have DNA genomes when they're replicating, they release small Army competence doing the replication process. Um, and that's what Prz able to recognize is what that is. For example, in herpes simplex virus. That's what happens. Okay, so now that we have identified that the recognition off a virus happens through PR, ours in 100 XL, the kind of P R R reckons on with today are called told, like receptors told like receptors are a type of pathogen recognition receptors. It's like passing your circulation, except it is like an umbrella term. And then t l. Ours is one type, and that's the kind of most concerned with in the context of a viral infection. Okay, so these pr ours, um, where they present, where can you find them. Well, you can find them in three possible place is the most important place, and the most relevant place is within an endo zone Within a dendritic sell. You have these compartments got endos. Owns on these have t l ours number numbers 378 and nine. You need to know these numbers by the way, it please memorize them. That quite important, you can also find these pr's on the plasma membranes of energy excels, and they're here. You find tr's numbers 124 and six. These are less important. Uh, but they are present in a certain proportion. And finally, quite rarely. Occasionally you can find period ours on your nuclear membranes off the 100 XL is what? Which is over here. Great. So now what happens? What happens once a dendritic cell recognizes, um, a virus using the t l ours? It's going to, um, initiate an inflammatory response, and this means is going to really side to kinds and chemo kinds. So firstly, Agenda XL is going to release interleukin six TNF alpha interleukin one beater, and these are implicated in generating fever in your body. They basically act on the hypothalamus to increase body temperature and the also act on your muscle to increase fat and protein utilization. And all of this contributes to increase in body temperature. And the reason you increased body temperature is because lots of pathogens and viruses cannot survive at higher temperatures, and therefore your body thinks that increasing temperatures that probably kill them with the virus is which works. Sometimes your generics are also released. See X E L eight, which is involved in chemo taxes, which is basically means is going to attract other immune cells towards the site of infection. It's going to release interleukin 12, which is involved in the activation of natural killer cells that we talked about earlier and most importantly, in a virus infection. It's going to release type one interference that are interference. I'll phone beater. And these are the most important chemicals released in the context of a viral response. So let's talk about those type born interference. Type one interferons consist of interference. Alpha and interference beat up the other kind of interference that exist that you probably see type two interference that includes interference gamma that is different, and we're not going to talk about that today. So what? Our interview arms. They're basically signaling proteins, and they're released mainly by white blood cells on virally infected cells during an infection. Okay, and the main cells involved in releasing type one. And if your owns our plasmacytoid injured excels so really, er, we saw a conventional gender XL, but now there's another type of generate cell cause. A product called a Problem Aside engine dendritic cell that releases, um, a buck off these type of interference and we'll get you down a bit as well. Type one interferons are your first line defense in viral infections on there Really important, and we'll get to wise well, and the way they are produced is that your toe like receptors, once they are, have detected a virus, they will initiate the transcription of genes that produce, um, these type one in different proteins. So here's what happens. So you have the T. L. R. 37 and nine in your endos owns their activated. These are going to activate transcription factors called interferon response factors. These interferon response factors are then going to get 44 elated and the fourth floor elated. I refs our then going toe, go into the nucleus and trigger mRNA synthesis off interference. And then the mRNA will then be translated to produce the interferon proteins, which can then be secreted from the cell. I hope that makes sense. Notice how I've given example of DHEA 37 and nine and how these Taylor's only present on the end of June. What happens if a different kind of t l R that is not in and is, um, is activated? What happens if the PTL ours on the plasma membrane or the nuclear mom being activated? You actually have a different interferon production pathway for those, um so how? Whilst in the context of the end of zones, we had t l r 3789 activating your interferon response factors here in the context off other, um tl ours you have rigged like receptors. What's gonna happen is your, um, viral or any is going to be detected by receptors that are already present in the side. Applause, um called triglyc receptors are are Lars. These really receptors are going to then, um, for another pathway and eventually also lead to the same outcome basically, But you just need to know that, um, tailor's the end zones trigger interferon response factors, whereas T L R is not. In the end, it's own struggle rig like receptors instead. But the end product is basically the same. I hope that makes sense. Maybe to go over that again. That's confusing. So what is the effect off having interference, What interference actually do? Well, firstly, um, the inhibit viral protein synthesis in cells. So they kind of induces resistance to viral replication in in cells all over the body. Whether the cells are infected or no, they're also going to increase expression, um, off receptors that will attract natural killer cells. You want natural killer cells because they're able to kill infected cells, and therefore you want to increase the expression of receptors that will attract these natural killer cells, and therefore it promotes recognition or vial. In fact, it sells and finally interferons are able to activate natural killer cells directly, themselves as well, so that this encourages killing or viral. In fact, it sells and viruses. Okay, so now on the screen, I'll have to amount to micrograph of two cells. Can anyone tell me what the cell on the left is and more percent on the writers. Uh, what's on the left and what's on the right. Okay. Yeah. Perfect. Amazing. Yeah. So the cell on the left is a plasma site is a conventional dendritic. So which is the squiggly blue? So we've been seeing this whole time. And on the right, you have a plasmacytoid dendritic so which are involved, like you mentioned earlier in producing type one interference. So let's talk about the difference between these type of these two types of digits cells to Conventions 100 XL. It's like we've been seeing this whole time here are mainly involved. The main function is in the activation off T cells that we will see. That's the main function, and where you can find them is usually in in just perfect issues. Um, whereas plasmacytoid genetic cells, their main function is the produced production of interference. So it's not activation of T cells. It's production of interference. And these are mainly found in the blood and implantation there usually circulating around, um and importantly, these express high levels off T L R. Seven and nine, because this helps them induce interferon production. So the the main difference is you need to know. And if you look at this micrograph for a second, you'll be able to see that this problem aside, a gender XL, has insane amounts off and applause make ridiculous, um, the's quickly bets are all in the clinic reticulum, because their main function is protein production, which is the production of interference. Hope that makes sense. So that's the induced in a response in induced immune response, where you have your dendritic cells using the toilet receptors to identify a viral infections and then to release type on interferons to try and induce an antiviral state in the body. So let's see. Even this doesn't work. To help combat the viral infection, you then move onto the adaptive immune response. To be honest, the induced in it inducing the response is not always very effective on its own. It's usually just buying your body time between the immediate response and the adaptive response. So if you've got into the point where you need the induces wants, you almost always need the adaptive immune response as well, Which is what this is so definitely response. The main goals is one is the activation off cytotoxic lymphocytes steal emphasize it's cells that are able to kill them, the kill cells on their own and also the production of neutralizing antibodies. Cells that will, um, are able to fight pathogens but also able to retain the memory of the pathogen and be able to fight the secondary infection and feature. So these the two main goals of your doctor been, you know, stones. And so now I'm going to talk about how this happens and how it works. So in order for your body to transition into a adaptive immune response, you need your conventional 100 excels to mature. Initially, when they're immature, they are in and in capturing mode. All they want to do is capture, um, capture the protein on the virus and just eat the virus. Basically, that's their primary goal, and they don't they're not. They're quite simple that way. However, it's a bit more complicated when you want adaptive response. What's gonna happen is that you certainly going to start expressing more receptors, So the main receptors you need to be concerned about in a mature convention 100 XL here is the CCR seven receptor. The minute a dendritic cell starts to express a CC or seven receptor. That's when you know it's a mature gender XL. Okay, on it starts expressing three other receptors as well that we'll get to in a second. Also note, um, that they have their MX see, um, molecule designed, which we'll talk about now. So if these molecules and committed to you, that's great. Emirates see, molecules are basically they sound for major history compatibility complexes. They're basically the proteins on the plasma membrane off cells that are able to present the antigen peptide to T cells and B cells todo to induce an immune response. So they're the androgen presenting proteins okay to the very, very important. So they are presented the plasma membrane off your gender excels. Okay, if you're done, Dried XL wants to stimulate a CD eight positive T cell that is a cytotoxic tea, so it requires a M XY Class one molecule on this puzzle membrane. Every gender XL want to stimulate a CD four positive T cell or a T helper cell. Then it needs a M I C. Class two more acute on its membrane. And the way I remember this is that the combinations need to add up to eight. Okay, so in MHC Class one, um times a CD eight at some, up to eight a. M etc. Class two times a CD. Four also some up to age. That's how you remember the combination of what is required for what? So I hope that makes sense. The problem is that actually the problem and also a useful thing about M XY receptors, the very diverse me and you everybody here We all have different expressions off different types of MNC molecules in our bodies. We all don't have the same on. That's what makes us different on that's what makes us respond to different infections differently. So if you look at these these the different types of Emmett C, Class One and MSC class two molecules, you might have seen this diagram before. Basically, all you need to know is that HLA a is the name off the gene. That code's a maxi molecules. So HDL a HLA b NH lacey, our names of different genes that code for MHC class one molecules. Obviously, you know that a gene is made up of like a different DNA code, right? So you and me will have different codes in that in that gene, and that's what makes us different. And that's what makes that I met C class on that see molecules different so I would memorize HLA a chilly actually be a B c as coding pharmacy class one aged A d p d q d r as coating for class two. I would memorize this because it comes up in exams. Um, yeah, mostly asian about that. Great. So now let's talk about what happens, how how the embassy molecules work and how did the activate T cells? Well, all this happens in the nearest draining lymph node. So what's gonna happen now is that in your own during lymph node, you have lots and lots of T cells, distressed ing there waiting to be activated, and they're waiting for an infection to come to. They can fight it. So how other gender excels going to approach these D cells? Well, you should know the T cells have these things called T cell receptors on the membranes which look a bit like this. Onda used to see that he said receptor has four blocks, right? So two of these blocks over here are alpha blocks and two of them are beat of blocks. Okay, on the ones in the bottom of constant and the ones on the top are variable, which is what the V stands for. And that's what makes every T so unique. Because you have different T cells for different kinds of infections and therefore the variable blocks are on top and the constant one's ability Great. So what receptor is going to react with D C cell receptors? Your genetic? So has the Emmett see um, molecule on it. So if this was a CD eight t cell, you would have a m etc. One receptor m xy one molecule, which is what I have here. Um, it's the one molecule has the antigen from the virus, the viral antigen peptide, and it's going to present this to the T cell receptor. And that is what is happening here. This is the primary. This is the primary receptor interaction that happens between a T cell, and he didn't do it itself. Okay, so it's the interaction between it's the presentation off the antigen peptide by the M XY molecule to the T cell receptor by this. So like I mentioned earlier. This variable region on your T cell receptor is important. It's called how it's hyper variable and it's antigen specific and therefore means that it's able to respond to a ah, very specific kind of antigen for a specific kind of pathogen. And therefore you have a huge variety of T cells with the huge variety of hypervariable areas that makes sense. So this is the structure of a T. So receptive. Let's go back to our gender XL on do, um, Artie so complex we have going on. Unfortunately for our students there, a couple of more interactions we have to learn about in terms of receptors, um, on those are as follows. So if this was a CD four positive t So, um, you would also have a CD four receptor that stems from the CD four. So also, by the way, sorry. This is meant to say I might see to please excuse that that's going to make things very confusing. I'm just going to add it to their Okay, So you have a CD four receptor that is going to also interact with your MSCC molecule. So now you have your emmett see molecule interacting with the T cell receptor. And um, it seems like you've also interacting with your CD four receptor now to add on to the chaos further, a very important further receptor interaction need to have is your be seven and CD 28 preceptor interaction. Okay, so the CD 28 receptor is present on the tea so and the B seven receptor is present on the dendritic so on you require these two receptors to also interact. Teo fully recognize the this whole interaction and to validate this interaction and therefore, in conclusion, the receptor interactions that need to take place. Um, activate 80. So is these three things except this is in the context of a CD eight molecule. So you have the teeth are receptor and the m it see molecule. You have the CD eight receptor the CD four receptors in the emergency molecule, and you have the be seven and CD 28 receptor interaction. So you need to remember these three things and this is an order for a T cell to be activated in the nearest draining lymph node. So this basically just simplifies at the three types of interactions required to activate 87. Hope that makes sense. Great. So now that you're antigens so we've talked about how the antigen is presented to the T cell by the M it see molecule, but we didn't really talk about how a dendritic cell processes nitrogen in order to present it in the first place. How does the antigen get from the virus to the surface of the gender XL to be presented? Basically, you have two types of antigen. You have intersex alert or exercise or antigens. Pathogens that live and replicate in the spaces between human cells are called are producing extra cellular infections and therefore extracellular antigens and passages that replicates inside human cells, produce intracellular infections and therefore have our interstellar antigens. And these are both processed quite differently within a dendritic cell to let's talk about that. So if we first talked about a the intracellular processing often antigen by virally, in fact, it's l such as and dendritic cell. What's gonna happen is firstly, as you can see, you have your viral antigens present inside the cell because it's an interesting you infection. And these, um, proteins are going to be, um, transported to the protein zone that is inside the cell proteins. Oh, miss an organ inside the cell that will break down these antigens into smaller peptides that can be understood by the cell, these peptides, and then transported to the end of plastic. Ridiculous where they're they're attached to a might see class one molecules, as you can see over here. So the peptide is broken down on, then transported the end of positive. You'll, um, attached to an M I C Class one molecule and then presented on the peptide prevent, then presented on the plasma membrane. As you can see you, that's how it looks. An exercise regular antigen, on the other hand, works differently because the androgen is on the outside. It needs to get inside the cell first. So what's gonna happen is in Endo side effects tickle is going to form, and the antigen is going to enter through that. So, by endocytosis on end is, um, is formed, the adage in enters and then it forms. It fuses with a lysosome to form what is called a fog, a lysosome. And this finalizes, um contains hydrotic enzymes that's going to break down the antigens into many, many small peptides and then these peptides Instead of going to the end of plastic reticulum like it happened in this side, the MSC molecule is going to come and find the cycle is is, um and pick up the peptide instead. So instead of the peptide going to find the M e T molecule, the embassy molecule is coming to find the peptide. Instead, it's kind of the other way around and then this time it's an M XY class two molecules instead of MNC Class one. So intracellular, um embassy Class one and Xeloda is m A C class too. And then the peptide binds them, etc. Molecule and it's presented the plasma membrane. So that's how intracellular and exhale antigens are processed. I hope that makes sense. Great. So now we've presented on Trajan to our tea. So on our T cell is activated. What happens next? How do you produce an immune response from the T cells? Be activated? Well, these decell are called naive T cells because they've never been activated before and they're seeing this infection for the first time on because they respond to a very specific antigen. Chances are you only have a very small amount of the specific T cells. And ideally, you need to generate a very large amount of the C cells in order to eradicate this infection for your body. So what's gonna happen now is that once the correct e cell has been identified in the lymph node, they're going to undergo clonal expansion, which basically means they're going to differentiate into the correct specific kind of T cell and then proliferates you getting many, many, many clones off these T cells. And this process of clonal expansion is mediated by interleukin two, which is a chemo kind. Great. So now this doesn't just happen in like a few hours is actually take some time. So by the time your body confined every T cell in every lymph node that is specific to that specific infection they contain a couple of days. So initially, what's gonna happen is that in the lymph node that is nearest to the site of infection, you will only have, like, a handful of T cells that are specific to the infection. Okay, All the other T cells that are not specific to that infection will leave that lymph node and make space. Okay, And that's why the number of antigen specific T cel, um t cells reduce initially in that draining lymph node. But then what's gonna happen is your body is going to start trapping more T cells that are specific to that infection and gather them into that draining lymph node. So you want to get all the specific T cells to the lymph node that is closest to the site of infection. All these specific T cells are going to come and gather at this lymph node and become activated. And then when they're all here, you certainly see this huge rise in the number of antigen specific timpte E cells in this lymph node. On you get a massive response face ically. And now you have a whole host. You now have a whole collection off antigen specific T cells to that specific virus that you want to kill off. Basically. So now you've activated these T cells. How are these T cells going to go on on tackle the viral infection. So, as you know, there are two types of T cells that you have CD eight postive T cells. There are cytotoxic cells that can kill and you have CD four positive cells, their T helper cells that don't directly kill but assist in killing. And so we're going to talk about these two types of cells and how they killed. So let's talk about CD eight positive T cells first. So how do they call cell death environment Infection cells? Oh, God, Please explain. Excuse my inadequate animation. Adding on the slide. Sorry. Didn't realize this earlier. You know everything on the screen except for the CD A T cell over here. Okay. CD A T cells when they're activated by a dendritic. So have these Granules in their side of plasm. And these Granules. These green dots contain hydrolytic enzymes. Okay, These are what mature activated T cells have. Naive. He sells. Do not have these. Okay. The's mature CDC cells with t cell receptors, if you remember from earlier Ah, going to encounter a viral infected. So a cell that is think with the virus and is but basically dying. So what is going to do is that this T set of receptor is going to recognize a viral infected cell because the viral infected cell is going to present the viral peptide on an m it see one protein. This Alice, in fact, with the virus, is going to present the peptide to the T cell receptor. And that's how a CD itself. We identified the cell that it wants to kill, as you can probably already anticipate. When a CD a T cell kills the virus, it's also killing the human cells that is infected by the virus. So you do that every collateral damage, however you do get killing of the virus at the end of the day. So it is kind of or when you win symbolism essentially with these cells. So what's gonna happen now is that this CD eight T cell is going to release a, um, chemical called Perforin and perform is going to perforate a hole into the man brain off your viral. In fact, itself, it's then going to release. These got these hybridizing enzymes in these Granules into the viral infected cells, which is what's happening here. And the result of this is that these hard logic enzymes, first of all, we'll start breaking down the cell anyway. The will start breaking down the viral infected, so to initiate the process of killing it But it's also going to activate host enzymes called Caspian's is. These cast bases are intrinsic to the host cell itself, and these cast bases are going to go into the nucleus off yourself on degree, the comet and degree, the DNA. And therefore, what's gonna happen is that is going to induce a polyp Tosis on that. Essentially, how CD eight cell immediate. So difficult. So it's going to find the in fact, the cell by MSD one receptors. It's going to release perforin to create a whole. It's going to inject. It's, um, little hydrolytic Granules into the cell is going to activate cast faces and eventually, India's A pump. Doses help them extensive. How to see the full positive cells work so these are involved. These are more like delayed gratification cells, so the CD eight cells are like instant gratification. They need to kill right now. Get it over with, then bam boom CD. Four cells are more delayed gratification. They're like, You know what? Let's think long term. If this Vice Brean fax us 10 years from now, we need to make sure that we're not going to respond. It's drastically, as we have done the first time, and that's what they're involved in doing. So the make things more complicated for you and for me and for everyone who learns medicine. CD four cells differentiates into different types of cells for the run, so you have T cells and you have see the 80 cells and city 40 cells. The CD 40 cells are going to further differentiate into other kinds of CD four T cells on. This happens under the influence of various chemicals on Dumb Side Kind, for example, under the influence of interleukin 12 and interfere on Gama, a CD four T cell will differentiate into a D hatch one cell a day hatch. One cell is a kind of T cell that's involved in the activation of macrophages to initiate phagocytosis. If you have interleukin 16 into look and 21 this is going to stimulate your T cell. Few day 40 sell to differentiate into 80 hit 17, so that's involved in enhancing a neutrophil response. Most importantly for us, though, if you have a if you have presence of interleukin 16 TDF beater and interleukin 23 you're going to induce the CD four T cell to differentiate into a T follicular help yourself, which is what the F H stands for ti follicular help herself. And these cells are so important because they are what are involved in activating B lymphocytes and kind of inducing the process of producing neutralizing antibodies, which is essentially what, exactly what we want in the adaptive immune response. And you also get th two cells, which we're not really concerned about. This involved in parasitic infections and therefore are not the topic of today's Doc. Just talk more about B cells we spent like about half now and are talking about T lymphocytes. What about B lymphocytes on where do these follicular T cells help out? So B lymphocytes, as we know, are also located in lymphoma in limp in lymph nodes. However, when they encounter a viral anti agent in a lymph node, they differentiate into plasma cells. The B cells differentiate in the plasma cells, and what is the function of plasma cells? Plasma cells produce antibodies immunoglobulins. Importantly, you should note that plasma cells initially produced I G M antibodies. However, RGM antibodies do not have the ideal amount of penetrance that other antibody, such as I G a r I g would have. And therefore ideally, you want these plasma cells to switch from producing allergy am antibodies toe I g A and I g antibodies. How does this happen? Well, surprise. You have your helper t follicular cells to do this for you. So that is one of the main roles. So in order for your follicular t cell, which we talked about earlier to help out your plasma, be so it needs to interact, and it's going to interact by recognizing these two receptors. So you have the CD 40 l receptor on your tee follicular help or so and you have your CD 40 receptor on your plasma. Be so And once these interactions happen, it's going to trigger the activity of an enzyme called a I D. In um, your plasma be so, um a I d stands for a second. Sorry. I've learned right now I can't remember for film put in the chart, but I do remember what it stands for. Um, but if anyone remember what the idea stands for, please put it down. Um, it's basically an enzyme in B cells that is going to trigger the process off switching the antibody type from I g m r i e g r i g a When it's also going to trigger a process called somatic hyper mutation. So what's going to happen is now your problem ourselves are very happily going to start producing IGA and I G antibodies, which have good penetrance on a regular fighting infections. As both GM on also, um, it's going to do so much of hyper mutation. So what is somatic hyper mutation? When I first learned this, I was like, this sounds like a huge, complicated world, and I have no idea what it means. Um, Andi, to be honest in a long time, I understand it. But in essence, literally. All you need to know about somatic cover mutation is the word mutation. Okay, it's this a idea. Enzyme is going to catalyze a reaction where small tiny point mutations are induced into the light chains of your immunoglobulins. So this is an immunoglobulin cracked. So your plasma cell is producing all these immunoglobulins. Now your air, the enzyme is going to catalyze the induction of mutations into the light chains off these immunoglobulins. And this is actually really good because As you know, some mutations in our body can be helpful where some count on survival, the fittest or Darwin's theory states that, um, those who have more beneficial mutations will survive longer, whereas those who have more disasters mutations that predispose them to a disease will not live longer. And it works the same way. With these antibodies to the antibodies that receive more beneficial point, mutations will become stronger to fight. Infection will be better at fighting infection, where some antibodies were world received, less useful mutations, and we'll make them less efficacious at fighting infection. Why is this relevance this is relevant? Is actually now in called it. Because if any of you have gotten your booster jobs, the reason you get boosted jobs is because booster jobs induce multiple rounds of somatic happen mutation, which means it's going to induce more mutations into your existing body. Um, in a globulins, which means you're more likely to generate a very high efficacy, a very high strength body off immunoglobulins that are really good at what they do, as opposed to some antibodies that are like, all right, what they do, If that makes sense, somatic so somatic have initiation basically matures immunoglobulins to produce a very high, efficacious body immunoglobulins that are strong and fighting infection. Great. So that is the immunological side of things I have for today. That is a very quick summary. I say quick, it's been about 40 minutes about the molecular mechanisms you should know for your exams. I didn't cover everything, but I covered the main receptors in the main mechanisms that you need to know. Now I'm going to go on two vaccines. I dreaded this topic because I was, like, the same types of vaccines. They work in some of the different ways on. But I'm going to some of the main points that you need to know. Okay, I stopped about the basic principles of vaccines and how they work. I'm just gonna check the time for us. I can actually Sorry. About 46 minutes in. Okay, Cool. I'm like, brush past this, but I find some up. Everything in the slides that you need to know is I hope it helps. Okay, So, vaccines. What is the point of vaccines? You need to induce an adaptive you immune response in somebody. That is the purpose of a vaccine and, like we discussed earlier, what that means is that you're generating a T cell memory response and you also generating a antibody production response with memory. Okay, Tough of vaccines achieve in various ways now, Ideally, like you saw earlier CD eight. Cytotoxic cells are really good at what they do. They are really licensed to kill. And that's really good, because they get rid of the vaccine very well on their four. Generating a CD eight response is like literally the most ideal thing that your body conduce. However, this is not always possible because in order to generate a CD eight response, your infection has to infect a dendritic so or so that is capable of doing antigen presentation. To put this simply, if your virus does not infect a convention and Riddick so chances are it will not generate a CD set CD eight cell response, which is not ideal. And unfortunately, that's the case for lots of vaccines. Okay, and I'll talk about why this is relevant in a bit. This is mainly relevant to live attenuated vaccines that are capable of generating a CD eight response and are there for very good vaccines. Okay, so just remember it. CD 87 member response can only be generated when the androgen directly infects an adage in presenting south, such as a generic. So also note that T cells in lymph nodes get only be activated by protein antigens many times. You'll see, for example, in the context of bacterial infections that sometimes polysaccharide are uses antigens. These will not produce a T cell response, as diesels cannot recognize antigens that are not proteins to these a relevant in the context off sub unit vaccines. You might have heard of adjuvant adieu into basically chemicals added to vaccines. Addition to the bugs are addition to the sub unit that enhance the vaccine, then make the Mac vaccine more likely to generate a efficacious response in your body. And the most common type of adjuvant used vaccines are you mean themselves. So the main types of vaccines that are who, uh, wh are approved are live attenuated, where you use a little of the whole life bug. You inject that into someone to pretty the response subunit vaccines. We use one pot off a bug and you inject that into somebody like a protein or something toxoids which are relevant to bacterial infections, bacterial vaccines where some bacteria produced toxins and then in the lab you can about these toxoids and then injected into people. And then you have inactivated vaccines where you take a bug. You kind of make it really weak. And then you inject into somebody I would go into further detail about these, but I don't really think we have the time for that today. But I summarized the main bits in this side. If you just remember the basic principle, the vaccines and which kind of vaccines they applied you. For example, a live attenuated vaccine generates a CD eight response, and therefore it is the most ideal kind of vaccine. Now you might ask, actually, can anyone tell me why all vaccines can't be that dictated vaccines? Like, what is the problem with live with anyway, too active vaccines hold away is a chance. Side effects. Okay. Yep. Perfect. Last goods. You're compromised. Okay. Amazing. Okay. Yeah, Exactly. So if you I mean a compromise where you are and even in general, like between a vaccines because you're giving let you literally infecting someone with a fully function organism. chances are they will have side effects and they will feel ill after it, especially with Immunocompromised patients, is really It's really dodgy to give them this stuff because it can be really fatal. I think Megan's going to cover more of this later in her Doc's. I'm gonna brush past this, okay? And this is just a list of accent you need to memorize. So if you in your case nine, you get a list you get your immunization schedule for for babies on and you need to know from other immunization schedule which vaccines are what kind of vaccines. So example your measles vaccine is a live attenuated vaccine. So I have some that all most of it up for you here. So if you just memorize this, you would be good to go cool. And finally, the last bit of my talk, which I'm also going to rush past very quickly is the flu. So we know that you get a flu job every year on D. I actually never question this, but until Case nine, but I'm like it made me question why you need a flu job every year. Surely it's the same virus like it's the same influenza virus. Why do you need a whole new flu job every year? And why do people get the flu every year? And why do you get just a zill every year? So let's talk about that right quickly is break it down. So your influenza virus looks a bit like this. Okay, so you've got an RNA genome over here, you got a lipid membrane, onda. Most importantly, you've got these proteins on the A service off the influence of ours. On one is called hemagglutinin. In this case is the green ones. And you have new ram in a new ram in a days, which is the yellow ones. Yellow proteins. Okay, now he move. Your send in, you'll see, is the short form, which is a cheek. And depending on what kind of humor gluten it is, will be 81 h 283 on the same from your Amitiza's. Well, so And one and two and three and six and seven. Okay. What's gonna happen is that things mutates. Things are exposed of environment, you and me, viruses, every cell, my body exposed to environment that accumulates mutations over time, right? That's gonna happen to the influence of ours as well. So over time the influenza virus is going to accumulate small mutations, okay? And this is completely natural. And this means these mutations are going to change the way the virus is seen. It's going to change the structure of the virus. So if you remember the previous diagram, it was yellow and green. Now, suddenly this influence of ours is yellow and pink. So age one hemagglutinin one has now changed to hemagglutinin three. However, this is not a huge problem for your immune system. Your immune system is like I can deal with this because I've seen the yellow and one before. I haven't seen the the Pink Age three before, but I've seen the yellow and one before, and therefore it seems fairly familiar and therefore I'm still going to generate and your immune response. But it's not going to be anything too drastic, okay? And this is usually what happens every year where you have small mutations and small changes in the influenza virus that have to generate a whole new immune response because it's kind of unfamiliar virus, and that's why you get the flu every year, and that can lead to a risk of an epidemic, which is where you get a flu epidemic. However, sometimes that's called antigenic drift. Sorry, antigenic drift is small changes and can lead to a little risk of epidemic. However, sometimes you can get big mutations that completely change of ours on so yellow and green has now become pink and purple, which is like completely different. So it's one and one has now changed to 83 and five, which is completely different on this is called antigenic Shift on, because this is a completely new, unfamiliar virus this can present with the risk of a pandemic. Don't ask me what is what happened with Covitz, because it's not cause Cove. It is in new virus to everyone, and therefore it's irrelevant in the sense. However, influence of viruses can result in a pandemic. If you get a huge mutation, a huge chunk imitation that causes antigenic shift. That's what you need to know. Um, for flu. Thank you so much for listening to me. Sorry around on for Ms and our but I hope that's been really useful. I will put this side Any questions, please message me the chatter. I'm happy to respond to them now. I want to see some. I'm gonna pass over to make it now. Thank you again. Sorry if I over on. No, you're fine. So on a thank you, Honestly, for such a good talk. I know those people really find immunology really hard. So that was super Super useful for going through all that. I will do my best. Everybody to fish as close to half eight as I can. But we might as heads up might run slightly over. Um, I'll get going Nice in. Probably. So I'll show my screen. I'm going to be honest questions now as well, everybody. So if you want to do anything, just send it now. Sorry. I'm just gonna share again. You see? That's a Honda. Yes, it can go for it. Radiant. Thank you. I mean, sorry. I still can't use the polling functions. You might have to do the pull yourself and really sorry. No, that's fine. I'll do. I'll do my best to do that is that's going Thank you. A brilliant. So how everyone? My name's very good. I'm sure most of you know me by now. today, I'm going to be covering the pediatrics part of case nine. For those of you that kind of students and also these topics here on this side for those of you that ants for those of you that a college student as well I've just included a little list here of the learning objectives that you need to know if this case on the ones that are be covering in my presentation today. So I'm going to start off by talking about viruses. So I'm not good. Obviously talk about every virus and Sana's beautifully already touched was I'm already, eh? So I'm just going to talk about the common ones that come off in exams. You're often the exam be given a presentation of, um, someone presenting with the features of a virus or maybe some of the complications that might occur. And so that's kind of the main things that I focused on, the main things that you need to recognize. So stop starting off with herpes virus is So I think there's a misconception that herpes virus is one thing. It's no, it's a family of viruses, specifically, eight different viruses. I'm not going to touch on them all today on this is herpes. Viruses are a say, a family of DNA viruses. So it's hard to talk about. Different viruses have their genetic material in different forms. Maybe are in a DNA is these old DNA viruses and they are characterized. The main characteristic of herpes virus is is that they have, um, a life long latency. So they remain inactive in your bodies are really long times. Almost everyone will become infected with them at some point in the life. And usually most people infected with the majority of them. Um, but they may be asymptomatic, and you may not know. Site. Excuse me, You guys. Sorry. So I'm gonna start talking about help. Ease. Virus. Uh huh. P Simplexvirus first. Sorry. So there's two different strains of herpes virus from what I didn't tell you, one mainly causes your or cold sores onto Is what causes genital herpes on this presents the sores on doses. The way I like to remember. This is kind of top to toe. So your type one comes first. It's higher up in the body, so it's never the top of the body. Sorry, guys. Um, therefore, that's your type one. And where is Type two is causing a problem lower down in the body. So think top two tone. That's how you remember that. Um, however, there is quite a considerable overlap between the two. Sorry, you may have Type two and have cold sores. There is overlap, but that is the general picture, and the virus is secreted from the cells themselves. So hey, tres be can be spread by direct contact from the source. And as I said with these viruses, many people are unaware that they've had it. They may be asymptomatic on, but the thing with herpes virus is that you need to know is that they remain later in your nerves. It was the side herpes virus is, um, have quite long late, since he periods periods where they're in active in herpes simplex those viruses. There's actual virus cells remain later in the nerves on for type two, especially this virus to be passed on through either or vaginal sex. So it's really important that people informed to not have sex until the source of cleared because they said the virus is secreted from the source and it's very contagious. Um, So if there are any sores present or there is any kind of tingling or itching sensation, which of the early signs that someone has a hatred, any infection? Well, it's important I don't have sex on their Barrett. Later, they need to use barrier methods to cover any infected areas. And what's also important for you guys to know is that anti virals, either Ultram pickle ones. Typically, a sick Provera is used or aunt. If I was mainly drug sending in there, that's kind of there. And that was, and they help to relieve the symptoms, such as the source on prevent them from worsening. But sadly, there's no cure for hepatitis C on the sores will self resolved. But as I said, because the virus stays in active in the body, it may return later. So then moving on tonics. Herpes virus in the family is varicella zoster virus. So when you're fasting by infected with visa be and that presents his chicken box, Yeah, and and then when, um, if you'll once you have that virus is that it stays in active in the body, and then when it really activates it presents the shingles and the virus spreads from the rash site itself. So once again, it can be, um, quite contagious if you touch the rash. Is that the people present with, um I'm sure we all know what chicken box is like, because I'm sure many of us have had it before, but just to go over shingles is on, um, usually presents is quite acute union actual. So on one side, painful, blistering rash on as I said, this is caused by the reactivation of this virus on with Visa VI is like a trustee. The virus remains latent, dormant in the nerves. Specifically, the dorsal root ganglia off one of your nerves in your body, and it's completely random. And when it reactivates, assay causes shingles. And that tends to happen in older or immunocompromised individuals. No. What happens is when the virus reactivates in that one nerve it causes a rash. Took her along the dermatitis of that nerve. And I think the common ones are kind of in your thoracic and lumbar region. See, you will get a rash along the dermatitis of, say, t 10 or 11. Um, you also along with that rash, you get really burning pain for about 2 to 3 days. And that's like a nerve pain that's described is post herpetic neuralgia. So break the word down. Post hepatic supposed herpes virus Neuralgia being nerve pain. Um, there is a vaccine that you can give. It's called Zostavax. It's offered to people aged between 70 and 79 years old, Um, and it's only given once. It's not like the influenza vaccine works given annually. It's only given once on these vaccines don't stop shingles from occurring, but they stopped the this horrible and neuralgia. There's nerve pain, which is, um, really horrible experience. They helped to dampen that down. However, if anyone's had shingles previously in the last 12 months, they'll have a sufficient immune response against the virus so they don't need to have vaccine. Um, but or if if the patient has cancer or is taking high dose steroids, or is it any other way? Immunocompromised. They can't have this vaccine because, as someone said, it's a live attenuated vaccine. So that's no, that's not a good idea to have some months immunocompromised because it would just overwhelm their immune system. Next one that we have his EBV, you don't need to know as much up the remaining three is the first two. So, uh, MDV causes gradual fever, which is also known as infectious mononucleosis. It's an infectious mononucleosis or, gradually, fever isn't always caused by EBV, but it is caused by a BB in 90% of cases on this classically presents with the triad of a sore throat fever. I didn't have lymphadenopathy, um, that's when your limp limp loads on glimpse. Guys become really enlarged and swollen. Basically Onda grandeur. A fever is also one of the few causes of white, puffy, puffy tonsil. So if you see a patient that's got white pasta tonsils, they could have tonsillitis, but they could also have You can get a fever. Um, it's spread through saliva. That's its main motive. And it's red. And one of the main complications that you guys need to know is that it can cause various lymphomas on. But, um, so those ah accounts is of your immune system. You're white blood cells. Typically, um, such as Burkitt's lymphoma, Onda um, Hodgkin's that moment as well. And then, if we move on to stand be, this is cytomegalovirus. This is spread by direct contact with bodily fluids. So things like saliva, any breast milk, genital secretions or urine anything like that. On this time, instead of remaining late in the nurse, I called first two visa be and he just be These viruses remain late in the bone marrow road on the circulating circulating monocytes in the body. Um, you don't With this one, people tend to be asymptomatic. However, it can be noticeable in those that are immunocompromised just because they they're musicians on too strong, basically. But the main thing that you need to know about CMP, I would say for exams, is that it can cause severe birth defects if a pregnant woman becomes infected and CMB during her pregnancy on But that caused as a different birth defects such as growth retardation Mike Mike carefully So an incomplete but development of the brain on day. Typically, patients present with a small head, also causing capsulitis so information of the brain and also isn't sensory neuro deafness in the child as well. So the final hate herpes virus. I'm gonna go through hate TV. There are different strains of it, So the main ones that you need to know that type six and 11 cause genital warts. There's type 16 and 18 cause survived cancer, and you might have heard recently about the success of the HPV vaccine. This is given to now both boys and girls between ages of 12 to 13. So if you're in the UK, that's when you're in your rate. And that's reduced the rates of cervical cancer by 90%. And those vaccines contain for those strains. And 6, 11, 16 and 18, um, as well. There is, um, cervical screening, which can reduce the risk of get somebody developing cervical cancer by picking up nice and early. That's offered to women age 25 to 64. Um, and between 25 49 they're offered cervical screening every three years, and then between 50 and 64 it increases in length of time to every five years. On these, um, these screening programs basically detect strains of HPV on on and around the cervix just to see if they're the person is likely to develop survival cancer. So next that a lot of viruses that you need to know about is Emma. Um, so you will probably heard of the MMR vaccine, So I'm gonna break down the three viruses that it protects against. So we've got measles. A zar first one. So this is a single stranded RNA virus. So it has its genome as a single strand of RNA, and it spread by droplets. Does anyone know what the images showing? Can you pop in the chat? What the image shows here? Does anyone know what this feature is that you might see kopecks? Felts, yet? Brilliant. Yeah, pretty. And that's great. So yeah, little clear on the slide on the complex spots are small, kind of bluish white dots surrounded by a red zone appear on mucous membranes, typically in the streets or the lips on. That's a character. Six. I'd of measles, so you can kind of see them here on the cheeks if you can see my see my cuts around about here, Um, degree is well, I'm sure you guys know you can also get a rash with measles, and that usually appears a couple of days after you start to develop symptoms, and that typically starts behind the ear and then spreads down to the whole rest of the body. Measles also has other complications such as pneumonia on my card itis. So that's why we like to vaccinate against it. But the one that you guys probably need to know, for example, is the rare complication of sub acute sclerosing Palin. Careful itis on this is basically a chronic brain inflammation that causes scarring of the brain on, but it has no cure. It's it's quite a devastating diagnosis to receive. So then we'll move on to months. So this is also a single stranded RNA virus. Um, you tend to get outbreaks of this in the winter and spring. Um, Andi. It's typical features that you might hear about in exams are puffy cheeks, parotid gland swelling as well. Fever muscle pain Generally feeling under the weather for the puffy treats, especially, is quite characteristic on the major complication of months is meningitis. If the virus then spreads to the meninges. Finally we have rubella. This is also known as German measles, and it is spread by drop. It's in in someone who's infected, who's coughing and sneezing on similar to months. You often get the outbreaks in the winter in the spring. The main feature of this one is that you get a red rash all across the body that begins on the face, um, and then spreads a say all over the body and also into the back. Um, it is. It was already dangerous because if it's contracted in pregnancy, there is a risk of congenital rubella syndrome, which also causes congenital malformations in babies. Such a Z, a sensory neuro deafness, cataracts, congenital heart disease is and various other things. So it's really important that I'm it's it can be avoided that pregnant mothers don't contract this virus. So finally, I'm just gonna go through some travel related viruses that you'll need to know for exams. So these are all viruses that these three transmitted by vectors. So animals such as mosquitoes mice, which will go into more now. So starting off a dengue fever. So this is typically found in theoretical a zone North and South America. Is that East Asia? Eso someone you might hear in exam questions someone's travel back from there or trouble from their lives there. That's quite characteristic of dengue fever. Onda. This is transmitted by mosquitoes. Um, it has four subtypes, which I'll be going into a bit more shortly, and explaining that on. But why? That could be so dangerous for someone that has thank you. Fever. Just the fact that there's different subtypes. Um, the main symptoms that you get are on a headache, fever, muscle pain and aches. You can get some facial flushing. Onda rushes a swell. It's quite noncharacteristic. Really? Um, yeah. Um, But the dangerous thing about dengue fever is that this virus infection can progress to a health something called a viral hemorrhagic fever, which is basically where someone has a fever on and they're bleed. They have a tendency to bleed. Um, and they can also develop something called disseminated intravascular coagulation, which you don't need to know too much about. But basically they're clotting system isn't working properly, so they conform. Lots of clots, but also be it. The risk of bleeding is a bit not what you'd expect if someone's crossing and greedy at the same time. But basically the vast vascular system is doing with things, so they're at risk of bleeding on there, often present with very high fevers on the best way to avoid dengue fever is to use preventative regimen measures such a Z, a mosquito control through trapped repellents on debt ing and things. If you go on holiday to one of these locations, then you have yellow fever. This instead is found in sub sub Saharan Africa on South America. It's also transmitted by mosquitoes and can also present with a viral hemorrhagic fever. Once again, it can present quite non specifically so, like high fever, you might have chills. No nausea and vomiting is also quite common for yellow fever, but probably the main difference between dengue and yellow fever in terms of how they present is that yellow with yellow fever someone's more likely to present with jaundice. Hence, hence the name. That's how I remember it. Yellow fever. So if someone is jaundiced, they will look yellow. So that's why it's associated with yellow fever. On they was in May present with hematemesis. So vomiting up blood Um yeah, similarly to dengue. There's no effective anti virals. You can't use any and if I was against it, however, there is a vaccination called the 70 devascularization, which when you travel to a country that has high rates of yellow fever, you could ask your GP on Get this vaccination ahead of time Finally, our last trouble related virus is hantavirus. You don't need lots about this one. This is spread by mouth droppings in urine. Um, also, similarly, presents with a hemorrhagic disease with fever can also present with kidney failure as well. Um, Andi, it it's quite hard tree. There's no vaccine for it, and you just have to support the patient's symptoms. So if they're dehydrated, giving them fluids and things like that, so just supporting however they present to you so that they can get better, there's no way to treat the virus itself. So I said I'd speak a little bit more about dengue fever. One of the major features of dengue fever in each night, for example, is something called antibody enhancement. So, um, why this is such a problem for trying to deal with dengue fever? Basically, so there's four main sub types, which I've indicated by are different colors here. So the process of anti body enhance one is that if a person is infected with one type of dengue fever, so in this case, in this diagram that's in the green version of dengue fever and their immune system. As the whole nose talk to you. Well mounted immune response to it. Um, Andi should hopefully clear it, which is great. If the same person is exposed to the same type of dengue fever. So once again or green subtype a two later day, the immune system will do even better. It will recognize it. It's the same type of virus. It will use those memory cells and just produce a more effective immune response against there. The problem with dengue fever comes when the same person it's exposed to dengue fever again, but this time a different subtype. Um, so in this case, and then use the pink subtype of dengue fever virus. This second virus is similar enough that the anti dengue antibodies will still recognize it and bind to it. How is Ah, The strain is different enough that the antibodies won't be able to destroy it, and they won't be able to inactivate that virus. So the different antibodies that they will try and get rid of this virus, but they just can't do it basically on eventually. This creates that live virus, which is just coated in lots of anti dengue antibodies. Um, then what happens is various immune cells. Such a macrophages will have receptors on their cell surface, which bind to this antibody virus complex basically on it's trying to do this because it's trying to stimulate an immune response. Is trying to say Hello? Look, that here's this foreign object that our immune system or antibodies have found that's do something against it. But actually in dengue, this is really problematic because that interaction between the anti dengue and bodies on the receptors on the immune cells such as macrophages, basically allows the virus to infect the music's and cells. Such a smack a charges, um, and allows them to be taken into those cells are not more easily, um, this convention asana talk through these cells can then my great to the lymph loads on this combined wreak havoc on your immune system. Um, on often these people will need to be admitted for intensity in intensive care visit as their body just becomes really overwhelmed trying to come back to infection. Um, and this is the main reason why I've accede hasn't been produced against thank you for it, because if someone's already been infected with one strain, the vaccine is just going to cause this exact problem of antibody enhancement where you're going to give them a different subtype and then their immune system is going to recognize it but not be able to activate it. And then it's gonna cause of the immune system problems and on. But you can't get around it by creating a vaccine toe all of the subtypes, because then that just causes shut down on the immune response. So it's a real problem and something that you guys will need to understand for your exams. So I heard that made sense. Now I'm just gonna be going over some of the principles of immunizations. So Hannah's talked about some of them already. So just quickly into the trap, can anyone put in some of the main reasons? Why do we even immunize people? Why do we give people vaccines? What's their benefit? But even some great suggestion is coming in her demeanor. A. Anything else? Just throw out loads of ideas. Just reduce mortality. Yep. Reduce more. Yeah, that you guys are getting the right idea. Trying to radical way diseases yet Brilliant. Yes, I have put down well, I think on the main full. So a Z, I said to prevent serious diseases and their complications. So I've just talked about some of the disease is on the viruses that we can get on their kind of life. Threatening complications on factors of luckily meant that the that infectious diseases from bacteria viruses no longer the major cause of morbidity and mortality in the developed world, however, they are still a big cause off morbidity and mortality in the developing world because they're availability of vaccines is much lower. Is also really important to immunize people to protect the individual, yes, but also to protect the community from contracting these diseases. So you guys talked about her immunity. I'm sure a lot of you have heard about that during the copay 19 lb limit. Onda. It's just the idea that if enough people have a good immune response against a virus or against a package in, then the pathogen has fewer people in the population that it could effect on their four. There's kind of that's it's less likely to pass between people because because there's less chance of the virus is going to come into contact with someone that it can successfully. In fact, um possums somebody else. It breaks that train of infection. Immunizations also put for controlling outbreaks, so preventing massive epidemics and pandemics. Before Kobe 19, you would often get small outbreaks in hospitals of certain viruses like norovirus, for example. But as we know, you can get larger global scale after mix up, and that makes a swell. And you guys also regimen this so it's really important to contain, eliminate or eradicate diseases as well. So I'm gonna go into those definitions and little bit more side. I'm going to give you a little bit of a definition. Can you then tell me what level of control we won't have over the pathogen based on where it is in the community? So it's a We have a disease which no longer constitutes a significant public health problem, but it can't be removed from the environment. Can you guys just type in the chapped? What type of, um, kind of protection? We went over it. Brilliant. Someone's got it already. Yeah. Any any other suggestions? See, if anybody else knows that it might make sense. Something sweet done. One that's fine. So if that's the case, we want Teo be able to contain this virus. So you want to obtain a state of containment. So this is really important. For example, with tetanus, this is probably the biggest example you might have heard off. So in these scenarios, where and a pathogen isn't causing a big public health problem. But you can't entirely remove the causative agent, um, from the world because it might have an animal hosts. So such a tetanus, you often get them from things like dog bites. You might also get pathogens from the environment. Um so maybe, like plants and things like that. Or, um, it might be a pathogen where you're completely asymptomatic and you don't realize you have it. That makes it quite hard to remove. Um, and the problem with these pathogens is that you'd have to remove all of those those things from the environments, the animals or the plants or whatever, in order to really destroy the pathogen on that largest mail. So for these, we need to maintain a really high level of immunization as the virus is still there on people could still get it. So it's really important that people immunized against these, so our next one so Let's say you have a disease which has been removed from a large area that has the risk of being reintroduced from transfer from another location. How? How would you describe the level of the pathogen in the initial area? How would you say, How well would you say you contained it? Got one ounce of coming through any ideas? Don't worry. No, I'm just going to move on for the sake of time. So for this one, it's elimination. So, as as I said in the definition, this is basically when I pathogens been removed from an area or continent. But it could be reintroduced from another area, another continent. So if someone traveled from a different area, they could reintroduce that pathogen, bring it with them, and then it could start to become an infection risk in the area that originally did not have the pathogen present. So I just like to remember this is you've eliminated the pathogen from that area. Um, once again, with these packages with this level control, we need to maintain a high level of immunization as well, because we can still get the, uh, pathogen from another place. And we can the risk of infections don't persists. So the last month, how would you describe a disease which has been removed worldwide? How would you describe that? Can you pop it in the chapped for me? How would you describe it? Yeah, brilliant. Yep. Eradication. That's correct. So this is basically, as the name suggest, the disease. The pathogen isn't anywhere in the world. There's no way that it can, um, it can in fact, anybody, because it's just no, it's just no honor anymore on eso the famous example. This is small cup pox, which is eradicated in the 19 eighties. Um, and the difference with this one is that because the pathogen is gone, we now know need to vaccinate against that. So I will just touch. It is very, very briefly because it's something you need to for exams, and that's just the yellow card scheme. So this is something which is a way of reporting ever struck reactions to various medications. It's run by the medicines in healthcare products, regulate story agency or the M H r. A year. I'm sure you've had a lot about the last on two years I've written on the side when you should report and side effects to this scheme. Um, can anyone just pop in the chapped for May? Just really quickly. Does anyone know who can report to this game? Is it Is it doctors? Is it patience? Is it random members of the public to who can report to it, present themselves? And yet you guys know brilliant. Yet so patient's healthcare professionals, anyone can report to the Elocon ski Brilliant. So just going on to the types of vaccines really quickly. So you know, so hard to talk about this is Well, what I've done here is I've just created a little kind of tree map to explain the different types of vaccines and how they fit into each other on, because this is something I really struggled to understand. Um, so So Haman talked about go through a brief briefly. The live attenuated Tenuate of vaccines are ones that contain a whole bacteria or whole virus in a weakened form. On these are the closest things that we have to a natural infection, and they provide the best immune response, and that's just because it is the whole pathogen. So it goes to the normal processes of activating the immune system. That's 100 went through. Um, as he said, It's not recommended in immuno. Immuno compromised patients because it could really overwhelmed They're immune system on. In very rare cases, the inactivated virus in these vaccines may revert back to the original form, but that is quite red then we have inactivated vaccines, and this is an umbrella term for basically any vaccine that isn't a live one. Basically, eso this can contain whole bacterial viruses, which have been killed, which named whole killed viruses that just does what it says on the 10. It's an inactivated virus particle completely it activated. It's it's not. It's not active or jumping down. It is just completely an active um, or it can contain smaller parts of the package in such a protein and sugars, which we can then use to stimulate you mean system. As the home said, these inactivated vaccine is tend to have less side effects on, But just because the reason why you have side effects to vaccines is because your body is trying to is reacting to the pathogen in order to kill it. So, for example, when you get a fever after a vaccine. That's because your body is trying to kind of heat itself up in a way in order to to effectively kill the virus. So within a inactivated vaccine, if you're not producing as strong and then immune response, you're not going to get has major side effects. Basically. So I've talked about the whole kill type of vaccine. The other three types are under the umbrella of a sub unit or a cell your vaccine, which you might hear about. So you're talks talk. So ones are inactivated toxins, basically, So we know that pathogens bacteria, they make kind of toxic particles which they used to, um, kill body cells so we can use those toxins in the vaccine so that the immune system makes makes the immune response against talk same rather than the pathogen itself. Then we have conjugate on Contrave it. Let's just means connected to or join, too. So these vaccines are when you have the material that you want to induce. A immune response against is joined to something else that the immune system can recognize. For example, if you have a polysaccharide or carbohydrate back seen, they're made using sugars from the surface of a bacteria, but they work best if they're attached to something else that creates a strong immune response. Um, so usually that's a protein from, um, usually it's a diphtheria or a tetanus protein that is attached to that carbohydrate, so that induces a better immune response. Um, finally, you have recumbent, and this is basically this is to do with how the vaccine's actually made. So a small piece of DNA is taken from the virus of the bacteria that you want to protect against. And during that, during the manufacturing of the vaccine, the DNA is inserted into other cells, typically bacteria or yeast onda. Um, when that DHEA is inserted into the cells, it you know, it does. What does it access? Instructions for those cells to produce large quantities off like parts of the virus of the bacteria that you want to protect against using that DNA code, which then can be inserted into the vaccine to them be injected some into someone's body for them to produce an immune response against those active ingredients. So I'm not gonna talk through this here, but I've just taken a screen grab off the immunization schedule in the UK on by just labeled which type of vaccine is each one, um, in terms of why we give vaccines to people I spoke about kind of why it's important that we immunize. But as you can see here, we give these immunizations. Two different people are eligible different ages, um, based on other demographics. So when you're deciding whether it is indicated for someone to have a vaccine or not, you want to think about who's at risk of the infection. So maybe there's a room you know, compromised those that are young. Such babies are very elderly. Um, all those weak immune systems you want to think about as well who is a risk of contracting the virus in the first place. So, for example, healthcare workers are offers things like the influence of flu vaccine. Maybe you won't want oh, for your vaccine to someone who's living with someone, Um, who's immunocompromised, or risk of contracting the pathogen. And also boost is a given, so you might want to give a booster to somebody if they're particular risk off contracting a virus. And also, as I talked about, if somebody's traveling abroad a swell, you might want a prophylactic the so ahead of time. Give them a vaccination. So I'm just going to talk a little bit now about childhood milestones, which is another important part of pediatrics. So the main types of milestones you have are listed on the slide. So gross motor, fine motor vision, social skills and communication. So just roughly to explain each term, gross motor skills are the abilities your body has to perform kind of your whole body movements. So those are the task involving kind of large muscles in your body, so involving your legs, your arms, your torso so walking, rolling over things like that, you'll find motor skills are your ability to do more precise movements, so kind of the small movements, but then your fingers and your feet in the rests. For example, hold your pen will be quite quite a precise movement because you're doing something quite small, then your vision that's self explanatory babies vision usually starts off quite blurry and then develops as they do. Then you have social skills, set up playing to interact with other people, forming relationships, developing their own personality and that self esteem on then communication, which incomes is both their verbal communication of the speech on about fluently, all with what they say, um, and also the language that they develop swell. So learning words and the words they use and what they mean And things like that major thing about milestones is noticing what a child is not meeting the milestones that they should be meeting for their age, or if their skills for their age start to regress and start to go backwards on their their termed red flags in terms of milestones. So I think the major type of milestone that you guys need to know that probably come up most exams are the gross motor skills on the way I like to remember. This is the head to toe method, um, so I'll briefly explain the method, and if anyone has any questions, do pop it in the channel, try to answer afterwards. So with the head to toe method for gross motor seals, you start off in the first year of life with three month intervals. So in the first three months you start off with heads, So at three months old, the baby is able to hold the head up right. They can also turn the head to the side when they're supine eso when they're kind of blowing facing upwards on. But when you pull them to sit, so when you have a baby lying down and then you pull them up words into a sitting position the But when they're below three months, their head kind of lights and doesn't doesn't want to pull itself up, but by the time I get three months, that isn't too much of like anymore. So at three months, your main gross motor skills are to do with your head. Then three months later, it's six months we're gonna move down from head to the torso. So that's six months is typically when, um, the baby starts sitting. They also at this point from roll prone to supine as well. But I think the main one comes on Exams is sitting at six months, then nine months we're gonna move down down the body to the knees. This is typically when a child starts crawling and then finally, we're going to move down to the feet. Um, on this at 12 months, that's when typically 12, 13 months. Baby starts to walk on, def. The child is no walking independently by two years, two years old, that that's a major red flag. So then moving on, we're going to now go in six month increments. So 18 months. That's typically when a child learns to run on the way. I like to remember this is 18. You become an adult, you might leave home. For example, if you go to university, you go to university. So you're running away from home. 18. Um and so therefore, 18 months old. A baby loves to run, and then at two years old, so 24 months a baby will learn to jump and climb up the stairs on dialect. Remember, this is when you're when you're jumping both feet of 2 ft, leaving the ground. Therefore, you jump when you're two years old. And then finally, we're going to do one year intervals. So, three years, um, child should be able to ride to try school, which I think it's quite easy to remember. Try school. Try three. That happens at three years old. Um, on day, four years old, a joke and hokum, um, fit and and I like to remember this is kind of when you hop when you bring one leg up, it kind looks of it like a tree tree pose, which kind of looks like the number four. I think I'm just about so do that. And that's how I remember it. So I hope that's helpful. I'm just for the sake of time, because I appreciate we're getting on a bet. Um, I've, um, written in some fine motor skills for you to test yourself on later as to the timings of them. So feel free to read these through in your in time, but these are the common fine motor skills that come up in exams. Um, and these are the other important milestones that you need to know based upon the the vision. So she's goes in communication, um, categories of mom strains. I will just point out, um, that, um in terms of, uh, social skills, A child will demonstrate different types off pointing at different ages on, so you can see one years old that a child will start to do a demonstration thing called pro to declare it'd pointing. So when you when you do Protonix or it'd pointing, that's done as an indication to say that you desire to take part in the experience with somebody else So you won't be pointing so child. What point is something that they're really excited about? Like a toy, for example, They might points like, Yeah, I wanna play with the toy. Um, I'm But they do it in a way that's to do with being with other people. So it's like I want to play with the toys with somebody else, where as a younger age, they demonstrates ankle proton perative pointing, which is more of a kind of It's a desire to have a knob ject so like they might point in something that they want so they might see a big scales on the appointed the biscuit. So just noticing the differences between those two. Finally on this my last section just gonna go through growth charts very quickly in one side and just everything you need to know. So growth charts are basically how we assess growth, um, in Children and growth is a really important marker of health and kids. Eso, if filed, isn't growing well. That can be a sign of something that's quite a serious chronic underlying problem that needs to be picked up, Um, needs to be investigated. And during the first couple of years of life, the main stimulant of growth is nutrition. So if a child is malnourished, there's gonna be less growth, and that will be picked up on the growth charts over two years old, um, is usually growth is mainly due to hormone changes. So such a the release of growth hormone from the pituitary gland. Now, in terms of the growth charts themselves, there's three main variables that will be plotted on growth shots on day or wait, Um, height, although for height. Remember that, um, so you can see it here. This says, lengthen. This is high is the same. You're measuring the same thing. You're measuring how long the child is, but under twos, you need to measure them lying down to measure that late. Um, where is over to? She measure their height, and you may notice here where this kind of speech bubbles coming out, but there's a little bit of a little bit of a jump in the like a step down in the growth chart and line on. That's just because when you measure a baby's link. You haven't because they're lying flat on my table for you to measure it. You haven't got the effect of gravity, so and that means that they're a child's length is slightly more than a child's height, because when you're measuring that right, that spinal kind of column is being compressed ever so slightly. But gravity. So that's why there's that Lucille Jump there, and and also the final measurement that you could measure is head circumference. And this is only done in under twos, and that's just because their skull hasn't fused yet, so it still has the capacity to grow. Whereas when you get over the age, the skull wasn't changing in size. And from those three measurements, you can calculate various things which are on the other side of the growth chart, which I haven't shown on this side such a growth velocity on. So that's basically the rate at which you're growing, which, as you can imagine, is highest when you 1st 1st born on Dalser. So when enduring puberty, when you have a traditional growth spurt that you have, you can also calculate a child's bm I, which is obviously really important. The moment with them on NBC Epidemic. It's really important that we calculate being mind Children Onda, also the body surface area of Children as well. And that's really important if you're giving Children a medication, because often the dose that you give is based on their surface area. So there's four charts that used as you can see here on the side. So you have different charts for girls and boys, and you have 0 to 4 chart, which is shown on the slide, Um, on a 2 to 18 year olds chart as well. Um, when you're using a growth chart, you need to know that you brought the measurement with the DOT You don't cross it on. You need to correct for prematurity in a in a child. So if her child is born before for two weeks, you need to correct for that when you're putting them on the growth chart. So what you do is I'll show you here. You draw the doctor for what they're measurement is at the week as to how old they are, and then you just draw a little arrow across based on how many weeks they were premature on. But It's just so that, um you don't get unnecessarily concerned if a child is smaller than normal. Um, on, um, you don't go to worry about them Bisky when your accounting for prematurity I've written as well on this side when you need to think about assessing it all when you're bit concerned about their growth. So if they're very race malls, the below the North 0.4 center and if he noticed, as you plot there measurements over time that there's a drop in over to the center. Also, you can see the lines here that use to mark different centers. If there's a drop of over to that's concerning, um, and also on the back of the chart, you can also calculate something called the Mid Parental Line on. This is basically where you take the height of both the parents and calculate roughly how much growth the child should be having. Um, and if the height is no as high as expected, that suggested there not meeting, they're kind of genetic potential for their growth, so that's also quite concerning. So that was everything I wanted to talk through. Apologies once again for running over. I've got a few s p A s. If you guys would like to try them, feel free to stay and we'll do them. But if you need to go, the feedback form has been censored. Feel free to believe these will be answers to these will be on metal if you feel in the feedback from so I will quickly launch the pole. You want to answer this first question? Don't worry. If you don't know, just put a guess. I'll give you 10 more seconds. Okay? We'll stop the pull back. So I think the most popular answer was D, which I can see why you would say that the correct answer is actually okay on that is basically because when you're asked a question about what's the most worrying red flag in a child's development, you want to pick the developmental milestone, which, because earliest in their age So apologies. You guys were a bit of disadvantage because after Skip Teresa, the slides but smiling occurs at three months on. The rest of these occur later on too. So 6 to 9 months and 12 months. So the most concerning thing, no matter what time he's ages is that if he is unable to smile, that's the earliest one. And therefore it's the most concerning because he should definitely have developed that by now. I heard that makes sense. When you go over the size, that should also hopefully become clear. So just remember that development occurs in a really predict border. We know roughly when I each development will occur on what order they a current. So the most concerning red flag is the most in occurs of the earliest age. If you ask that exam questions, so next question, I'll re launch the pole. I get five more seconds. Just if you don't know, just put a guess. What? Guess. Okay. Brilliant. Okay, so we were tied between C and D World unto those of you that. But see, that's really good. Um, so for this question, it's basically just testing how much you know about the immunization schedule. So I've written here, um, all of the answers here and what type of vaccine they are so an inactivated complete very on and so very early is a virus particles, basically, And if it's inactivated, it's gonna be one of the whole killed type, which in this case. The only option on overall, the only one in the immunization schedule that is a whole killed is the polio I p v. Virus. Um, no virus. Sorry fact. See, there we go. So, last s t A. I will relaunch the Po for you. Yeah, You keep the answers coming in, and I'll give it say, five more seconds. It's pretty good. We go overwhelming majority here. The Royal. And so which is pretty and see, guys. Thank you. So in the poll there, Sorry. That was a bit quick for some people on. Yet we had a majority on this one, and you guys are all correct. That's amazing. Well done. He also see So it was I was trying to get then give fever. So if we break the question down, you have severe shock. Major bleeding, which I said were, um characteristic of a viral hemorrhagic fever on About one in 20 people are sick with dengue. Actually developed that on. But as this question lose, too, it can result in shock in total bleeding on Google could sometimes die from it. And then I spoke about South America, so we said that dengue fever typically comes from the Americas in East Asia, and he's also visits there often, so he's traveled there before. So if you've had any in the past more likely to develop and severe dengue or that vial hemorrhagic fever, the bite mark on his left forearm was in very a mosquito bite. Um, so this could be both of the yellow fever or dengue. It's less likely to be the hunter virus, because that's spread by mice, droppings and urine. On the maculopapular rash is a side of dengue fever as well. He's not jaundice. It's less likely to be yellow fever. But you can't. You can't be certain there's some patients with yellow fever, don't develop jaundice and that I didn't give you yellow fever. Supportive care is an option, so hopefully that still, um, made it made the answer obvious to most few, and most of you got it right so really well done. Um, the main things that you need to remember is that there's no effective anti virals for dengue. For you, uh, or yellow fever or hunter virus on devices just won't work for any of them. Um, you can see viral hemorrhagic fever in all three of those diseases on deported care is really important. So managing the airways and they're fluid levels acceptable to keep the patient and stable. Healthy. Um, and remember, if you take one thing away from this presentation, um, dengue fever and also had a had a virus as well. But dengue fever does not have a vaccination available due to the antibody enhancement that we talked through because you can't develop a vaccine against dengue fever because as soon as you give somebody a subtype of dengue fever one of those four subjects that they haven't come across before, then it's just gonna overwhelm their immune system on the viral, particles were entered into their immune system and cause have it. So vaccination is definitely not the rounds of this one. But don't worry. If you put that you can go this lights, I hope here that makes it more sense to why the answer is See, So that's we done. Thank you so much for joining. I hope it was helpful. Um, and I'll prospect, it's a Honda. Oh, great. That was amazing. Magen. Thank you so much. Now you buying stuff? It's so much time, um, has really get with