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So this is your first question. I think you in would put the poles up. Um, yeah. Which statement currently identifies the features of dendritic cells? Um, just have a go. Basically, we'll see old take your time to read as well as quite worthy. Mhm. Yeah. Now it's it. Okay. Last kind of 10 seconds. Okay. And we'll just end the pole. Okay. So I'll just There you go. So, um, most of you have gone for deep and my thing works. The great answer is deep. Yes. So, um, there are conventional dendritic cells, which are the sentinel cells that are found in your actual peripheral tissue. Um, And when they come across the pathogen, they migrate in the nearest lymph node and presented to the T cells, which you have to see people in the city eight. So this is the slide covering basically the two types of dendritic cells. So, um, I think it's quite, um, important to know the difference between the convention and the plasmacytic plasmacytoid. So there's a diagram in on the right. So the plasmacytoid dendritic cell, which is the one on the right, Um, that is the one that is found in your lymph or in your blood, and it has loads of toll like receptors you can see on. It's a first. There's a toll like, uh, toll like receptor 79. they brace for these loads of interferons, so interferons are released by an infected cell. They can release alpha beta interferons, and that helps that sell kind of get into an antiviral state. Um, and they can then activate natural killer cells through through the interferons as well. So that's more that's that's Those are some plasma still a tentative cells that are found in limp or blood. But as conventional dendritic cells, which are the ones that the ones are acting like sentinel cells, antigen presenting cells like macrophages and your mast cells. Um, and they're the dendritic cells, which you mean when, when you're thinking of the sentinel cells or the antigen presenting cells, they're your conventional dendritic cells, and they're the ones that when they come across pathogen, they migrate to the lymph node, and they present this antigen two on their M E C. Two to the T cells. Um, so they contain be seven and CCR seven receptors, which will go into more detail about what they do, but it's a question of what they do. But they contain with MHC one and mph see, too. So these are surface level differences between them. But their main Axion difference is is that one of them migrates to and presented DSL. Um, but yeah. So the convention Xopenex both MHC at one and two, and it contains the be seven and the CCR 7%. Okay, so, uh, I think we get the slides at the end of the feedback home as well, so you don't have to right now. Okay, So the next question which statement correctly identifies the roles of toll like receptors on the release of interferons. So what do the toll like receptors do in terms of, um, interfere on release? If the poll is Yeah, it's up. So have a go again. Take time to read that you need, and we'll stop in about a minute. The poll, Uh, 8, 30 seconds. More that 10 more seconds. Okay, So most of you Okay, So, um, I can see most of you have gone for B. So, and the correct answer is deep. So total like receptors. 378 and nine. So intracellular receptors that respond to the foreign nuclear kassid So these can be double stranded or single stranded RNA, and they activate the interferon releasing factor. And that's what then causes the production of lots of interferons for that antiviral. Say this is in response to a virus. So, um, interfere, uh, interferons still like receptors. So what are the types of interferons? Um, there's type one into type one is split into alpha and beta alpha is released by infected luke sites, whereas beta interferons are, uh they are released by fiber of us. Um, and they bind to the interferon receptors and stimulate the interferon stimulating gene that you talked about various side. Um, so the type two, uh, interfere on they are the gamma insurance, and they're released by activated T cells and natural killer cells. So, um, on the right eye just put an overview of the innate response to the virus just because they're going to go into the adaptive response. But just to get a kind of a background of what the innate has been in response to a virus. So when a virus invades the sell, it entered the cell, and it's replicated inside. The cell is identified by sentinel cells like your macrophages mast cells. Remember, it's your conventional dendritic cells, not the plasma supplied via their PR are. So these are your toll like receptors that can detect past associated molecular patterns. And they then release interferons and natural killer cell activation. Um, to identify abnormal MHC. Want to MHC. One is the one that you every cell presents, and when it's attacked by a virus, the MHC one is not self identifying. It's not exactly correct, and that's how the natural killer cells recognize that these are viral cells are virally infected cells, so that is not clear the virus. Then we go into adaptive immunity, and that's what the next few slides are going to be on. So, um, so the types of toll like receptors, um, the oh yeah, OK types of serotonin receptors on your cell service membrane. You have 124 and six and then you end is so you have to like receptor three, which is in relation to, or it binds to double stranded R N A seven and eight find single stranded RNA and nine finds the C p G bridge our DNA, which is from the slides from the US of confidence in case line. I forgot who's lecture, actually, but it's from that lecture. Um, So how are interferons? Release the virus activates these toll like receptors, so those can be the toll like receptors on the cell surface. Always give me the total receptors on the end zone. And, uh, then the cell produces the interferon releasing factor. And, um, this causes the nucleus to cause to produce, uh, mRNA production for the interfere on and its interference and produced. And it binds to the receptors on cells, and that's then activates the interferon stimulated Gene. I think this is the slide. Um, I was referring to for the interferon stimulated genes. And these genes are what when you activate them, suppresses viral entry. Um, just on the side of put these p. R. R s, like the TLR are what recognized pumps and dance. The pants are pathogen associated molecular patterns, whereas damps are the damage associated molecular. Okay, so next, um, next s be a um I don't know if the poll It's a which statement relating, um relating in relation to this process of being correct. It was after migration. There's about the dendritic cell activation, um, of CD four and CD eight expressing T cells 30 more seconds. Okay, Uh, I'm gonna end it now. Okay. Okay. So most of you have gone for B, which is right, which is incorrect. So T cell answer, which was the CD? Four cells are activated by the C one. That's the one else incorrect. So T cell activation. How do they change from naive to affect our cells. So there are two types of the cells the T helper cells and the cytotoxic T cells. And I've just made a table here summarizing the main difference in terms of receptors. And and then the last bit is the co stimulation, which they both need, but so does the receptors. The T helper cells contain the CD four co receptor, whereas the Cytotoxic T cell contains a CD eight co receptor. And I think in the back in here we've said let the CD four binds to MHC one, which is incorrect because it binds to MHC to um And you can remember this because they've kind of multiplied to make eight, which is uh, that weird, but like CD four and M A C two and four times to make eight and CD eight and it makes the one because eight times one makes eight. But yeah, so T helper cells they can do the CD four co receptor. So this is what binds to the MHC too. So the MHC to these HLA d p g q d are examples of MHC to use if it says it's binding to the HLA DP, that basically means it's a It's a type of MHC two receptor. Um So the PCR binds to the antigen, which is a T cell receptor. Bind to the antigen that is present on the MHC to, um, and the CD four binds to the MHC to itself, and you get close stimulation from other factors as well. For both, he helps us and let us see T cells. So moving onto cytotoxic T cells, you have the CD eight co receptor, which is present on the surface of a cytotoxic T cell and that binds to the MH. The one receptor on the actual, uh, antigen presenting cell and the H L. A. A, B and C are examples of MHC one, and that's quite easy to remember because A B and C is just 11 letter and D. P and P. Q. R. Two letters. You know, if I'm 82 then again likely help ourselves. The T cell receptor itself binds the actual androgen, and then you get co stimulation. Don't worry. There is a diagram on the next slide, pretty sure so that we can actually visualize this and I'll say it again. So there are three signals for T cell activation, and you can break these up into what is binding with what and what type of signaling is happening. So the first signal, the actual MHC, is binding to the T cell receptor. The second signal, which is the post stimulation. This is to prevent energy, which is the lack of energy, which is the a n e r g y. And that is where the be seven, um, on the actual antigen presenting cell binds to the CD 28 which is on the T cell. And so the B seven binds to the CD 28 that's form of co stimulation. And that is the second signal and then your third signal is the signal. Um, that induces the production of interleukins by the T cell. So interleukin two is the main one that is produced by the T cell itself and that combined to the receptors on the T cell itself as well, so it can basically stimulate itself. Um, and that is auto keen signaling. Um, And, um, there's also paracaine second link because they these these I'll to include include can also stimulate other T cells, so that can create loads and loads of clones of the T cell. So you have the first signal, which is where your MHC is binding to the T cell receptor, whether it's CD four or CD eight binding to MHC to or MHC one. Then you have close stimulation by the B seven binding to the CD 28 that's to help give it some more energy and prevent it from creating a lack of immune response. And then your third signal is an interleukin released by the T cells and that is going to stimulate itself to create clones of itself. Um, and this activation, I mean, you have probably haven't come on two immunosuppressive drugs But this activation is what's inhibited from immunosuppressive drugs. So, T cell activation, this process of signaling with the three signals. Okay, um, just gonna Oh, great. Sorry. Let me just do that. Sharing. Ken. Sorry about that. Okay. Okay. So diagram to explain the actual signaling. So you can see on the top is your actual antigen presenting cells. So this can be your conventional dendritic cells, your macrophages, the mast cells, whatever is going to present the antigen. Okay, so if it's presenting it on the MHC one, like we said, it needs to multiply up to eight. That's going to be presenting it to the cytotoxic. T cell. If it's presenting the antigen on MHC class to, then that's for the T Helper cells. The CD four cell, right? Because four times two. So, um, when this, uh, so, yeah, so then that's the first signal. Binding of the teas are receptive to the M A C. And the second signal is the be seven to the CD 28. And that signal is interviewing, which is not shown on this image. Okay, so moving on to the next s be a. Which statement identifies the main source of each, um, interleukin. Um, is the pole going up? Yeah. So? Currently, and find the main source of each of the interleukins and the sources of interleukins are quite a difficult one, actually, because there's loads of ones you can learn. All right. Saving him. Mhm. 30 more seconds. 10 more seconds. Just want to have a go. Just one of them we've kind of mentioned with that helps. Okay, be Interpol here. Okay? So miss it. You've gone for C. That's right. It's, uh okay. So, into looking one is released by mark stages, which is correct, which is, I think, uh, for for, uh, what's he going to but into looking to is released by t Helper one cells. So Okay, the explanation to this comes after the SBA. Just because I have a list of different interleukins. Um, So I actually ask you guys to also answer this one, and then I'll write an explanation. That's okay. So if we could get the pole back up, you in, uh, main source and function of TNF Alpha A TNF. Our first question. Importance kind to know. Wow. Um, okay. 20 more seconds. Okay. Um, 10 more seconds. And so I might just end the pole here. Okay, So and mhm. Yes. Okay, so this is the correct answer, I think was I think everyone got that one that answered. The main source is macrophages, and the main function is NutraCal. Chemo taxes, chemo taxes is always coming towards where this is all being released from. So if, uh, the neutrophils are coming to where the TNF Alpha is going to be released from and it's also important introduction of fever. So the fever actual rise in temperature. TNF alpha is one of the three main courses of it, so we'll talk about that here. Um, so the main source of these interleukins this, um, image on the left. I actually got it from peer wise who also who got it from past net. But it's basically just a big, giant list of all the interleukins and their main sources and function. So interleukin one, the main source macrophages and one of the main functions is acute inflammation as well as induction of fever. Um, TNF, alpha, uh, two necrosis factor alpha, which is on the bottom, uh, second to last main source. Macrophages and the function induction of fever and, um, neutrophil commit access. So, um, you don't have to know all of these interleukins, by the way, just the ones that you've covered with the ones that you've come across you can add and make your own list. Um, because you don't need such an exhaustive list to memorize in your too. So, um, so what we've got to so far is say these T helper cells are activated specifically the T Helper one that the CD four T helper cells are activated. They can activate to form either T helper one cells, which help in the fighting of virus, and of the virus of the bacteria. And these are activated by interleukin 12, which is thirds last on the on the list, uh, interleukin 12. And they leave the lymph nodes and release interfere on gamma, which can then stimulate macrophages. So, um, again, on the list it says about stimulation of macrophages by a gamma, but they all kind of ties in on the on the thing. I'm just kind of repeating a little bit of what's basically on the on the list. So t l perks one f, which is the T follicular cells. They are also important in the fighting of virus and bacterials. Um, they do not leave the lymph loads they instruct with these cells. And with these cell proliferation proliferation, the T follicular cells are what's important in helping with class switching and clonal expansion. So we'll come to those We'll talk about those, um, in the next slides on B cells. But T particular cells are what is important for these processes to happen. So you must have a, uh, class switching and somatic mutation. So that's what the T follicular cells are are helping with T helper to cells. They're activated by interleukin four, and they produce into looking four and five are basically aid and stimulate with clonal expansion. And then t l per 17, which is, um, specifically for bacterial infections. They release interleukin seven and stimulate neutrophil productions. And neutrophils obviously are important in the fighting of bacteria. And for um so uh, so yeah, the list. I think you get it in the slides. But, um, it's quite useful just to summarize the main sources and main functions because I think when you look around, there are loads of functions for loads you know, like loads of vague little functions and stuff, But you just have to learn, like, one or two main ones. Um, and that'll be good. OK, so, um, now I'm going to quickly go through the second L0 So the second L0 uh, that I'll be covering it is about being emphasize. So it's a differentiation. And the actual antibodies produced by B lymphocytes once it's been exposed to the antigen. So we looked the T lymphocytes and how they've been activated. And we've also specifically looked at the bridge between T and B lymphocytes, which is the T follicular cells. So once we've activated and we fully expanded the correct T cells, we can now stimulate the B cells and the B cells important because they're what produces the actual, um uh, antibodies. Right. Okay, so we'll start off with an S B A. Um, so identify the current statement describing the circulation. Just take time to read it. And if not, just have a go. We'll talk about it anyway. Okay. 30 more seconds. Okay. I think that's everyone that's coming. So I'm just going to end the pole. Okay, So most of you put Si Oh God, which is correct? I don't know if this is showing its correct, which is correct. So C is correct. Um, MHC one. It's found in all nucleated cells. It's It's the self identification, uh, thing. It's what every cell needs to show that it's it's It's your own body's so that it shows the natural killer cells not to attack it, because remember from the previous lives. If you have kind of something's wrong with your MHC one, it's kind of giving that virus is in the cell. Then it can't. The natural killer cells will kill that cell, so the M A C one is not at all nucleated cells. For that reason, to prevent natural killer cell from killing is a self identifying one. So when the group is empty, so this is about the production of the MHC one itself, so it will make more sense again with diagrams. But when the actual group of the MHC one is empty, it's only found the end of last. In particular, it's not on a site assault. It's not found on surfaces always in the ER, the end of last in particular, and the virus is present in the CYTOSOL. And it's broken down by protease. Um, so when the virus actually enters, um, I'll just go on to think so. MHC one versus MHC to, um m a t one is for endogenous antigens. So antigens that are already in as exogenous antigens, which for MHC to our external kind of questions coming in and releasing there antigens and stuff. So MHC one is for used mainly for posting off, um, endogenous antigens. So these are antigen as the the antigens derived from inside the cell. So a normal self antigen or in new antigen. So it doesn't always have to be, um, a normal identifying self-antigen Antonio and dinner or cancer. And it can also be present in MHC one cells. Uh, sorry, MHC one. Um uh, in the m A c one group basically the antigen. Um whereas M A C two is for exogenous antigen. So these are quite a simple ones. You have excess eyelid bacteria coming in, and it's kind of being broken down. You're taking the antigen of that bacteria and presenting it as an antigen presenting cell as a macrophage or as a mass or a conventional center itself. You're going to present this antigen, and that will present it on. UM, H C, too marries if it's self-antigen is to show that it's yourself or if it's a cancerous one or a viral one that will be shown in the MHC one, Um uh, group. So for M A. C one pathogenic proteins are broken down. Small peptides by Proteus owns and its presence of Proteus homes that are that could there are kind of a big differentiation factor by MHC one and two. So the actual proteins are coming in and they're broken down by pro twosomes. And it enters the end of plastic, particularly by Attack Transporter, which is just a transporter, Um, and in the end of last in particular, it fills the group of an empty MHC one. So you have an M a C one, and it's just empty. It's just sitting in the ER, and then this pathogen is coming in. It's broken down by party zones broker Donald's androgen, and it goes into enterprise in particular, where the MHC one and androgen kind of fixing it's into its groove. And from here it's carried within an endo zone and it goes to the cell surface membrane where it confused with the cell surface membrane and present this MHC one with the antigen in its groove. Okay, whereas how does this differ from an MHC to press thing? So initially m a c too, because it's an extracellular bacteria. You need that figure cytosis. You need to get that bacteria inside, right? So you have figure psychosis, and inside this faga zone, you're going to have the bacteria of the androgen. So the figures and Eliza Zone, which is basically a interested in that kind of end, is, um that has, um hydrolase is so the status, um, and let's infuse and they form a Fagel is is loan, which contains hydrolase is that can break down, um, through hydrolysis the bonds down to peptides and this fuse with this end of this vagal I zone, which contains Now these antigens confused with endo zones containing the MHC too. So whereas m a C one was in the end of class particular, then maybe two is within an end zone and going to fuse with this, um, antigen containing figure license. Um and then the, um students going to fill the group of the MHC to similar to MHC one. It's going to now be transported to the south service membrane and be presented, uh, to to wherever it needs to be presented to. So yes, yes, finally there is an image. So the MHC one, we've talked about it coming through a protease. So this is the intracellular antigens. Uh, this can be self and general can be cancerous, or it can be viral because, you know, virus comes inside the cell. So it is intracellular, and this is the protease own for the purpose. This is on the right, by the way that we see across one. So the purple, uh, thing is the producer, and that's breaking down this, um, understand. It's going to break it down, and it's going to go This, uh, these antigens, the freely in the side, the soul, and they're going to go to the end of last in particular. And within the end of this particular there is MHC. Class one is going to fill the groove and going through the Golgi apparatus, and it's going to the cell surface membrane. You can see that the peptide is going to present present ID at the cell surface membrane. But as M A C class, too, you can see that the actual pathogen never touches the side to Seoul. There's no it's not intracellular. It's coming from the outside, and because of that, it's always going to be enclosed within an end zone. It's never going to touch the side to themselves. It's going to be presented in an an end zone that's gonna fuses. The lysosome that's going to fuse with another end is, um, that contains m A C two and then it's gonna be presented to the surface. I guess you can see the difference within the images. And here is the table kind of summarizing what's going on. But the fact that the, uh, you know, the actually never touches the side soul is also a big difference too, too. I understand. OK, so another SBA which statement about lymphocyte formation or selection is incorrect? That's BS. I, um so poll is up? Um, yeah, again, just have ago Which statement about B and T lymphocytes information. Mhm, mhm data in most seconds. Okay. And then I'm just going to end this one here. It must be a con for a A is correct. So, um, so the T lymphocytes mature in the thymus? They must undergo positive or negative selection before migration to secondary lymphoid tissue. So I will talk about that more in the on the okay. So lymphocyte formation and selection. Um, both B and T lymphocytes are produced in the bone marrow. It's where they mature that differ. B is for bone marrows. They mature in the bone marrow, whereas tea is climbers, they mature and Sinus. Um, that's simple enough. But with the actual, uh, kind of differentiation of lymphocytes, how do we get these lymphocytes that are low? The right one's well, we have both positive and negative selection. So in positive selection, that's why you keep. That's where you do a positive thing in a way and you keep the ones that bind to foreign antigens. So you want to emphasize that can bind to foreign antigens, and you want to destroy the ones that don't. So teal imprecise is that they do the right thing by binding to the right antigen, right? And then a negative selection. You destroy the ones that bind to the self-antigen, the self-antigen like we talked about is the one the MHC one, and you don't want to keep the emphasize that bind to your own cells. Otherwise, we'll go and kill all your own cells. So you want to keep the ones that bind to the correct anti gin and that you want to destroy the ones that do deliver that bind to the self-antigen. So keep the ones that bind to foreign antigen and destroy the ones that binds their self antigens. So, um, the negative selection bit where you destroy the ones that bind to the self-antigen, and you keep the ones that don't bind yourself Antigen that is known as self tolerance. So, in summary, yeah, bind of wine and gin. Don't bind to yourself basically, so you can see in these Say you have 14 emphasize. It's These ones are undergoing apoptosis, the last two because they just don't bind to the right one. And after two that do bind to the correct antigen. One of them also binds to yourself, so you need to kill that one because you need to keep the one that can bind to the right antigen. But don't buy into yourself. It makes sense Okay, so, um, how do CD four cells stimulate the cells in in place? So we need to stimulate the cells after the T cells have been stimulated. And how do they do That is what this is. Uh um, So, yeah. Thank you. Call us up. Um, 8. 30 more seconds. Okay. Just gonna end the coal now, and we have a tie between b and C. Um, okay, so the right answer is see, the T cell receptor buys that makes you too complex. C d 14 buys to the CT 40 Ligon and release the site can, uh, sightlines to induce somatic mutation and class switching. So, um, it's the m a c too complex. So, um, get easier binds that meets the too complex. And, um, there's no be seven and CD 28 binding the CD 40 and the CD 40 ligand. Binding is what's important for B cell activation for T cell activation. You have the be seven and c D 28. finding. In fact, T cell receptor binding to MHC one is what you would see with a cytotoxic. T cell being activated by ABC. You'd have to be seven in the CD 28 A. T, a, C R and M A C one but with T C R M A C two and the CD 40 and see Pretty ligand and the somatic mutation in class fishing that's present for B cell activation. Okay, so clonal selection the nine b cells, the B cells before they've been activated Just how they're just chilling. Um, they are covered in B cell receptors and, um, these B cell receptors Which of the immunoglobulins um they bind and engulf antigens. And when they buy Lingle of these antigens, they display these antigens on their MHC to molecule like an antigen presenting cell. And they present this via the M A C T molecule to the T cell receptor of the T helper to cells. So you can see that on the image here. The MHC to market with the peptide on it is binding to the T cell receptor um co stimulation just to go to the last point. The co stimulation is via the CD 40 Ligon. So CD 40 which is on the B cell binding to the T helper salvage, contains the CD 40 Ligon. So this is important, and it's only specific for the b cell activation for donor selection. So, um yeah, uh, so just to make sure to differentiate that from the be 70 88 which is the T cell activation. Okay, so, um b cell receptors binding engulf antigens. Um, it's played on that makes you, too. And they bite itself receptor on the T two cells, and the th 2000 really signifies that induced B cell proliferation. Um, so when um, uh, the B cells proliferate, they synthesize and secrete antibodies with the same recognition as the B cell receptor initially had to the antigen. So they're going to make the b cell receptor like the um on the B cells of red, uh, antibody. They're going to make the ones that initially bound to that antigen. So when the B cell, before it became the anti presenting cell, is gonna bind to a specific antigen, it's going to be that exact B cell receptor that's going to be made with the exact recognition as antibodies when the B cell eventually proliferates. Because that's the one that combined to the correct antigen. That's the one that can stimulate the T helper cells. So that's always gonna be the one that's going to be proliferated. Um, so the co stimulation by the cd 40 and see what I can and we talked about. Okay, so the next, um, next s p A. Which statement correctly identifies the structure and function of the immunoglobulin. So we created IMMUNOGLOBULINS. Now, um, So what ones are we going to be making and what is their structure and where they found, um, is what this question is Do we give the Yeah, Thank you all. Okay. Um, so he has a ballot. 30 more seconds. Okay, 10 more seconds. If you just wanna have a code, I'm going to end the pole here. And thank everyone that has answered has said be it is correct. Um, so it's coming a little bit of vision of pay, seven rate, but it's the i g i g. G is a monomer. And it, uh, it can pass with presente. Um, but I can explain that in the next slide here. So this is the structure of, um a you know, goblin, You have the antigen binding site here. There's a variable region, and there's a constant region there's a dye sulfide bond in between, but that's not labels here, but it There's a variable region, a constant region. Right. So there are monomers Dimas in Pen Timmers, which are kind of expansionary with the image. But it's the amount of antigens that are going to bind to Episode two a dimer it can present to antigen at the same time. The pen tumor can present five. So, um, I g m is a pen to my, uh I g a is a dimer And then I g g e n d r monomers. Um, so the pneumonic to remember is games to remember your immunoglobulin So it's g a m e d. Um, So the main points. I mean, there is, uh, on this person, But I just found on Google, but I just summarized the main points on the on the bullet points. I d. G is the most abundant. Um, it can pass through the placenta. Um, I g a is fine and your mucous membranes on this image, you can see that kind of in the lungs and the bronchus. Um, so that's, uh, that's the mucus producing membranes. Um, and it can pass the breast. So this is the one that does pass through the breast milk from mothers child, which is again from case seven or eight. Um, I g m is finally blood and lymph. So this is the one the first antibody that is made by the body to fight a new infection. So when the B cells eventually, you know when they need to produce an antigen before this before this, uh, these antibody before that antibody becomes specific before it undergoes somatic hike a mutation in class switching It's an eye GM antibody. And because it's an i d. M. Because that's the first one that is just released that's released very quickly, very suddenly, in response to, um, any kind of Axion i g e is the one in allergic reaction. So type one hypersensitivity reactions with Marcel driving. Uh, type one hypersensitive reaction is when you have you have to have an initial exposure to an antigen so that your mast cells are kind of primed to release histamines when they in town to the antigens, or the antibodies combined to the antigen really, really quickly. And the next time you have that reaction the next time you kind of come across, say, uh, Pollin as an allergic reaction. Um, you will really, really quickly release these IgE antibodies, and that can cause you to, uh, feel ill and feel kind of get an allergic reaction to it. Um, that's quite important for type one hypersensitivity reaction. I, g, um, and I g d activate space fills and masked cells. So, um, I g d I don't know. It's not much to know about except myself. But the main thing is, I g g is the ones that passed with Presenter, and it's the most abundant one. Um, and hence it's in the beginning. It's gamed that I g g first because G is the biggest one. Um, uh, yeah, And then a is, uh, Lucas membranes. It passed through the breast milk ends the first one to be made an infection Ease the one with the allergic reaction, the type of hypersensitivity one, and these kind of their activate basal cells and muscle. Uh, but yeah, just really important to kind of know the main points of it. And, um, the pentasa dimer monomer. You know, the structures of it are also quite good to know. Okay. Another s p A. Which statement currently just described Somatic mutation in class or chilling so you can put the poles up. Yeah. So I know I've mentioned this a few times, but do we actually know what it is? Um, yes, I have a minute to read. Give you a bit longer on this one, because the better the read. Okay. Last 10 seconds. Okay. Um, so just gonna end it here. And most of you have gone for D, which is also correct. So which two statements correctly Type D and a mhm, um, Andy are both correct. I didn't actually take note of what the 2nd 1st 1 was, but if you've got a you're also correct. All right. Um, so it's a Andy Cluster jink. Refers to change Is that in the genes coding for the constant region, So it causes the change from i g m two i g g a or e. So there's I g m as we said, the first one that's produced. So the actual class switching occurring the constant region. So remember when we looked at images? The constant region is the region at the bottom here. That remains constant for the the type of antibody is so to make it that constant region. That's what we call class. Switching the change from i g m two i g a r e um, and then D is talking about somatic mutation. So somatic mutation refers to point mutations in the genes coding for the variable region and the higher affinity these antibodies have to the anti gin. They're the ones that multiply, and that makes sense because the variable region is obviously the region that binds to the antigen itself. It's antigen binding site. So the variable region you have point mutations. Uh, and that's the somatic mutation class switching constant region. Because you can remember that because classes see constant regions. See, um, but yeah, class itching in the constant regions. Somatic amputation in the variable region. Um, and that's what getting higher affinity antibodies that bind to the correct actions. So just to describe that in a bit more detail with somatic mutations, they're the ones that are happening in the variable genes. They're point, mutations, mutations in the variable region. The bit that that that's like the the the bit that the antigen is fine so in it you have winners and losers. So the winners are the higher affinity antibodies and the the the the term to use is high affinity antibodies, so that can compete for antigens. So that's where you're kind of expansion. And you're going to notice these because they compete with the correct, they can compete for the correct antigen. The losers in this case are the lower affinity antibodies. And so they can't compete with the antigens, and they will undergo, as most things do, a proctor test If you can't, if they're not useful. Yeah, class switching, constant region. The the C Um so these are the changes that occur in the genes that could for the constant region region. That's the kind of tip of the Y. So, um, the here is where you get the change from the i g m. To the higher affinity I g a or E. So where in with the variable region you're competing for high affinity antibodies in the class switching. You're competing. You're basically changing it so that it goes from the I g m that's initially produced to I g g a or E. That can be more um, higher affinity for specific things. Um, and we talked about what specific things. Uh, these these antibodies are used for in the previous slides. The IgE is for the allergic reaction. So, uh, b cell encounters pathogen. The advice of the B cell receptor releases the i g m. And then the t follicular cells interact, and they cause with the B cell, and they cause the somatic mutation and the class switching. Um, so you can get I g g production, which are higher affinity to than, um, I GMs and Okay, Um, yeah. So that's the end of the slide to me if I just stopped share ng? Um, yeah, that's that's it. You and, uh nice. Alright. We'll hand over to Tabatha now. Thank you, Sandra, for that of lunch. We've revised a lot, to be fair from that, um, a lot of things I've forgotten, but yeah, if I will hand over to Okay. Hi, guys. So, uh, my name is Tabatha, and I'm just gonna go through your first learning outcome, which is explaining the general principles of virology. Um, so your first question is a registered nurse presents to occupational health, having sustained a needle stick injury. It solicited that she's up to date with all her vaccinations against which of the following viruses may post exposure prophylaxis be given. So I'll just give you a couple of seconds on the pole. Don't worry if you get it rolled. Mhm. I'm just thinking, Okay, we'll close the pole. Okay, so most people have gone for D. A couple of people have gone for see, so I'll just talk through Why D is the answer. So the answer is D, and this is why. So what you should be looking for when you do these questions maybe highlight the most important information. I was finds helpful. So needlestick injury up to date with all the vaccinations and post exposure prophylaxis and let the key points. So because it's a needle stick injury, you know it's going to be a blood borne infection, so that narrows it down to hep C, Hep B and HIV. You know she's up to date with all of her vaccinations because she's a registered nurse and also because it said so in the question, which means she will have had her hep B vaccinations that excludes that one and then post exposure prophylaxis. You have to think about which ones actually do have vaccinations. So the reason why it wouldn't be hep C is because there is no vaccine for that one. So the answer is HIV. Um so these are sort of like the little mini learning outcomes that you're supposed to get out from from this sort of question. Um, so there's horizontal transmission, which is transmitted between individuals of the same generation and vertical transmitted between individuals of different generations. And then there's just a nice little image there, which kind of summarizes the different ways you can transmit viruses, and then I'll let you look over this in your own time. But it's kind of like a little table that just sort of summarizes which ones are waterborne, blood borne, fissile, etcetera. Um, so we move on to the next question, uh, so just open the pole for this one. So Mo presents to his GP with fever and pneumonia. When the doctor looks into his mouth with a pen torch, um, he sees these spots on his mucus membranes, which you can see in the picture there. Which of the following best describes the structure of the causative agent. So I'll give you a couple of seconds. Okay. We'll close the Pollner. Okay, So most people have gone for D, which is the correct answer a couple of people have gone for see, so I'll just talk through, um, so first of all really important. Um, Koplik spots are little white spots found on your mucous membranes, and they're indicative of measles. So I'd say that's quite a key piece of information which will be useful in like, your SBA exams and also in progress test. So if you see that it means it's measles and then I'm just going to go through cause I was found This quite complicated. Um, is what it means the difference between positive and negative when we talk about what we mean when we when we say that So basically, ribosomes, as we all know, make proteins, ribosomes will only read mRNA a and positive r n a is mRNA. So, like, as you can see in like the little diagram at the top, there positive r n a goes straight into making the protein, um, then with negative RNA, you have to make the positive complementary strand before you get the protein. And then if you've got D n a the positive strand. Actually, the code on the positive strand will make you a functioning protein. But the code on the negative strand will make a useless protein. But the negative strand is the template for your functioning protein. So if you've got positive D n A. You need to make the negative strand of that to then make the positive RNA strand to then make the protein, which you can see which I've made a little diagram there and then with the negative D n A. You can make the positive r n a and then make the protein, so I hope that makes sense. If not, you can look over it sort of in your own time, and that will hopefully make sense. And then this is again something you can look over in your own time. Because I won't. I won't bore you by going through it. But I basically just summarized everything that you need to know in little boxes of the viruses, which ones like got RNA. That's positive. Which ones have negative r n a. All that sort of thing. But as I say, it's just something that you have to know. But I've summarized it for you there so you can just go in and make them into flash cards. Um, so move onto the next question. Uh, just open the pool for that one. Um, Ella returns from a backpacking trip. Um, sorry. Hang on a second. I can't actually see the I've just given you the guys the answer. Apologize for that anyway. So Ella returns for a backpacking trip in the gaps here and presents to the A and a couple of weeks later, having developed hemorrhagic fever, swollen ankles, shortness of breath, which she describes as feeling like a pillow over her face, which the follower being would be the best exposure prophylaxis measure, Um, for the disease responsible for a presentation. So this is kind of a hard question. Um, and as we can see by my slip slip of my hand, I certainly we can see that it is the answer d using mails and wrap drops. So I'll just explain why that is so key bits of information that you need to pick out from this question is hemorrhagic fever, swollen ankles and feet and a pillow over her face or feeling like a pillow over her face. Um, and the best exposure prophylaxis. So these symptoms hemorrhagic fever, swollen ankles and feet and the pill over the face are kind of like indicative of hand to virus, which I will I will show you in a minute and exposure prophylaxis. That basically means what? How can we prevent from this disease being transmitted? And the vectors for hantavirus is mouse and rat dropping. So, in the question, it said using mouse and rat traps. So that would be your exposure prophylaxis. So, um, these are the little mini learning outcomes at the top there. So key definitions that need to be aware of, um, what zoono Cicis that basically occurs when the disease is transferred from animals to humans. So when Ebola was transferred to humans by bats in the 2013 Uganda, um, pandemic, that happened, and then we've got the vectors. So the organism that transmits disease from one animal plant to another. So, for example, mosquito is a vector for the transmission of malaria to humans. So we've got three of these sort of weird and wonderful things that you have to be aware of. So is hantavirus, dengue virus and yellow fever. And again, just for time. I won't talk through it all, but that's just basically what you need to know with regards that the key symptoms, whether there's a vaccine for it, what the vectors for it and what its genetic material is within it. And and again, that's something you just sort of have to know. Um, so move onto the next question, which is kind of a recap of, um uh, year one. Hang on a second. I can't actually read the question. So Mrs Sprigg, a 46 year old, um illicit IV drug user for the for the last six months experience chronic fatigue in the rapper rapper and also got pain in the upper right quadrant. Her GP refers her. She's referred to a GP and she takes a blood sample for serological. Testing is discovered that she has a chronic active hep B infection, which is the following describes the serology of her hep B infection. So and which one do you think it is? I'll just give you a couple of seconds. Okay. We'll close the poll now. Okay, so a lot of people go on for e. So I'll just show you what the answer is. The answer in a I'll just go through quickly. Um, what the surrender means? I just can't get rid of the pole. Okay, so this is just a recap of kind of like your Year one hepatitis B serology. So HBs a G is found on the outside, and that's a surface antigen. HBC. A G is a core antigen, and that's sort of like in the little green there. And then h b e a. G is, um, an antigen that's found on the inside. And it's indicative of how much the virus is replicating, which I talk about in a minute. And then obviously you got your d N a. In there, and you've got your enzyme. So that's what it looks like. Um, going into detail into each of those. So HBs a G basically is, as you saw it on the surface, and that peaks when the patient is at their most ill, and it indicates either a recent or a chronic infection if it's present, so basically it could be acute could be chronic. If you've got antibodies against that. That basically indicates that you're cured. Um, And if you've only got antibodies against that and everything else is negative, then it indicates that you've been vaccinated against it. Because obviously, the whole aim is to produce antibodies against the surface proteins of your of the virus. Um, the next one, we've got the court antigen, so we don't actually measure the court, um, protein directly. We only really measure the antibody against it. So you'll only really see that in the in the serology When, um, the anti hbc a G is present in the I G M form. That represents an acute reaction to an infection because you know that I GM is produced first when u c h b c a g i g. And that means it's got a long term infection or you could be cured from it. So you know that I G is produced second in either a memory reaction against it or if you've got long term infection, Um, and again, if you're cured, it can sometimes still be there just because it persists for a long time. Um And then, as I was saying earlier, h b e a G indicates virus is actively actively replicating cause if you remember from the image before it's on the inside. So if you imagine when viruses enter cells, they sort of dispersed all their contents inside. So if you've got that present, it means that it's actually replicating. And if you've got antibodies against it, and it means that there's low infectivity because you're you're basically stopping it from stopping it from trying to replicate. And so in this situation we've got something called acute chronic, which basically means that it's chronic and it's active. So chronic means that it's not cured. So it will be negative basically for anti HBs a G, which is the surface antigen. But it will be positive for the surface antigen being present, because obviously the virus is there, but we don't have the antibodies against it. Uh, and then active basically means, um, that the H P E. A. G is will be present and be positive and your anti h p e a G should be negative. Um, and we should also see that h b c. A. G is present and we might see anti HBC a G. But not always So if that one's by the by, if you see that it's an acute chronic, um, and then this is just when you get the PowerPoint. Afterwards, you can have a go at trying to work out which one is which, and basically put them in the right order. Positive, fun game, Um, and then, finally, viral latency is something that you need to be aware of, so virus is basically like dormant in her sells. This basically means that their genome is maintained without any lighting actions. So basically means there's no viral budding taking place. But they're just being maintained, and they basically evade your immune system by remaining in non dividing cells. And they don't produce any viral protein so they can. They can also be integrated into the house chromosome. Um, and then I just put down the bottom here, kind of like three key ones. I would say that you have to know for SBA exams and also for progress tests. So E B V is basically latent in the bone marrow, and you can remember with the B and the B. C M V is present in monocytes and marrow viral latency. So that's remember that with the M in the middle, and then HSV is in spinal nerves and trigeminal. So that's a way of remembering that. And then I just put in the corner your viral replication cycle, which make sure you know the order of that, because that's something that they might ask you in an exam. Question is, is this in the right order? Um, so moving on to the next question. So Susie has brought her five year old child, um, into her GP for her preschool vaccinations. She asked the doctor why her daughter can't have vaccinations against the common cold. Which of the following is the phenomena responsible for this? Um, so I'll just give you a couple of seconds. Okay, look, how is the pole? Okay, so we've got a bit of a mix there. Just going to Sorry. I can't. Okay. Right. Um, so the answer is D. It's antigenic drift, and I'll just talk about why so these are some terms you sort of have to be aware of. So antigenic shift. So this is you can see in the image. Antigenic shift is basically when you have two different types of viruses that sort of combined together to form a completely new one. Um, and that causes a great difference in it's genetic variability, which can cause a pandemic, Um, which happened with coronavirus. And then we've got antigenic drift, which is basically where you get little mutations over time, which happens a lot of the time with that, the common cold, which is what happens with the common cold. You get lots of little mutations, so it's slightly different so that antibodies that we made against the last common cold are don't work against this one, but it doesn't cause a massive problem, but it can cause an epidemic. So I don't know, the way I remember it with antigenic shift is that a shift is a really, really big change. You've got completely new virus, and pan means everything or a large area so that I just that's the way I remember it, um, and then talking about, uh, the dengue vaccine, um, an antibody enhance, which is basically why the dengue vaccine doesn't work. And I always used to find this complicated when I covered it in here, too. But basically, when you're infected with dengue virus there, there are four different types of dengue virus. When you're infected with one of the types for the first time, we get the vaccination that they created. And then they found that the vaccination didn't work for this very reason. You basically your innate and adaptive immune systems will fight the infection and obviously create antibodies against it, or you'll get those artificially from the vaccine. And then the next time that that same person is reinfected with a different strain of the virus. Um, the antibodies that they produced against the last one or against the vaccine will actually aid the virus to enter cells and and help it to infect you further. So that's why the vaccine doesn't work anymore. And then the other two terms somatic mutation and B d. J sequencing. Um, I think Sandra covered in hers. Um, so then that brings us onto next Hello? Which is outlined primary and secondary responses to antigens. So I'm just going to the next question. So, uh, Mrs Sands, uh, hang on a second. I'm sorry Mrs Sands presents with her newborn baby and describe him as having shortness of breath, salty skin and bowel movements. Such a large and greasy looking who's referred for genetic testing. And it shows he has a deletion on chromosome seven. Which physical barrier to infection is most likely to be compromised in this baby. So just give you a couple of seconds. Okay, What causes the pole? Okay, so a little bit spread. I'll just move on to the next one. So I think with some of my questions, I've tried to sort of, like, combine several topics into one, which is sort of what it's like and when you actually get the exam question, but it can make it a bit harder. The answer is C, which is mucociliary clearance. So looking at the key information again, key information is shortness of breath. Salty skin. Bowel movements are large and greasy, looking at a deletion of chromosome seven. These are all indicative of, um, cystic fibrosis, which is is just something that you have to know. And then I've put in the corner what cystic fibrosis is. So it's a mutation in your CFTR channel with protein, which basically means that hopefully you can see in the corner like basic chloride. Arms can't move to the outside of the cell, which draws water with it. So you basically end up with really, really thick mucus. Um, so that means your mucociliary escalator will be compromised. And that's why patients with cystic fibrosis often have recurrent chest infections. Um, that explains that one, um, and so basically the little mini in early outcome from that was explained how the immune response protects against infection and function distinct phases. So I found this image. I think it's quite useful just because whenever I used to go back through immune the immune system, it was used to not make much sense because obviously it's all over the place, and it sort of it all happened sort of at the same time, but not at the same time. So I feel like this image just kind of like, summarizes it nicely with what the stages are and how they interact with each other so you can have a look at that. And then I basically just put aside innate immunity has two stages immediately induced. Immediate is all the mechanical barriers which we saw in the question answers. Just they're those are all your immediate ones and then induced is all the cellular components that detect Pam Ppsv, RPR, ours and then adaptive immunity is triggered by dendritic cells and involves T and B cells with the aim of producing high affinity antibodies. Mhm. Um, so next question, we have got a 66 year old Caucasian male presents for a routine colonoscopy as part of the bowel Screening Wales program, A polyp is found, um, in the transverse colon and on histological evaluation is found to be cancerous. On examination, it is found that these cancer cells have decreased. MHC class one expression on the surface, which immune system cell is most capable of killing these tumor cells. So this is a difficult question. So don't worry if you don't get it right. Mhm. And also, I'm going to go over the answer very briefly for this one. But I have put in the when you get the slides after I put in the notes a bit more of a detailed explanation because I feel like I can't do it justice in the time. Yeah, okay, so we'll close the pole. The case we've got a bit of spread again to see which answer is it is D natural killer cells. So basically, I'm going to talk through why each answer is wrong. And as I say there'll be. There'll be a clearer explanation in the in, sort of like the notes at the bottom. But basically, B cells bind and present antigens to t cells by MHC Class two receptors and have no direct cytotoxic effects, so that's why they won't be. They won't operate in this instance. Macrophages figure to toes cells upon optimization with compliment or by FC receptors after specific optimization by antibodies. So again they won't be very effective. In this case. Eosinophil is D granulating allergic reactions and have no direct cytotoxic effects. Either cytotoxic T cells or CD eight T cells carry out there killing function when they recognize the specific antigen MHC one. But because we've got reduced expression on these cancer cells, they're unlikely to target it. Um, the natural killer cells are the answer because they have both inhibitory and activating receptors on their surface, and the balance of these decides they're Axion, and they're also we'll talk about this later, but they also don't have any. They don't have to be triggered by MHC one or MHC to to operate. So that's why they? The answer. This is just a summarizing slide for explaining that the T C r recognize the complex of processed androgen bound to major hista Quanta bat ability Complex one and two. So basically tells you what MHTS are major histocompatibility complexes. They enable the host to detect foreign antigens by presenting them to a T cell receptors, or neither. CD four CD eight cells. Where are MHC s? MHC one is found on all nucleated cells. MHC too is only found on professional entered in presenting cells that should be cells, macrophages and CDCs um, water, tea, CRS, their T cell receptors that are found on CD eight and CD four cells. And you basically when MHC and TC are sort of combine and they activate the T cells and then I think Sandra talked about this as well. But there's differences in MHC one and MHC to processing that you have to be aware of. So MHC one processing. Basically the androgen has been processed in the cytoplasm directly via a protease own, so the peptide will then be displayed ready to a CD eight plus cell, and then MHC to processing the MHC. Class two will be end visible, and it's basically processed in a fatalist zone, and that will then be presented to a CD four plus T cell. But that will actually never make contact with the cytoplasm. So important distinctions you have to be aware of. Um, so next question. A 29 year old Reese's positive lady p three g two attends the delivery suite. A child has jaundiced when born, and the midwife explains that it is due to her baby being recess negative, which, I mean a global in produced by the mother is most likely responsible for her baby's immediate presentation. Hmm. Just give you a couple of seconds. Mhm again. Don't worry. If you don't get it right again of these questions, they're kind of like drawing on lots of different areas of knowledge. So, um, don't worry. If you don't get it right, The case we're closed pole. Okay, so most of you've got it right, which is good. Um, so the answer is I g. So hopefully you'll have covered in your case groups by now a bit about what recesses. So that's a protein on blood cells. And if you've got a lady who's got Reece's um positive, for example, and her babies. Reese is negative if her baby's blood cells come in contact with hers, then she'll launch an immune to launch an attack against those cells. Basically, and it becomes more serious when she's had something called a sensitizing event, which means that it's already happened in the past, which has happened to this lady because she's a P three g two. So I just have to look at the question. Um, so this is basically just trying to highlight the distinction between primary and secondary immune responses and basically saying that your primary immune response you produce I g m. And in your secondary memory response, you produce I g. So one of the learning outcomes is explain why secondary or memory immune response is different from primary immune responses. Um, and so I've just written a little table out for you with all of the important information there, which again, it's one of the things you have to go in. Just have to go away and learn, but basically in your primary response. So when she had a sensitizing event, she'll only produced I g m. But then the second time that she's exposed to her baby's blood cells. She'll produce a a larger response to it, and it'll end up with humility. Disease of the newborn, which is why he's and why her babies jaundiced again. There's a bit more of a detailed explanation in the notes section when you get the sides back after, um, and then moving on to this question. So a student at university residences contracted influenza Type A. They described feeling fatigued and Iraq sick and have achy muscles. Which of the following is most likely responsible for the students? Symptoms? Um, I'll just give you a couple of seconds. Okay, What kind is the pole? Okay, so whatever spread there again again, Notorious is kind of difficult. So the answer is A, which is interferon type one. So basically have to explain the importance of interference and depending against viral infection. So I think Sandra talked a little bit about this. This is really I think all you really need to take away about interference. So three important things that they do. They trigger antiviral state in cells via the jack and stat pathways, so basically they trigger antiviral states and cells around them. they induce apoptosis n virally infected cells, and they also recruit immune cells like natural killer cells, to do killing of virally infected cells as well. And this sort of overall effect, basically, is what they call a cellular firebreak, which basically means it stops it from spreading to too many cells in the body and something you need to just something you just need to take away and remember is that interference are responsible for symptoms such as malaise, sleepiness, my algia and lots of appetites and myalgias. Just achy muscles. Um, but your interleukins are the ones that are responsible for the fever, but the interference are the ones, and it's interfering Type one that's responsible for those symptoms. Um, specifically, it's interferon type one. Um, so last question. So natural killer cells are important in our body's defense against viruses. Which of the following best fits The TLR is carried by these cells. This is just a sort of again, like a sort of fact based one. So you just have to I have to just try and remember it, okay, so it will end the pole so most of you have gone for C, which is the right answer. So well done. Um, basically, uh, natural killer cells. This is just some important facts about them. So they're located in the blood, mainly, But you can also find them in the peripheral tissues. Um, they bring about direct license of cells, but that are virally infected, and they carry TLR three and T L R. Eight. And this makes sense because these ender zonal receptors and natural killer cells are primary responsible for killing virally infected cells. And most viruses infect intracellular early, so it makes sense that they have these t L R s. Um they also have three methods of inducing cell death. So production of cytokines, secretion of cycle, it'd Granules, and also the use of death receptor mediated mediated cycle Isis. So I'd say those are all the important things you need to know about natural killer cells. And then the last slide is literally just a picture of where they're located, which again, it's just one of those things you sort of just have to remember. But I think that's something that would say is quite important for your exams. But yeah, that is me. Down. Thank you. Have you got any questions. Feel free to just, like DM them to be or whatever. Or you can send them to my email, put my email on the chat, and I'm happy to answer them. All right, thank you to be for for that. And that was very informative. Thank you. So, um, next we'll have Alice who will explain ellos five and six for us. Um, okay. I'll ask you Them. Yeah, she is. Uh, okay, never mind. Sorry. I'm trying to find my thing to share. I'm really sorry. A cup of tea or something? Have a break. Also, we'll have a feedback form at the end, so that will give you the slides and all the in depth explanations. Uh, don't forget to follow our instagram and Facebook and become a member today. Okay, Um, Alice, should I share your slides and you can talk through it and I'll just flick through. Oh, never mind. There you go. Right. Sorry, everyone. Yeah. Okay, right. Let me just I got my slopes. Okay. Um, so I'm covering l a five. So that's explaining the immune response to vaccinations and how vaccinations work to provide protection to the individual and the community. Um, so my first question teenagers at a secondary school are being offered, uh, the Gardasil vaccine against HPV. Which strains of HPV HPV does the vaccine protect against This should be a bit of revision for you all. Okay, so everyone has gone for B. No. Which is the correct answer. Well done. Um, so the HPV vaccine is offered to girls and boys, Uh, and the age between 12 and 13. Um, and that's part of the NHS vaccination program, which I think Sophie is going to cover later. Um, so it helps to protect against cervical cancers, which is, um, brought about by strange 16 and 18 and genital warts, which is six and 11. Um, so there is a new, uh, Gardasil vaccine, which protects against nine strains of HPV. Um, and this being brought in, like, this year, which I've listed there, uh, and they're also associated with an increased cancer risk. So the next question a 12 year old child presents, um, I can't actually read it. Uh oh. Sorry. I get rid of that. Okay. So a 12 year old child presents with a two week history of cold like symptoms and in the past two days has developed a characteristic, uh, whooping cough. And the vaccination against the cost of organism is classified as which type. Um, I think I gave you a sneak preview there. So the answer is oxide. Um, and so I just run through the vaccine type. So, um, live attenuated. Contains weekend hold pathogen viruses. Um, and inactivated contains dead hall pathogens and viruses. Uh, the recombinant protein vaccine. It's basically where, um, they use, um, genetic modification to insert the answer gyn, uh, gene into the DNA of the cells and then that you sell can produce the answer gin, which you want to create an an immune response against, uh, then you have to toxoid vaccine, which contains inactivated toxins. Um, and the Contrave it vaccine. Okay, so the next question a preschool child age three, um, presents for, uh, therefore in one booster. Uh, this includes vaccination against tetanus. The recognition of tetanus toxoid proteins by the CD four cells primarily stimulates production of which type of immune agog blue. Okay, so most people have gone for either. Um, the correct answer is actually C um, because immunoglobulins so the tetanus toxoid protein is processed and presented the MHC class two receptors on the conventional dendritic cells. Um, and this eventually stimulates a strong I g g response. Um, so your initial response will be an eye GM response. But the main response that you're aiming for is an IgG response because these antibodies able to neutralize the toxins with the tetanus, um, bacteria produces, um, and I g is the most abundant antibody in the blood. Um, so I've just included a little slide here, which gives an overview of the functions of the different I G uh, immunoglobulins. Uh, but that's been covered quite a lot so far today. Okay, So you are a g. P. Morgan. A first time father has been reading about the six in one vaccine offered to influence at eight weeks. He comes into the practice to ask you why this vaccination contains aluminium salt. Using your knowledge about the concept of vaccine adjuvants. What would you tell Morgan? Okay, so a few of you have gone to do there. Um, and that is the correct response. Well done. Um so adjuvants are added to the vaccine, basically with the aim to strengthen, uh, the quality of the immune response, which is stimulated by that vaccine. Um, so there's various theories as to how adjuvants work. Uh, one of these is called the Depo Effect, where the absorption of the antigens onto the adjuvant molecules, which in the case of this vaccine is an aluminium salt. But it can also be, um, molecules like squalene. It prolongs their presence at the injection site and allows them time to stimulate a more effective immune response. So basically, it hangs around in the bloodstream longer, Um, and so you'll get a strong response. Or another hypothesis is the danger hypothesis, um, where the actual molecules used as adjuvants create a pro inflammatory environment, um, promoting the recruitment of innate immune cells, um, and subsequently dendritic cells, which will go on to activate an adaptive immune response. So the next question is a 48 year old healthcare professional is found to have contracted hepatitis B following a needle stick injury at work. They are very shocked because they have because they state that they had received their vaccinations against hepatitis B in 2013. Which host related factor in primary vaccine failure could explain how this might have happened. Okay, so I've got a few of you going for E. Um, which is correct. Well done. Um, so with this question, it's basically talking about the reasons for vaccine failure. Um, so waning antibody levels would be, uh, secondary. Um, cause of vaccine failure. Uh, secondary vaccine failure as individuals basically do make an immune response initially. But then protection wanes over time as antibody levels drop. Um, so that wouldn't have been the correct answer. Incorrect storage of the vaccine again can be a cause of vaccine failure, but this would have been a vaccine related factor rather than a host related factor. Age related decline and obesity related to Munich suppression are also things that can cause, um, primary vaccine failure. But in this case, we haven't really got enough information to have. That's the best answer. Um, so the best answer is the non responder HLA phenotype, which I will talk a little bit about now. So, um, the major histocompatibility complex or the human leukocyte um an surgeon complex, as it's known in humans, is located on chromosome six. Um, and this is a complex of genes which codes for the MHC class one and two molecules which we've been speaking about this evening, Um, which aim to present antigenic peptides to t cells. HLA genes are very polymorphic, which means that there's a variable a little frequency within the population. So, um, this polymorphism or this variation occurs in domains which are responsible for the Epitope binding. Um, so the parts of the MHC molecules which bind the antigenic material, um, from the vaccine. Uh and so if if an individual doesn't have, um, the correct receptor for that for this particular episode, then the individual will be a nonresponder. Um, and this is a sort of a genetic predisposition to vaccine failure, and this does tend to occur with hepatitis B. Um, but it's not very frequent. Um, so I've listed some useful resources there which go into more detail. Um, so you'll have access to those at the end of the session. Um, so my next hello is L 06. And this is to outline the public health principles. Sorry. The public health principles of immunization and surveillance of infectious diseases. So the first question is that Nell is preparing to travel. I can't read what it says uh, to Thailand. Um, and the travel insurance company have recommended that she received a tetanus booster. What is the aim of the tetanus vaccination program worldwide? Okay, so I've got a little bit of a mixed up. Um, the correct answer is the containment of the disease, and I'll talk about why that is, um So the general objectives, um, of vaccination programs are to prevent serious diseases and complications to protect individuals and communities and to control outbreaks of the disease. Um, so I realized that I put protection of vulnerable and protection of resources, but those would be more general rather than specific. Um, to the tetanus vaccination program. The reason it's containment rather than elimination and eradication is because tetanus has environmental reservoir. Um, and so you can't ever actually eliminate it because you'd have reservoirs of it, which could bring back the disease. Elimination is the aim to reduce, uh, an incident disease to zero within a specific geographical area. So again, you still need high vaccination rates to keep the disease, um, classified as eliminated because it could still come back from another area of the world. And eradication is the reduction of zero um Worldwide. So Mr and Mrs Clifford, our holiday holidaying in Peru. Four days into their tropical South American trip, Mr Clifford develops a high fever, severe headache and extreme fatigue. After a week, Mr Clifford begins to feel better and enjoys the last week of his holiday. Once back in the UK misses, Clifford noticed that Mr Clifford has become quite jaundice vaccination against which disease could have protected Mister Clifford. So I think about the symptoms that he's getting and also the course of the disease. Okay, so I've got some people going to see. Some people are going to e what? The correct answer is e because of his history, um, foreign with foreign travel. Uh, so yellow fever is quite prevalent. Um, in South America. Um, so this L0 is Basically this question was about adult immunization, which was covered in this L0. Um, and there's various reasons why adults might need immunization. Um, so for older people, once you reach the age of 65 you'll get influenza yearly. Um, and also the PPV vaccine, which is a pneumococcal. Um, And once you're over the age of 70 then you'll be off the shingles vaccine as well. Um, you'll also be offered immunization in pregnancy. So influenza and pertussis from 16 weeks, Um, and pertussis is the causative Asian of, uh, the weeping cough that we spoke about earlier. Uh, so I just included here a little slide about all of the different diseases that you, uh, will be protected against if you have underlying medical conditions. Which is another reason why you might need vaccination as an adult. But I'll let you go through that in your own time. Uh, and then obviously another reason would be is if you were traveling to a country where these diseases put you at risk. Um, I think the polio typhoid in cholera, you can get for free on the NHS because they posed the biggest risk if they were brought back to the UK But the others, you'd have to go through travel insurance companies. Um, Gotsche. Okay, so, uh, seven months, um, pregnant women, uh, goes somewhere. I can't read it. Sorry to receive her covid 19 visa. Three days ago, she received her flu vaccination. Upon questioning by the Vaccinate er, she experienced some tenderness around the site of administration after her last dose as well as experiencing some diarrhea. A few days later, she developed a painful, red swollen leg. Which, um so which of the following is an absolute contraindication to her receiving the covid vaccination. Okay, so I've got some people going for be some people going for a, um the correct answer is B. Um, so this questions about vaccine safety, um, and a history of a painful red swollen leg might point you in the direction of a DVT. So a deep vein thrombosis. Um, and that was a contra indication, Uh, from covid vaccination. I think it was the Pfizer one because some people were experiencing, like, from both OSIs after the vaccination. So I was just going to go through what's a contra indication of caution and an adverse reaction. Um, so a contra indication for, uh, using the covid vaccination as an example would have been anaphylaxis, um, or an allergy to any of the vaccines ingredients, Um, and a history of thrombosis. Following a previous dose, a caution would be acute illness. Um, so if she'd been feeling under the weather, this would be a caution for receiving the vaccine rather than something that would be a contra indication, meaning that you wouldn't be able to have the vaccine. Um, and that was mainly to do with, um, the symptoms. Um, may be masking any side effects of the vaccination. Um, allergic reaction. So if you had experienced hives or angioedema again, that was a caution or myocarditis a caution. So these things don't mean that you can't have the vaccine? It's more that if you have the vaccine, you'll need to be monitored more closely. Um, but they weren't necessarily absolute contraindications for not receiving the vaccine. Um, and adverse reactions. Um, so a local reaction at the injection site is a little bit of redness, a little bit of tenderness, um, systemic reactions. So experiencing some tiredness, headache, muscle aches, um, a fever as well are just side effects of the vaccine and not reasons why you couldn't have the vaccine in the future. I hope that's clear. Um, so there was also an L0 about reporting adverse reactions, and this can be done through the yellow card scheme, and this serves as an early warning scheme for vaccine related safety concerns. Um, and people who have received the vaccine can report this through the website. Um, and also healthcare professionals. Um, so data collected through which of the following methods is commonly used for disease surveillance. Okay, so quite a few of you there have gone from D, which is the correct answer. Well done. Um, I haven't really made a slide on this, um, mainly because it was just a small L0 um, like a miniature ello within l 06. but statutory disease notification. Uh, there's a list of notifiable diseases which I will provide the link to, um and it's basically a healthcare professional's duty to report these if they see these come into their clinics. Um, and also, laboratories who process blood samples and things also have a duty to report these diseases if they come up. And then this allows, uh, public health, um, to surveil diseases. Okay, So Roger, a 76 year old patient has had a splenectomy due to complications of his lymphoma diagnosis. And prior to his surgery, he was up to date with all of his routine vaccinations following the splenectomy. Which vaccine will he now require? Every five years. So this is just testing your knowledge of when adults require vaccinations. All of them again. Okay, just quite a tricky question. I'll go through it. So a few of you have put e, which is the correct answer. Um, so this is about yeah, Like I said, immunization of individuals with medical conditions. Um, so this patient has had a splenectomy. Um, and the spleen plays a very important role in protecting against infection of the bloodstream by bacteria. Um, specifically encapsulated bacteria. So resident macrophages within the spleen removed encapsulated bacteria from the bloodstream. So if you remove the spleen, you're gonna struggle to do that. Um, and also marginal zone B cells, which are abundant in the spleen, but less so in, um, the lymph nodes are crucial for immune response to polysaccharide antigens, which are presidente on, uh, sorry present on encapsulated bacteria. Um, so the marginal zone B cells eventually produce anti capsular antibodies when there is infection by encapsulated bacteria. Uh, so it's crucial that Hispanic patient received vaccinations against such bacteria's, which includes pneumococcal and meningococcal. The reason why I haven't put meningococcal as the best answer here is because you don't require, um, this vaccine every five years. Um So this is the A splenic vaccine vaccine schedule. So for older Children, um, so from the ages 10 plus And adults, um, should receive, uh, the meningococcal vaccine here. Uh, men, B and men A C W y. If they haven't had that before, Um, an additional dose four weeks later. But that's them done for the meningococcal B vaccine there. And an annual influenza vaccine. Because if you get the flu as an a splenic patient, then you're at greater risk of bacterial infection. Um, so that was all of my questions. Thank you. Perfect. Stop sharing. So thank you so much for that, Alice. That was very detailed and in depth. And last but not least, we have Sophie, which is our preclinical deed for med, and she'll be presenting to you the last bit. So it's the final stretch. Um and yeah, just stay tuned for the feedback form, but take it away. I thank you. I've I'll be covering the last few ellos for this case, and they should. They're a little bit easier than all of the immunology. So hopefully it will help Just revise some of the important aspects of the pediatric section Um, first of all, I've got some, um, slides that will be on medal after we've done the feedback form that have, like, an overall a bit of information about some of the most important aspects of this these two ellos and also, um, some information, like some timelines for child development. Um, so hopefully that'll be useful for you in Eurovision. But because of time, we'll just move straight onto the SBA s. So if I start my can you see that? Okay. So are you in? Is that Is that okay? Perfect. Thank you. OK, we'll move to that SBS. So the first learning objective is about describing how the child vaccination program is organized and implemented, um, specifically within the UK. And so the first question Mr Jones presents to the GP with his one year old daughter. He appears very anxious about his daughter receiving her MMR vaccine, and most of all, he wants to know why she has to wait until she is three years and four months old for her next dose. Which of the following would be the best answer to this question? If you were the GP that had to answer this Oh, okay, so we've got some of you going for B and some for C. Okay, so the answer is B Well done. Um, so the MMR vaccine is an attenuated live virus, um, live virus vaccine, and it protects against mumps, measles and rubella. It's given 12 months old or after the 12 after the child's first birthday. And the second dose is that three years and four months, um, it can cause mild fever and rash around 6 to 12 days after the vaccination. And this is due to stimulation of the immune response. And this triggers the usual physiological processes. Um, and as it was mentioned before, we have the interferons, which are responsible for an antiviral response. And this is the reason that the two doses can't be given, um, quite quickly after each other. Um, so I think it might have already been mentioned earlier. But the antiviral state is triggered by, um, the activation of the interferons alpha and beta, which bind to the interferon receptor and start a signaling pathway which inhibits viral viral replication and also creates these gene products that can inhibit entry viruses into the cells, blocking further viral replication So if we were to give a child the MMR vaccine, Um, a week apart or separately? Um, the interferons would stop the virus. Is the vaccine from being effective as the aspects of the virus? The vaccine wouldn't be able to replicate. Sorry. Okay, does that? I hope that makes sense. The next question is a mother presents to her GP with her son, who is 16 months old for his scheduled immunizations. He's having the six in one vaccination and one other which of the following diseases with the other vaccination he receives on this day protect against. Okay, so we've got a few people going for E and some for B and some fatty nose. Uh, okay, well, in the poll there and move on to the answer. So the answer to this question is, um meningococcal Group B. And unfortunately, it's just quite a difficult thing to do. But there's just a lot to learn for the different vaccinations that are given at different times. So the I've put a little bit of a summary here. Um, some people prefer to learn this as a table, which you can do from the big post that I'm sure you've seen in your lectures, and but sometimes it's easier to just have a little summary like this. And so I wrote a virus usually given at eight weeks and 12 weeks. MMR is given out 12 months and three years and four months. Um, new a topical is given at 12 weeks and 12 months. Um, meningitis, B eight weeks and 12 and 16 weeks and pertussis at eight weeks, 12 weeks and 16 weeks. Um, so in this question, we had, um the, uh, child was 16 months old, So if we have a look back at this, um, sorry. 16 weeks old, it should have. Sorry. It should have been 16 weeks old. It was a meningococcal group B. So meningitis B. Sorry. That was me that confuse everyone there. Okay, Next question. Holly is eight weeks old and due to have her first immunizations. Her mother is very anxious and wants to know if she can wait until Holly's older before having these vaccines, the G p explains that the rotavirus vaccine in particular should be administered before 15 weeks. Which of the following is the best explanation for why this is the case? Oh, I'm sorry. Have we got a pole? We've got one person at the moment for B. OK, split between A and B at the moment. Okay, most of your gone for be. So if we end the pole and we'll move on to the explanation So the answer is B is less likely that the side effect of interception will, um interception will occur if the vaccine's start before 15 weeks. And so I've got a little bit of information about Rota. Virus is the cause of most gastroenteritis and young babies, and the symptoms are commonly watery. Diarrhea, vomiting, fever, and it can be very serious. Um, and 1 to 6 out of 100,000 babies vaccinated will be affected by the vaccine and develop into susceptive in where a part of the intestine mean slides into an adjacent part of the intestine that you can see in this diagram here. And, um, this is more likely to occur before 15 weeks. Um uh, sorry. After 15 weeks. So this is why it needs to be administered before the baby reaches this age. Josie is seven years old. Her parents bring her to her GP as she has been complaining of a headache and a runny nose. Her temperature is 39.6 degrees Celsius. On examination, she has a maculopapular rash and Koplik spots. Where would these spots usually be found? I think this was mentioned earlier on. So it's hopefully be a good provision for you. So on the inside of the cheeks, on the tongue, on the tonsils, in the eyes or around the s. Okay, most of you are getting this right, which is great. Okay, we'll end the polar, so most of you have gone for a, which is brilliant. Um, so it's usually found on the inside of the cheeks. Um, so in general, um, measles has the symptoms of high fever, cough, runny nose, which sometimes is described as Korisa and also conjunctive itis. The maculopapular rash usually appears around 3 to 5 days after the development of the first symptoms. So they seem to get these sort of like fever and cough and cold, normal common colds and, uh, symptoms tend to appear before the rash, and the rash looks like this. Um, the Koplik spots are small white spots which can have like a bluish white tin in the center, and they usually found on mucous membranes like inside the ***. Okay, next question. Alfie is six years old, and he has come to the GP with his mother for his yearly nasal flu spray. Which of the following would explain why the G P refused to administer the spray? So which one of these following options would be a Contra indication? Alfie had felt unwell for three days after the nasal flu spray Last year, the G P noticed that Alvey had a noticeable wheeze when breathing. Alfie's never had the nasal flu spray before. He has a temperature of 37.6 or he hasn't had any other vaccines as part of the childhood immunization program. Okay, so most of you are going to be at the moment. Well, enter that. So the answer was B and that the G P had noticed that Alfie had no school wheeze. And so the contra indications to the flu spray is any child with an impaired immune response. Any child that's gone active, we's and such as Children with severe asthma as well. And also, um, if a child is using um, antiviral therapy for influenza at the same time, they won't give it to so. And the side effects of the nasal flu spray are usually mild, and they don't last too long. Um so that's why Alfie being on well for a few days after receiving the spray last year wouldn't be a contra indication, Um, such as having a runny or blocked nose, a headache, tiredness, loss of appetite. Um, those are all normal side effects from the flu spray. Another important point to note that. Remember talking about in case last year, is there any Children receiving the spray? Should have voiced close contact with people with immune weakened immune symptoms for two weeks after the vaccination. Um, so those undergoing chemotherapy or anyone on immune suppressants Anyone isolating in preparation for a transplant, anything like that would be important to stay away from them for two weeks. Okay. And the final L0. Thank you for staying for this long, um, is to outline the key stages in normal child development from not to five years and also the general principles of developmental examination. So the first question, um, these It can be quite tricky to know the different developmental milestones, so hopefully the timelines I've put on the slide to be helpful. Um, but I think for me the best thing was just keep doing questions on them, and these tend to sort of sink in a little bit more. Um, so James's 19 months old, however, his mother is concerned that he's not hitting his develop Mild developmental milestones. Which of the following would be a red flag for James? Um so at his age, So being unable to walk, being unable to jump, being unable to make a tower of six building blocks, being unable to join two or more words to make a simple phrase or not being potty or toilet trained. Yet great people are going for a excellent Okay, so the correct answer is a not being able to walk. So developmental milestones are divided into four functional areas, which are gross motor vision and fine motor hearing speech and language, social, emotional and behavioural. Um, I've just popped this on there cause I found this quite useful my vision last year, and it's quite useful for working out and what the red flags would be. And sometimes that will help in exams as well. If you know when it would be a red flag for a child and, for example, not to be smiling or, um, not to be speaking. Yeah, you can sort of work out a ballpark of what their developmental milestone should be next or what they've missed so far. Um, So I've just put this on there for you to have a look at, um, when you get the slides. But for the motor milestones, I've taken this from the lecture. I found this quite useful. Um, so if we have a look, James was 19 months old, so you can see here. That would be a red flag for him not to be walking at 18 months. Um, so that's why this was the correct answer. Okay, Next question. Uh, Susie wants to know at what age her baby should start saying some words such as Mama Dada juice, those sorts of words. Which of the following would be the best answer for Suzy if you were the GP explaining this to her, Okay, it's quite split is quite tricky. Okay, so we split between C d and e. Okay, well, in the polar. So the answer is, um, 7 to 12 months. Um, so with speech, I've got a little summary here, and I haven't put a timeline for it, but this is, um, from the beginning of the examples at the beginning of the presentation. But the this is a speech summary. Um, so from not to three months, baby should be able to react a lot of noises from 4 to 6 months. They should be able to follow sounds with their eyes and sort of pay attention to music a little bit more from seven months to a year. They should be able to understand common words and, um, say one or two words like Mama Dada dog. So this would be the answer to our question here. So between and seven and 12 months, um, from 1 to 2 years, they should start learning different parts of the body and start picking up words a lot more often start getting more words into their vocabulary and also start putting some words together from 2 to 3. They should be able to start saying sentences that have more words in them and more than four, and between four and five. And they should be able to understand most of what said at home and and new sentences that give many details. Um, it can sound quite vague when you go through the list like that, But if you sometimes I find it helpful if you've known any Children as well, um, any like younger siblings or cousins, nieces, nephews, that sort of thing? If you can sort of think back to what they were doing at different times, I find that quite helpful, especially in exams and a sort of a last resort. If you can't remember, um, but also importantly, if parents are concerned, or any family members or guardians are concerned, their child isn't meeting their developmental milestones. And the health visitor is a really good port of call for that. And they can give advice to parents with different exercises or activities that would be able to help the child. And if they with specific to speech and language, if they're unable to improve from the advice the health visitor has given, they can also be referred to speech and language therapy. Okay, next question. Doctor Jones is testing the reflexes of a five day old baby. She strokes the corner of the baby's mouth and the baby turns their head towards the stroking and opens their mouth. What is the name of this birth reflex? So we've got grasp reflex stepping, reflex, supporting reflex, more a reflex and routing reflex. Okay, lots of people going for E. She's brilliant. Okay, we'll move on to the explanation, so the answer is a routing reflex. Um, I did have a video for this. I might. I'll try and find it and play at the end. And for me, it really helps. There's lots of videos on YouTube that have, like a quick one minute, 32nd video that shows the baby doing the reflex, and I found that quite helpful. There's also a really useful table here, and that goes through all of the different types of reflexes. Um, so the more, oh, reflex. You can test this by extending the baby's neck and if they then extend and then flex their arms and legs and this is like a positive reflex, and it will show that the baby still has this, um, ni NIH should have all of these reflexes. Known as primitive reflexes or birth reflexes. They typically disappear between 4 to 6 months of age. And and if these reflexes persevere as the child is older, um, it can indicate a neurological issue. And this can go because by trauma, such as during birth or after, um, or um, as a baby gets a little bit older from it's sort of like first month. If there's a a lack of sort of tummy time or opportunities for the baby to lay on their front, these can persist for a bit longer. And and the perseverance of primitive reflexes can also be associated with disorders such as autism and a D. H d. Um, I'll leave this table here for you to look through once you get the slides to go through each reflex. But the right answer for this was that a stimulus is placed near the edge of the baby's mouth and the baby turn their head towards the stimulus, and and that is a routing reflex. Um, and this is mainly for, um, like a primitive reflexes for babies to be able to breastfeed. If the reflexes do persist, um, Children can go through a vision therapy program, which is a program of exercises to improve the maturation of a baby's brain and their neural pathways. And the way this works is using rhythmic movement training techniques that mimic how an infant would move as they develop. And it helps Children to be able to integrate the retained reflexes into their usual movements. Um, I don't think you need to know too much about it. But just to know that the Visual vision therapy program is really useful for helping babies that have, um, these reflexes persisting. Okay, Next question. Which of the following is the most important step when examining a child and their development so you can observe the child playing? Ask the child questions and note how they respond to you. Observe the child walking, ask the parents about their child or test the child's reflexes. Okay, so we're split 50 50 between A and D. We'll move on to the explanation. So the answer is D, asking the parents about their child and even the half of you went for observing the child playing. That is still a really good answer. However, the best answer here was asking the parents about their child. Um, so during a developmental examination, it's important to text the four functional areas. Gross motor vision and fine motor hearing, speech and language, and also the social, emotional, behavioral and aspects of a child's development. And within this examination, it's really important to us, the parents about their child and the milestones that they've already hit. And, um, more specifically, you can ask them if they're developing at a similar rate to how they're older. Siblings have developed, or also how the other Children in their class are getting on, because in one of these development examinations, you have quite a limited time with the child. And it's very difficult to see um, like the whole the whole picture about their development, without knowing how they've been over a more longer term period. But observing the child playing with toys walking around the room can be really helpful and also will make the child feel much more comfortable. So there'll be more respect receptive when you ask them to do specific things, Um, such as like asking them to walk so you can assess that or, um asking them to complete different actions or activities. Okay, and next is a growth chart question. So on Maddie's growth chart, there is a small dip in her chart around two years of age. Which of the following is the most likely explanation? So the the child could be malnourished? Is there a change in the way the child is measured? At two years? The child is naturally short. The the child has a chronic disease or the child was born prematurely. Oh, excellent. Lots of you going for B. Great. Okay, So B is the correct answer. There is a change in the way the child is measured at two years. And so I've got a bit more information here about growth charts, but specifically at two years before Before this, uh, babies are measured laying down a length ways. But at two years, the child is measured standing, which causes compression of the like, the vertebrae. So it seems like the child just from looking at the growth chart, has become shorter or not as long. But really, it's just the change in the way that the child is measured. Um gives the appearance of a dip in the growth chart, and that's something really important to be aware of. Um, because there could be a change in the center aisle that that child is growing out. And it's important to know that that isn't being caused by any chronic disease or any impact that the child has been born prematurely or anything like that. That it could be just from the way that the growth chart is measured. And you would be able to tell the as well by comparing what cental that child is measuring at before two years and also from afterwards. Um, so if there is an abnormality or if the child is measuring much smaller or much taller, um, you would be able to sort of assess that and determine whether this has changed before the two years or afterwards. Um, so growth charts are produced from by comparison with data obtained from a normal population. Um, and this is described as a stock definition as healthy, non deprived, breast fed Children of mothers who did not smoke. Um, and these are done from age two weeks to four years. Um, and the key factors that determine growth our genetics, um, sex of the child and also in the first two years, nutrition is the main factor. But over two years of age, hormones such as growth hormones and thyroxine are really important. And then during puberty, um, sex hormone moans takeover and become the main factor in determining growth. And that's quite important fact to remember from, um, one of the tutorials that we had Um, there's also, um, sorry. It's a bit a bit of a squash growth chart, but for corrected measurement for premature babies, it's another important thing to note that if a child is born prematurely, you measure their, um, Lenk slightly different on and weight on the growth chart. So, uh, an example here, the measurement was taken when the baby was 14 weeks old, but they were born eight weeks premature. So you draw the little dot at the actual age of the, uh, baby the number of weeks since they were born. But then you can also draw another dot with an arrow towards it as um what the age of the baby would be if they hadn't been born prematurely. And they've been born on their due date. Um, so you would just go backwards if that makes sense. So this baby was born at, um, this measurement was taken at 14 weeks old, but the baby was born eight weeks premature. So you would make the second measurement at four weeks. Sorry. Six weeks. Okay, that's the end of my