 Okay. Yung hindi naman siya itim as in the entire screen kita. Yes sir, kita po. Okay. Sige-sige. Daddy, you can record this now and then just inform us if we're already. Okay. So again, good afternoon. Good morning to everybody. So for today, we'll be continuing our discussion on your innate immune system. Okay. We'll be discussing your innate immune system. For today, we'll have a quick review first of what we discussed last time. Okay. By the way, can you guys hear that my dogs, naririnig nga ba yung dogs? Pwede nga pa-comment kung naririnig. No naman po sir. No? Okay. So masapay siya sa akin eh? Okay. So last time we talked about the different cells involved in your innate immune system being your neutrophil, your basophil, eosinophils, and then your monocytes, your macrophages. Also your dendritic cell. And for today, we'll be discussing the last cell included in your innate immune system, which are your natural killer cells. But before we go there, let's also have a quick review first of your phagocytosis. Okay. So last time we talked about phagocytosis and we talked about the different stages of phagocytosis. So last time, this is coming from Stevens. Okay. The picture I'm presenting to you now is coming from Stevens. So as you all remember, the first stage in your phagocytosis is technically your adherence. So our body will be producing proteins and soluble compounds that will help your phagocytes adhere to that antigen. So for example, in this case, we have an extracellular bacteria. So your bacteria now, okay, your bacteria will now be captured by your phagocyte. So as you all know, there is a process called opsonization that will enhance your phagocytosis. So there are various types or various examples of opsonins, these are soluble compounds that allow opsonization to happen. So once that your phagocyte is now already adhered to the bacterial cell, it will now start to have its pseudopods. Okay. The pseudopods is now a signal that engulfment will be starting to happen. So during engulfment, okay, during engulfment, there will now be information of your phagosome. Your phagosome is where your microorganism will be located at, okay, once that you have your, once that phagocytosis happens, okay. Now when phagosome is already inside your cell, your lysosomes in return will try to fuse with them. So this is now your fusion. In your fusion, the lysosomes, okay, will fuse with your phagosome, forming your phagolysosome, where your digestive enzymes will be released, okay. Your digestive enzymes will be, again, released. So once that your enzymes, your digestive enzymes are released, your digestion and destruction will now start to happen. So in digestion, once that it already finished, your bacterial debris, the debris from the phagocytosis will now be excreted through exocytosis, okay. It will now be excreted through exocytosis. So moving forward, let's just have a quick review first of what happened inside your phagolysosome. So inside your phagolysosome, there can be two mechanism on how your phagocytosis eliminate your organism. So what are those two? I think I already mentioned this last time, okay. It is through the process of oxygen-dependent, oxygen-dependent processes. And it can also be through oxygen-independent processes, okay. Oxygen-dependent processes and oxygen-independent processes. So oxygen-dependent processes is where reactive oxygen species will be produced inside your cell. And in return, this will now be the one to destroy, okay. It will be the one to destroy the bacterial cell wall so that it can be lies and it could be digested and it could be destroyed by your phagocytosis. Aside from oxygen-dependent processes, there can also be oxygen-independent processes. This time, we do not need your not ph-oxidase enzyme anymore because we simply have your different scenes in your ketepsyin G. So they are the one that will elicit the elimination and the digestion of your antigen. So antigen being a bacterial cell or other protein that our phagocyt had encountered. So here, as you can see, you have your not ph-oxidase, okay. Your not ph-oxidase. Remember, your not ph-oxidase came from your HMP, your hexose monophosphate, Sean, okay. So now that you have your not ph-oxidase, your reduced not ph, okay. Your reduced not ph, it will now form superoxides, okay. Superoxide and other other reactive oxygen molecules or species that will again destroy the cell wall of your bacteria, okay. Or your cell or any invading cell that enters our body. Now, okay, this is the normal scenario that happens inside our body. But then again, there are also diseases that can be associated with phagocytosis, okay. So what are those diseases associated with phagocytosis? The first one being your chronic granulomatous disease. In your chronic granulomatous disease, it is a disease that is characterized by the absence of your not ph-oxidase. So because your body or your cells doesn't have your not ph-oxidase, they cannot perform the oxygen-dependent processes for the elimination and digestion of your antigen. And to tell you, this is actually the most common one that is being done inside our body. So most of your macrophages, especially your macrophages, they do have your not ph-oxidase that allows them to digest and destroy the bacteria or the antigen that they engulf. So in your chronic granulomatous disease, we'll have a separate slide for that later. But aside from your CGD or your chronic granulomatous disease, because of the absence of your not ph-oxidase, please add this to your note. In your chronic granulomatous disease, there is persistent bacterial infection among these patient, okay. Because again, your body or your phagocytes cannot address the bacteria or cannot destroy the bacteria. Your bacteria will start to persist or will start to survive inside your body, okay. So aside from chronic granulomatous disease, we also have your lazy leukocyte syndrome. In your lazy leukocyte syndrome, again, there are two types of activity or movement when it comes to our neutrophils. So there is a random movement. So remember, just like what we told last time during phagocytosis, your leukocytes or your right blood cells, they are moving all throughout your body in random manner. So some will go to the left or the right, but they will follow the blood flow of your, of course, of your system. Now, when it comes to, when it comes to infection, there will now be the release of your chemotoxins to be specific, your positive chemotoxin that will stimulate or will trigger your chemotoxins. Now, when chemotoxins happens originally or ideally, this neutrophils or this leukocyte should be responding to the positive chemotoxin. Dapat kung sang papunta yung chemotoxin or kung sang sila tinatawag, they should be going there. Now, the problem is if your cells or your neutrophils does not respond to the chemotoxins or they have abnormal chemotactic activity and they also have abnormal random activity, the disease now or the syndrome now is what we call your lazy leukocyte syndrome. Again, lazy leukocyte syndrome. So remember, in your lazy leukocyte syndrome, you have abnormal random and chemotactic activity. Okay, random and chemotactic activity of your neutrophils are both abnormal. Now, we also have your jobs syndrome. Your job syndrome is also very much similar with your lazy leukocyte because it does involve a particular WBC which are your neutrophils. In your job syndrome, the random activity is normal. Again, the random activity of your cells are normal, but the one abnormal now is your chemotactic activity. So in job syndrome, when infection is already happening inside your body, your cells cannot respond to the chemotactic activity. The chemotoxins that are being released in your body. So in short, hindi nakakarating yung mga neutrophils natin dun sa site of infection. Okay? So are we clear so far? Can I see a raise of money for clear so far? Okay. So if you have any questions, by the way, you can type it in on the chat box and then I can address that or email me so that I can address your questions as soon as possible. Now, just a quick review, baka you guys forgot, remember that when it comes to your lazy leukocyte syndrome and your job syndrome, we can make use of your boyden chamber assay or your boyden chamber test because this particular test will now allow us to study if your neutrophils are having abnormal or normal chemotactic and random activities. Okay? So now when it comes to your chronic granulomatous disease naman, we can actually diagnose or we can actually identify the absence of your natph oxidase production through the test called your nitro-blue tetrazolium test. Okay? So again, your chronic granulomatous disease affects your neutrophil, microbicidal action. Okay? So meaning to say, they are incapable of killing your ingested microorganism. Okay? So they just engulf it but they cannot destroy it. Okay? So again, that is because of the impaired natph oxidase production. Now, for our test, we are using your nitro-blue tetrazolium. Remember, ladies and gentlemen, that your nitro-blue tetrazolium is colorless by default. Okay? Colorless puyan. Okay? Now, if there is, I want everybody to listen carefully, no? There is a presence, okay? If your natph oxidase is present, that colorless nitro-blue tetrazolium will now form your blue precipitate. Okay? Again, if you have your natph oxidase, that colorless color, that colorless nitro-blue tetrazolium will form your blue precipitate. Okay? So here, you can see that there is no presence of your blue precipitate. That is a negative nitro-blue tetrazolium test that will signify the presence of your chronic granulomatous disease. Now, for your positive results, you can see the blue precipitate forming in your stem. Okay? Remember ha, that your nitro-blue tetrazolium was reduced. Okay? There's a reduction that happened because of the product of your natph oxidase. Remember di ba dito? Your natph oxidase will form your superoxide, forming your hydrogen peroxide, your hydroxyl radical, and also oxygen and water. Okay? Now, because of these ang product, specifically your hydrogen peroxide, okay, your nitro-blue tetrazolium has been reduced. Now, forming your blue precipitate. Okay? So that's how you check your chronic granulomatous disease. Aside from your nitro-blue tetrazolium test, there's also another test we can do, okay, to identify your chronic granulomatous disease. And that is through your flow cytometric acid or your flow cytometry. So this is a new procedure to diagnose your chronic granulomatous disease. It is said to be more objective and it is quantitative. Because in your nitro-blue tetrazolium test, you just identify the absence or the presence of the blue precipitate. Okay? Again, the absence or the presence of your blue precipitate. So you just technically report a positive or negative result. But then again, you would want to quantify that. You would want to quantify the extent of your cells that are affected by this disease. Now, we can use your flow cytometric acid. And your flow cytometric acid, your neutrophils will now be labeled by your dihydrorodamine, your DHR. So remember, this is a dye that will be attached or that will be bound to your neutrophils. Now, kapag yung dihydrorodamine natin is already labeled or is already attached to your neutrophil, we will be activating your neutrophil. Why do we need to activate your neutrophil? We need to activate your neutrophil so that your NADPH oxidase could be released. Okay? And how do we do that? We activate your neutrophil through the help of your four-ball meristate acetate or your PMA. Now, your four-ball meristate acetate will be added to the solution. And afterwards, since this is a flow cytometric acid, we will be checking the fluorescence of your cell. So patient with chronic granulomatous disease would have less fluorescence. Why would they have less fluorescence? Because there were not enough NADPH oxidase that will react with your dihydrorodamine. Okay? So yun nyo ano natin, okay? That is what we do with your flow cytometric acid. So are there any questions so far when it comes to that nitroblutetrazolyum test and your flow cytometric acid? If there's no question, can I see a raise of hand please? If there are no questions, okay. Thank you so much. Now moving forward, okay. Now moving forward. An important, we always say that phagocytosis is important. But your phagocytosis is as equally important as your inflammation. Okay? Sir, is inflammation good for my body? The truth is, it is good for your body. Again, it becomes a problem when the inflammation becomes uncontrolled and the inflammation becomes systemic. Usually, the inflammation, for example, you have your wound in your hand. Usually, it's localized. Yung hands mo lang yung affected. But when it becomes systemic because of your hyper-lead triggered immune system, then that would lead now to more serious problems when it comes to your immune system. But again, remember that your inflammation is good because it only wants to arrest what is happening inside your body. Okay? Pag may infection, if there's injury, inflammation, only the only aim of inflammation is to help in your recovery and in your immune response. That's why hopefully you're still following me with your book. Okay? So we're going to talk about inflammation for today before we go to your natural killer cells. Remember that your inflammation is the overall reaction of your body to your tissue injury or invasion. Invasion of what? Invasion of your infectious agents or your microorganisms. Again, the primary purpose of your inflammation is to attract more phagocytes to the site of injury. Because during inflammation, there are various positive chemotoxins that are being released so that we can recruit more phagocytes into the site of infection or to the site of injury. So remember ha? Your inflammation is both a humoral and a cellular process. It involves both your humoral and your cellular component. Humoral in a sense that because it will be secreting your chemotoxins, your interleukin so that we can recruit more cells into the site of injury. And of course, having said that, there are also the involvement of your cells. Now, cells that will perform your phagocytosis and cells that will also be responsible in the repair of that injury. Okay? Now, having said that ladies and gentlemen, I guess you are very much familiar with the five cardinal signs of your inflammation. Which are your robot, tumor, calor, dolor, and functiona or your function, laser, or loss of function. So when we say robot, this is the redness of the site. The redness of a site is because of the increased blood flow. Okay? There is an increased blood flow because of vasodilation. Vasodilation because of the different humoral components that have been released from your body. So remember when there is robot, there is redness in the site of injury. And that redness is because of increased blood flow. Again, why is it, why do we have an increased blood flow? We have an increased blood flow that is because of your vasodilation. Now, the bigger question is, why is there a need for increased blood flow or vasodilation? Please write this down. That is to recruit more cells. Okay? More phagocytes. And since we're talking about hematology too in this semester as well, it will also help in the recruitment of more platelets into the site of injury if that is an open wound. Okay? But remember robot, that is redness, that is because of increased blood flow. Now, we also have your tumor. Okay? Tumor or your swelling. This is now due to the accumulation or the exudation of fluid in that particular part of your body. Tumor or swelling is because of the release of different tissue fluid and the accumulation of those in the site of injury. Now, aside from that, we also have your calor, calor or the presence of heat. Okay? Heat, it is also because of your increased blood flow. Okay? Increased blood flow, exudation of fluid, and of course the release of your mediators. Okay? There are different mediators, specifically your interleukins that causes an increase in the temperature, but in the temperature sometimes not only of the localized site, but also of your entire body. That's why did you know guys that fever is actually an immune response. The presence of fever, okay, is that there are reasons why we have fever is to increase obviously your body temperature. We need to increase your body temperature. Remember in your bacteriology before last semester, your bacteria, most of your pathogenic bacteria thrives at our normal body temperature, which is 37 degree Celsius. Now, your 37 degree Celsius would need to be increased so that these pathologic or pathogenic or infectious agent will not survive inside our body. Okay? So remember that, okay? Remember that your heat actually is an immune response. Okay? The increased heat is actually an immune response. Now aside from heat, we also have your dolor, okay? Dolor, which is the presence of pain. So pain is the physiologic rationale for pain is that your stretching pain receptors and nerves because of your inflammatory exudate or chemical mediator. So remember, di ba you have the exudation of your fluid? Because of the exudation of your fluid, there are some nerves that are being pressed on or that are being affected leading now to the presence of pain or dolor. And lastly, we have your loss of function or functionalisa. This is because of your pain and the disruption of your tissue structure, especially if you have a massive or a big injury that is present. So there will really be a loss of function in that particular area. Okay? So remember that, okay? Dolor, functionalisa. So please remember what does they mean so that is redness, swelling, heat pain and loss of function respectively. Okay? Now, similarly, okay? Similarly to your phagocytosis, okay? Similarly to your phagocytosis, there are also stages of your inflammation. So there are three major stages. The first stage in your inflammation is your vascular response. In your vascular response, this is now the release of your histamine. Your mast cell, remember your mast cell, okay? They will be releasing your histamine. And that histamine will now be an active vasodilator. Okay? So again, please write it down on your notes. Remember that when there is injury, a lot of cells will be recruited into the site of injury. One of those are your mast cell. Your mast cell now will be releasing your histamine. Your histamine, a vasodilator, will again increase your blood flow and will increase your capillary permeability. Okay? Your capillary permeability. Now, the capillary permeability would now be the result of your capillary permeability will now be your swelling. Okay? That is because magilig out na yung mga tissue fluid out of your cells. Next, we also have your vascular, we also have your cellular response. So in your cellular response, we have now your neutrophils and your macrophages. So they will be recruited to your, they will be recruited to the site of injury. So the first to migrate, sabi ko nga sa inyo, the first to migrate are your neutrophils. Okay? And the second to migrate are your macrophages. Technically, we call them macrophages already because once that they go out of your, once that they go out of your blood vessel, they will now become macrophages. Again, what do we call the process of your cells traversing your blood vessel? What do we call the process whereby your cells goes out of your blood vessel? Okay? I'll give you five seconds. Five, four, three, two, one. Okay? That is what we call your, your diapidesis. Okay? That is what we call your diapidesis. So your diapidesis is the process whereby your cells goes out of your blood vessel. Okay? And your cellular response, a final, a final response, event or a final stage will happen, which is your resolution and repair. In your resolution and repair, this is usually initiated by your fibroblast proliferation. Okay? Your fibroblast is our stem cells that are found usually on your tissue whereby sa kanila yung new cells that will participate in the repair. Okay? So remember, ha, there are, I just want to mention two, na two pala, just one. Okay? A while back I was mentioning about your interleukin that causes your, that causes heat or that causes an increase in your body temperature that is your interleukin one. Okay? Stimulate or recruit the migration of your lymphocytes or T cells that is for next meetings discussion. Okay? And aside from that, it is also a pyrogen, okay? A pyrogenic interleukin meaning to say they increase your body temperature. Okay? That is your interleukin one. So just to visualize, this is what's happened. Okay? So once that there's injury, there will be capillary widening or your vasodilation and increased capillary permeability. Okay? The capillary widening or your vasodilation will result to an increased blood flow. Your increased capillary permeability, I hope you're following my laser. The increased capillary permeability will result to a release of your fluid. That is now your tumor. Aside from that, there will now be an attraction of your white blood cell that is because of your chemotaxins. So as you can see, we have cells that are undergoing diapidesis and they will now migrate to the site of injury. And now as a systemic response, okay, there will now be fever and proliferation of more white blood cells. So this is now your color. Okay? This is now your color whereby it is initiated by your interleukin one. Okay? Your interleukin one. Now finally, please do remember the five cardinal signs of inflammation. We have heat, we have redness, swelling, pain, and loss of function. So those are the five cardinal signs of inflammation. Are there any questions so far? Can I see a raise of hand if there are no questions? Okay, there are no questions. So now let us proceed to our next discussion which will now be about your natural killer cells. Okay? So as you all know guys, remember that one of the things that we highlighted during phagocytosis is the fact that your phagocytosis is only for your extracellular pathogen, extracellular antigen. Now the big question is, sir, if our phagocytes are only capable of killing extracellular pathogen, what happens now if I have an internal or an intracellular pathogen within my cell? Okay? And we're still, guys, let us just try to be on the same page. We're still on your innate immune system. Meaning to say, we are talking about cells that are naturally found inside your body. Okay? Naturally found inside your body and their role is in your innate immune system. Okay? I hope we're clear with that. Now, we have your natural killer cells. Okay? Your natural killer cells was first thought to be part of your adaptive immunity. Why, sir? Because if we're going to look at the hematopoietic lineage of your natural killer cells, your natural killer cells, unlike your neutrophil, AO, baso, and monocyte, they all came from your common myeloid progenitor or your common myeloid lineage. Unlike your natural killer cells, your natural killer cells actually branch out from your common lymphoid progenitor. Okay? It came from your common lymphoid progenitor, the lineage where your B cell and your T cell are produced. Okay? Now, the reason why we are going to talk about your natural killer cell is because just as we need your phagocytosis to arrest the extracellular pathogens, we also need your natural killer cell to arrest those that are intracellularly invading our body. Okay? These are now your intracellular pathogen, and not only that, this also involves abnormal cells of your body, abnormal cells such as your tumor cells, and even your cells that should be undergoing apoptosis already. Okay? Now, what is the action of your natural killer cell? Your natural killer cell, ladies and gentlemen, are your first line of defense against your intracellular organisms and even your tumor cells. Intracellular organisms such as your viruses or other parasite in other bacteria, and also your tumor cells. We say that it is the first line of defense because it is part of your innate immune system. Now, your natural killer cell has this unique ability among all the innate cellular components, again, I want to be clear, among the innate immune cells, among the innate cellular components of your natural immunity, they have the ability to kill target cells without prior exposure to them. Okay? Sir, what do you mean by prior exposure? Remember that your lymphocyte, to be more specific, your cytotoxic T cell, do not worry, will be discussing that on our next discussion, okay? We'll be having that on our next meeting, the different types of your lymphocyte. Your cytotoxic T cell can kill any cell, any cells from your body and also any antigen, parasite that comes inside your body. But your cytotoxic T cell needs prior exposure. That is now what we're going to talk about when we discuss your antigen presentation. Are we clear? Can I raise your hand? So in your cytotoxic T cell, okay, thank you. In your cytotoxic T cell, they need antigen presentation. So meaning to say, somebody needs to introduce something or your cell, your antigen presenting cell, needs to introduce the antigen first before your cytotoxic T cell can kill them or can identify them, right? That's how it happens in your antigen presentation, which we'll be discussing separately when we go to your adaptive immune system. I opted to put that on your adaptive immune system because it doesn't have any relation at all to your innate immune system. Although some of your innate cells or your innate cellular component like your macrophage and your dendritic cell, they are the one that presents the antigen, okay? Mag-going back to your natural killer cell. Your natural killer cells, okay? Your natural killer cell. Once that they identify that the cell is infected by virus, virally infected, or if these cells are abnormal, they can immediately kill them at first interaction. How? How do they do that, okay? How do they do that? But before I go further, no? There are around 10 to 15% natural killer cells inside your body. An na isingit ko lang yan. Okay, now, how does our body or how does your natural killer cells identify the cells to kill? How do they know that this is a virally infected cell? How do they know that this is a tumor cell? Simple. They have their receptors. And one of the most important receptors that are found in your natural killer cell are your CD16 and your CD56. Sir, why did you highlight that CD16 later? Your CD56 is just an identifier for your, it's just an identifier for your identifying protein for your natural killer cell, okay? Again, we'll get to identify your CD, we'll get to identify your natural killer cells because of the presence of your CD16 and your CD56. Again, CD16 and your CD56, okay? Again, these are their identification tags, CD16 and CD56. Aside from that, okay? Your CD16 is also a receptor for your antibodies. So please write that down on your notes, okay? Your CD16 is a receptor for your antibodies, okay? Again, a receptor for your antibodies. I'll explain that later when we go to the antigen-dependent killing or the antigen-dependent cell cytotoxicity of your natural killer cells. But in general, the reason why your natural killer cells are very much powerful and are able to kill your target cell that is because they possess enzymes such as your granzymes and your perforins, okay? They do contain your granzymes and your perforins. One moment langa, one moment, okay? So again, your natural killer cells, they do contain your granzymes and your perforins. Your granzymes and perforins are very potent enzymes that are being released by your natural killer cells so that they can kill the bacteria, okay? They can kill the bacteria. Now, before I move forward, I also would like to include in this discussion your interleukin-15, okay? Your interleukin-15 is an important interleukin of your natural killer cell development, okay? Again, how do you not get confused? CD-16 is the one found on your cell as a receptor. Your interleukin-15-15 is a cytokine that is important for the development of your natural killer cells. Can I see a raise of hand for clear, please? Okay, good. Now, moving forward, okay? Let's talk about your enzymes, okay? There are two enzymes expressed exclusively on your natural killer cells and another cell, which are your cytotoxic T-cell. Okay? Your cytotoxic T-cell and your natural killer cell, they are the only two cells that possess your granzymes and your perforins, okay? Your granzymes, okay, they induce your programmed cell death in your target cell and this is what we call your apoptosis, okay? They induce your apoptosis. That's why not only can natural killer cell arrest your virally infected cell and your tumor cell, even yung mga old cells ninyo in the body that needs to go, okay? That needs to go. They will just simply release your granzymes, okay? They will just simply release your granzymes and they can induce your cell death or your programmed cell death or what we call your apoptosis. Aside from that, we also have your perforins, okay? Your perforins is a membrane disrupting protein. It is a membrane disrupting protein that will form pores or holes in your cell wall, okay? Or the cell membrane, rather, they will form holes or pores in the cell membrane of your cell and once that happen, everything that is located inside your cell will start to leak out, okay? Will start to already leak out, okay? So, are we clear so far when it comes to granzymes and perforins? Can I see a race of handing for clear? Now, moving forward, okay? Moving forward, let's proceed to our... Let's now proceed to how your cells, okay? Let's now proceed to how your cells, okay? How your cells... Wait lang. Okay, how your cells are specifically your natural killer cell perform their function. So, sabi ko nga kanina, haven't you wondered how your natural killer cells identify that this cell is our own and this cell is a target cell that needs to be killed. So, here, you can see this on your Stevens. So, there are two receptors, okay? There are actually two receptors found on your natural killer cell. This is aside from your... This is aside from your CD16 and CD56, okay? Again, aside from your CD16 and your CD56, there are other receptors found on your natural killer cells, pa. What are those? Very simple lang yung name nila. These are your activating and your inhibitory receptors, okay? Your activating and your inhibitory receptors. As you can see on this figure, the inhibitory receptors are your... are colored red and activating receptors are the one colored green, okay? We're only gonna talk about A and B for this particular slide, okay? In your A, we have your antibody independent cell cytotoxicity. Meaning to say, there are no antibodies involved. It's really just your cell, okay? Your natural killer cells and the target cell that will come into contact, okay? As you can see in figure letter A, we have your natural killer cell and your natural killer cell, okay, was bound to this protein. This protein that you see here the one I'm pointing at my laser right now, I hope everybody is looking at your screen. This protein that you see on your target supposedly target cell, these are your major histocompatibility complex, okay? These are your major histocompatibility major histocompatibility complex protein, okay? Major histocompatibility complex protein that are found on your cells. These are usually found on normal cells. All cells of your body, all nucleated cells of your body has your MHC. Your major histocompatibility complex antigen or your HLA antigen, okay? They're one and the same. Now, because of the presence of this protein it will now send a signal an inhibitory signal to your natural killer cell. Again, because of the MHC interacting with your inhibitory receptor, okay? Inhibition will happen and there will be no killing, okay? There will be no killing. Now this happens to your normal cells. Kaya hindi sila napapatay. Kaya hindi sila na de-destroy ng natural killer cells natin is because of this phenomenon. Now, what happened if there is a virally infected cell now inside my body? Let's go to letter C. Okay? This again is antibody independent. There is no antibody involved yet. Okay? Now your virally infected cell as you can see um, they will start because they hijack, okay? Because they hijack your DNA machinery they will also be producing proteins proteins that are usually not found in your normal cells. Now this virally infected cell produce proteins okay and are now express on their membrane, okay? And as you can see this natural killer cell will try to inspect. I inspect lang natin. Do you have the MHC? You do not have the MHC. Okay? Walado MHC. Now, because there is no MHC or HLA antigen present on this cell it will now start okay? It will now start to bind to the unknown proteins and that will now signal or that will now send an activation signal okay? An activating signal to your natural killer cell and want that activation of your natural killer cell happens. What will what will be the next what will be the next happening in your in your system? It will now release your granzymes and your perforines leading now to the apoptosis of your virally infected target cell. Ken, did you get the difference between the two? You have two genes the inhibitory and the activating gene or rather the inhibitory in your activating receptor okay? Want that it sends an inhibitory signal because of the presence of your HLA antigen or your major is the compatibility complex antigen it will not result to the destruction or the killing of your cell but once there that activation of your natural killer cell happens once that the virally infected target cell is encountered it will release granzymes and perforines and will lead to apoptosis are we clear so far? okay? so thank you so much now that is just one way okay? that is just one way of how your um how your um natural killer cells that is just one way of how your natural killer cells identify and kill the target cell so aside from that they also do your antibody dependent cell cytotoxicity what does it mean? okay? eto yung letter B okay? now before I explain this part okay it's very important to get to know your antibody first okay? your antibody ladies and gentlemen also known as your immunoglobulins has different classes okay? about that yet today okay? um I just want to highlight two important parts of your antibody yes your antibody are very small proteins but they do have different parts as well do not worry because we'll be discussing this um as we go along this preliminary period okay? now what are the two parts of the antibody that I want to highlight? okay two things we have the fab region hopefully everybody's looking at the screen right now and not doing anything else okay? we have the fab region and we have the FC region okay? your fab region ladies and gentlemen okay? your fab region is where the antigen attaches okay? take for example you have your bacteria the Y shape there the fab region that is where the bacteria will attach to okay? that is where the bacteria the pyrocyte or any antigen will attach to that is what we call your fab region now aside from the fab region we also have your FC region specifically the other end of your antibody your FC region is where your complement will bind and this is also the very same position in your antibody where your CD16 okay? remember ang sinabi ko kanina this one your CD16 okay? this is where your CD16 will attach to okay? again your FC region okay? your FC region is where your CD16 will attach to okay? sabi natin kanina CD16 is a tag to identify your natural killer cells CD16 and CD56 now when it comes to antibody dependent cell type toxicity we will now have your CD16 bound to the FC region of your antibody so that your natural killer cells can get activated now hold your horses we will try to explain it step by step little by little so that you can understand how your antibody dependent cell cytotoxicity happen again ladies and gentlemen your antibody cell antibody dependent cell cytotoxicity cell cytotoxicity happens for your natural killer cells okay? so before we proceed are we clear with the two parts of your antibody the fab and the FC region? can I see a reason behind okay? now that we have those two parts late in our discussion now what happens? remember that your antibodies okay? your antibodies will bind to your antigen take for example the green one that you are seeing right now on your screen this is a bacterial antigen there are different scenarios okay? your antibody can bind to the antigen on the surface of your target cell because you can see they bind to your target cell how did they bind? through the FAB or the fab region again through the fab region now this process that you are looking at right now is also partially opsonization para yung opsonization para yung opsonization yung nangyari now since we are talking about your natural killer cell your natural killer cell has your CD16 correct? your CD16 now will bind to your FC receptor your FC receptor recognize cells bound to your antibodies your CD16 is a FC receptor that can recognize antibodies that are bound to your cells you can see your antibody your natural killer cell now your CD16 bound to your FC region and that crosslinking what do you mean by crosslinking? the binding of your CD16 and your FC region will now trigger the activation and eventually the granulation of your natural killer cells okay? the granulation into alytec synapse it will be releasing the granzymes and the perforines and what will happen next? boom! okay? your tumor cells will die by apoptosis okay? your tumor cells will die by apoptosis now your antibody-dependent cell cytotoxicity is a promising a promising solution to cancer but again later on when we reach your tumor immunology you would know and you would realize that there are also proteins released by your tumors that mimics that mimics your HLA that's why your natural killer cells can no longer identify them as tumor cells but again for certain types of tumor cells this is what happens same lang yan I hope the story a lot of the things in immunology are based on stories mechanisms, processes so I hope you guys are listening step by step so here similar then here we have your natural killer cell you have the antibody as you can see the fab region is the one attached to the antigen of your cell of your target cell and then your CD16 your CD16 will come into contact with your FC region that cross-linking will trigger the activation and the degranulation of your natural killer cells releasing your granzymes and perforations therefore eliciting the apoptosis or stimulating the apoptosis of your cells are we clear can I raise your hand if we're clear on how your natural killer cell perform the antibody dependent cell cytotoxicity so imagine all of these things are happening inside your body as we are speaking right now so this is really fascinating now please remember that once that your natural killer cells done their job have done their job atanaman yan your natural killer cell the debris will now be engulfed will now be engulfed by your macrophage and will start to further digest it and dispose it out of your body okay so similarly to what I have been mentioning during the beginning of our topic for today about your natural killer cell your natural killer cell was first thought to be part of your adaptive immunity that eventually now we classify your natural killer cell as part of your innate immune system but please do remember that your natural killer cells play an important role as a transitional cell bridging the innate and the adaptive immune response against your pathogens okay again ladies and gentlemen please remember that your natural killer cells they bridge the innate in your adaptive immune system sir why here's how that is because of antigen presentation your antigen presentation as you can see your dendritic cell the most efficient the most efficient the most efficient antigen presenting cell will now eat your bacterial it will phagocytose your bacteria okay and then part of the bacteria goes to the surface of your phagocyte sir why do they select a particular protein this particular protein is unique to the bacteria it's like an identifier later I'll try to explain it in a different analogy so that you can get it easier okay now your dendritic cell or phagocyte will present that protein take for example I have an entire book take example I have this entire book and then I just want you to get the gist I just want you to get the gist of this book I will try to read it summarize it and in this process your phagocyte are processing the bacteria in that case and then when I found the last page that will summarize everything that summarizes everything that I will tear it up take for example that's a paper I will tear it up and this is the only piece of paper out of this book that I will present to you take for example your t-helper cell and one that your t-helper cell is activated one that your t-helper cell is activated it will simply make an announcement in your immune system in your entire immune system informing all of your cells natural killer cells and cytotoxic T cell to kill all bacteria or all cell that would possess this particular protein in their membrane let's try to put it in a different analogy take for example I have my cute bears here that I got from a dedication I will use this as an example can you guys see if you guys can see the dial take for example I have this I have this bear this is an antigen this is a pathogen now your dendritic cells your macrophage will identify them take for example this is an antibody there is an invader inside the system so they will try to arrest that they will try to engulf, phagolize your soul and then it will now be engulf inside your cell and phagolize your soul will be produced and then your dendritic cell now will process this particular antigen and the goal is to choose the protein that is most unique to this particular antigen and in this case I would like to present the head I would use the head so this particular the head the head of your antigen or the identifying or the unique protein of your antigen will now be the one presented by your dendritic cell now I would go to each helper T-helper cell is the ultimate maritase your dendritic cell is your ultimate maritase why? because your dendritic cell will go to all of your T-helper cell this is how the bacteria looks like okay? this is how the bacteria looks like this is how the bacteria looks like and the T-helper cell now will get activated and will T-helper cell now, is like the marites that will deliver the message that will activate the entire immune system so that the next time that they see another okay the next time that they see another bacteria okay the next time that they see another bacteria they will be able to kill those pathogens and antigens inside your body so that is generally a um a quick um introduction of antigen presentation did i made myself clear guys um did you have an at least an idea now how antigen presentation happens uh i will be discussing this separately naman uh when we go to your mhc are we clear with antigen presentation can i see a reason for it clear so again no you always try the your bacteria again this phenomenon is not yet fully explained how your um how those are dendritic cells select a particular protein to present to the antigen actually even i myself um i've been reading immunological books but there has no no explanation yet malay natin tayo makadiscover how this dendritic cell um process the the bacteria and select a protein that is really unique dun sa mismoong bacteria that's why they're able to identify them okay now in a nutshell okay for just trying to explain it antigen presentation is a process whereby the degraded peptides or protein within your cell what type of cell your antigen presenting cell like your dendritic cell are transported to their plasma membrane they put it on their plasma membrane where the t cell can recognize them okay so uh once that um this happened once that your antigen presentation happens okay take for example activate um your t helper cell was activated what will it do okay okay your t helper cell okay over here antigen was found okay as you can see they will now try to um they will now try to disseminate the information okay t helper cell this is how it looks like okay i must alert everyone now everybody ian now t helper the cytotoxic t cells now okay cytotoxic t cell everybody come here invader alert invader alert now your match cells all of the different cells of your body both innate and adaptive cellular components of your body will try to synergistically address and kill the invader inside your body so your interleukins your interferons and your chemokines will all be released in the sole purpose of arresting your um pathogen inside the body okay so that is how your natural killer cell does its job okay again please do remember that your natural killer cell um they serve as an important bridging or an important cell in bridging your innate and your adaptive immune system again if you miss it how i'll just try to go back because your natural killer cell like for example there's a cell na hindi natin kayang patayin okay a cell okay remember your phagocytosis is only for extracellular bacteria or extracellular pathogens what about if the problem is an entire cell a tumor cell the first one to do the job is your natural killer cell your natural killer cell will first um destroy the bacteria leading to apoptosis and once apoptosis is done okay the enemy cell dies by apoptosis it will now be engulfed by your macrophage and your macrophage will be the one to process it process it and then present it present it to your adaptive immune system that's why in a sense your natural killer cell plays a transitional cell bridging between your innate and your adaptive immune system did i make myself clear with that statement now can i see a raise of hand if we're clear people hello okay may nakakamiyot na nagtupapatogtog okay are we clear so hopefully we're clear with that okay so ladies and gentlemen thank you for listening to our discussion um i will now be opening the floor for any questions or clarification um if you have any questions you can send me an email or send me a message but for now thank you so much for listening please end the recording now thank you so much