 Sige, let's get started. So again, um Danny, just tell me if you're already recording and we're good to go. And if we're good to go, okay. So thank you so much, Danny. Excuse, inabutan ng obo-obo ko. Kainang morning, konti lang. Anyways, so last time we talked about your history of your immune system and everything that was mentioned there contributed to everything that we know now when it comes to immunology. But again, just like what I mentioned during our orientation, immunology is fairly in new and a young science. That's why there's a lot of things yet to be discovered. So if you want to venture out into immunology, that's very, very welcome and that's very fine because there's a lot of things, a lot of phenomena inside our body involving the immune system that we need to explain and elaborate how they really happen in our body. And last time, we also did talk about the two types, correct? The two types of immunity. We talked about the innate immunity and also your acquired immunity. And we started off discussing the different components of our innate immunity. So innate immunity, when we say innate immunity, we're pertaining to the natural immunity of our body. Meaning to say, when you were born, all of those were normally present. You don't need to be exposed to a particular infection or a particular substance for you to develop it. It just really came naturally. So when we talk about innate immunity, I'm doing this review as Angkor for our next discussion for today. So when we talk about innate immunity, isn't it? There are two parts of your innate immunity. The external defense system that corresponds to the anatomical barriers that we have, your intact skin, the celia on your mucosal membrane, even the biochemical substances that also is present together with your external defenses, your lactic acid in your sweat, your lysozymes, the acidity in your gastrointestinal tract, even the acidity in the vagina of our women, and also even the normal flora that you can see not only in your gastrointestinal tract, but literally all over your body. So those are part of our external defense system. When you were born, they naturally develop alongside with your development as an individual and also, aside from external defense system, we also have your internal defense system. Here comes now the cellular and the humoral or the soluble components of our immune system. Last time, we already started off discussing the different acute phase reactants. So I hope you also finish that part of the video. So when we talk about the acute phase reactant, those are internal defense system found inside our body. If you are reading other book, as it was mentioned in Stevens and also in other references, they consider the internal defense system as the second line of defense. First line of defense are the external ones, second line of defense are the internal defense system, which are usually mechanisms of our body that are able to recognize specific molecular components of a particular pathogen. So later on, as we move along our discussion for today, we'll be discussing how is our body capable of recognizing molecular components from these different pathogens that allows us to respond into a particular bacterial or a pathogenic evasion inside our body. So last time, we started off already with the humoral components or the humoral components of our innate immune system. So we talk about your acute phase reactants, we talk about your interferons. We'll be talking about your complement protein in a separate discussion, hopefully by fourth week of our discussion. So we'll be discussing complement proteins. But last time, we talked about your what? We talked about different acute phase reactant such as follow. So you have your seriactive protein, your serum amyloid A. So as you all know, most of these acute phase reactants are very important in identifying early inflammation. So remember that these are nonspecific, nonspecific in a sense that when your seriactive protein are increased, it doesn't mean that you have this specific disease immediately. So they can increase in a various number of infections, bacterial, viral, and even parasitic. Even non-communicable diseases, they can also increase. Some of your inflammation, your serum amyloid A together with all the other proteins that you see in front right now are all acute phase reactant. So let's just set the record straight. When we talk about acute phase reactant, there are positive acute phase reactants and negative acute phase reactant. Remember in your amino acid and protein in clinical chemistry one, when we talk about positive acute phase reactants, these are the proteins that increases during times of inflammation. So if you have inflammation, infection, your acute phase reactant, your positive acute phase reactant will increase. Again, they will increase. And on the other hand, if these acute phase reactants naman decreases during infection, we call them negative acute phase reactant. A classic example of a negative acute phase reactant are your albumin. Your albumin decreases during inflammation. Now this acute phase reactant give us an idea that there is something going on in the body that needs to be arrested, that needs to be addressed. That's why these acute phase reactants are also increasing. Not only that, your acute phase reactants can also serve as obsonins. Remember when we talk about the history of immunology when they discovered phagocytosis? Together with that, they also discovered some soluble compounds, acute phase reactants in that sense that quotes your antigen, or quotes the pathogen present in the body, increasing the efficiency of your phagocytosis. So these are different acute phase reactants. And just like what I was mentioning, and just like the discovery during the early stage of immunology, our immune system is not just composed of your humeral or your soluble compounds. They are also composed of different cellular components. And in this case, we will now be talking about the second part of our discussion about innate immune system which will focus on your white blood cells. Some of these will be reviewed since you just finished your hematology one. But yeah, let's get started with your white blood cells. So when we talk about your white blood cells and innate or your natural immune system, we have to exclude and remove one. And not all your white blood cells are part of your natural or your innate immune system. So your neutrophil, eosinophil, basophil, your monocyte, generally your granulocytes, all of them are part of your innate immune system except for your lymphocyte. Your lymphocyte is particularly part of your acquired or your acquired or your adaptive immune system, which we will be discussing in the coming weeks. Now, when we talk about your white blood cells, of course, these will be a review of your hematology one. Some of your white blood cells increase in a particular type of infection. So the first one, let's go and start off our discussion. The first ones are your neutrophils. So your neutrophils are said to be the most abundant white blood cell inside the body, amounting to around 50 to 70% of the total peripheral white blood cell in an individual one. Your neutrophils are very much abundant inside the body that they are the first cells to address or to go to a particular site of infection if any is present. So your neutrophils, ladies and gentlemen, mga kababayan, your neutrophils are the first one to respond. Ok, dahil silang pinakamadami, they are the first one to respond. So they are capable of phagocytosis, meaning to say they eat the antigen or the pathogen present inside the body. So your neutrophil are able to kill, destroy and digest these foreign materials because they contain large amount of neutral granules. Granules, particularly your primary or your azorophilic granules and your secondary granules that helps eradicate and digest the antigen or the pathogen present in the body. Now when it comes to morphology, your neutrophils usually has 2 to 5 lobes. 2 lobes specifically for band cells, ok, for your band cells but as your band cells mature, they can have as much as 5 lobes. Remember that there's also a WBC anomaly that I also want you guys to remember, your hyper segmented neutrophils, hyper segmented neutrophils would have more than 5 lobes and usually our indication of its severe bacterial infection. So generally your neutrophils are increased because of bacterial infection and it's very important for us to also know that your neutrophil are part of the phagocyte. Phagocyte meaning to say cells capable of phagocythosis which we will be discussing later on, ok. So remember that your neutrophil, they are the first again, first one to the respond in times of infection. Aside from neutrophils, we also have of course your eosinophils. Your eosinophils are considered to have the most important role when it comes to neutralizing your basophil and mast cell products. Specifically what are those products that we're talking about, your heparin and your histamine, ok. Those two products of basophil and mast cell elicit a severe immune response if uncontrolled in the body. I'm not saying that histamine is bad, ok, but excessive amount of histamine and heparin can be detrimental to our body such as we call your anaphyloctic shock. Now your eosinophils are usually the one blamed for an allergic reaction but the truth is they are the one you see last because they are the one trying to fix what basophils and mast cell cause inside your body, ok. So your eosinophil has a very important role in regulating our immune response. Regulating particularly your mast cell and your basophils, ok. So they do have that hemotactic regulating or regulator capability when it comes to inflammation. Aside from eosinophil being present during times of inflammation and allergic reaction, your eosinophil are very much famous because they are present in increased amount in times of helmetic infection, ok. If you have any parasitic infection, your eosinophils will also be increased, ok. Your eosinophils will also be increased. Eosinophils are increased in times of helmetic infection because they are the only cell inside the body that has, ok. Of course, aside from natural killer cells, your eosinophils does have a very unique protein, your major basic protein that allows the destruction and the digestion of your helmetic parasites, ok. Aside from that, they also have your eosinophil ionic protein and peroxidase that helps them arrest the effects of your basophils in your mast cell. I hope we're clear by this time, no, that your basophil in your mast cell, in times of, for example, there is a particular irritant inside our body, your basophil in mast cell also wants the best for you. It's just that when they go in excess it becomes detrimental inside your body. That's why, again, eosinophil are the one usually being detected after a particular allergic reaction. Now, after eosinophils, ok, remember eosinophil hemostatic regulator of inflammation, parasitic infection, allergic reaction, next we have your basophils. When you talk about your basophils, your basophils are considered to be the smallest granulocyte, not only the smallest, but the cell that has the least amount of time inside our blood. So they only live for a few hours in your blood. That's why you don't usually see them when you are extracting blood. So your basophils, they do have this dark blue to black granules that contain cytokines, growth factors, histamine and heparin. Histamine and heparin that are the ones notorious when it comes to allergic reaction. Then you know that your basophil can also stimulate the production of your immunoglobulin. Ok, specifically your immunoglobulin G or rather your immunoglobulin E or your IgE. Your IgE kasi, your immunoglobulin E is very much important when it comes to allergic reaction and even parasitic infection. So your IgE will be the one that will turn on more basophils and more mast cells. Ok, so if the inflammation is really needed, your basophil will again, they will stimulate the production of your B cells. Your B cells will become plasma cell producing IgE, your immunoglobulin E inside your body. So that's about basophil. Your basophil produce your histamine that is evasoactive amine that is generally present in allergic reaction and even inflammation. So aside from your neutrophils, your asinophil, your basophil, the fourth one on the different cell in your innate immune system are your what? Your monocytes. Your monocytes as opposed to your basophil, they are the largest in your peripheral blood. Normal and largest. So your monocytes are, aside from size, your monocytes is also different from your basophil because your monocytes can stay up to 70 hours in your blood. They can stay up to 70 hours in your blood and they do contain important granules that should help your neutrophil in your phagocytocin. So they do contain type 1 granules that contains peroxidase, acid phosphatase, and aryl sulfatase. And your type 2 granules they do contain your glucoronidase, your lysozyme, and your lipase. I mentioned your monocytes helping your neutrophils. So your neutrophils are the first one to respond. But there are times that they also get overwhelmed. So at times that your neutrophils are overwhelmed by the infection, and your macrophage are to the rescue. Again, your monocytes in your macrophage are to the rescue. Let me just differentiate monocytes and macrophages later. So aside from type 1 and type 2 granules, they also have your leukotraines. Your leukotraines is a newly disidentified class of compounds among your monocytes that helps mediate inflammatory function of all of your leukocytes. So your leukotraines are like an activator of your WBC especially in times of infection. Now before I move forward to macrophage I want to highlight your lipase. Your lipase is a unique enzyme found on your monocytes not found in your neutrophil. That's why there are certain bacteria that cannot be killed at be arrested by your neutrophil because they do not have lipase. An example of these are your mycoplasma and your mycobacterium species. Only your monocyte can arrest them because it is only monocyte that has the enzyme capable of digesting the outer membrane of these bacteria. Now when we talk about monocyte, monocyte is the one found in your peripheral blood. As we are talking right now inside your blood vessel, you can see monocytes inside. Now if your monocyte starts to think na sabi niya I think I need to grow, I need to mature and I need to move out from the blood vessel. That monocyte now becomes your macrophage. All macrophages arise from your monocyte. That's one reality that we can never ever change. All of your macrophages are monocyte to start with. Your macrophages is far more different because your macrophages committed to stay in a terminal organ. Meaning to say nung piniri nilang kumunta sa liver they will stay in the liver forever and ever amen. So those are your macrophages. Again, your macrophages similar to your monocyte helps your neutrophil. In the event that the neutrophil is not efficient enough during phagocytosis, your macrophages and your monocyte will be the one to finish the fight. Okay, neutrophils kasi are fast. Macrophages and monocytes are slower compared to your neutrophils. That's why they arrive in the site of infection later compared to your neutrophil. But they perform a very important role which is to arrest anything that the neutrophil was not able to finish in that particular site of infection. Not only is that macrophages and monocytes are like back-ups when it comes to phagocytosis. They're also important because they are keep up somehow bridge the innate and the adaptive immune system. Again, they bridge the innate and the adaptive immune system. How? Because of the phenomenon which we call antigen presentation. Antigen presentation is somehow the window between natural and your adaptive immune system. The reason why you have memory, the reason why your immune system have memory can first be trace because of your innate immune system. So remember that. When it comes to your macrophages your macrophages together with your dendritic cells collectively we call them your antigen presenting cells. Your antigen presenting cells. That's why there is somehow a feature between macrophage and dendritic cell that merge that merge or bridge the innate and the adaptive immune system. Now since we're talking about macrophages living in a terminal organ residing in a terminal organ there are specific terms we call these macrophages specific name to correspond to their terminal organ. As for your lungs in your histology na bata niya na ito in your lungs we call them your albular macrophage in some textbook we call this your DUST cell DUST cell or DUST alikabok. So your lungs has your albular macrophage in some textbook we call it your DUST cell in your liver you also have your cup for cells please take note of the spellings in your brain you have your microglial cells in your connective tissue you have your histocytes in your skin you have your langer hand cell in your bone you have your osteoclast in your kidney you have your macroglial cell okay so those are those are the different macrophages that you can see all over your body so your macrophages can stay there for longer period of time okay so if your macrophages can stay for around 70 min 70 hours in your blood vessel they can persist for longer period of time when they are on their terminal organ okay so those are your macrophage next we also have your mast cells okay your mast cell is very similar to your basophil similar in a sense that the effect that they elicit inside our body is very similar for the reason that they actually contain the same their granules contain the same enzymes like your acid phosphatase alkaline phosphatase your protease and even your histamine now when it comes to your mast cell as you can see they don't have the large dark granules as your basophils have your mast cell have granules pero as you can see yung granules nila doesn't cover okay doesn't cover hindi ko makita yung it doesn't cover your nucleus okay doesn't cover your nucleus so just like what i was mentioning then kanina your mast cell aside from the size your mast cell is larger than your basophil and when it comes to lifespan your mast cell can stay for around 9 to 18 months okay for 9 to 18 months so it's very important to remember that so that we can easily classify or differentiate a mast cell from a basophil in addition to that as you can see we have your immunoglobulin E here so kanina I mentioned that your basophil stimulate the production of your immunoglobulin E, IgE and those IgE not only respond to your basophil and your eosinophil they also respond to your mast cell they attach to your mast cell and once another antigen is present, for example a particular individual is allergic to nuts kumain siya ng P not so the antigen will be binding to the IgE will be binding to your antibody and the binding will lead to the granulation what do you mean by the granulation? itong lamban niya to ACP, alkaline post, protease and histamine all of this will be released into the blood stream leading now to leading now to an inflammation or allergic reaction in our patient so are we clear so far o what can I see are you ready for clear so far please okay so those are your mast cells okay those are your mast cells we're still in chapter 1 of Steven's song aside from mast cell we also have your dendritic cells are covered with long membranous extension the reason why we call it dendritic cells is because it resemble the nerve cell remember your nerve cell has dendrites it looks like dendrites of your nerve cell but your nerve cell is in your central nervous system your dendritic cell are also phagocytes their main function is to phagocytose antigen and similar to your monocytes and macrophages they also present it to your T helper cell it's very important for you guys to remember your dendritic cell please write this down it will not come out of the power point but your dendritic cell are considered to be the most efficient antigen presenting cells again your dendritic cells are considered to be the most efficient antigen presenting cell sir what is antigen presentation ba again we'll be discussing that next meeting kasi matatapos ako kong ay sa phagocytosis we'll discuss what is antigen presentation on our next meeting but to give you an idea always remember that the dendritic cell and the macrophages they process the antigen first take for example sabi na natin we're studying compliment system the compliment system is a foreign body something that you do not know yet me, my job as a professor is to simplify it explain it to you well so that you'll be able to understand it in this case i'm like the dendritic cell i would be the one to study the compliment system simplify it study it and then present it to you you guys are the you guys are the t-helper cell t-helper cell needs bite size information that they can process so that they can elicit an immune response they can produce antibody they can go on and trigger an immune response a generalized immune response your lymphocyte your t-helper cell needs that so in that case parang ganoon din yung nangyari sa atin we have an information i process it first i presented it to you then hopefully you'll be able to understand it better faster and you can respond faster and also better that's the job of your dendritic cell when they have or when they engulf a particular pathogen they process and digest the pathogen first and then what they will present to your t-helper cell are only the key protein of that particular pathogen para makagawa tayo ng antibodies at makapag-elicit ng immune response yung ating immune system this is also the very same reason very same concept of how vaccines are produced we do not introduce the entire entire pathogen to an individual although there is a case like that atinyo waited vaccine but that's na takwento today so ang ginagawa natin we just choose a particular part ng bacteria para ganoon siya dendritic cell they choose a particular part that they will present at any that's something that our cells will immediately recognize so are we clear so far are we making sense when it comes to dendritic cell antigen presentation antigen presenting cell so I will call them I will call them phagocyte phagocyte cells capable of phagocytesis dendritic cell monocyte macrophage neutrophils but the one capable of antigen presentation are only two monocyte macrophage and your dendritic cell they are the one that present the cell are the one that present the antigen I'll explain the next meeting promise so now like what we were talking about this particular cells are capable of phagocytesis which I've been mentioning all along since the start of this discussion before we head over to that let us first talk about sir how does this cell how does this cell identify that this particular molecule here is an antigen that needs to be killed that needs to be arrested correct so not every cell are capable of like capable of that and if you all know that's the essence of autoimmune disease because your body is attacking its own but remember your innate immune system even if even if their response is not specific when I say not specific general kasi yan e kung baka lahat ang makita nila na ganito ok, unlike kapag nakikita ka ng port laging luto mo adobo for the rest of your life adobo adobo adobo lang yan general lang yung treatment mo unlike apag specific kung masok dito si si si batas a dahil si batas gusto niya masinigang ang dito naman si baroso ang luto naman ito paksiyo so as you can see specific pag-adaptive ang ating innate immune system general lang yan and I want to go back dun sa isa nating in a particular statement that we mentioned that our internal defense system they are capable of recognizing specific molecular components of a particular pattern are able to identify a molecule present only on your pathogen na wala sa katawan mo para hindi na inaatak yung sarili mo so they are able to differentiate which one to kill and which one to kip ok which one to kill and which one to kip now those capacity or capability of our cells rely on what we call generally as your rely on what we call generally as your pathogen recognition receptors these are your PRR so your pathogen recognition receptors they act as sensor for extracellular function so ikaw mga kababayan mga kapatit your blood cells your phagocytes in particular has pathogen recognition receptors they act as sensor para kapag may dumahan na ok wait lang kalaban yun they would know who to kill now important na, nahil alam natin ok, our cells do contain pathogen recognition receptor so what do they recognize what is it that what about this sensor that are recognizing in the pathogens that they are able to respond so your PRR your PRR detects your PAMP or your PAMPs your pathogen recognition receptors are sensors that identifies or that identifies your pathogen associated molecular patterns so when we say pathogen associated molecular patterns these are only found on your pathogen, nakikita lang sila sa ating mga pathogen and these molecules are specific only to those pathogens such as what peptidoglycan in your gram positive your lipoproteins in your gram negative your zimosan in your yeast in your flagelline for your flagellate bacteria now some of you will be wondering sir may lipoprotein may lipoprotein din ang tao but these are different type of protein lipopolysaccharides lipoproteins that are usually found in your gram negative bacteria again ha your pathogen recognition receptor are able to distinguish molecules present from our body and from the pathogen and in return they are able to elicit an immune response they are able to elicit an immune response in the case of our phagocytes alam nila kung sinong kakainin again ha let me reiterate your pumps are only found on your micro organisms again ang pumps natin nakikita lang po sa ating micro organisms nakakaintingihan ba malinaw okay good now an example magbigay tayo ng example ng pathogen recognition receptor na meron tayo ngayon as we speak and these are what we call now your TRL or your tall like receptors okay remember ladies and gentlemen your tall like receptors okay your tall like receptors ito na yung mismong pathogen recognition receptor nakikita sa ating cell can I see a race of hand if we're clear so all of your phagocytes all of your leukocytes has increased levels of tall like receptor sir ano bang ginagawa ni tall like receptor okay bago natin siyikahin kilalanin muna natin siya your tall like receptors Janeway panin nila na discover yung tall like receptor they actually found they actually first discovered it in drosophilia fly drosophilia fruit fly drosophilia fruit fly your drosophilia fruit fly kasi has a characteristic of antifungal property meron siya antifungal nagkaka fungyay when siya nai-infect ng fungyay and they actually wondered why? So when they discovered they actually discovered proteins in your drosophilia fly that eventually later on they also discovered a similar again na hindi yung nakikita sa langaw nakikita rin sayo hindi they actually found a similar protein that has is the same purpose or the same function that's why they call your tall like receptor para silang tall kaya nga sila din ako na tall like kasi pa silang tall na na sa surface ng cell that is found on yourself So what does your tall like receptors do? Your tall like receptors recognize molecules that are commonly found in your microbial pathogen yung pumps yung pinag-usapan natin kanina they recognize molecules that are found in your microbial pathogen your pumps pathogen associated excuse your pathogen associated molecular patterns na wala sa human host okay so they were able to identify that and what is ang nangayari kasi is that your tall like receptors becomes like a signaling pathway that will trigger the production of cytokines na mag-enhanse ng inflammatory response will also call out other cells in the infection side so those are these tall like receptors are very important because these are like first line this are like second line of defense inside our body that will wake up inside our immune system hey hey para tung mga marites para tung mga marites na taga taga pakalap ng mga nagbabagang balita so you're going back here your tall like receptors ladies and gentlemen you're you're tall like receptors your tall like receptors okay your tall like receptors concentration among your phagocytes which are your monocytes your monocytes your macrophage and your neutrophils your monocytes, macrophage and your neutrophils of course ka sa matidyan si then dredic cells para ganyto I have a short animation for you guys this is how tall like receptors act inside our body e.g. example e.g. tlr makita siyang incoming bakit siya nagsignal? makita siyang incoming infection may incoming pathogen so ganun dun sa at ganun yung ginagawa nila sa ating gatawan they identify they signal the entire immune system so that it can elicit and it can enhance an inflammatory response para i-arrest yung pumasok na infection sa ating gatawan nakakaintingihan ba tayo? can I see Arisa kan, kung malinaw tayo so far? okay now next now that we have your tall like receptors it's also important to know sir maybe some of you will be wondering sir, are tall like receptors the same for everyone like the tall like receptor that identify the peptidoglycan is the same that will identify the lipoprotein, dimosan, flagellin things like that that there is no that's why this table that you see now in front of you you need to memorize now we have different tall like receptors tall like receptors 1 through 10 some can be found inside our cell which we call your endosomal endosomal trls we have endosomal trls because there are some intracellular pathogen such as some bacteria are intracellular but they're also most importantly viruses viruses are always intracellular so they are obligate intracellular so we also need tall like receptors that will identify any foreign material that has already been inside our cells aside from that of course we have your trl that are found on the surface so those that identify lipopeptides are trl1 trl2 for your peptidoglycan, lipoprotein, and dimosan there are overlap but during my exams I do not ask the overlap I ask the one to the particular trl so you have to memorize that there's only one that has your peptidoglycan that is only trl2 only one that attaches to your lipopolysaccharide and fusion protein and even manan that is only trl4 your flagellin is only trl5 lipoticoic acid is only for trl6 so please remember those for our upcoming exams and now just to wrap it up for you guys know we have different our innate immune system has humoral your humoral components the acute phase reactance, seroloblastmine, haptoglobin things like that and they also have the cellular components your granulocyte your neutrophil, eucinophil, basophil, monocyte, macrophage dendritic cell mast cell and also sasusunod nating discussion because natural killer cell is another topic of its own so you see that we have your white blood cells okay your white blood cells except for your lymphocytes okay so they do have their pathogen recognition receptor an example of that is your tall like receptor that are able to identify pumps or pathogen associated molecular patterns okay that are only seen in pathogens that's why our cells are capable of identifying okay this is one is kalaban, this one is kakampi you don't need to kill this we need to kill that so our body is capable of identifying that through this pathogen recognition receptors okay now are there any questions or clarifications so far if not can I see a raise of hand please and we can move on okay thank you so much now let's talk about your phagocytosis your phagocytosis not all cells are capable of phagocytosis in this particular level when we talk about phagocytosis okay napintot ko na magreview question sana ako anong first name ni Metshnikov anong anong first name ni Metshnikov the one who discovered your phagocytosis it is Elie Metshnikov okay Elie Metshnikov is the first to describe okay single L lang ha single L okay Elie Metshnikov one L only okay sinabi ko na ha so wala akong ikon consider na maling sagot sa quiz so Elie Metshnikov single L okay was the first one to describe phagocytosis they observed he was able to observe cells eating other cells bacterial cells in particular so your phagocytosis is a process of engulfment and destruction of foreign cells or particulate matters by your leukocytes, macrophages and other cells so remember that our cells are capable of endocytosis, exocytosis your endocytosis is divided into two phagocytosis and pinocytosis cell drinking yung pangalawa phagocytosis is cell eating remember that phagocytosis is only for extracellular organisms okay extracellular in a sense that kapag nasalabas lang kaya nilang kainin pero kapag the bacteria or the pathogen is intracellular that's another story for another time dun magbabalik ang ating natural killer cell next meeting okay malinaw tayo so kalmakal malang tayo dito para maintindihan yung ng mabuti ang ating mga kwento okay so your phagocytosis this is how it happened your WBC your leukocytes are able to engulf the bacterial cell and not only engulf kasi pagkinain mo so what? an diyan parin siya sa log ng katawan it needs to be destroyed and as we go along we will now be talking about the different steps in phagocytosis so the first step in phagocytosis can vary from different books kasi ha it can vary from different books but we're gonna follow the one from Stevens so I'll just interject some of the information coming from the other book para you can write it down in your notes para maging masustan siya ang inyong mga notes okay so the first step is your initiation stage your initiation stage this is the time where there's an increased surface receptor that allows for adherence adherence of what sir? adherence of your phagocyte your phagocyte needs to adhere in the site of infection so that phagocytosis can start so sir what specifically are these receptors that increase receptors that can increase can either be adhesion molecules p-selectin can help in the adherence of your WBC or it can also be other substances and proteins such as your acute phase reactants yung mga acute phase reactants natin naging increase at the very moment na meron kang infection bakit? why? because it needs to increase so that it can also enhance phagocytosis which is what we call your opsonin opsonization the first thing that happen is your adherence a lot of compound is released to help the phagocyte adhere to the site of infection or more importantly adhere to the pathogen itself next after the initiation stage meron tayong problema what will happen next we will now start to recruit and this process is what we call your chemotaxis chemotaxis is the process where your neutrophils monocytes, your other phagocytes migrate to the site of infection eto yung mismong transit nila papunta doon sa site of infection we call it chemotaxis a very common misunderstanding very common term that is being substituted to chemotaxis is diapidesis what is diapidesis diapidesis is the process in which your white blood cells or let's just say cell diapidesis is a process whereby your cell transverse or tumatagos nila sa my blood vessel remember your blood vessel is made up of different layers vascular entima which is one the one we will be talking about tomorrow for hema your vascular entima diba yung vascular entima mo tight yan kaya nga hindi nakakalabas yung dubu pero yung white blood cells mo they are capable of penetrating and passing through your blood vessel and yung process mismong na yun is what we call diapidesis are we clear? so take for example your white blood cell will go out of your blood vessel so that it can go to the site of injury yung paglabas niya mismo sa blood vessel that is diapidesis but the entire process of the blood of the white blood cell going into your site of infection that general process is what we call chemotaxis nagkakaintindihan tayo guys kasi baka mali ito kayo sir diapidesis po kasi sinagot ko sir kasi chemotaxis po kasi sinagot ko okay are we clear with that kasi diapidesis diapidesis yung mismong kona re pag pupunta ka sa pag pupunta ka sa koron yung flight mo mismo that is chemotaxis pero yung paglabas mo ko na rin ang bahay paglabas mo ng gate paglabas mo yung karean that is diapidesis nagkakaintindihan tayo malinao okay now your chemotaxis is a phenomenon happening inside our body during phagocytosis chemical messenger that influences our cell these are what we call your chemotaxins what are chemotaxins? chemotaxins are substances that stimulate or trigger your white blood cells to migrate but before I go ahead of myself remember that there is a test that we can perform to test your chemotaxis ang cell ko ba ang white blood cell ko ba nakakapag-respond ng maayos sa chemotaxins well it's one way to find out let's perform your Boyden chamber assay okay so your Boyden chamber assay sa test for chemotaxis eto in this particular test we expose the cell to chemotaxins and see if they are able to respond to the chemotaxins okay so what are chemotaxins again? chemotaxins are simply substances that are released by bacteria or by injured tissue and also white blood cell that stimulate the movement of neutrophil and other white blood cells to that injured site okay chemotaxins are like chica okay etin mga chica na na experience na yun na ano man do ganyto sa may patio sa may quadrangel di ba lahat naman ng tao po punta do nang mga may great lahat ng tao po punta do sa site of happening ganyto sa ating mga white blood cell your chemotaxins are substances that are either released by your bacteria, ng injured cell mo or even ng white blood cell mo guys hindi namin to kaya we need more so your white blood cells are able to go to the site of infection okay so those are chemotaxins remember also that your chemotaxins has two types meron tayong positive chemotaxin meron tayong negative chemotaxin okay parang ihalin tulad natin siya sa green yung mga nausong green flag red flag yung green flag ay parang positive chemotaxin the more you see the more it attracts the more you are attracted to go to that particular site of infection di ba? ganun yung positive chemotaxin parang green flag parang po-shocks eto yung hinahanap ko sa isang tao parang ikaw mas nagiging affinity mo dun sa taong yun parang ganun din sa mga cell pag nakita nila oh my gosh positive chemotaxin they will migrate towards the site of infection meron tayong mga negative meron tayong mga negative chemotaxins parang naman to mga red flag the more you see it the more that you run away the more that you don't go to that particular site of infection kanina during my 730 class ng immuno somebody asked me sir what are instances na meron daw negative acute phase reactants negative acute phase reactants are usually released in that particular too much na dun sa particular killer taong ito too much na dun sa part area so kung narin paning steroids para para kumalaman yung mga white blood cells mo di ba instead na oh my gosh nakabalik na ba ako hello i'm here i'm back hello hello ginsambaditel nan dito na ba ako ola okay na ako na wala sa negative acute phase reactants sa nakapart na wala okay negative chemotaxins yun na hindi negative acute phase reactant negative chemotaxins kasi kung negative acute phase reactant ang layo ko nga ilunong na wala ko so negative chemotaxins to ha negative chemotaxins not negative acute phase reactant that's different okay going back okay lang tayong your negative chemotaxins would would repel okay wag na kayo dito magsilayas kayo doon na kayo sa wag kayong pumunta dito sa site of infection this is actually the first thing that happens during phagocytosis as you can see so bakit kailangan may chemotaxins always remember this guys the movement of your white blood cells inside the body are random para silang have you ever tried naglakat ka lang pa rin di mo alam kung san kapapunta parang example namin kanina para ang barang gaitanon ang barang gaitanog umiikot nagruranda so parang ganoon ang white blood cells very random hindi mo alam kung san pupunta ngayon di mo alam kung san san x so very random yung movement nila until nari sa situ uno merong isang nagaaway may nagsuntukan otomatically, lahat ng barang gaitanon magsuswarm yan papunta lahat sa situ uno nagigets tayo that is chemotaxis okay so on a normal basis ang mga WBC natin random lang parang rumoron na lang sa ikot-ikot lang hindi alam kung san pupunta pero once na meron ng chemotaxin specifically a positive chemotaxin also the most common lahat sila sabay sabay nga ni Marian Rivera sabay sabay tayo sabay sabay silang pupunta doon sa site of infection so nagkakaintingtihan ba tayo naggat naman ninyo na on a normal basis random yung movement ng cell kaya kailangan natin ng chemotaxin to call them this is what we're going to do this is where we're going to go okay so you guys need to follow me parang ganon so yun yung nangayari yung chemotaxis malinao ba tayo can I raise of hand if clear tayo sir question kailan pa ulit sir nabalabas sir yung sa negative chemotaxins po okay yung negative chemotaxin mo number one over-loaded na yung immune response mo we need to kasi ang immune system natin meron tayo mga pro-inflammatory meron din tayo mga cytokines na pang anti-inflammatory tayo mismo yes hindi mo kailangan ng minum ng gamot meron ka okay that regulates your immune that regulates your immune system yung mga yun okay can be released kapag over-loaded na yung isang immune response mag-resend na yung negative chemotaxin para tumigil na yung pag-migrate nang mas madami pang mga cells dun sa site of infection malinao tayo clear okay po sir yun yung example although mas madalas talaga rin kasi mas madalas yung positive mas madalas yung positive chemotaxins rather than yung negative ones okay yung anin natin sa chemotaxin okay clear tayo dun no ang nangyari meron ng bacteria na yun na na chemotaxis na sila lahat na pagaharap nagkaharap-harap na yung mga cells at yung mga bacteria yung mga pathogens nakailangan natin po kusain what will happen next is your engulfment the process called engulfment in your engulfment your white blood cells would start to show or would start to have your pseudo-pods yung pseudo-pods nila parang dito sa GIF sa picture na to yung pseudo-pods na yan mag-open up mag-open up yung cell mo magkakaran ng pseudo-pods at engulf yung ating pathogen okay in the process of engulfment na the pathogen is enclosed in a phagocytic vacuule which we call your phagosome magkakaroon kaya ng phagosome parang siyempre hindi tayo kumakain hindi tayo kumakain ng candy na na sa wrapper siyempre or baka meron kumakain sa inyo ng wrapper parang nangyari dito your engulfment kinain tapos nagkaraoon ng vacuule that will quote the pathogen that is what we call your phagosome afterwards your phagosome will fuse with your lysosome forming now your phagolysosome this process is what we call now your fusion fusion of your phagosome phagosome is where your pathogen is and your lysosome lysosome is an organ of your cell that contains digestive enzymes that will help digest the pathogen so what will happen kapag nandyan na yung phagosome sa loob ng cell ng phagosite natin siysosome magfufuse na rin magfufusion na sila ok magperform sila nang phagolysosome and after phagolysosome what they would do is to digest destroy and kill that pathogen but before I get ahead of myself ok during engulfment pwede naman natin e enhance pwede natin e increase pa yung efficiency ng phagosytosis and that is through the help of substances that coats the particle that makes the organism or that makes the pathogen more susceptible to phagosytosis and these are substances which we call generally as obsonins ang obsonins natin yung obsonins natin can be of different types your obsonins can be your antibodies your obsonins can be your complement protein your obsonins can be your acute phase reactance yung mga obsonins na yan kung na rin ito yung pathogen yung obsonins na yan para yung mga iralop nila yung ating pathogen para si phagosite or sedendritic cell mas mabilis niyang makita mas nabilis niyang main gals yung pathogen that is present inside your body are we clear are we clear with obsonins and that process that is what we call your obsonization your obsonization is a process whereby your obsonins or soluble compounds coat a particular pathogen para mas mas mabilis yung phagositosis are we clear can I see a race of honey for clear please malino tayo so begin natin ang real life situation di ba parang have you ever meron pinigay sayo si meron pinigay sayo si si jonas guys namin siyo nabay yung quick quick sa tapat ng 7-11 kundari si jonas nandala siya ng quick ang fish ball marami sa atin, unang anapin kaya jonas atin yung sawsawan parang ganun kasi yung obsonin your obsonin parang sawsawan na nagkinot niya yung pathogen para mas masarap ang kain nagigay sayo doon yung obson di ba ikaw yung fish ball na walang halong-halong sawsaw parang di mo bet kainin agad yung fish ball may sawsawan ay pak, agad-agad baka ubus mong ayan agad parang ganun din sa phagocytosis yung sa engulfment yung process ng obsonization is needed para mas mapabilis yung engulfment ng pathogen at para mas mapabilis mapatay yung bacteria o yung pathogen sa loob ng ating katawad malino ba tayo? can I say raise your funny for clear? ok, kung ako say para pag times na hindi mo paano na kaulit yung obsonization ganun matatandaan mo kung ano paano sa nangyayari now after all of that is said and done what will happen? siyempre kailangan i-digest at kailangan i-excrete yung ating i-excrete yung ating pathogen so your digestive enzymes that are found initially in your lysosome will fuse with your phagosome phagolysosome and madad-digest na yung bacteria or your pathogen I'll say pathogen na lang para general it will digest your pathogen and in return it can now be excreted excreted through the process exocytosis EXO ok, so EXO exocytosis so the release of your cellular substances contain in a cell vesicle by fusion on a vesicular membrane with your plasma and then it will be released from your exterior to the exterior of your cell, parang ganto so kapag ok nang lahat kailangan mo na siyang i-release out of the cell ok, and here comes antigen presentation dito importante si antigen presentation kasi sabi kung ako na remei na imagine yun na parang give me something I'll produce something else out of it parang ganun kasing antigen presenting cells natin antigen presenting cells natin what are the two antigen presenting cells na sinabi ko kanina anyone or on the chat box what are the two antigen presenting cells that we mention ok, dendritic cells aside from dendritic cells ano pa we also have your macrophage or your monocytes so those are your antigen presenting cell kapag meron silang konwari konwari itong wrapper natin pag-pre-lesend ito ng antigen presenting cell natin yung pinaka-importanting detail na lang yung kanyang i-pepresent dun sa ating lymphocytes ok, so i-explain ko sa inyoy ng may ayos next meeting ok, so ay ato yung fago sa etosis natin kung makikita ninyo ayan sabi natin kanina di ba nag-adhere tapos nakaroon ng receptor etong receptor pano ito na nanggare sir ok, yan yung ato like receptors mo pwede rin yan yung mga receptor mo tapos may opsonin ayan, so yung sudopause phagosome nagfysilisosome, naging phagolisosome nadigest exositosis to secrete your soluble debris ok, now after that eto, mas malinao na ano ay a diagram nata diagram it's a animation on how your phagosome etosis happen ako na tichika, ok hindi na yung audio so here, as you can see we have a pathogen a bacteria yung, a bacteria in a phagosome so this bacteria was initially coated already by an opsonin ok, how did I know? I know, kasi na panod ko na itong video and as you can see guys once that your once that your phagosite adhere ok magzuzungin tayo yan you can see that there are some opsonins that attach itself to the bacteria so you have your bacteria and you have your complement proteins yung C-3B na yan complement protein pwyan pag-aaralan natin yan siguro mga 4th week na ating discussion so yan yung mga ito yung ating complement protein complement protein na nag-coat dun sa ating bacteria anong process ulit yan, opsonization aso anong tawag natin sa complement protein na ito these are your opsonins ok, so it will adhere ok, certain receptors will now bind ok, at once na magbind yan immediately agat-adad ok, it will now enter your it will now enter your cell ok, it enter your cell in a vacuule called your phagosome and then it will now start to be introduced with your lysosome so your lysosome will fuse with your phagosome creating now your phagolysosome and releasing the digestive enzymes now the digestive enzymes are secreted we can now digest the bacteria and after that we can excrete it out of the body ok, where pwede pwede pwede gi-introduce sa lymphocyte or talagang tapos na ang laban at debris na lamang siya so in a nutshell that is how your phagocytosis happen ok, so are we clear, can I see a raise of hand kung malinaw tayo so far with phagocytosis malinaw ok, so kanina sabi kung your cells or your pathogen needs to be digested and excreted and there are actually two ways how we eliminate organism via phagocytosis ok, how how the carabao that is first through oxygen dependent process it a lot of your a lot of your what do you call this a lot of your enzymes are oxygen dependent they create ok, we increase oxygen consumption and it occurs as soon as the zodopodia enclose the particle within the vacule and this is how it looks like so our cell has of all of producing super oxides these super oxides yung mga reactive oxygen molecules na ito like hydrogen peroxide ayan, your catalyst your hydroxyl radical all of these are generated and are all targeted to your microorganism remember that these these enzymes yung may yellow peroxidase oxygen the oxygen radicals or yung mga reactive oxides natin they will bind to the cell wall or the cell wall of your bacteria and it will lyse the bacteria kaya napapatay natin yung bacteria that is kapag oxygen dependent simple lang naman, pag oxygen dependent kailangan yung oxygen kasi kung makagita ninyo lahat ito are from reactive oxygen variants another way on how our cell destroys are through the help of other humoral components like your defense scene and your ketep scene ito yung nila kailangan ng oxygen it is not oxygen it is oxygen independent so it only needs your defense scenes and your ketep scenes so yung yung ano natin process natin oxidative burst oxidative burst where the microorganisms are killed through oxygen dependent processes ito po yung pangyayaring yan now for our next meeting I will anchor our next meeting with this already ito ko kuhubutan I will discuss this part bag para next meeting direct tayo ng natural killer cells so sabi nga natin ang normal na mission sa buhay ng mga phagocytes natin kumain ng mga pato ang isang kailangan nilang gawin is to kill the bacteria through oxidative burst but there is a disease chronic granulomatous disease in your chronic granulomatous disease ang problema natin dito wala yung enzymes nakailangan for oxygen dependent processes ok sulat mo na to wala nang other kemi na lalabas so chronic granulomatous disease is very important for us to take note because our body lax enzymes that is needed oxygen dependent processes to take place pag chronic granulomatous disease na engulf flungin bacteria hindi napatay and in this case sakit ito kasi hindi napapatay yung microorganisms nakakaintindihan tayo so that is chronic granulomatous disease yulak you have an abnormal oxygen oxidative burst na hindi napapatay yung mga cells next, mayroon tayong lazy leukocyte syndrome mayroon tayong jobs syndrome sa kanina sabi ko di ba, mayroon 2 types of movement or 2 types of activity ang ating white blood cell anong dalawang yun random and yung chemotactic activity nya ano ulit yung test natin for chemotactic activity what is the test for chemotactic activity moiden chamber assay okay, correct your boiden chamber assay your boiden chamber assay is a test for your it is a test for your chemotactic activity so anong mayran kapag may lazy leukocyte syndrome tayo kay, lazy leukocyte syndrome ang problema natin may abnormal na random mayroon din siyang abnormal na chemotactic activity in a sense that instead na papalapit lumalayo siya okay, so lazy leukocyte syndrome may abnormality both movement okay, both activity random and chemotactic activity parehas na may problema okay, again lazy leukocyte syndrome is a type of abnormality in your leukocyte where your random activity and your chemotactic activity are both abnormal, okay na gags po tayo kay lazy leukocyte syndrome can I see a race of honey for clear okay, that is lazy leukocyte lazy leukocyte random at chemotactic both abnormal when it comes to jobs syndrome na may jobs syndrome we have a normal random activity but abnormal chemotactic activity okay, normal yung random abnormal si Kimotactic activity okay, that is for your jobs syndrome okay again for your job syndrome normal random activity abnormal chemotactic That is for your jobs syndrome Are we clear? Can I see a race of honey for clear? So yun ha, chronic granuloma 2s, abnormality in your oxidative verse, lazy loco site, abnormal random and chemotactic activity, job syndrome, abnormal chemotactic activity, normal random activity. So maybe sa mong yun, sir, ay nung ngayon sir, kung abnormal yung chemotactic nila, ibig sabihin kapag oras na kailangan sila dun sa site of infection for phagocytosis, wala sila dun. Yung chemotactic activity nila, hindi responsive, nagigets tayo dun. So kahit gano ka daming positive chemotaxins, ang ipadala, no show, ginose ka na nang mahalo ko sites mo, okay? So yun yung problema, yung isa naman nag show up, sa chronic granuloma 2s disease naman, ang eksen na natin, at least I showed up. Nag show up pero wala naman ginawa, okay? Kasi hindi niya rin napatay yung mga pathogens na kailangan niyang puksa it, okay? So with that, I still have five minutes for your chronic granuloma 2s disease. And your chronic granuloma 2s disease, sabihin na natin, it affects the neutrophil microbicidal action kasi nga impaired yung kanyang NADPH oxidase production. So what test can we perform? We can perform your nitro blue tetrazolium test. Your nitro blue tetrazolium test, your nitro blue tetrazolium is a colorless compound. Okay, anong gagawin natin? Imimix natin si nitro blue tetrazolium, kung ikaw nag-dodrawing ka, blood plus nitro blue tetrazolium, okay? Irreduce niya, okay? When reduction happens, okay? When reduction happens, the colorless, yung colorless, obviously ng nitro blue tetrazolium will create a blue precipitate, okay? So anong ibig sabihin niya, okay? So this is to make sure kung kaya ba natin e-convert yung colorless nitro blue tetrazolium, top blue precipitate, and it can only happen, okay? It can only happen kapag meron kang enough na NAD oxidase or yung mga enzymes, okay? So again, we are using this to test, okay? We are using this to test your, what? We are using this to test your chronic granulomatus disease. So kung makikita ninyo, yung chronic granulomatus disease natin, walang blue colors, walang nag-change, kasi positive to, okay? Positive siya sa chronic granulomatus disease, negative siya sa net-nitro blue tetrazolium test. Yung positive natin merong blue precipitate within the cell, that signifies a positive result, okay? That signifies a positive result. Ibig sabihin, present yung NAD-PH oxidase sa iyong katawan. Malinaw po ba tayo mga kababaya? Gany C.R.A.S.H. for clear. Malinaw pa tayo sa part na to. So again ha, pag-micronic granulomatus disease, anong color, anong nakikitang kulay, colorless, walang color. Pag nag, may blue precipitate, okay normal, okay, kasi okay po ang ating pasyente, meron po siyang NAD-PH oxidase, okay? So yun lang din, and aside from that, there's also a flow cytometric assay, last two minutes, a flow cytometric assay. So dito naman sa flow cytometric assay, simple lang. Yung mga nitrofils natin, they will be labeled with dihydrorodamine, okay? Color orange to, yellowish orange kanya. So makakaroon siya ng dihydrorodamine. So ilalabel natin yung nitrofil natin ng dihydrorodamine. Tapos, i-activate natin yung nitrofil. Ang activator natin are your four-ball meristate acetate or your PMA. Again, your four-ball meristate acetate or your PMA, okay? Tapos, patients with chronic granulomatus disease would have less fluorescence. Bakit less yung fluorescence nila? Because even in the presence of your four-ball meristate acetate, hindi sila na-activate kasi nga. Ola silang NADPH oxidase, okay? Nakailangan for that, okay? So this is a new procedure to diagnose your chronic granulomatus disease, ha? So less fluorescence, CGD. No blue precipitate, CGD paren, okay? Your chronic granulomatus disease, okay? Anong meron kay chronic granulomatus disease impaired yung NADPH oxidase production nga or yung oxidative burst during bacterial digestion, okay? With that, okay, that ends my discussion for today. Okay, maraming-maraming, okay? Maraming-maraming salamat for listening. So now, I'll give you some time if you have any questions or clarification. Dany, please stop the recording.