all right this is going to be the part two video for the immune system chapter and in this one we're going to begin the process of learning about the adaptive defenses so uh if we just figured out all about the innate defenses which are the elements of our immune system that we are born with and that don't target specific pathogens but instead focus on just like general protection of uh the body the adaptive defenses are kind of like the exact opposite uh they are slower to respond to pathogens but they're much more specific in their process as in instead of just looking for any bacteria or any you know virus or or like any pathogen for that matter instead they're focused on one and one only you know pathogen to target and what we're going to find is that the main cell types that are going to be involved in acting as these like specialists of our immune system are lymphocytes so much like in the blood chapter we learn about lymphocytes like b cells and t cells that is going to be the major cell types involved in our adaptive defenses in terms of making a few like major comparisons between like innate versus adaptive let's see some of the things that we can use to describe here like our adaptive defenses so first is what i've already alluded to right specificity our innate defenses things like our skin mucous membranes phagocytes they are your generalists right your skin and mucous membranes are trying to keep out all pathogens phagocytes will gobble up anything they encounter that is like you know pathogenic on the other hand our lymphocytes like let's say for example that there's a lymphocyte specifically activated to fight uh you know a cell with the flu and that t cell encounters a cell with a different virus that t cell will ignore it because that's not its target or similarly if there's a clone of a b cell producing antibodies for a specific bacterium but if an antibody from that b cell encounters a different bacterium it won't stick to it because it is specific to its one and only one target so that's the first major difference with our adaptive defenses is that while they're slower to respond to say a pathogen they are taught like really targeting that exact pathogen okay the other thing we saw is that our innate defenses were largely localized you know you got like a cut or scrape or injury well you saw inflammation happen right there and phagocytes moved to that location but something like a virus right can be traveling can have viral particles traveling through your bloodstream and when we learn about like activating b cells and t cells to fight a specific pathogen we're going to find that the clones of those bmt cells will circulate systemically so unlike our innate defenses which generally fight like local infections our adaptive defenses are a more full body systemic response the other big difference is when we use our innate defenses our immune system doesn't like learn anything to make those innate defenses get any better because your skin is just your skin and your mucous membranes are just mucus membranes and phagocytes especially ones that are short-lived they do their job and then they're done on the other hand as we'll soon learn when you activate and clone b cells and t cells you not only make activated b and t cells for right now to fight whatever the pathogen is that is you know causing disease but you also make what are called memory cells and those memory cells can be quickly activated should you ever encounter the same pathogen again that's again why we tend to refer to this as the adaptive defenses because the idea of immunological memory is for example the idea that you know as we get older we theoretically should be getting fewer infections than say a child because as our immune system has become more robust over the years and we're exposed to more pathogens our immune system adapts and therefore makes it where those pathogens become like less risky to us because we already have cells that have seen them before so those are the major differences our adaptive defenses focus on specific targets they do so by sending things like antibodies and activated clone cells all over the body so a more systemic response and it gets better over time right because every time we make b cell and t cell clones we make memory cells that are going to be used in future encounters all right the thing though is when it comes to our adaptive immunity we're going to find that there are like two arms or two like subdivisions of our adaptive responses those being humoral immunity otherwise called antibody mediated and that's going to be the primary job of our b lymphocytes or b cells and they're clones called plasma cells on the other hand cellular immunity otherwise called cell mediated immunity is going to be generally done by t cells or our t lymphocytes what's interesting is like what these names imply and what that means about the path kinds of pathogens that they're targeting so you want to realize humor refers to fluids so if we're talking about humoral immunity we're generally talking about looking for pathogens that are found in your body's fluids in other words not inside your cells but in the fluids between your cells well what do we find there often bacteria right if you have a bacterial infection the bacteria is not like jumping into your human cells to cause the infection it's in the fluids of your tissue so outside the cells well b cells and their clones called plasma cells can make antibodies but antibodies can't jump into your cells they can only migrate through your body's fluids so in that regard humoral immunity is using antibodies which travel through your fluids looking for pathogens that are in your fluids and that's going to be primarily bacteria since bacteria can't get into your cells like you know say viruses can the thing though is do viruses have to exit a cell to move into a new host cell yes so in that regard we do eventually still make antibodies to fight viruses because every time a virus replicates inside a host cell and virus particles are released to go travel to find new host cells for that little interim period of time there those viral particles are in your fluids and that's where your humeral immunity can be utilizing things like antibodies to help clear that virus so in terms of kinds of infections that we use for our humor that we use humoral immunity for it's primarily bacterial infections but also for viruses when they are in between host cells so hence the name humeral immunity looking for stress pathogens in your body's fluids because these are you know utilizing antibodies that can't get into your cells but then we have to realize that there are of course pathogens that do invade your cells right a virus as we learned in our first video takes over the like uh the dna of a host cell kind of tricking that host cell into making more virus well no antibody can like jump into that host cell to kill the virus so what do you have to do instead we eventually have to actually trigger the death of the host cell and for that we'd use cellular immunity and that's the idea that if you can't if this pathogen is not outside your cells in your fluids but inside your cells you have to kill that cell before that infection can spread and that's where we can use things like t cells to kill cells that have become cancerous or kill cells that have an internal virus or even some parasites get inside our cells so that's the idea right pathogens can be either in your fluids between your cells or can be inside your cells so how do we target the pathogens that are outside our cells in our fluids antibodies and antibodies are going to derive from clones of b cells however right there are pathogens that get within our cells or that are our own cells going wrong right in terms of cancer so if a cells become cancerous or if a cell has an internal parasite or is infected by a virus no antibody can target that because an antibody can't enter the cell but cellular immunity from t cells can target those cells triggering their destruction triggering them to do that apoptosis that we learned about so in that regard it's kind of like the natural killer cells or nk cells that we learned about in our last video but now it's after a specific target like a cell that specifically has this strain of the flu but that's the idea of like humoral immunity done by antibodies looking for things in our fluids versus cellular immunity generally done by t cells or t lymphocytes that can target the cells that have cancer infections internally all right so in this video we're mostly going to focus on like the adaptive defenses in general and then we'll do a video specifically for all the details about humoral immunity and then eventually a video for all the details about cellular immunity but let's go ahead and kind of continue the idea of like learning generally about our adaptive defenses all right so here's the next thing to consider we've been referring to all the disease-causing microbes so far as being pathogens so an entire virus an entire parasite or an entire bacteria right is that pathogen but your immune system is not going to have receptors big enough for the whole pathogen instead your immune cells are going to have receptors that might recognize molecules on those pathogens so what do we call the molecules on a pathogen that can stick to a receptor of our immune cells that our immune system then kind of recognizes that well we call that an antigen so an antigen is not the whole pathogen it is the molecules of that pathogen that can specifically stick to like receptors or eventually to things like antibodies uh so it's like the molecular the molecular recognition of this substance being something what we call non-self right so over the course of this uh immune system we'll see that we'll use the term non-self to refer to like anything foreign that comes into the body whether that be you know some a piece of a pathogen or even transplanted tissue from another human if it's not part of you it's non-self so the idea is if you receive like somebody else's blood or a virus enters your body or a bacterium enters your body that is something foreign and so what if we have immune cells whose receptors can stick to molecules on that foreign item well those molecules are antigens the idea being that it's a molecule that our immune system can recognize and it therefore provokes a response from the immune system well that makes sense right gen as in to generate or to create implies like okay this is triggering the formation of something or or triggering an event and so an antigen is any molecule that can trigger an immune response because our immune system for example would have like receptors to recognize it well what's interesting is these non-self molecules that we can call antigens if they're large and they are complex that means that they have more like you know nuance to them that allows our immune system to really get a good sense of how this is shouldn't be here so the larger and more complex the structure is the more likely it is to be what we call a complete antigen so here's the idea of that when a molecule is that large and not complex it's probably activating numerous different immune cells because it has so many different uniquely shaped molecules that are all non-self that means that we're going to get a pretty strong immune response like pretty robust of a response and so we might say that this complete antigen is more immunogenic in other words it is generating a greater immune response so what does a large immunogenic response look like well it can activate new b's and t cells as in let's say you have b lymphocytes and t lymphocytes living inside your lymph nodes and stuff like that that have never been activated before well a complete antigen has enough complexity to it that it probably is able to activate numerous new b and t cells as in generating a brand new immune response but maybe this is not the first time you've seen that pathogen maybe this is a subsequent encounter for something you've seen in your body previously so what can that complete antigen do this time if it's not the first encounter well it triggers what we call reactivity which is where you are activating b cells and t cells that were previously activated and now you're like reactivating them as in the idea of the memory cells for example that we've alluded to so far but haven't quite gotten to yet so that's the idea if something comes into the body and that something has large complex molecules those are going to be like complete antigens that can both activate new b and t cells assuming maybe it's a first encounter or reactivate like other bnt cells that are more like memory cells from previous encounters however every once in a while when something non-self comes into the body and it's very small and lacks molecular complexity then it might not be strong enough uh to actually trigger a full immune response and that's what we then call some we tend to then call those things incomplete antigens or sometimes called haptics again that's where their smaller size and lower complexity means that they're they're not like um you know robust enough for our immune system to really recognize as a full threat so how then if they can trigger any kind of immune response how do they work well they actually have to attach to molecules of our own bodies like cellular like carrier molecules and the idea is that once this non-self molecule the haptin plus our own human molecule combined now it's large enough and complex enough for our immune system to recognize as a threat so take for example there are some molecules from various uh allergic triggering substances that act as these haptics so take for example the oils from poison ivy the um the reaction that we get uh as like an allergic reaction to like you know getting poison ivy is where those molecules are too small but they bind to our human blood proteins then they're now large enough to trigger the allergic reaction with like the itching and this and like you know little blisters and so on so if an antigen is large and complex it's a complete antigen that is able to trigger its own responses from the immune system but incomplete antigens are haptens are too small lack complexity and therefore have to bind to carrier molecules if they're going to be able to trigger any response from us what's interesting is i'm here already talking about the idea that there's potential for a lot of complexity of an antigen what that even means is that if you can um you might actually be able to activate different b cells and different t cells and therefore kind of target the same pathogen from like multiple angles so to speak in other words you don't have to activate just one b cell and one t cell to fight the infection what if the infection has antigens that are complex enough that different pieces fit into different receptors on different b and t cells well that's the idea of the antigen having multiple what we call antigenic determinants so for example what if this is a molecule from a virus or a bacteria it doesn't really matter if this antigen is the molecule what if the molecule is so big and so complex that this piece of the molecule activates one b cell and this piece of the same molecule activates a different b cell and then this one activates yet another b cell well that means we are making clones of specialist cells that are all going to fight the same thing but from different angles like you know coming after it from for it's like different properties well that is great for our immune response because that means that we are targeting the same pathogen but making different antibodies or different t cells that are all working together so it's like having multiple slightly different specialists whose target is all the same so that's the idea that really large those like really large complex complete antigens can have multiple of those antigenic determinants the actual true pieces that stick into the receptors of our b cells and t cells and that means that when there's many of them we're fighting the same pathogen from a multi-pronged approach because we have many specialists going after the same target cell or target structure all right so that's the idea what an antigen is it's not the whole pathogen it's the molecular pieces that our immune system can can have receptors for recognizing and that will then trigger our immune response okay what we then have to realize then is that there are some molecules that in our body we would deem to be self but if you were to transplant them into somebody else their non-self right so for example when we learn about blood transfusions and who can donate to whom and who can't it's because you know one person's agglutinogen that is self is somebody else's non-self agglutinogen right so therefore any molecule that is diverse from one individual to another that we kind of accept as being ourselves but if it were put into somebody else would be kind of rejected we call that a self antigen so as i just described right a self antigen is any molecule that is found on our own cells surfaces and our immune system should know to ignore it and the idea of course is our immune system better have what we call self-tolerance as in we don't want autoimmunity right right if we've learned before autoimmunity right is where a person's immune system is attacking their own cells or tissues and that's the last thing we want so the idea of a self-antigen is that it's something that the immune system could target but if it's yourself you should be ignoring it because if you're not ignoring it then you have an autoimmune condition but of course right if you were to transplant a tissue from one person's body into another well then that person that is receiving that transplantation might now of course have an immune system that's going to attack these antigens because they're not self they were self to the from the donor but they are non-self for the recipient so that's the idea what we mean by self antigen something that you should ignore but other person's immune systems if that tissue were transplanted or transferred right would be targeted so our self antigens should be ignored through what we call self tolerance okay well what's interesting then is there are some molecules that are found on some of our cell surfaces called mhcs major histocompatibility complexes and the reason that these are self antigens is because my mhcs would be different from somebody else's mhcs which would be different somebody else's mhcs their proteins and proteins are built according to our genetics so inevitably everybody's mhc molecules are all a little different so that's why you can't just donate any tissue from a donor to a recipient because even if the blood type is the same what if their mhc molecules on their cells are significantly different well then that recipient might find their immune system rejecting the transplanted tissue because what was the donor's self-antigens are now non-self to that recipient so take for example mhc molecules which we'll talk about what they do for us in a moment are a major thing that has to be looked at to make sure that a donor and an uh and a recipient of transplanted tissue are like a close enough match and i'll mention that it's very common that any person receiving any kind of tissue or organ transplantation has to take immunosuppressant medications the idea is the last thing you want is for that recipient to reject the tissue that was just donated and so therefore if you suppress the immune system of the recipient you prevent the possible rejection of these self antigens which is now kind of non-self right for that recipient so basically then mhcs are an example of one of our self antigens so question then is what are mhcs how do we use them okay well so uh mhcs are going to be used to communicate from one cell type to another cell type and usually it's communication to immune cells so for example in our first video we talked briefly about natural killer cells and we had said that what if there was a cell in your body that has some kind of infection like a virus well uh let's start with healthy cell like let's assume that the cell which is let's say is here this cell right here is healthy well that healthy cell is going to use an mhc molecule like a little flagpole to put out on the outside of the cell a little protein and as long as this cell that is doing this is healthy then not only is the mhc molecule itself something that person should tolerate but as long as that protein is coming out of a healthy cell then the protein on the mhc molecule is also self so should a natural killer cell or a cytotoxic t cell that we'll learn about later attack this cell trying to trigger its apoptosis no because the idea here is that because this cell is healthy it is showing self antigen on that mhc and the idea is now like that's like communicating to the immune system everything's fine in here don't trigger my apoptosis i'm healthy but the idea of course is if this cell were to have a can a word to be cancerous or if this cell were to have a virus the next thing you know when the mhc is presenting on the surface of the cell right here it's no longer going to be presenting something self it'll now be presenting something non-self and that's now like a warning flag right so it's almost like the mhc is like the flagpole that sticks out of the cell and as long as it's like a self-antigen it's like the white flag to the immune system like everything's fine but if there's something going on wrong in this cell cancer virus parasite well then the mhc shows something non-self and that's now like an alert to the immune system like come kill this cell because this cell has a problem and we don't want that problem to spread so what kind of mhc molecule is doing this job specifically the one classified as mhc class 1. mhc class 1 is found on all nucleated cells so in other words you don't find them in red blood cells because red blood cells don't have a nucleus but virtually any other cell of your body that has a nucleus is going to have these and that makes sense because pretty much any cell in your body can get some kind of infection or can become cancerous and that's all inside the cell so that means that cell better put something on the outside of the cell as a warning so the mhc takes a warning molecule from the inside and presents it on the outside but if that cell were healthy there's no warning flag to put up so what is put out on the mhc-1 is something self but if that cell had cancer virus internal parasite now when that flagpole mhc class 1 molecule moves from the inside of the cell to the cyto to the cell membrane to like put the flag on the outside of the cell now it's going to show that non-self molecule and that alerts immune cells like this is your target this is the cell you want to trigger apoptosis okay eventually though we're going to have to learn about another type of mhc which is mhc class 2 and instead of being found on like your body nucleated cells these are found on immune cells and they're used to mobilize immune responses so for example remember how in our first video we talked about long-lived phagocytes things like macrophages and dendritic cells and we said that they gobble stuff up but they don't then die off they gobble stuff up and then bring that to places like the lymph nodes for example to show it to b cells in t cells thereby mobilizing the specialists so mhc class 1 is how cells of your body that could be healthy or unhealthy give that heads up to the cells of your immune system the mhc class ones show something self when those body cells are healthy or they show something non-self when those body cells have something wrong within but the only way you activate b cells and t cells uh to do your specialist adaptive defenses is to have your cells like macrophages and dendritic cells actually communicate to them and show them like this is what you have to go find and so in that regard only your immune cells like macrophages dendritic cells are going to have the type class or the class ii type of mhcs we'll learn more again we'll we'll be putting these pieces together basically as this chapter goes on but mhcs are examples of self antigens because if your body has a tissue with your mhc class ones and you move that tissue into somebody else's body their immune system is going to say well wait those molecules don't i'm not used to them and therefore i might reject that tissue all right but that's the idea of our mhcs they are an example of a self antigen and we have mhc class ones and class twos playing a vital role in like showing the immune system what is going on all right so now the next thing to think about are what are these major cell types of our adaptive defenses well we've already alluded to them but we can now kind of take a closer look at them so we already know that b lymphocytes commonly called b cells right which we're seeing over here are going to be the cells that are primarily in charge of that humeral immunity and that's again going to be this the job of making antibodies that are going to like circulate through our fluids and as i've alluded to before the only way a b cell or a t cell can respond is if they have receptors and the antigen has to like fit like so like into the like the binding sites there of those receptors so what we're seeing here for example is a b cell with its b cell receptors ready to possibly you know stick to and respond to a specific antigen but then when it comes to our cellular immunity which is again where our t cells or t lymphocytes are involved and remember their primary target is to look inside of cells like is there virus in there is there cancer in there and you can almost maybe start to think well oh that's where those mhcs are going to be important because how can a t cell look into a cell it can't it needs the cell to put those little warning flags out to let the other cells know like this is what's going on inside but that's the job of your t lymphocytes and they're going to have to have receptors for that right and t cells receptors are going to stick to the antigens triggering those cells to respond so the whole idea though is the b cells that do humeral immunity and these t cells that are going to do uh cellular immunity they have to have two important major or like characteristics they first have to have functioning receptors this b cell would do nothing if the receptor here didn't adequately have the ability to stick to like an antigen same thing for these t cells if these t cell receptors don't work right here that's going to be a problem and here's something additionally uh problematic when it comes to t cells t cell activation requires those mhcs kind of putting things into these receptors so what if these t cells receptors don't like doc or like join up correctly with the mhcs well then those t cells are worthless so the ability of a t cell or a b cell to have a functioning receptor that can respond to a specific antigen is like the bare minimum ability for those cells to do their jobs what do we call that ability immunocompetence well that makes sense if the word competence refers to an ability to do your job and your job is to do immune responses then your receptor better work it better be able to bind to antigen and it better be able to interact with those mhc molecules that show the antigens so that ability of a receptor to have the functioning ability to respond to antigens and stick to mhcs for presentation of antigens that is called immunocompetence okay but what if what sticks to a receptor of a b cell or t cell is something self so what if something like of your own molecules sticks to a b cell's receptor or a t cells receptor should that b cell activate or should that t cell activate no because then that's a cell of your immune system that is turning on yourself and is therefore autoimmunity so of course our b cells and t cells we've already alluded to the term already right it should have self tolerance in case a b cell's receptor ever bumps into a molecule that's your own or if an mhc is showing a self antigen instead of non-self then at no point should like a t cell start to activate and go to attack that cell because that's autoimmunity so the idea is that your b cells and t cells should have working receptors and be able to like uh dock or stick to an mhc for presenting the antigen at the same time if they bump into something that is self or if an mhc is showing something self then those b cells and t cells should be able to ignore that and that of course is the self tolerance so it kind of then begs the question how do we make a diversity of b and t cells and how do we make sure that they've got these characteristics of immune competence and self-tolerance well that's what we go like for the next couple of slides is figuring out exactly like how we do that okay so let's take a look so the next thing we want to look at is like the story of the development of lymphocytes like where do we make them where do they kind of get educated uh where do they then go after that so let's kind of look at like the story of the development and movement of our lymphocytes uh and you know focusing on both b cells and t cells at this point kind of simultaneously okay so first of all whether we're talking about a b lymphocyte or a t lymphocyte does not matter the origination point of course is our red bone marrow right because b and t cells are both blood cells and red bone marrow is where we produce you know blood um all of our blood cells that is the starting point of this like journey or you know story of these b and t cells it all begins at your red bone marrow the thing though is our b and t cells now have to become what i want to rephrase it as like becoming educated right the education is where we make sure that they have the immuno competence a working receptor and self-tolerance avoiding autoimmunity what's interesting is that education process as i typically phrase it the b in b cell and the t in t cell tells you where that education process happens for b cells it stays it's like the b cells are like this the like the cells that stay home for school in other words like because their education process happens right there in the bone marrow so b for bone marrow is telling you okay the education process of becoming uh immuno-competent and self-tolerant that happens in bone marrow for b cells t-cells they kind of go away to school where do they go a thymus t cells leave the bone marrow and go to the thymus and that's where they become immunocompetent and self-tolerant but here's the thing once you have made sure that these b cells and t cells have those properties of immune competence and self-tolerance we can now refer to them as what we call naive cells as in they have their education so to speak we know they have those two characteristics they need but they've never been activated before so it's almost like a fresh graduate it's like in theory they know what they're doing but they've never yet maybe had a job to put it into practice so these cells have been we've made sure that they have the properties that they need to be a an effective immune cell but they've never done it yet so the idea is these cells that we now call naive b cells and naive t cells they don't stay in school now they don't stay in the bone marrow or thymus anymore they migrate where do they migrate they migrate out of what we call these primary lymphatic tissues or lymphoid tissues like the bone marrow and thymus and move into what we now call secondary lymphoid tissues the things we talked about in the lymphatic system chapter like your lymph nodes your spleen tonsils appendix patches right anywhere we said that there are lymphatic tissues that house immune cells that's where those cells go once they are educated but naive so what's the idea here now they wait for activation by encountering their specific antigen that will perfectly fit into their little receptors we call that first encounter the antigen challenge it's like and what's amazing is this imagine that in your younger years you populate your lymph nodes your spleen and other secondary lymphatic tissues with these naive cells many of those naive cells will never be activated why because what if you make a whole bunch of b and t cells that are going to be really good at fighting chicago and you never travel anywhere in the world where there is that infection or maybe you have some b cells and t cells that would be really good at fighting yellow fever but you never go anywhere in the world where there is yellow fever that means you would have never had an antigen challenge for those b or t cells and so you would have never cloned them and therefore never used them and they just stay naive indefinitely but what if you have some b and t cells that have receptors that are really good for fighting a specific thing like a specific strain of the flu and you get that strain of the flu well now those b cells and t cells that happen to have the right shaped receptors that are sticking to that variant of the flu are now activated and what do you do with the activated cells you clone them over and over again so you have like a whole bunch of like the same specialist that can now travel systemically through the whole body making antibodies and killing the cells that have the infection and so now it's like your specialists that were waiting waiting waiting to see if they would ever be activated are activated and cloned and what's amazing is when you activate bnc t cells you activate them for now and you also activate them for later why because as we'll learn eventually every time you kind of select a cell in this process for cloning you make clones for right now that we call like effector cells which are like the cells releasing the antibodies or the t cells that actually kill or trigger the apoptosis of the infected cells but whenever you make those you make memory cells that do nothing right now they wait around because maybe in six months or six years the same pathogen will come back into the body and so do you have to go way back to the original naive cells to start this response no because you made memory cells on the first time around and that means you can start an immune response on this subsequent account encounter much quicker and more effectively because you've adapted already right your immune system has already been challenged by that particular pathogen so amazing that in your younger years you're producing a ton of b cells and t cells in your bone marrow and they migrate to or or stay in the bone marrow or migrate to your thymus to become immuno-competent and self-tolerant once done there they leave those education places and kind of take up residence indefinitely in secondary lymphatic tissues like your tonsils pliers patches your appendix lymph nodes etc and there they wait maybe they will be activated at some point maybe they never will but if they do become activated we make numerous copies of them for now and even memory cells for the future all right so that's the general idea of like lymphocyte like development and movement around the body and like the series of events like the story of of how our lymphocytes work it's also why we learned in the um lymphatic system chapter that your thymus at some point degenerates and becomes mostly fat because once you have fully populated all of these secondary lymphoid tissues with all these naive b cells and t cells we don't need any more it's like we have so many specialists waiting around to see if they'll ever be activated that we don't need to make more specialists they're just waiting for their opportunities interesting all right so that's the general idea of like lymphocyte movement the next question is how do they become like educated how do we make sure they have the immune competence and the self-tolerance actually even the first question before we get to that is how do we have such a diversity because here i phrased a few moments ago like what if you have b cells and t cells that have a receptors that are like really good for chikagonia or yellow fever or dengue fever all these things that maybe are not common in the us because we don't have those specific pathogens here well it's not like your immune system knows what those infections are it just so it's just the idea instead is that you have such a tremendous diversity of shapes of your b cell receptors and your t cell receptors that almost no matter what pathogen gets into your body there's going to be some immune cells that have a receptor with a shape close enough to respond to that antigen how do we get them such a diversity of receptors well that's interesting here's why b cell and t cell receptors i can just show for example that in the diagram on the left they're showing a t cell here and i see that these little green things are its receptors well the receptor is meant to have something bind to it so if the shape of the receptor changes then its target changes because if this t cell's receptor sticks to the flu then it's not going to stick to something else so the idea then is in your secondary lymphatic tissues you need a huge diversity of b cell and t cells with a huge diversity of receptors that way if you travel around the world and encounter different pathogens hopefully you've got b cells and t cells whose receptors are going to be really good at dealing with that pathogen well here's the problem the receptors are proteins proteins are encoded in your genetics humans only have about 20 000 different genes and most of those genes encode for structural things collagen keratin hormones etc which means you can't have an indefinite set of genes to encode for the receptors for all the different pathogens that exist so what do we have to do randomness what's amazing is every receptor for a b cell and t cell is encoded in your genetics but the gene for those receptor shuffles itself every time your bone marrow makes a new b cell that new b cell's receptor is different from the last b cells receptor every time your red bone marrow makes a new t cell the receptor of that t cell is different from every other t cell it has ever made why because the genes for b cell and t cell receptors undergo somatic recombination the letters of the dna in that gene move around that way every time a new b cell is made its receptor is a new shape every time a new t cell is made it's a new shaped receptor so you don't have a gene for every new shape you just have one gene that's constantly shuffling and that way every time you in your bone marrow make a new brt cell it's unique and that means you have a huge diversity of these receptors you don't need a tremendous number of genes you just need one gene that is shuffling itself but here's the problem when you are doing it that randomly some of those b cells and t cells are going to have receptors that don't work at all right we'll learn soon enough as we've already alluded to though that sometimes b cells or t cells have to communicate with body cells or immune cells using mhcs that the the molecules right that act like little flag poles that show the antigen well sometimes the cells have to line up with each other so for example what if this t cells receptor can't fit an an interlock or dock with this mhc molecule right here if you can't bind that mhc molecule at all then what's the point of that t cell it is completely functionless so why keep it around instead just destroy it so this first event recall we call positive selection is the idea that you want to look at the receptors and make sure that they can interact with the molecules that show them antigen which are mhcs if the t cells receptor can't communicate to the mhc then this t cell will never be activated and so what's the point of that t cell if it can't communicate to the mhc then destroy it what about if it can communicate to the mhc okay then we keep it it survives that first step so the first step of this like education process is making sure that it has immunocompetence right if it can bind to the mhc and its receptor can you know respond to the antigen then it's immunocompetent it can do its job so therefore it survives it if that t cell in this situation can't bind with that mhc which means it can never be communicated to and activated then there's no point so we trigger its apoptosis all right so that's our first round positive selection where we're choosing the ones that can respond to antigens by way of mhc and getting rid of the ones that can't okay so now the question is all the ones that survived the first round what if we go put them go ahead and put them through a second round and what do we do in the second round we specifically use an mhc and show it something self and we see how that goes why because the first round only made sure that the t cell in this diagram could receive the antigen and we're like okay it can great you you you survive but what if we go ahead and put something self in that receptor and what if that t cell starts to react well that's bad because that t cell is reacting to something that is self and that t cell should be self tolerant so if it starts to recognize something as self and starts to activate then we should say whoa whoa we should get rid of that cell because that cell could be a part of autoimmunity so the second round called negative selection is where we present something self to the cells receptor and if the cell starts to activate then that's a problem because that could trigger autoimmunity and we want to get rid of that cell so we trigger its apoptosis what's amazing is very few of these like t cells going through this education in the thymus actually get through all of this most of them were destroyed in the first round or the second round not that i would hold you responsible for the numbers because i didn't put it in the notes but the diagram shows you only about two percent of the cells survive this process in the thymus but the idea is that is a giant weeding out process because the receptors were first made by a random shuffle then that means that some of that random shuffle could produce cells that don't work at all or that overreact to ourselves and we need cells that are immuno-competent and self-tolerant and so getting rid of the ones whose receptors don't work gets rid of all the non-immuno-competent ones and getting rid of the ones that overreact to self gets rid of all the self-intolerant ones and so the two or so percent that are left are the ones that are now considered to be naive b and t cells that are they're kind of past the education process they have immuno competence they have self-tolerance now they can go out of the education places like the thymus and go to your tonsils and your lymph nodes and and things like that to to wait for their activation so that's the idea is that they only get to be naive cells populating and waiting for activation if they survived this multi-step process of education where the positive selection again was getting rid of all the ones that aren't immuno-competent and then negative selection getting all rid of all the ones that are not self-tolerant pretty amazing all right here's the one more thing i want to make sure we're seeing here notice how it's mhc class 2 here being used to show uh this t cell um you know the antigen and then we see though in this dendritic cell down here mhc class 1 being used to do that the idea basically is right sometimes you literally have to put the antigen into the receptor of the b cell or the t cell and and that process of like using an mhc to take an antigen or at least a piece of a little antigen and like show it to a b cell or t cell that's an important step in our immune responses so that's like i think from remembering correctly right i think that's what we're going to on the next slide here exactly yep is the idea of these cells that are doing that job of antigen presentation so here's another one of those three letter acronyms in this chapter right we've seen um macs and eight um uh you know mhcs and so on uh member macs right membrane attack complexes so now we have apcs antigen presenting cells so here's the idea cells like your macrophages and dendritic cells are what we call apcs which are short for antigen presenting cells the idea here is that unlike the neutrophils like our short-lived phagocytes that gobble stuff up and die off we said that the long-lived phagocytes should gobble stuff up and then travel and show them to mount more robust immune responses specifically mobilizing the adaptive responses so antigen presenting cells jobs are to make sure that we end up with activated b cells and t cell specialists uh like taking them from the naive cells to the activated effector cells so antigen presenting cells then what we think about it are hugely important and i can what the way that i or what i mean to imply there is how they are an important bridge in between innate immunity and adaptive immunity so let's see what i mean by that they're showing a dendritic cell in the diagram but this could also be a macrophage right both macrophages and dendritic cells are good classic examples of our apcs well we talked about those cell types earlier as part of your innate immune responses because they are phagocytes so if this dendritic cell gobbles up some bacteria or some virus protein or anything like that that job of engulfing stuff is an innate action but if that phagocyte gobbles something up but then takes it and puts it on an mhc molecule and shows it to a t cell or or possibly like a b cell then that is activating cells of your adaptive defenses so that makes antigen presenting cells hugely important because we know that if you're adapt i'm sorry if we know that your innate defenses prove to be not enough we at some point better be activating our specialists of our adaptive defenses like our t cells for example so how do we bridge from the innate over the adaptive antigen presenting cells because those antigen presenting cells gobble stuff up but then present it on the outside of the cell by way of the mhcs and the idea is the mhcs then put the little antigen right into the actual receptor of the t cell it's almost like saying hey t cell this is what's causing an infection right now i'm gonna have you activate and go fight it so that cloning of this t cell into a bunch of clones that are gonna go fight that infection that's your adaptive response this cell gobbling up by way of phagocytosis that was innate but this presentation where the apc communicates to the t cell saying like go do your specialty job that's the bridge that is crucial to go from an innate response to an adaptive response so that's the importance and role of these apcs or antigen presenting cells and i think that's going to bring us to the end of this video because yeah from here on we start to go more in depth about purely humoral immunity than purely cellular immunity and so we'll do separate videos for each of those