Antibody Structure and Diversity

Hi in this video I'm gonna be talking about antibody structure and variety. So first let's focus on antibody structure. So we know um antibodies are used. Their proteins are created by B cells they mark the pathogen for destruction but what's their structure. But first um antibodies are actually also called immunoglobulin. So if you ever see immunoglobulins or you C. I. G. Um this is they're trying to antibodies. So first the structure for the antibody is A. Y. Looks like a Y. It has two chains or actually it's four chains. Two of them are light. Two of them are heavy that's based on the size. Obviously Heavy is bigger and light is smaller and um actually both the light and heavy chains are actually able to interact with the region where the antibody binds to the antigen. And B cells produce a ton of antibodies. They can secrete when they're activated, can secrete around 5000 of these per second. Um And these are very specific with each B. Cell producing only one type of antibody. So here we have you see the y it looks exactly like A Y. Um And so you see the two heavy chains. They're the bigger ones here and here and then you see the two light chains here and here and you also see that the yellow region here this is gonna be the antigen binding site. So there's a portion on the heavy chain and a portion of the light chain and this recognizes different antigens. Um They're very specific though so you can see that the yellow antigen binding site is only going to buy the yellow and again and not any of these other colors up here so that's what it looks like Now there are multiple classes of antibodies. So there are five classes based on the heavy chain, five based on the heavy and each one of them have different functions. So here they are. I G. M. I G. D. I G. A. I G. E. N. I G. G. Immunoglobulin M. Essentially your antibody M. They're located in different locations. You see that I. G. M. And I G. D. Aren't secreted. They're actually located in the plasma membrane where A. E. And G. Are secreted. And then you see here that they have kind of different functions they activated different places. They're secreted in different places. So the I. G. M. And D. Are usually present before the activation. There's sort of the initial responders to um different antigens and once they sort of activate the B. Cell what you get is this switch to different antibodies that then can be secreted in tears or in blood. Um or you know even be passed to the fetus in the case of I. G. G. Um And they all have these different functions interesting if any of you have allergies you can blame the I. G. E. Antibody for that which I definitely do. Now there are two different types. So remember the heavy chains are these bigger ones so there's five different types of these now there are two types of light chains but we're not really gonna talk about them, they're virtually indistinguishable. But there are two types. So I just wanted to let you know but they're kind of expressed everywhere and it doesn't really matter. Um they're just indistinguishable. And so antibodies work by binding antigens in their antigen binding site. And so of course the strength of this interaction um is going to be dependent on bonds. And so the antibody actually makes non covalin bonds with the and again by using the light and heavy chains to make those connections with the and again now they're on each the light on each of the light and heavy change. There are two regions there's constant regions and these are going to be sort of the same sequence for the same class of antibodies. So all of the I. G. M. S have the same constant sequence. All of the I. G. E. S. The same constant sequence. But then there's a second region called the variable region. They're on the same size but they vary between each B cell and then within the variable regions there's even further variation called hyper variable regions. These are the 5 to 10 amino acids location where the antigen is actually going to bind. So here we have an antibody. This is an I. G. Antibody. Now you can see this notation here C. H. And B. H. C. L. V. L. So just when I get you used to this notation. So this is going to be the constant region and the heavy chain and the constant region in the light chain. This is the variable region in the heavy and the same variable in the light. So you see here that you have these variable heavy variable light, constant heavy constant light. Now the constants are going to say these are gonna be the same sequences. So that anything with the C is going to be the same sequence for antibody classes. So all I. G. G. S are going to have the same sequence. All I G. M. S are going to have the same sequence for the variable regions. All the kappa light for all the kappa for the light chain while all have the same sequence. But when you get to the variable these are the variable regions and these are gonna be different based on every single antibody because this is where the antigen binds. So of course you need it to be different because those binding sites are gonna be different based on the different antigens. And so um the variable region is around the same size and it's going to be different. And then there are the specific hyper variable regions that are even more unique and that's really where the antigen makes its most connections is in those regions. So that is the structure of an antibody. So with that let's turn the page

Okay. So in this video we're gonna be talking about the variation and antibodies. So we know that antibodies have to be there has to be a ton of them. So how do we actually create that diversity now you may say oh it's just encoded in the genome Right. Like of course we have all these different proteins. Why wouldn't antibodies just be encoded in the genome? Well they are encoded in the genome. Of course there are protein but it's not that every single antibody that could ever be produced is encoded in the genome. It's just not feasible. We don't have enough room. It would be so much DNA that it would just like we have a huge creatures that it just wouldn't work. So instead we use this process called V. D. J. Recombination and this is responsible for creating these variable regions in the antibody that can recognize these you know millions if not billions of antigens. So to do this cells use this special gene recombination to produce the antibodies against as many antigens as they possibly can. So how we do this is there are three antibody segment genes located in different genomic locations in the cell. So there's a V. Gene segments A. J. And A. D. And so the V. And J. Focused on the light chain variable regions. Whereas whoops whereas the D. Gene segment encodes for the heavy chain variable regions. And so um there are multiple V. J. And D. Regions um in a in a genome and they're recombined in different combinations to form an engine binding site. So for instance for humans we have 50 V. Five J. And 35 D. Which when all of those recombination czar made will actually form 1.9 times 10 to the sixth antigen binding sites. So it's a huge huge huge diversity. Um that allows us to create this without actually having to encode every single antibody itself. So what this looks like is if you were to look at the genome, what you see is you just see a string of the regions, a string of the regions and a string of J regions. And then eventually a constant region. Now if we had to encode each one of these individually we'd have to do this one compared to all of these paired to all of these. And it would take up so much room in the genome. So instead we just order them all of these all the Ds all the days. Then through a variety of steps which I'm not gonna go through, we start cutting them out. We start saying okay we don't want these reasons. We don't want these J regions. We don't want these V. Regions. So what we end up with is a V. D. J. Region that can be connected to a constant. That is unique because it has this vi compared with this D in this J. And this will go on to create an antibody that's specific for one antigen. So super important in creating this diversity without filling our gene up with all these genome up with all these different combinations. Now that's obviously not enough. Right. There was 1.9 times 10 to the six which is a lot. But isn't actually the number of bacteria on earth you know that's a much higher number. So we have to create variation in other ways. So one of the ways we do this is through some somatic hyper mutation. And this is a characteristic which B cells have um at the variable gene segments either on the light chain or on the heavy chain. And essentially somatic hyper mutation means that there's a mutation in the variable region about once every division. So it's super high. I mean none of our other cells do that if we did we'd have all sorts of cancers and mutations and we wouldn't live very long. But the antibody regions these variable region segments actually mutate once per division. So you can imagine B cells divide so quickly so fast. Um So all of these variable regions are constantly being mutated after every division and that's called somatic hyper mutation. Now most of these aren't going to do anything right. They're not going to change the affinity but some of them will increase the affinity for antigens. Some of them will actually recognize different pathogens or different antigens. And that will result in further diversity and further strength of the reaction. And then finally all the cells undergo what's known as class switching during development. So remember that there are all these different classes of antibodies. I G. M and I G. D. Are called the primary antibodies because these are the ones that B cells first produced. These are found in the plasma membrane, they're not secreted and B cells produce either or both. Then um somatic hyper mutation occurs after B cell activation. And so the class switches so the type of antibody produces switches to E. A. Or G. Depending on what kind of response it needs. And this is called the secondary antibody repertoire. So what we see here again, we've seen this image before but don't worry about any of the text. Should have taken it out but just I'll leave it there in case you feel like reading it. But essentially what you see here will say that this is I G. M. And this is a B cell that's recognizing an antigen. Eventually it goes through all this maturation process which we'll talk about. But then what you get is you get a class switching to a different antibody will say this is I. G. So class switching occurs and the antibody that was originally produced on the surface, this gray thing here is not the antibody that is released. So that is going to be a different antibody that can actually be secreted but it's specific for the same androgen. So with that let's now turn the page