 Welcome back to our MedSmarter Lecture series, where we're taking a smarter approach to preparing future physician. Before we get started, if you'll take just a quick minute and click that like button, and also subscribe and turn the bell on so that you'll be notified when we post new videos. And let's go ahead and finish up with our lymphoid structures, as we discuss the diversity and specificity of antibodies. So antibodies generate diversity through an antigen-independent system. So they have three different ways that they can diversify. The first one is going to be a random recombination of the VJ or the VDJ chains. So the VJ remember is our light chains and our VDJ are the heavy chains. So as you can see here on this particular segment, the L is going to be our light chain and the H in the middle is going to be our heavy chains. So those particular locations have genes that will undergo random recombination and that will help diversify our antibodies. Another way antibodies can diversify is by undergoing random addition of nucleotides in the DNA. All right, so we're going to be adding some nucleotides. And specifically this is done by using the terminal deoxy nucleotidal transferase or TDT. And finally, we can also just have random combination of the heavy chains and the light change. So we can have recombination where the light chain will cross over and become the heavy chain. And so the yellow will cross over, become the pink. The pink crosses back over, becomes the yellow. So there's just your random combination of heavy and light chains. And then antibody specificity, which is antigen-dependent, is going to undercure due to a somatic hypermutation and affinity maturation in the variable region. And remember that variable region of these two tip ends down here. So you have the variable light, variable heavy on both sides. Those are the areas where the somatic hypermutation and affinity maturation will occur. And then finally, we can also see isotype switching in the constant region. And the constant region is the ones that start with the C and that's down here in the base portion of the immunoglobulin. So let's talk about the different isotypes of immunoglobulins. Specifically, the isotypes can all exist as monomers. So a monomer example is over here on the right, the red color. This is mostly going to be seen as IgG, IgE, and IgD. However, all of these can exist as a monomer. So for immunoglobulin isotypes, they start as mature, naive B cells. Then they're activated to express the IgM and IgD on their surfaces. They can differentiate into germinal centers of the lymph nodes by isotype switching in the plasma cells, which will then secrete IgA, IgE, and IgG. And specifically here, the affinity will refer to individual antibody-antigen interaction. So the antibodies, which is the big portions, and then the antigens will come in and interact here, those are going to be the affinity, whereas avidity describes the cumulative binding strength of all antibody-antigen interactions in a multivalent molecule. So that's going to be how strongly these can interact together, not just their actual interactions. So let's talk about IgG. So from that previous picture, it's that red one that's a monomer. It is actually the main antibody in the secondary response to an antigen. It is also the most abundant isotype that we see in the blood serum, and it fixes complement. It opsonizes bacteria, neutralizes bacterial toxins, as well as viruses. This also is the only isotype that will cross the placenta, which gives the ability for it to provide infants with passive immunity that starts to wane after birth. So something to remember here, and this is going to be a little different. We'll talk about when we get to IgA. IgG is the only one that crosses the placenta. Now, you can get confused. IgA goes through breast milk into the babies. However, crossing the placenta is only going to be IgG. So we can remember that for IgG greets the growing fetus, because that's going to be crossing the placenta. So let's talk about IgA. Now, IgA is a dimer. So these are two monomers connected together to form a dimer. These will prevent the attachment of bacteria and viruses to the mucous membranes. So a lot of times you see these function on the mucous membrane areas. So in the lungs and the GI tract, that's where you're mostly going to see the IgA productions and they do not fix complement. So in circulation, like we said a minute ago, you're going to see these as monomers. But when they are secreted, that is where you see them as dimers that are fixed with that J-chain. These do cross through epithelial cells using transcytosis. They're produced in the GI tract. So the pyres patches specifically are producing them in the GI tract and they protect against infections like Giardia. They are the most produced antibody overall. However, their serum concentrations are going to be lower. They are released into secretions and breast milk. So this is where that, like we said earlier, the IgG goes across the placenta. The breast milk infants will get IgA throughout breastfeeding time as an additional immune support from the mother. IgA picks up secretory components from the epithelial cells, which will then protect the FC portion from luminal proteases. Let's continue on and discuss IgM. IgM is the large pentamer that we saw earlier, has five monomers attached. These are produced in the primary or the immediate response to an antigen. So anytime you are exposed to an antigen, the first thing that's going to be produced by the body in terms of immunoglobulins is IgM. IgM also fixes complement and it acts as an antigen receptor on the surface of B cells where that actually will be a monomer. So we said these can all exist as monomers. So you could see just one single one on the surface of a B cell. Or when it has a J chain with it, which we'll see here in the middle, they are secreted with a J chain as a pentamer. And the reason for that pentamer here is it actually enables binding to an antigen while the humoral response will evolve. Moving on to IgD. IgD actually has an unclear function. It only exists as a monomer and it's found on the surface of many B cells and in the serum. If you found this material helpful for your studying, please like and consider subscribing to the channel. Also, share this video so that more people can benefit from it like you have.