Before we get started talking about B cells, let's spend a moment just reviewing the differences between B cells and T cells. Both B cells and T cells are components of the adaptive immune response, the part of the immune response that is slow but has memory. B cells are part of the humoral immune response, and they are those cells that produce antibodies, and antibodies help eliminate pathogens that are. outside of your cells. T cells, specifically cytotoxic T cells, they're responsible for attacking cells that are abnormal or infected.
Okay, so these are invaders inside cells, and we will learn later on in this set of lecture videos that T cells, like natural killer cells, are also part of what prevents cancer cells from continuing to grow. Nevertheless, T cells attack invaders inside cells or they're... attacking infected cells or abnormal cells. B cells are attacking invaders outside the cells.
So this is the humoral response here, and this is the cell-mediated response. Let's take a quick little detour and talk about these self-proteins that are present on the surface of cells, because this is going to be really important as we differentiate the way a T cell protects you versus the way a B cell protects you. And I want to remind you, we've talked about the fact that your cells, your white blood cells, recognize you as self. And we said that they do this by looking at proteins on the surface of your cells. So all nucleated human cells have class 1 MHC molecules on their surface.
Erythrocytes, red blood cells, do not have class 1 MHC because they are not nucleated. But all of your other cells do. So this is that special self protein. It's on the presence of all of your nucleated cells.
It's called MHC class 1. And it can bind to antigens. And we're going to talk about how this works in the immune system later on. But basically, all of your cells have class 1 MHC. So for now, you're thinking of this molecule as having a role of communicating to white blood cells that might be patrolling that, hey, it's just me itself.
I'm a good guy. Don't destroy me. There's another MHC. class two that you need to know about.
So notice that this is also a cell that contains MHC class one. So all nucleated cells all have MHC class one. All right.
So all of them, that's both of these cells. But some specific cell types also have class two MHC. And these are what I call professional antigen presenting cells. That means that their major role in your body is to present antigen.
We'll talk more about that in a minute. But their major role in the body is to present antigen. There are three cell types that we typically think of as antigen-presenting cells. We've talked about two of them already, macrophages and dendritic cells.
And then your B cells are also antigen-presenting cells. So B cells, macrophages, and dendritic cells. They have class I MHC because they're nucleated. but they're also professional antigen presenters.
That's their major job in the body. So they also have class 2 MHC. Now a liver cell, its main role is to actually be part of your liver and do the jobs that liver cells do.
So it's not a professional antigen presenter, so it won't have class 2 MHC. It'll only have class 1 MHC. Let's talk a little bit about the origins of B cells and T cells for a moment. So B cells and T cells both start in your bone marrow.
We talked a little bit about hematopoietic stem cells when we did our blood lab. So all of your red blood cells and white blood cells start out as a hematopoietic stem cell. So we think of the fertilized embryo that's formed when sperm meets egg as being the most primitive kind of stem cell, a totipotent stem cell.
And then there are, as the embryo begins to develop, that you... end up with a ball of cells that end up turning into the human. Those are pluripotent stem cells.
So those are very special embryonic stem cells. In an adult, you also have some stem cells that persist throughout your life. Now they can't differentiate into your brain or your liver or your toes, but they do in many cases differentiate and replenish some specific cell types.
And so hematopoietic stem cells are cells that can... can grow, they can differentiate into all of the different cells. your blood system including red blood cells but then all of the white blood cells too. So T cells and B cells are lymphocytes, they are a type of blood cell and they originate in the bone marrow from these hematopoietic stem cells. When hematopoietic stem cells differentiate in the lymphocytes, if it's a B cell because they're different lymphocytes, the B cell will mature, it will differentiate and mature in the bone marrow and it's going to produce these Ig.
molecules, these immunoglobulin pre-antibodies in a way, on their surface. Okay, so this happens, and then these naive B cells, they're not active yet, they're going to migrate to the lymph node where they're going to be part of that, we talked about the screeners, right? They're going to sit in the lymph nodes looking for strangers to bind to. T cells undergo a similar process.
They differentiate in the, instead of the bone marrow, they differentiate in the thymus, and that's where T cell comes from. So T is for thymus. They also make receptors on their surface. And so it's called a T cell receptor, whereas here it's called a B cell receptor.
And then once it's differentiated and it has the cell receptors on it, it's going to also migrate to the lymph node where it will hang out with these antigen presenting cells. And they're all going to wait to see whether or not foreign antigens show up. and an antigen presenting cell will present them to T helper cells and that's going to allow these B cells and T cells to become active. Let's just take a quick peek at the surface of T cells and B cells.
Let's do T cells first just for the heck of it. So our T cells matured in the thymus and they ended up with these receptors on their surface. So that's what this is showing here is that specific T cell receptor.
Alright, and then if we were showing everything, we would also see that this has an MHC class 1 molecule on it, because we know that it's a nucleated cell. All nucleated cells have MHC class 1. Our B cell receptor has a different shape, but it still does the same thing. It binds to foreign antigens on the surface. Here, this also binds to foreign antigens.
Remember that our B cell is a professional antigen-presenting cell, so we see the MHC class 2 markers on it as well. and it also has MHC class 1. They're not drawn here, but it's as a nucleated cell. It will contain MHC class 1 as well.
Okay, so this is kind of an up-close look. One of the things that this is CD4 and CD8, you might have heard of CD4 cells and CD8 cells, particularly if you have any experience, clinical experience working in hospitals. These are two different kinds of T cells.
So CD4 refers to T helper cells. CD8 refers to cytotoxic T cells, and they have different jobs. So this CD4 slash CD8 is referring to two different cell types.
Now, this is the idea behind clonal selection. So one of the things that we said, and when we watched that little nature video, you got the idea that we could make billions of different receptors. So they refer to them as antibodies, but... even antibodies start off as receptors, either a B-cell receptor on the surface of a B-cell.
And so we can't draw billions on this slide, but we can draw a few. So I just want to point out that process with RAG and the gene shuffling that happens when B-cells and T-cells are maturing. Again, it's in the thymus if it's a T-cell, it's in the bone marrow if it's a B-cell.
We're going to get billions of these different receptors, okay? And these cells are all going to migrate to the lymph nodes. Now before they do that, do you notice these X's here?
These are B cells or T cells that have been removed because they bind incorrectly to self antigens. And so hopefully these get taken out because you don't want to have specificity to yourself. You want only lymphocytes that are going to bind to foreign molecules.
So we talk about this as immune tolerance, this idea that we're going to eliminate Because the process of building these receptors is random, there has to be a system for removing lymphocytes that might actually accidentally bind to us. All right, so after they're removed, then we have, these are our repertoire. This is our group of lymphocyte clones, and this could be B cells or T cells, that end up in those lymph nodes. And they're sitting there. These are naive lymphocytes.
So they are not active yet because they have not yet found an antigen to bind to. So each one of these looks different. Okay, so they're sitting in the lift notes waiting. They're on Facebook. They're sending tweets Um, they're instagramming doing nothing useful until at some point an antigen shows up in the lymph node.
And of course, the process of the antigen binding to the cell is a little bit more complicated than this, but let's talk about the basics first. So here we have this antigen, and you see that it doesn't bind to these guys, doesn't bind to these two, but it does. It fits perfectly into this particular binding site of this particular receptor.
And when it binds, that's going to result in the immune system saying, hey, you are... The cell we need, we want you to make lots of copies of yourself. So these cells are going to be expanded.
They're going to become activated. They're going to expand. We'll go from one cell to millions of these cells. And they will begin circulating through your body, either producing antibodies or active as cytotoxic T cells. And they're going to protect you against whatever this antigen is, whether it's a virus, whether it's a bacteria, et cetera.
Okay, so. This is called clonal selection because these are different clones, right? We've eliminated the ones that might harm us.
We have a bunch of naive cells that will bind to different receptors, and they're not going to do anything until a receptor shows up that we need to fight against. And then the one that's correct, the one that gets selected for, is going to be expanded a million-fold. You're going to have tons of these circulating in your body, making antibodies.
killing infected cells and that's what's going to help you finally get better from this pathogen that's caused you to get sick. All right, so the next thing we're going to talk about are T helper cells and get a sense of how they function as the linchpin of the immune system.