C17L7 Acquired Immunity: T Cells, B Cells and Antibodies

Acquired Immunity

Acquired immunity is an immune response to a specific pathogen that can be reactivated if the pathogen is ever encountered again. Most people are already familiar with this concept. For example, everybody knows that if you've had chicken pox, you won't get it again because you've developed immunity to it. But how do we actually develop this immunity? Would you believe that acquired immunity is initially based on chance and large-scale trial and error? It may seem odd, but that's how it all starts.

The workhorses of the acquired immune system are lymphocytes, which are white blood cells that recognize and respond to a single molecular structure. Each lymphocyte is very specific and can only recognize a single antigen, or molecular structure, that is recognized by the acquired immune system. The strange part is that the antigen-binding site that a lymphocyte uses to recognize an antigen is created in an almost random fashion before the lymphocyte ever comes in contact with a foreign protein or pathogen!

So what are the chances of creating a binding site by chance that can recognize a random peptide that is made by a virus? One in a million? One in 10 million? Maybe one in 100 million? It's impossible to know what the odds really are, but if they're close to this, we're not in bad shape because immunologists estimate that our immune systems typically have about 1 trillion lymphocytes, which can recognize about 100 million different molecular structures. Even though the odds of matching a particular viral peptide with a randomly created receptor may be close to the odds of winning a multimillion-dollar lottery jackpot, our immune systems can buy enough tickets to even up the odds. In addition, all pathogens make multiple different proteins, and most of these can be chopped up into several smaller peptides that can be recognized by lymphocytes. So not only does the immune system buy 100 million tickets, but the lottery it's trying to win probably has at the very least a few hundred different jackpot winning combinations! With so many potential antigens and 100 million different antigen-binding sites to try against each foreign peptide, our immune systems stack the odds in our favor so that we win the jackpot almost every time!

Creating Antigen Receptor Diversity

Now you may still be wondering how immune cells can create so many unique antigen receptors and antibodies. Think of it in terms of creating a sandwich if you had a choice of 250 different types of bread, 200 different cheeses, 50 kinds of lunchmeat, eight different vegetables and five different condiments. Think about all of the different types of sandwiches could you make combining one bread with one vegetable, one meat, one cheese and one condiment. You could make 100 million different sandwich combinations! That's basically how a lymphocyte determines what the binding site of its antibodies or antigen receptor will be. You see, the binding sites are actually composed of five different modular amino acid sequences, and for each module, the cell has several, sometimes even hundreds of options available to it. Creating all of the possible modular sequence combinations and adding a couple of genetic tricks to multiply the combinations a couple more times would create about 100 million unique combinations. Once the combination is determined in a lymphocyte, it's locked into place for that cell and all descendants of that cell.

Now let's take a look at the different types of lymphocytes. There are two major types of lymphocytes: T lymphocytes or T cells, and B lymphocytes or B cells. These two types of lymphocytes are named and classified based on where they mature in the body. T cells mature in the thymus, and B cells mature in the bone marrow. Where they mature isn't the only difference between T and B cells. As we'll soon see, there are some major functional differences between T cells and B cells.

T Cells

As we talked about earlier, T Cells are lymphocytes that mature in the thymus. There are several different types of T cells that serve different functions in the immune system, but we're going to just talk about two of them in this lesson.

CD8 and CD4 T Cells

The first type of T cell that we're going to talk about is the Cytotoxic T Lymphocyte, or CTL for short. This type of T cell is also called the CD8 T cell. Its main function is to destroy infected cells before they release mature parasites. If the immune system can destroy infected cells before they release new parasites, it will be much easier to control the infection, but how does the CD8 T cell know which cells are infected with parasites? If the parasites are inside the cell, they're hidden from the CD8s, right? Well, not completely, because cells are always displaying sample peptides of internal proteins on the outside of the plasma membrane. The cells display these peptides just so that CD8s and other immune cells can monitor them and see a sample of what is inside the cell.

Diagram of an antigen binding two cells

CD8 T cells have CD8 glycoprotein on their cell membranes that act as the antigen receptor. If the antigen receptor of the CD8 T cell binds an antigen presented on the cell surface, the CD8 will kill the cell and make sure that DNA inside the cell is also destroyed so that an infected cell doesn't release viable parasites when it is killed. So what happens if a cell is infected with a virus, and then the virus instructs the cell not to present antigens on its surface? Wouldn't this allow the virus to hide from the CD8s? The short answer is yes, this allows the virus to hide from the CD8s. However, the molecule that presents antigens on a cell's surface is none other than the MHC 1 molecule, and you may remember that natural killer cells kill cells that do not express MHC 1 molecules on their plasma membrane. So, the virus may evade the CD8s only to be destroyed by natural killer cells.

The second type of T cell that we're going to talk about is helper T cells, which are T cells that activate other lymphocytes. This type of T cell is also called the CD4 T cell. These cells have the CD4 glycoprotein on their cell membrane that acts as the antigen receptor. Helper T cells are important regulators of immune responses to specific antigens. Some helper T cells, called Th1 cells, can activate CD8 T cells, and other helper T cells, called Th2 cells, can activate B cells. For now, we'll talk about Th1 cells and how they activate CD8s. Before a Th1 cell can activate a CD8, it must first be activated itself, meaning that it must encounter its specific antigen somewhere. If a viral infection is under way, then macrophages and other immune cells will come in contact with the virus and display viral antigens on their cell surface with MHC 2 molecules. Cells that express foreign antigens with MHC 2 molecules are called antigen-presenting cells. If a Th1 cell comes across an antigen-presenting cell that has an antigen it can recognize, it becomes activated and takes the antigen with it to present on its own cell membrane with an MHC 2 molecule. The Th1 cell then goes in search of a CD8 that can also recognize the same antigen and has already come across that antigen too. If the Th1 cell can find such a CD8, then the viral infection is serious enough to warrant a full response, and the Th1 cell activates the CD8 to proliferate. This creates a large number of CD8s that can respond to this particular antigen, and the immune system will now hopefully have enough antigen-specific CD8s to eliminate the virus.

B Cells

B cells are lymphocytes that are capable of producing antigen-specific antibodies. If a B cell has not yet encountered its target antigen, then it only produces antibodies that stay on its surface and act as antigen receptors for the B cell. Like CD8s, in order for B cells to be activated, they need to encounter their antigen on an antigen-presenting cell and be activated by a T helper cell, or Th2 cell, that has also seen the same antigen. Once the B cell is activated, it proliferates to produce lots of activated B cells, most of which then become antibody factories that secrete up to 2,000 antibodies per second for about four to five days until they reach the end of their lifespan. The rest of the B cell progeny become inactivated and wait at the ready for the next time the immune system encounters the antigen.

Antibodies

We already know that antibodies are produced by B cells, and you may have also figured out that all antibodies produced by a B cell can only recognize the same single antigen that the B cell recognized when it was being activated. Now let's look a little bit at the structure of an antibody. Your basic secreted antibody is shaped kind of like a capital 'Y'.

Diagram showing the structure of an antibody

It has two identical antigen-binding sites located at the tips of the two branches of the antibody, here and here. This part down here is called the Fc domain. It does not bind to antigens; however, it is very important for some key antibody functions.

Speaking of functions, we haven't talked about what secreted antibodies do yet. Yes, they recognize and bind their antigen, but then what? It turns out that secreted antibodies serve four main functions: The first function is neutralization. If enough antibodies attach to a pathogen, they can completely coat it and block it from interacting with the body's cells. The next function is to mark pathogens for phagocytosis. When an antibody binds to a pathogen, the antigen-binding sites face the pathogen, which leaves the Fc domain sticking out from the side of the pathogen. Not only that, but when an antibody is bound to its antigen, the structure of the Fc domain changes to a structure that receptors on neutrophils and macrophages recognize as a signal to phagocytize whatever the antibody is bound to. In addition to marking pathogens for phagocytosis, antibodies can also cause agglutination, or binding of pathogens together in clumps due to the fact that antibodies have two binding sites, each of which could bind to separate pathogens and join them together. These clumps of pathogens are easier for cells to phagocytize as a group rather than one at a time. And finally, antibodies bound to a pathogen can stimulate complement formation of membrane attack complexes and kill pathogens that way.

Lesson Summary

So in review, acquired immunity is an immune response to a specific pathogen that can be reactivated if the pathogen is ever encountered again. The workhorses of the acquired immune system are lymphocytes, which are white blood cells that recognize and respond to a single molecular structure, or antigen. Three of the most important cell types in the acquired immune system are Cytotoxic T Lymphocytes, CTLs, or CD8s, which are lymphocytes that destroy infected cells before they release mature parasites, helper T cells, or CD4s, which are T cells that activate other lymphocytes and B cells, which are lymphocytes that are capable of producing antigen-specific antibodies. In addition, antigen-presenting cells, or cells that express foreign antigens with MHC 2 molecules, play a very important role in the activation of T and B cells.