>>Dr. Ketchum: This is the part three of six for Chapter 23: The Immune System. And in
this chapter, we’re going to look at characteristics of the B and T cells in this
particular part, in part three. So remember that there are two different types of immunity:
there’s innate immunity and there’s acquired immunity. So here we’re focusing now on
acquired or adapted immunity. Remember that these are slower responses than an innate
response and the responses to very specific microbes. So before we actually get into the
different types of responses, what we need to do first is to kind of look at the outline
of where we’re going to go in this particular section.
So we’re dealing with the adaptive immune response, and this actually involves two different
types of immunity. So you have what’s called humoral immunity and cell-mediated immunity.
If it’s humoral immunity, we will always be working with B lymphocytes. Cell-mediated
immunity, on the other hand, you will always be dealing with T lymphocytes. So these two
different types of immunity involve lymphocytes, howev—however they involve different types
of lymphocytes. So what we’re going to be doing first is looking at characteristics
for these lymphocytes before we get into the process of how they actually function as part
of the immune system. So first off, let’s look at the origin for the B and the T cells.
And so in Chapter 15, which was on the blood, we talked about how various blood cells are
produced. They’re a precursors stem cell or a hematopoietic precursor cell, and we
talked about how those can give rise to red blood cells, platelets, monocytes, granulocytes,
and so on. But now what our focus is going to be on is how those hematopoietic stem cells
or precursor cells become lymphoid stem cells, and then those lymphoid stem cells become
lymphocytes. And that occurs in the bone marrow.
So once we have these lymphocytes then they can start differentiating, and this is where
they can differentiate into B and to T lymphocytes. So first let’s focus on the
B lymphocytes. The B lymphocytes—they’re pretty straightforward in the sense that they’re
going to differentiate and mature in the bone marrow. One they mature into these B cells,
then the B cells are going to move into the peripheral lymphoid tissues. And when they
move into the peripheral lymphoid tissues, we’re talking about them moving into the
spleen, Peyer’s patches, lymph nodes, and tonsils. Just to give you an example of some
of your peripheral lymphoid tissues. Once the B cells invade these lymphoid tissues,
they’re going to hang out. They’re going to stay in that area, and they’re just going
to veg there, okay? So once they’re there, they’re waiting. And what they’re waiting
for is an invasion by some foreign component. So once there’s an invasion—let’s say
it could be a bacterial invasion, for example—the B cells then leave the peripheral lymphoid
tissues. Not all of them at once are going to leave. You’ll always have some left
behind, but once those—some of those B cells have left, what they’re going to
do then is they’re going to mount what’s called an antibody-mediated immune response.
So right away you need to link B cells and the fact that they’re going to mount or
cause, in other words, an antibody-mediated immune response.
Now the T cells work a little differently. So what T cells are going to do, T cells—
you actually have the immature T cells that are going to leave the bone marrow. And when
the immature T cells leave the bone marrow, they’re going to go to the thymus. And if
you recall, we briefly mentioned the thymus when we talked about hormones. And we talked
about one hormone in particular that suppresses the thymus. And if you recall, that hormone
was what? The hormone that suppresses the thymus is cortisol. Okay, so what’s going
on in the thymus then? When these immature T cells arrive in the thymus, they get trained
and tested before they’re able to leave. So what I mean by training and testing them—I’m
going to come off over here to the left a little bit—and here’s the thymus. So what
we’re going to do is we’re going to take some T cells. So we’ve got a T lymphocyte,
which is the same thing as just saying a T cell; T lymphocyte and T cell are the same thing.
We’re going to present this T cell on this side with what’s called a non-self cell.
In other words, it’s a cell that’s not part of the body. So the T cell should recognize
that non-self cell as foreign. And if the T cell recognizes that non-self cell as foreign,
then it should kill the non-self cell. It should attack it. If it attacks and kills
that non-self cell, then the T cell graduates. It’s passed its test, all right? So if it
graduates then it gets to move on to the peripheral lymphoid tissues, all right? And if it gets
to go into the peripheral lymphoid tissues it’s going to do what the B cells do. It’s
going to hang out there, and it’s going to wait for a foreign invasion. Once that
occurs, T cells will move out of the lymphoid tis—tissues, and they’re going to mount
what’s called a cell-mediated immune response. We’ll talk in more in more detail about
the cell-mediated response as well as the antibody-mediated responses later.
Now let’s go back to the thymus again, because the T cell, like you said earlier, is
presented with a non self-cell. The T cell can also be presented with a self-cell. So
what I mean by a self-cell is this has to be a cell that is normally found within the
body. So should the T cell kill it? The answer is no; you do not want a T cell killing self-cells,
because then you would have an autoimmune disease. So when the T cell is presented the
self-cell, it should not kill the self-cell. And if it does not kill the self-cell—
guess what? It gets to graduate and it moves on to the peripheral lymphoid tissues.
Okay, but here’s the issue. Let’s say when the T cell is presented with a self-cell it kills
the self-cell. Is that a good thing or a bad thing? Okay that’s a bad thing, right, because
now you would have an autoimmune disease. So should the T cell graduate? Should it be
able to leave the thymus and enter into the peripheral lymphoid tissues? Would that be
a good idea? The answer is no. You don’t want a T cell now circulating throughout your
body that’s killing self-cells; you would be in real trouble if that would happen. So
what should happen now to that T cell? The T cell is going to commit suicide. So the
T cell undergoes apoptosis. So this is programmed cell death, and you should’ve learned about
programmed cell death in your Introductory Biology course. Now if you haven’t that’s
not a problem, just remember that apoptosis is programmed cell death. So that T cell dies.
It commits suicide. And it should, because if it doesn’t you will have an autoimmune
disease. Okay, so what we have then is the thymus training and testing the T cells. Thymus
trains and tests T cells. If the T cells pass the test, so they graduate, then they get
to move on to the peripheral lymphoid tissues, peripheral lymphoid tissues, and then they
get to leave those whenever there’s a foreign invasion, and then they will mount a cell-mediated
immune response. All right, so those are the origins for your B and your T cells.
Now what this table does here for you guys is it’s going to compare your B and T lymphocytes.
And in the left-hand column, you have characteristics for each of the B and the T lymphocytes. So
we’re going to actually be going through each one of these, so you may want to expand
on this table and use it as a study guide. I think it’d be a nice comparison for you.
All right, so before we go any further, we need to talk about antibodies and antigens.
So the first question is, well what is an antigen? An antigen is a foreign molecule
or an abnormal cell. So let’s expand on that before we go any further. So if we say
an antigen is a foreign molecule, that could be a protein, could be a polysaccharide. And
these are protein or polysaccharide components of a foreign cell. Okay, so these are foreign
molecules. Proteins, polysaccharides, that’re components of some sort of foreign cell.
All right, now what we mean by “of some foreign cell,” you can think about the, a foreign cell
as being a virus. You could think about it as being a bacteria, you could think about
this as being a—let’s see—fungus, a protist, a parasitic worm. Those are just
to give you examples of foreign cells and what we’re talking about here. Now abnormal cells,
on the other hand, we may be referring to a tumor cell, because a tumor cell would
be considered an abnormal cell, or it could even be a transplanted cell. So if you’ve
had an organ transplant, it comes with cells, right? So transplanted cells would be considered
abnormal because they’re not normally found in your body. Now regardless of whether or
not your antigen is this foreign molecule or it’s an abnormal cell, they all contain
what’s called an epitope.
So epitopes are recognition sites, which are called antigenic determinants. So if you look
at the diagram on the right, here’s the antigen—that’s the cell. The epitopes
here are on the cell surface. So the epitope is what binds to the antibody. So you can
see the epitope here, and then you can see it binding to the antibody. And when it binds
to the antibody, that’s going to trigger an immune response. So let’s
take a look at the properties of an antibody. So antibodies are all Y shaped, and you can
see the image here on the right-hand side of your screen for the Y-shaped antibody.
And you have four interlinked polypeptide chains. So when you look at these, there’s
two heavy and long chains, there’s two short and light chains. They have variable and constant
regions. What’s really important is that when you look at the antigen-binding site
is located, that’s on the end with the variable region. Hopefully that would make sense to
you, because the antigen-binding sites combine to a variety of antigens depending upon what
antibody you’re working with. So antibodies are specific; they have specific antigen-binding
sites. And the reason they can have that is because that site has a variable polypeptide
region.
All right, so the antigen-biding site will bind to the antigenic determinate. In other
words, it will combine into the epitope. And when it binds again, that’s what’s going
to trigger an immune response. Now if you remember from lab we’ve talked about blood
antigens and blood antibodies. This is a similar concept here, and—except that you’re born
with or you’ve inherited your blood antigens, and you inherited your blood antibodies. The
difference in this chapter is we’re going to be referring to antigens as something that
is foreign. You’re not born with these things, okay? And then the, the antibodies you’re
not born with either, because we’re not dealing with blood antibodies or blood antigens
here. This is completely different. We’re talking about foreign things that your body
is exposed to, and in response, your body will, will make antibodies to that.
Okay, so in terms of some more characteristics or additional characteristics of B and T cells,
they do illustrate specificity, okay? So B and T cells can both bind to an antigen. But
the way that they do this is somewhat different. So let’s look at the way that B and T cells
bind to antigens and what they use to bind to antigens. Now we’ve talked a lot about
receptors this semester, and so we’re going to return back to the concept of receptors.
If you have a B cell, as shown on the left, your B cell antigen receptor is going to be
a membrane antibody, okay? Or what’s called a membrane immunoglobulin. This is what binds
the antigen, and here is that membrane antibody—right there. So with a B cell, a B cell is capable
of binding or the B cell receptor is capable of binding two different—or two, not two
different—but two antigens. Then we look at the T cell. So the T cell on the right
also has an antigen receptor, but this time, this antigen receptor is a little bit different.
It’s not a membrane antibody. So it’s not Y shaped. Okay, this time we’re going
to call this a T cell receptor. TCR—T cell receptor. So by looking at that receptor,
how many antigens can this thing bind at once? The answer is one; it can only bind one antigen
at one time, whereas the B cell could bind two antigens at one time. Okay, so their,
their receptors are a little bit different when you talk about B cells versus T cells.
Now in terms of diversity, you can have one B cell or T cell and it can have a hundred
thousand antigen receptors. So what that means then is B cells and T cells can bind a lot
of different antigens.
Next then what we have is the concepts of memory. Both B cells and T cells have a memory,
so let’s look at primary versus secondary responses. And so what we see here—we want to
focus first on the primary response. Look at your axes, okay? Your x-axis is time after
infection, and that’s in days. Your antibody concentration is on the y-axis. So let’s
say at day is zero you get exposed to some antigen; so you’re exposed to some foreign
molecule. All right, so how long is it going to take for your body to produce antibodies?
Now this graph shows 10 days to make antibodies, where technically anywhere between seven to
10 days it will take your body to make antibodies, seven to 10 days to make antibodies.
That’s on a primary response, meaning this is the first exposure to the antigen. You’ve never
been exposed to this antigen before, so it takes seven to 10 days for your body to produce
antibodies. Then we move to the secondary response.
So the secondary response now says that you are exposed for a second time to the same
antigen—same antigen that you were exposed to during the primary response. Now how long
does it take your body to make antibodies? Now it takes anywhere from one to two days
to make antibodies. And you can see that here: one to two days to make antibodies. So what
this is telling us is that our B and T cells have a memory. And that’s a good thing to
have because when you’re exposed for a second time it takes less time to make antibodies,
which means you can amount an immune response a lot faster. So self, self-tolerance is the
ability to recognize self versus non-self. So if you remember when we talked about the
thymus and the thymus training and testing those T cells, that’s an example of self-tolerance.
And so you have to—these cells have to be able to recognize theirself versus non-self.
They have to be able to attack non-self cells. You don’t want them attacking self-cells.