Understanding the Humoral Immune Response

Okay, so let's talk a little bit more about the humoral immune response. So when our B cells or B lymphocytes encounter a target antigen, that's going to provoke the humoral immune response. And the humoral immune response is basically where we're making antibodies specific for that antigen that it encountered to go in and help market for destruction. So our B cells are considered activated once we have the antigen binding to the receptor on its surface. When we have the antigen bound to the receptor on the B cell, it's going to cross-link them. Once we have the cross-link, it's going to trigger receptor-mediated endocytosis of the cross-linked antigen receptor complexes. This is called clonal selection. So basically, it's going to bring it inside. both the receptor and the antigen complex together. Once we have that inside, it's going to cause proliferation and differentiation of the B cell into effector cells. So interactions with T cells are also usually required in order to help B cells achieve full activation. So most of the clone cells are going to become plasma cells, and our plasma cells are the cells that are actually sick. creating the antibodies themselves. So they can secrete specific antibodies at a rate of about 2,000 per second for about four to five days before they die. And we constantly have antibodies circulating in our blood or our lymph, and they're binding to free antigens or marking them for destruction by our innate or adaptive immune systems. So clone cells that don't become plasma cells, like I mentioned before. they are going to remain what we call memory cells. And the purpose of these memory cells are to help mount an immediate response to future exposures to the same antigen again. So we have clonal selection right here at the bottom. They're showing you the production of several plasma cells. That's going to be the bulk of the cells produced from the proliferation. These plasma cells are going to secrete antibodies down here. But a couple of our pre-treated cells. from the proliferation don't become plasma cells, they can become memory B cells. So we're talking about the primary immune response, meaning cell proliferation and differentiation upon exposure to the antigen for the first time. There is a little bit of a lag period of about three to six days after we encounter the antigen. The few B cells specific for that antigen have to proliferate and differentiate into plasma cells. Because again, we don't have any memory cells produced yet. So if we're talking about the production of these plasma cells, we have peak levels of them after about 10 days. And then after 10 days, the antibody levels are going to decline. Secondary immune response. So if we have re-exposure to the same antigen, it's going to help give them a faster and longer and more effective response because we made those memory cells from our primary exposure to it. So the memory cells provide for an immunological memory. And if we have these memory cells, instead of waiting a couple days in order to produce the antibodies, now they can actually respond with a couple hours. Or maybe even days, or not days, within a couple hours. And we can have our peak antibody levels within two to three days instead of 10 days. And the peak antibody levels are going to be much higher than those from our primary exposure. The antibodies combined with a greater affinity and our antibody level will remain for a lot longer, anywhere from weeks to months. So that's pretty much the basis of a vaccine. So here's just a graph showing you, here's our primary immune response right here, which is our first exposure to the antigen. We can see it takes a little while for us to be able to produce a high amount of antibodies and plasma cells here. And then if we have second exposure to the same antigen, We can see we have much lighter, I'm sorry, much higher concentrations of our antibody, as well as a much quicker production as far as time goes to get those antibody peaks in our body. This down here is just showing you if we're exposed to a completely different antigen. which would be antigen B, how we'd basically be going through a primary immune response again, where it takes a little bit of time to produce those plasma cells and antibodies, and we don't produce them at as high of titers as a secondary immune response. So when we're talking about humoral immunity, we need to talk a little bit about active humoral immunity. And active humoral immunity occurs when our B cells encounter the antigens and produce specific antibodies against them. So we have two types of active humoral immunity. We have naturally acquired and then we have artificially acquired. If we're talking about naturally acquired, This is going to be formed in response to an actual bacterial or viral infection. So again, naturally, we are going to be exposed to it. And then we're going to produce the antibodies against it. We also have artificially acquired. And this is going to be formed in response to some sort of vaccine. So we can have a vaccine with dead or attenuated, meaning just like it's not fully functional type of pathogen. And these are going to help provide antigenic determinants that are immunogenic and reactive, and they spare us symptoms of a primary immune response. We also have passive humoral immunity. Passive humoral immunity occurs when we have ready-made antibodies. So we're not actually being exposed to the pathogen at all. Instead, we're just basically getting the antibodies against them introduced into our body. So the B cells aren't actually challenged by the antigens, meaning that we won't form any sort of memory against them. So protection is going to end immediately when our antibodies basically degrade and are no longer functional. So there's two types of passive humoral immunity. We have naturally acquired and we have artificially acquired. For talking about naturally acquired, that's when we have antibodies delivered to the fetus via the placenta or through breast milk. if we're breastfeeding. Again, the baby's not actually producing any memory cells against those, so they would have to go through a primary immune response if they're exposed to the same pathogens in the future. Then we have artificially acquired, so this is where we're injecting some sort of serum, such as a gamma globulin, and typically we would do this if we're having some sort of rapidly fatal diseases that would cause. that would kill a person before the active immunity could actually be established. So something like botulism or poisonous eggs or rabies or something like that. But again, in either case, the protection ends immediately when the antibodies degrade naturally in the body. So here's our humoral immunity chart. Again, we have two main categories, active and passive. Active is where we have some sort of exposure to the pathogen itself. One would be naturally, the other one would be via vaccine or artificially. Passive is where we don't have any exposure to the pathogen at all. Instead, we're just receiving the antibodies. So we can have antibodies being delivered via breast milk or the placenta, or just an injection of the antibodies such as gamma globulin. So antibodies, these are going to be secreted by the effector T cells or the B cells, sorry, or the plasma cells. They're also called immunoglobulins or Igs. And they're proteins that are secreted and they make up the gamma globulin portion of our blood. They're capable of binding specifically with an antigen that has been detected by the B cell. So they regroup antibodies into classes. So there's five antibody classes. The structure of an antibody typically is going to be a T or Y-shaped antibody monomer, and then we have four polypeptide chains that are linked together by disulfide bonds, which means we just have two sulfur bonds that are connecting them. When we're talking about the four chains, two of them are considered heavy chains, and then two of them are considered light chains. We also have variable regions. And the variable region is going to be the region at which the antigen actually comes in and binds. We also have the constant region. So as you can imagine, the constant region is constant for each type of class of antibody. So the constant region is going to determine the antibody class. It's also considered the effector region of the antibody. And some common functions include... include the type of cells and or chemicals that an antibody can bind and how the antibody class actually functions to eliminate the antigens. So here's a good illustration of our antibody right here. We can see where we have our heavy chains. This is a heavy chain here in a bluish purple. And then we have two light chains here in the actual purple. The variable region is where an antigen can actually bind. So this is the variable region on either side. In this case, this Y-shaped antibody can bind two antigens because it has two variable regions. This down here is considered the constant region. So that's going to determine which of the five classes of antibodies this antibody binds. belongs to. So let's go through the classes. IgM is a pentamer. So it's one of the largest ones that we have. And it's the first antibody that's actually released. It's a potent agglutinating agent. meaning that it's going to cause clumping. And it's also going to help fix and activate the complement that we talked about before. So it's a pentamer, so we can see it over here, which means it has five. of the Y-shaped antibodies attached to it. So we can actually bind up to 10 different antigens because it has 10 different variable regions or antigen binding sites. We also have IgA. This is either a monomer or a dimer. It's typically found in mucus and other secretions. And it's going to help prevent the entry of pathogens. Because again, if you look at the location, mucus and secretions, that would be its function. IgD is going to be a monomer attached to the surface of the B cells themselves. And the whole function of the IgD is to act as the receptor on the B cell. We also have IgG. This is a monomer. So anywhere from 75% to 85% of the antibodies in plasma would be IgG antibodies. So they're from secondary and late primary responses. And they're able to cross the placental barrier. IgE is a monomer active in some allergies and parasitic infections and they can cause mast cells and basophils to release histamine. So when we're talking about plasma cells, we really didn't talk about what specific class of antibody the plasma cells actually secrete and release and produce. Plasma cells can actually switch from making one class of antibody to another. So it's not like we have a specific type of plasma cell that produces a specific type of antibody. But it does retain specificity for the same antigen. So IgM is released during a primary response, but then once, because they're the first ones. on scene, but then the plasma cell can switch from aging the IgM to IgG for some sort of secondary response. Almost all of the secondary responses are going to be the IgG. And then we can have switching between other different classes as well. So what are the targets and the functions of antibodies? So again, antibodies don't go in and actually destroy any of the antigens themselves or foreign microbes. Instead, basically they can mark them for destruction or flag them. or inactivate them. And when they bind, they form the antigen-antibody complex. So some of the things that they can do or defensive mechanisms used by antibodies are things like neutralization, agglutination of the clumping, precipitation, and complement fixation. So neutralization is pretty much the simplest defense mechanism that we have, or our antibodies are capable of. And pretty much what happens is our antibodies go in and block this specific site, either on the virus or the toxin or the bacteria. And as a result, the virus or the toxin can't bind to receptors of our own tissue cells. So the phagocytes will eventually destroy all of the antigen antibody complexes. The next one is agglutination. Because all of our antibodies have more than one antigen binding site, they can bind multiple antigens at the same time. When they start binding multiple antigens, what happens is that these complexes become cross-linked into really large lattices. And when they're cross-linked, that's also going to cause clumping. And if you remember from blood chapter, clumping is also referred to as glutination. So all these cells will come in and clump together. Like I mentioned previously, the IgM is capable of binding 10 different antigens because it has 10 antigen binding sites. So we would consider IgM a potent agglutinating agent because of its ability to go in and bind so many antigens. The next thing is precipitation. So a lot of soluble molecules are cross-linked into large complexes that are capable of settling out of solution and forming some sort of precipitate. So anytime we have precipitated antigen molecules, it's a lot easier for the phagocytes to come in and engulf them and remove them. And the last thing is complement activation, which we talked about before. So when we have a bunch of different antibodies that bind close together in the same cell, the complement binding sites on their regions are going to be able to align and become activated. And again, if you remember complement, that's where we had three different pathways that converged on C3. And C3b was able to go in and form the MAC complex or the membrane attack complex to trigger cell lysis. So that's kind of another thing that antibodies can do. So here's a good picture. Again, I like the pictures and the flow charts. I recommend looking at them. If we have an antigen that binds to antibodies, we form what's called the antigen-antibody complex. The antigen-antibody complex can go in and do a couple of things. different things. One, it can cause neutralization by binding to the receptors on the bacteria and the viruses. It's going to inactivate them because then their receptors can't go in or their antigens can't go in and bind our own cells. Agglutination, especially shown here, is IgM because it's capable of binding up to 10 different antigens. Once it starts binding, it's going to start causing clumping. Another way you can inactivate them is by precipitating. precipitation so if we have some sort of soluble antigens or something like that it's going to make it a lot easier for phagocytes to go in and engulf it if we form this precipitate and the last thing we can have happen is it can trigger complications activation where we have C3, which is shown here, which is going to split and then C3B can go in and form our MAC or membrane attack complex there. If we form MAC, that's going to cause cell lysis, but our C3B can also enhance inflammation and phagocytosis. If we're talking about neutralization, agglutination, or precipitation, these all act to enhance phagocytosis. Okay, the last thing I want to talk about in this section is monoclonal antibodies. These are being used a lot in clinical and research tools. So what are monoclonal antibodies? Basically, these are commercially prepared antibodies that are specific for a single type of antigenic determinant. So you can decide what you want these antibodies to be specific to. And how we produce them are by hybridomas. And these are... are cell hybrids from the fusion of a tumor cell and a B cell. Why is it important to fuse it with a tumor cell? Because tumor cells are undergoing constant and rapid cellular division. So we can make the B cell proliferate very, very quickly. And the B cell portion allows it to produce that single type of antibody so we can go on and use it for something else.

So our B cells are considered activated once we have the antigen binding to the receptor on its surface. When we have the antigen bound to the receptor on the B cell, it's going to cross-link them. Once we have the cross-link, it's going to trigger receptor-mediated endocytosis of the cross-linked antigen receptor complexes.

This is called clonal selection. So basically, it's going to bring it inside. both the receptor and the antigen complex together.

Once we have that inside, it's going to cause proliferation and differentiation of the B cell into effector cells. So interactions with T cells are also usually required in order to help B cells achieve full activation. So most of the clone cells are going to become plasma cells, and our plasma cells are the cells that are actually sick. creating the antibodies themselves. So they can secrete specific antibodies at a rate of about 2,000 per second for about four to five days before they die.

And we constantly have antibodies circulating in our blood or our lymph, and they're binding to free antigens or marking them for destruction by our innate or adaptive immune systems. So clone cells that don't become plasma cells, like I mentioned before. they are going to remain what we call memory cells.

And the purpose of these memory cells are to help mount an immediate response to future exposures to the same antigen again. So we have clonal selection right here at the bottom. They're showing you the production of several plasma cells.

That's going to be the bulk of the cells produced from the proliferation. These plasma cells are going to secrete antibodies down here. But a couple of our pre-treated cells.

from the proliferation don't become plasma cells, they can become memory B cells. So we're talking about the primary immune response, meaning cell proliferation and differentiation upon exposure to the antigen for the first time. There is a little bit of a lag period of about three to six days after we encounter the antigen.

The few B cells specific for that antigen have to proliferate and differentiate into plasma cells. Because again, we don't have any memory cells produced yet. So if we're talking about the production of these plasma cells, we have peak levels of them after about 10 days. And then after 10 days, the antibody levels are going to decline.

Secondary immune response. So if we have re-exposure to the same antigen, it's going to help give them a faster and longer and more effective response because we made those memory cells from our primary exposure to it. So the memory cells provide for an immunological memory. And if we have these memory cells, instead of waiting a couple days in order to produce the antibodies, now they can actually respond with a couple hours. Or maybe even days, or not days, within a couple hours.

And we can have our peak antibody levels within two to three days instead of 10 days. And the peak antibody levels are going to be much higher than those from our primary exposure. The antibodies combined with a greater affinity and our antibody level will remain for a lot longer, anywhere from weeks to months. So that's pretty much the basis of a vaccine.

So here's just a graph showing you, here's our primary immune response right here, which is our first exposure to the antigen. We can see it takes a little while for us to be able to produce a high amount of antibodies and plasma cells here. And then if we have second exposure to the same antigen, We can see we have much lighter, I'm sorry, much higher concentrations of our antibody, as well as a much quicker production as far as time goes to get those antibody peaks in our body.

This down here is just showing you if we're exposed to a completely different antigen. which would be antigen B, how we'd basically be going through a primary immune response again, where it takes a little bit of time to produce those plasma cells and antibodies, and we don't produce them at as high of titers as a secondary immune response. So when we're talking about humoral immunity, we need to talk a little bit about active humoral immunity.

And active humoral immunity occurs when our B cells encounter the antigens and produce specific antibodies against them. So we have two types of active humoral immunity. We have naturally acquired and then we have artificially acquired.

If we're talking about naturally acquired, This is going to be formed in response to an actual bacterial or viral infection. So again, naturally, we are going to be exposed to it. And then we're going to produce the antibodies against it.

We also have artificially acquired. And this is going to be formed in response to some sort of vaccine. So we can have a vaccine with dead or attenuated, meaning just like it's not fully functional type of pathogen. And these are going to help provide antigenic determinants that are immunogenic and reactive, and they spare us symptoms of a primary immune response.

We also have passive humoral immunity. Passive humoral immunity occurs when we have ready-made antibodies. So we're not actually being exposed to the pathogen at all.

Instead, we're just basically getting the antibodies against them introduced into our body. So the B cells aren't actually challenged by the antigens, meaning that we won't form any sort of memory against them. So protection is going to end immediately when our antibodies basically degrade and are no longer functional.

So there's two types of passive humoral immunity. We have naturally acquired and we have artificially acquired. For talking about naturally acquired, that's when we have antibodies delivered to the fetus via the placenta or through breast milk. if we're breastfeeding.

Again, the baby's not actually producing any memory cells against those, so they would have to go through a primary immune response if they're exposed to the same pathogens in the future. Then we have artificially acquired, so this is where we're injecting some sort of serum, such as a gamma globulin, and typically we would do this if we're having some sort of rapidly fatal diseases that would cause. that would kill a person before the active immunity could actually be established.

So something like botulism or poisonous eggs or rabies or something like that. But again, in either case, the protection ends immediately when the antibodies degrade naturally in the body. So here's our humoral immunity chart.

Again, we have two main categories, active and passive. Active is where we have some sort of exposure to the pathogen itself. One would be naturally, the other one would be via vaccine or artificially.

Passive is where we don't have any exposure to the pathogen at all. Instead, we're just receiving the antibodies. So we can have antibodies being delivered via breast milk or the placenta, or just an injection of the antibodies such as gamma globulin. So antibodies, these are going to be secreted by the effector T cells or the B cells, sorry, or the plasma cells.

They're also called immunoglobulins or Igs. And they're proteins that are secreted and they make up the gamma globulin portion of our blood. They're capable of binding specifically with an antigen that has been detected by the B cell. So they regroup antibodies into classes. So there's five antibody classes.

The structure of an antibody typically is going to be a T or Y-shaped antibody monomer, and then we have four polypeptide chains that are linked together by disulfide bonds, which means we just have two sulfur bonds that are connecting them. When we're talking about the four chains, two of them are considered heavy chains, and then two of them are considered light chains. We also have variable regions.

And the variable region is going to be the region at which the antigen actually comes in and binds. We also have the constant region. So as you can imagine, the constant region is constant for each type of class of antibody. So the constant region is going to determine the antibody class.

It's also considered the effector region of the antibody. And some common functions include... include the type of cells and or chemicals that an antibody can bind and how the antibody class actually functions to eliminate the antigens. So here's a good illustration of our antibody right here.

We can see where we have our heavy chains. This is a heavy chain here in a bluish purple. And then we have two light chains here in the actual purple.

The variable region is where an antigen can actually bind. So this is the variable region on either side. In this case, this Y-shaped antibody can bind two antigens because it has two variable regions.

This down here is considered the constant region. So that's going to determine which of the five classes of antibodies this antibody binds. belongs to.

So let's go through the classes. IgM is a pentamer. So it's one of the largest ones that we have.

And it's the first antibody that's actually released. It's a potent agglutinating agent. meaning that it's going to cause clumping.

And it's also going to help fix and activate the complement that we talked about before. So it's a pentamer, so we can see it over here, which means it has five. of the Y-shaped antibodies attached to it. So we can actually bind up to 10 different antigens because it has 10 different variable regions or antigen binding sites.

We also have IgA. This is either a monomer or a dimer. It's typically found in mucus and other secretions.

And it's going to help prevent the entry of pathogens. Because again, if you look at the location, mucus and secretions, that would be its function. IgD is going to be a monomer attached to the surface of the B cells themselves. And the whole function of the IgD is to act as the receptor on the B cell.

We also have IgG. This is a monomer. So anywhere from 75% to 85% of the antibodies in plasma would be IgG antibodies.

So they're from secondary and late primary responses. And they're able to cross the placental barrier. IgE is a monomer active in some allergies and parasitic infections and they can cause mast cells and basophils to release histamine. So when we're talking about plasma cells, we really didn't talk about what specific class of antibody the plasma cells actually secrete and release and produce. Plasma cells can actually switch from making one class of antibody to another.

So it's not like we have a specific type of plasma cell that produces a specific type of antibody. But it does retain specificity for the same antigen. So IgM is released during a primary response, but then once, because they're the first ones. on scene, but then the plasma cell can switch from aging the IgM to IgG for some sort of secondary response. Almost all of the secondary responses are going to be the IgG.

And then we can have switching between other different classes as well. So what are the targets and the functions of antibodies? So again, antibodies don't go in and actually destroy any of the antigens themselves or foreign microbes. Instead, basically they can mark them for destruction or flag them.

or inactivate them. And when they bind, they form the antigen-antibody complex. So some of the things that they can do or defensive mechanisms used by antibodies are things like neutralization, agglutination of the clumping, precipitation, and complement fixation. So neutralization is pretty much the simplest defense mechanism that we have, or our antibodies are capable of.

And pretty much what happens is our antibodies go in and block this specific site, either on the virus or the toxin or the bacteria. And as a result, the virus or the toxin can't bind to receptors of our own tissue cells. So the phagocytes will eventually destroy all of the antigen antibody complexes.

The next one is agglutination. Because all of our antibodies have more than one antigen binding site, they can bind multiple antigens at the same time. When they start binding multiple antigens, what happens is that these complexes become cross-linked into really large lattices.

And when they're cross-linked, that's also going to cause clumping. And if you remember from blood chapter, clumping is also referred to as glutination. So all these cells will come in and clump together. Like I mentioned previously, the IgM is capable of binding 10 different antigens because it has 10 antigen binding sites. So we would consider IgM a potent agglutinating agent because of its ability to go in and bind so many antigens.

The next thing is precipitation. So a lot of soluble molecules are cross-linked into large complexes that are capable of settling out of solution and forming some sort of precipitate. So anytime we have precipitated antigen molecules, it's a lot easier for the phagocytes to come in and engulf them and remove them. And the last thing is complement activation, which we talked about before.

So when we have a bunch of different antibodies that bind close together in the same cell, the complement binding sites on their regions are going to be able to align and become activated. And again, if you remember complement, that's where we had three different pathways that converged on C3. And C3b was able to go in and form the MAC complex or the membrane attack complex to trigger cell lysis. So that's kind of another thing that antibodies can do. So here's a good picture.

Again, I like the pictures and the flow charts. I recommend looking at them. If we have an antigen that binds to antibodies, we form what's called the antigen-antibody complex. The antigen-antibody complex can go in and do a couple of things. different things.

One, it can cause neutralization by binding to the receptors on the bacteria and the viruses. It's going to inactivate them because then their receptors can't go in or their antigens can't go in and bind our own cells. Agglutination, especially shown here, is IgM because it's capable of binding up to 10 different antigens.

Once it starts binding, it's going to start causing clumping. Another way you can inactivate them is by precipitating. precipitation so if we have some sort of soluble antigens or something like that it's going to make it a lot easier for phagocytes to go in and engulf it if we form this precipitate and the last thing we can have happen is it can trigger complications activation where we have C3, which is shown here, which is going to split and then C3B can go in and form our MAC or membrane attack complex there.

If we form MAC, that's going to cause cell lysis, but our C3B can also enhance inflammation and phagocytosis. If we're talking about neutralization, agglutination, or precipitation, these all act to enhance phagocytosis. Okay, the last thing I want to talk about in this section is monoclonal antibodies. These are being used a lot in clinical and research tools. So what are monoclonal antibodies?

Basically, these are commercially prepared antibodies that are specific for a single type of antigenic determinant. So you can decide what you want these antibodies to be specific to. And how we produce them are by hybridomas. And these are...

are cell hybrids from the fusion of a tumor cell and a B cell. Why is it important to fuse it with a tumor cell? Because tumor cells are undergoing constant and rapid cellular division.

So we can make the B cell proliferate very, very quickly. And the B cell portion allows it to produce that single type of antibody so we can go on and use it for something else.

Transcript for:Understanding the Humoral Immune Response

Transcript for:
Understanding the Humoral Immune Response