Video Transcript
In this video, we will discuss the specific part of the human immune response which involves antibody formation. We’ll learn what happens to B lymphocytes in response to antigen recognition. Finally, we’ll see how antibodies can help to fight an infection.
The human immune system has three lines of defense. The first line of defense is the physical barriers that are present in the body, which are specialized to keep pathogens and foreign materials out. The second line of defense is the innate or nonspecific immune response, involving inflammation, phagocytic cells, and certain aspects of the complement system. Specific or adaptive immunity can be thought of as a third line of defense when it comes to fighting pathogens and illnesses. The first and second lines of defense are both part of immunity we are born with, which stays the same throughout our lifetime for all infections, even for repeated infections by the same pathogen.
Upon infection with a specific pathogen, the innate immune response is the first immediate response of the body and, as mentioned, is the same for all pathogens. If the innate immune response is not sufficient to repress this infection, another immune response that is designed to target specifically this pathogen is activated. This response is part of specific or adaptive immunity. Together, the two immune responses fight the pathogen until it’s cleared from the body. In some cases, the infection is too severe for the immune system to clear it on its own and medical interventions are required.
Specific immunity is sometimes called adaptive or acquired immunity. It is part of the immune system that creates a response specific to the pathogen that needs to be eliminated. It does that by recognizing non-self-antigens and using them to target the pathogen and infected cells. After a first infection of a pathogen with a specific antigen, the specific immunity creates a memory component that allows the body to respond to a second instance of infection by the same pathogen more rapidly and more effectively than the first time it occurred. Because of this memory component, the adaptive immunity is the immunity you develop or acquire over time.
Let’s discuss the specific immune response in more detail. Our specific immune system is often described in two divisions: humoral immunity and cell-mediated immunity. The cell-mediated immune response is sometimes called T cell immunity, because it relies on the action of cytotoxic T cells that can find and destroy abnormal and infectious cells in the body. The humoral immune response is sometimes called B cell immunity or antibody immunity, because it relies on the action of B lymphocytes, a type of cell that makes proteins called antibodies, which are specific to the invading antigen.
Humoral immunity and cell-mediated immunity can be further differentiated because humoral immunity is only effective against extracellular pathogens, for example, viruses in the blood, extracellular bacteria, or toxins produced by such bacteria, whereas cell-mediated immunity is effective against intracellular pathogens, an example of which is a host cell infected by a virus. Even though they’re often described separately, cell-mediated immunity and humoral immunity work together and simultaneously in our adaptive immune system to fight infections. In this video, we will learn more about humoral immunity specifically. So that we have a bit more space to discuss it, let’s remove the rest of the information on the screen.
Let’s begin by getting acquainted with B cells. Generally, B cells, which are also called B lymphocytes, are lymphocytes that reach maturity in the bone marrow. They have B cell receptors on their surface, which can recognize antigens. The recognition of such antigens can activate the B cell, and the activated B cell then releases its B cell receptors as antibodies, which help to fight the infection. Before we talk about antibody production, we need to talk about B cell receptors. B cells have a specific genetic makeup that allows them to each make a different kind of B cell receptor. The genes that code for B cell receptors are mixed up by genetic recombination so that many random varieties are produced.
A single stem cell can differentiate into several different types of B cells with different B cell receptors on their cell surface membrane through genetic recombination. Since different B cell receptors are randomly produced, it is important to make sure that they will not react with the normal cells of the body. So, before the B cells leave the bone marrow, they’re tested to make sure that they do not carry receptors against self-antigens. B cells that fail this test are eliminated. Every B cell has only one kind of receptor on its surface. The B cell receptor is essentially an antibody that’s embedded in the B cell’s membrane.
Antibodies are globular proteins, which are released by an activated B cell and bind to substances that we call antigens. An antigen is basically anything that can bind to an antibody. And most non-self-antigens, which are those that do not originate in your own body, trigger an immune response. Antigens can be molecules present on the surface of pathogens, like bacteria or viruses, or other substances, like toxins. Remember, when antibodies are attached to the surface of a naive, not yet activated B cell, they are called B cell receptors.
Now that we are familiar with the most important cell in humoral immunity, let’s discuss how the humoral response helps to fight an infection. When a pathogen, such as a virus, enters the body, it is recognized and engulfed by white blood cells, such as dendritic cells and macrophages. They engulf the pathogen through a process called phagocytosis, a type of endocytosis that’s a part of the innate immune response. Without becoming infected themselves, these white blood cells break down the pathogen into antigens, which will then be bound to a molecule called the major histocompatibility complex, or MHC, whose function it is to present antigens on the cell’s surface.
The MHC–antigen complex is then transported from the inside of the cell to the surface of the cell membrane, where the antigen can be presented to other cells of the immune system. Such cells that are able to present antigens to other cells in the immune system are called antigen-presenting cells, or APCs for short. An antigen-presenting cell is therefore a type of immune cell that facilitates an immune response by showing processed antigens on its surface to other cells of the immune system. The APCs then travel to the lymph nodes of the immune system, where they interact with the lymphocytes that are housed there, including B cells. Alternatively, the pathogen itself may be present in the lymph fluid, which is a fluid derived from blood plasma that filters through the lymph nodes and may come into contact with immune cells in that way.
In the lymph node, an APC encounters a naive B cell with B cell receptors that are complementary to the antigen the APC is presenting on its cell surface. The MHC–antigen complex binds to the B cell receptor, which begins activation of the B cell. The B cell is then no longer referred to as naive. B cell activation can be T cell dependent or T cell independent, depending on whether or not T cells are involved. In T cell-independent activation, B cells are usually activated simply by the presence of a complementary antigen. Once the B cells have bound to an antigen that matches their antibody, they are activated. Activated B cells then multiply rapidly and produce large amounts of differentiated plasma cells, which release an even larger amount of antibodies secreted out of the cell and into the body fluids.
T cell-dependent activation, on the other hand, is where B cells require extra signals provided by T cells to become activated. In this case, when the B cell receptor recognizes a compatible antigen, the B cell engulfs the pathogen by phagocytosis, as we learned earlier. As with other antigen-presenting cells, the antigen is then broken apart, and the pieces are attached to a molecule called MHC. The antigen attached to the MHC is then presented on the surface of the B cell as an MHC–antigen complex.
Certain T lymphocytes called helper T cells have receptors that can recognize and attach to this MHC–antigen complex. These are called T cell receptors. Helper T cells are different to other T cells by the presence of a cell surface coreceptor called CD4. The T cell receptors along with the CD4 cell surface molecules together recognize and attach to the MHC–antigen complex on the surface of the antigen-presenting B cells, which activates the helper T cells. The activated helper T cells in turn release cytokines called interleukins. Inter- means between, and -leukin refers to white blood cells. Interleukins are a type of cytokine that regulate immune responses by helping white blood cells to communicate with each other.
The B cells have interleukin receptors. And when the interleukins bind to these receptors, they signal the B cell to become fully activated. As mentioned previously, the fully activated B cell can now divide. And some activated B cells differentiate to become plasma cells, which secrete large amounts of antibodies. The activated T cell also begins to multiply. And therefore, more interleukins are released, which helps to activate more B cells, but also other immune cells, such as cytotoxic T cells. In this way, helper T cells play a role in both humoral and cell-mediated immunity.
Do you remember that at the beginning of this video you learned that there are lots of B cells which have different B cell receptors on their surface? It is important to understand that not all of them are going to be activated in the presence of an antigen. As the B cell receptors have the same receptor structure as the antibodies they’ll release once they’re activated and have differentiated into plasma cells, only the B cells with B cell receptors that are complementary to the antigen will proliferate. Similarly, it is only these B cells that are activated by the cytokines released from helper T cells. We call this clonal selection.
As we know by now, the activated B cells multiply rapidly and differentiate into effector cells called plasma cells, resulting in lots of cells that produce the same antibodies as the original activated B cell. We call this process clonal expansion. These two terms derive from the fact that one version of a B cell is chosen or selected. Then, it is reproduced many times, or its population is expanded. All of these subsequent cells are clones of the first cell and produce the same antibody. Interestingly, pathogens often possess several surface molecules that function as antigens. In this case, more than one type of B cell may become activated and may go through clonal expansion so that more than one type of antibody is generated against the same pathogen.
Now, let’s talk about antibodies and how they allow the immune system to fight an infection. Antibodies are proteins, which are very similar to the B cell receptors present on the surface of B lymphocytes that once the B cell is activated and differentiated into a plasma cell are produced in large quantities and released into the blood and into the lymph. As we mentioned before, the plasma cell produces and secretes the same antibodies that it had on its cell surface as a B cell receptor. The soluble antibodies bind to extracellular antigens wherever they find them. This might be on the surface of a pathogen or presented by MHC molecules on the surface of infected host cells.
Antibodies cannot enter cells because they are relatively large proteins. Antibodies are therefore only effective against extracellular antigens. Antibodies are very specific. Each antibody only binds with one type of antigen. However, antibodies are extremely well adapted to help to cause destruction and removal of anything bearing the antigens they bind to. This is why antibodies targeting self-antigens would be very dangerous. It is also why immature B cells must be screened and carefully selected in the bone marrow to make sure that any B cells with receptors recognizing self-antigens are removed before they can migrate to the lymph nodes.
Antibodies can cause the pathogens in the blood to clump together through a process called agglutination. This makes them easier to locate and destroy. The antibodies attached to the surface of a pathogen cause macrophages to engulf the pathogen. If the pathogens or substances that these pathogens might produce, like certain toxins, are soluble, antibodies can make them insoluble. When antibodies and antigens are found separately, they’re both soluble, so they would be found as a solution. But when many antibodies bind to many antigens, it forms an insoluble precipitate. This process is called precipitation. Precipitation makes it easier for macrophages to identify and phagocytose the pathogen.
To help to fight pathogens, foreign cells, and virally infected cells, antibodies can activate the complement system. This causes a chemical complex to form that breaks apart the cell membrane, killing the target cell. The remaining parts of the target cell are then removed by phagocytes. Antibodies bound to a virally infected cell can also activate effector cells, such as natural killer cells of the innate immune system. Natural killer cells then destroy the infected cell by releasing cytotoxic molecules.
Finally, antibodies can neutralize a pathogen, such as a virus, by coating its surface. Because viruses use proteins on their surface to enter host cells, this prevents them from getting inside and causing an infection. Neutralization can also prevent viruses from releasing their genetic material if they do manage to breach the host cell membrane.
We mentioned at the beginning of the video that the adaptive immune system has a memory component, which allows it to mount a faster response against a pathogen it has encountered before. So, once our immune system has fought an initial infection, how do we retain the immunity to fight the same pathogen if it infects our body again? We’ve already learned that activated B cells differentiate into plasma cells, which can produce and secrete the large quantities of antibodies needed to fight an infection. But activated B cells can also differentiate into what we call memory B cells. Memory B cells do not secrete antibodies. They have B cell receptors on their cell surface, just like naive B cells.
Memory B cells are dormant cells that live in the immune system. These cells are specialized to have an especially long lifespan. They are adapted to allow the immune system to more rapidly respond to a second infection by the same pathogen. The presence of memory cells means that upon second or subsequent exposure, the immune system can react more rapidly. And we may not even notice or become ill in the process.
Now, let’s wrap up the video by reviewing the key points that we’ve learned. The immune system can be divided into specific, acquired or adaptive, immunity and innate, or nonspecific, immunity. The specific immune system includes humoral immunity and cell-mediated immunity. Humoral immunity primarily relies on the action of B lymphocytes. B cells possess antibody-like B cell receptors that are able to bind to the antigen of a pathogen actively infecting the body. This activates the B cell. Activated B cells differentiate into plasma cells and memory cells. Antibody immunity is effective against extracellular pathogens.
