Lesson Explainer: Specific Immune Response: Antibodies Biology • Third Year of Secondary School

In this explainer, we will learn how to describe the process of clonal expansion and antibody formation in response to an antigen.

Adaptive or specific immunity can be thought of as a “third line of defense” when it comes to fighting pathogens and illnesses. The first line of defense is the barriers present in the body, which are specialized to keep pathogens and foreign materials out. The second line of defense is the nonspecific immune response involving inflammation, phagocytic cells, and certain aspects of the complement system.

The first and second lines of defense are both part of the innate immune system. Innate immunity reacts to every infection or potential threat in the same way and is the immunity you were born with.

If an infection or pathogen makes it past these two lines of defense and persists in the body for a period of time, the adaptive immune system responds. Adaptive immunity is also referred to as “specific immunity” or “acquired immunity” because it is the part of the immune system that creates a response specific to the pathogen that needs to be eliminated. Adaptive immunity is the immunity you develop, or acquire, over time. A diagram showing the combined response of innate and adaptive immunity is shown in Figure 1.

The adaptive immune system is often divided into two categories: cell-mediated immunity and humoral immunity. Cell-mediated immunity is sometimes called T cell immunity because it mostly relies on the action of cytotoxic T cells.

Humoral immunity is sometimes called B cell immunity because it primarily relies on the action of B lymphocytes, a type of cell that makes proteins called antibodies. Humoral immunity is also sometimes referred to as antibody immunity. However, the B cells do not act on their own and often need the assistance of several other types of lymphocytes to mount an effective immune response.

Let’s begin by getting acquainted with B cells. Generally, B cells, also called B lymphocytes, are lymphocytes that reach maturity in the bone marrow. B cells have a special 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, as you can see in Figure 2 below.

Figure 2 shows us how 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 are tested to make sure that they do not carry receptors against “self.” 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 is embedded in the B cell’s membrane. Antibodies are globular proteins that bind to substances we call antigens.

An antigen is basically anything that can bind to an antibody, and most non-self-antigens trigger an immune response. Antigens can be molecules on the surface of cells, pathogens like bacteria or viruses, or other substances like toxins or parasites.

When antibodies are attached to the surface of a naïve, not yet activated, B cell, they are called B cell receptors or antibody receptors.

Example 1: Recalling the Characteristics of B Lymphocytes

The figure shows a B lymphocyte with antibody (immunoglobulin) receptors on its surface membrane.

Which statement is not true?

1. Each B cell will have a different type of antibody receptor on its surface.
2. Each B cell has only one type of antibody receptor that binds to one specific antigen.
3. The B cell antigen receptor has a similar structure to a soluble antibody.
4. The B cell can bind to extracellular and intracellular antigens.
5. The B cell antibody receptor is complementary to an antigen.

Answer

B cells, also called B lymphocytes, are cells involved in the specific, also called adaptive or acquired, immune response. This immune response is often divided into humoral and cell-mediated immunity. Humoral immunity relies on the action of B cells and is most effective against extracellular pathogens, whereas cell-mediated immunity relies on the action of cytotoxic T cells and is effective against intracellular pathogens. Both types of adaptive immunity work simultaneously to fight infections.

B cells have a special genetic makeup. The genes for antibodies are mixed up by some type of genetic recombination so that many random varieties of antibodies are produced. This means that each B cell has a different antibody on its cell surface, called a B cell receptor, and also means that each B cell has only one kind of antibody on its surface.

Antibodies are globular proteins that bind to substances we call antigens. Each antibody only binds to one kind of antigen. An antigen is basically anything that can bind to an antibody, and most non-self-antigens trigger an immune response. Antigens can be molecules on the surface of pathogens like bacteria or viruses, or other substances like toxins or parasites. Antibodies and B cell receptors are only able to bind with extracellular antigens, antigens found outside of the cells.

This tells us that the statement that is not true about B lymphocytes is that the B cell can bind to extracellular and intracellular antigens.

When a pathogen, such as a bacterium or virus, enters the body and begins to multiply, the first step in humoral immunity starts when a B cell with antibodies that can bind to the antigens on the pathogen encounters the pathogen. Once a B cell comes into contact with an antigen complementary to its B cell receptor, it can become activated and is no longer referred to as naïve.

The immune system facilitates this process in several ways. Some phagocytic cells carry bits of the pathogen with them on their cell surface. These cells, such as neutrophils and macrophages, engulf the pathogen through a process called phagocytosis, a type of endocytosis. They then break down the pathogen and present recognizable parts, called antigens, on their cell surface attached to special proteins called the major histocompatibility complex, or MHC.

Cells that are able to present antigens to other cells in the immune system are called antigen-presenting cells, or APCs for short. An illustration of a phagocytic APC is shown in Figure 3.

These cells travel to the lymph nodes of the immune system, where they interact with the lymphocytes housed there, including B cells. Alternatively, the pathogen itself may be present in the lymph fluid or in the blood that is filtered through the lymph node and may come into contact with immune cells that way.

When the antibody on the surface of a B cell binds with an antigen it recognizes, the B cell can become activated. This activation occurs in one of two ways, one of which is shown in Figure 4 below.

B cells can simply be activated by the presence of a complementary antigen, which you can see occurring in Figure 4 above. Once the B cells bind with an antigen that matches their antibody, they are activated. These cells multiply rapidly and produce large amounts of antibodies, which are secreted from the cell into the body fluids.

Sometimes, B cells require what is called T cell-dependent activation. In this case, the antibody, or B cell receptor, on the surface of the B cell recognizes a compatible antigen, which triggers the B cell to engulf the antigen by phagocytosis. The antigen is then broken apart, and pieces are attached to a molecule called MHC, which stands for major histocompatibility complex. The MHC attached to the antigen is then presented on the surface of the B cell. A diagram illustrating a helper T cell interacting with a B cell is shown in Figure 5.

Certain T lymphocytes called helper T cells have receptors that recognize and attach to this MHC-antigen complex. Helper T cells are characterized by a cell surface molecule called CD4. They also have receptors called T cell receptors. These T cell receptors along with the CD4 cell surface molecules together recognize and attach to the MHC-antigen complex on the surface of B cells, which activates the helper T cells.

The activated helper T cells in turn release cytokines called interleukins that complete the activation of the B cell. This fully activates the B cell, which then begins to divide. Some of the activated B cells differentiate to become plasma cells, which secrete large amounts of antibodies. The activated T cell also begins to multiply in order to activate more B cells.

Helper T cells can also be activated by antigens presented in an MHC-antigen complex on the surface of other phagocytic cells, such as macrophages. These T cells then release interleukins that can activate B cells that have antibodies bound to an antigen. The interleukins also activate other immune cells, such as cytotoxic T cells. In this way, helper T cells play a role in both humoral and cell-mediated immunity.

In this process of B cell activation, only B cells that possess antibodies that are able to bind to the antigens of the pathogen actively infecting the body are activated by cytokines. We call this clonal selection, which is illustrated in the first stage of Figure 6, where the B cell is activated.

The activated B cells differentiate into effector cells called plasma cells and multiply rapidly, resulting in lots of cells with the same antibody present on the original activated B cell. We call this process clonal expansion. You can see clonal expansion occurring as the activated B cell at the top of Figure 6 proliferates via mitosis.

We get these two terms 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.

Each pathogen often possesses 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 pathogen.

The process of clonal selection and expansion of B cells explains where antibodies come from. Antibodies are proteins present on the surface of B lymphocytes that, once activated, are produced in large quantities and released into the blood and lymph. Let’s now answer the question of how antibodies allow the immune system to fight infections.

Once the right B cell is activated, it differentiates into what we call a plasma cell. This plasma cell, also called effector B cell, makes and secretes the same antibodies that it had on its cell surface as a B cell. This secreted antibody is sometimes called a soluble antibody. Activated B cells multiply rapidly, creating more cells that make the same antibody. Effector cells are cells that actively respond to a stimulus and initiate a change. These plasma cells produce this soluble antibody in large quantities and release it into the bloodstream.

The soluble antibodies bind to extracellular antigens wherever they find them. This can be on the surface of the pathogen or on the surface of infected host cells. Antibodies cannot enter cells because they are relatively large proteins. Antibodies are only effective against extracellular antigens, or antigens found outside of host cells.

Generally, antibodies are very specific. Each antibody binds with only one type of antigen. However, antibodies are extremely well adapted to cause destruction and removal of anything bearing the antigens they attach to. This is why antibodies targeting “self” antigens are very dangerous and is also why immature B cells must be screened and carefully selected.

Let’s have a look at some of the many ways that antibodies can fight infections.

The antibodies attached to the surface of a pathogen cause macrophages to engulf the pathogen. If the pathogen is soluble, for example, a type of toxin, the antibodies can make it insoluble. This process is called precipitation. This makes it easier for macrophages to identify and phagocytose the pathogen.

Antibodies can also cause the pathogens in the blood to clump together, a process called agglutination, which makes them easier to locate and destroy. Antibodies can trigger the complement system to create a chemical complex that can lyse the cell membrane of the pathogen. This causes the pathogen to break apart, which kills it, and the parts are removed by phagocytes.

Finally, antibodies can neutralize a pathogen, such as a virus, by coating its surface and preventing it from entering cells to infect them, or by preventing it from releasing its genetic material once inside.

Once our immune system responds to an initial infection, how do we retain this immunity to the same pathogens if they infect our bodies again?

Activated B cells differentiate into plasma cells, which can produce and secrete the large quantities of antibody needed to fight an infection. Activated B cells also differentiate into what we call memory B cells. Figure 7 illustrates how B lymphocytes differentiate into plasma cells and memory B cells.

Memory B cells do not secrete antibodies. They have antibodies on their cell surface, like naïve 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.

Our body makes memory cells because if an organism is exposed to a pathogen once, it is likely to encounter it again. 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.

Humoral and cell-mediated immune responses are often described separately, but they occur simultaneously within the body. Many aspects of the humoral immune response impact the cell-mediated response, and vice versa. These two types of immune response are both facets of the specific, or acquired, immune system.