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.
Key Term: Specific Immunity (Adaptive or Acquired Immunity)
Specific immunity describes the antigen-specific immune response. Specific immunity is immunity that develops over time as a result of exposure to different pathogens.
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 also 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.
Key Term: B Lymphocytes (B Cells)
B lymphocytes are lymphocytes that mature in the bone marrow and are involved in the production of antibodies.
Key Term: Antibody (Immunoglobulin)
An antibody is a globular protein produced by B lymphocytes that is adapted to bind with a specific antigen.
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 antigens 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 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.
Key Term: Antigen
Antigens are substances that can trigger an immune response.
Key Term: B Cell Receptor (BCR)
A B cell receptor is an antibody attached to the cell membrane of a B lymphocyte. When a B cell receptor binds with a complementary antigen, it stimulates the B cell to begin activation.
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?
- Each B cell will have a different type of antibody receptor on its surface.
- Each B cell has only one type of antibody receptor that binds to one specific antigen.
- The B cell antigen receptor has a similar structure to a soluble antibody.
- The B cell can bind to extracellular and intracellular antigens.
- The B cell antibody receptor is complementary to an antigen.
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 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 a virus, enters the body and begins to multiply, the first step in humoral immunity is to find a B cell with antibodies that can bind to the antigens on the pathogen. Once a B cell comes into contact with an antigen complementary to its B cell receptor, it matures and becomes 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.
Key Term: Major Histocompatibility Complex (MHC)
Major histocompatibility complex is a protein that functions to bind processed antigens and present them on the cell surface for recognition by immune cells.
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.
Key Term: Antigen-Presenting Cell (APC)
An antigen-presenting cell is a type of immune cell that facilitates an immune response by showing antigens bound to MHC proteins on its surface to other cells of the immune system.
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 becomes activated. This activation occurs in one of two ways, one of which is shown in Figure 4 below.
Some B cells are simply activated due to 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 and differentiate into what we call plasma cells. These cells multiply rapidly and produce large amounts of antibodies, which are secreted from the cell into the body fluids.
Some 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.
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 marker 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. These plasma cells multiply rapidly and 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 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.
Key Term: Clonal Selection
Clonal selection is the process by which T cells and B cells with receptors that bind with specific antigens are selected for clonal expansion.
Key Term: Clonal Expansion
Clonal expansion is the production of daughter cells all arising from a single parent cell. In the clonal expansion of lymphocytes, all of the daughter cells are specific to the same antigen.
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.
Example 2: Determining the Effect of HIV on Antibody Production
HIV infects and destroys T-helper cells. How would an HIV infection affect the body’s antibody response to a new bacterial infection?
- The antibody concentrations would rise higher and faster.
- Only one type of antibody would be produced.
- The same level of antibodies would be produced but it would take longer.
- Fewer antibodies would be produced by B cells.
- There would be no effect on the antibody response.
HIV stands for human immunodeficiency virus, which is a bloodborne pathogen that, over time, can lead to acquired immunodeficiency syndrome (AIDS). The term immunodeficiency describes a situation in which the immune system is not fully functioning. The question explains that HIV infects and destroys T-helper cells.
T-helper cells are a type of T lymphocytes, a type of white blood cell that plays a role in the immune system. T-helper cells play a role in both the humoral and the cell-mediated aspects of the specific, also called adaptive or acquired, immune response. They become activated when the T cell receptors on their surface recognize and bind with a specific antigen on a phagocytic antigen-presenting cell.
Once activated, T-helper cells go through the process of clonal expansion, increasing the population of activated T-helper cells that recognize a particular antigen. These cells, in turn, activate B cells and cytotoxic T cells. These cytotoxic T cells recognize host cells infected with the virus and destroy them.
B cells are cells that make antibodies. Antibodies are globular proteins that are specific to a particular antigen. This means that each type of antibody binds with only one type of antigen. B cells are often activated by cytokines released by activated T-helper cells before they differentiate into plasma cells that make and secrete large quantities of antibodies into the bloodstream.
Since HIV infects T-helper cells and destroys them, there are usually fewer T-helper cells available during an infection to become activated. Since there are fewer activated T-helper cells, there will also be fewer activated B cells. This means that there will be fewer antibodies produced since there will be fewer activated B cells and, therefore, fewer plasma cells that can produce them.
This means that an HIV infection will affect the body’s antibody response to a new bacterial infection because fewer antibodies would be produced by B cells.
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 is a type of effector B cell that 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. The plasma cell multiplies 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.
Key Term: Plasma Cell (Plasmacyte, Plasma B Cell)
A plasma cell is a type of immune cell that makes large amounts of a specific antibody. Plasma cells are effector cells that develop from B cells that have been activated.
Example 3: Recalling the Immune Cells that Secrete Antibodies
What type of immune cells secrete antibodies?
- Memory cells
- T-helper cells
- Plasma cells
Antibodies, also called immunoglobulins, are globular proteins that bind to one specific antigen. Antibodies are made by B cells. Immature B cells have antibody receptors, also called B cell receptors. These B cell receptors are antibodies attached to the cell membrane of B cells. When the B cell receptor binds with a complementary antibody, the B cell becomes activated. B cells may also require additional signaling from helper T cells to become activated. Once the B cell is activated, it begins to proliferate. This creates a population of B cells that all possess B cell receptors that recognize a particular antigen. The mature, activated B cells then differentiate into one of two cell types. Some become memory B cells, which live for a long time in the immune system, ready to rapidly activate if stimulated by the same antigen in the future. The majority differentiate into plasma cells. Plasma cells are B lymphocytes that, instead of surface-bound antibody receptors, generate large quantities of soluble antibodies that they secrete into the bloodstream and other body fluids.
This means that the type of immune cells that secrete antibodies is plasma cells.
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 destroy and remove 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.
Key Term: Memory B Cell
A memory B cell is a cell formed following a primary infection. Memory B cells have a long lifespan and are able to mount a rapid response upon secondary infection.
Example 4: Describing the Difference between Memory Cells and Plasma Cells
How are memory cells different from plasma cells?
- Memory cells are no longer able to multiply and differentiate.
- Memory cells have only one type of antibody receptor on their cell surface.
- Memory cells have a higher rate of protein synthesis.
- Memory cells remain in the circulation for a longer time period.
- Memory cells are able to respond to a wider range of antigens.
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 also sometimes called B cell immunity because it primarily relies on the action of B lymphocytes, a type of cell that makes proteins called antibodies.
Antibodies are globular proteins that bind with one specific antigen. Immature B cells have antibody receptors, also called B cell receptors. These B cell receptors are antibodies attached to the cell membrane of B cells. When the B cell receptor binds with a complementary antibody, the B cell becomes activated. B cells may also require additional signaling from helper T cells to become activated.
Once the B cell is activated, it begins to reproduce. This creates a population of B cells that all possess B cell receptors that recognize a particular antigen. This process is called clonal selection. The mature, activated B cells then differentiate into one of two cell types. Some become memory B cells, which live for a long time in the immune system, ready to rapidly activate if stimulated by the same antigen in the future. The majority differentiate into plasma cells. Plasma cells are B lymphocytes that, instead of surface-bound antibody receptors, generate large quantities of soluble antibodies that they secrete into the bloodstream and other body fluids.
Using this information, we can conclude that memory cells are different from plasma cells because memory cells remain in the circulation for a longer time period.
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.
- The adaptive immune system includes cell-mediated immunity and humoral immunity.
- Humoral immunity primarily relies on the action of B lymphocytes that make proteins called antibodies.
- B cells that possess antibodies that are able to bind to the antigens of the pathogen actively infecting the body are activated.
- Activated B cells differentiate into plasma cells and memory B cells.
- Antibody immunity is effective against extracellular pathogens.