In this explainer, we will learn how to describe how T lymphocytes coordinate a response to virally infected and abnormal body cells, outline the role of suppressor T cells in the immune response, and compare cell-mediated immunity with other types of immune responses.
Adaptive immunity, also known as acquired or specific immunity, is the way that our immune systems are adapted to mount a specific response that is tailored to destroy and remove a specific pathogen. The adaptive immune system handles infections that are not prevented or completely cleared by the innate immune system. Our adaptive immune system is often described in two divisions, humoral immunity and cell-mediated immunity. A graph showing the progress of a complete primary immune response is shown in Figure 1.
Key Term: Adaptive Immunity (Specific or Acquired Immunity)
Adaptive immunity describes the antigen-specific immune response. Adaptive immunity is immunity that develops over time as a result of exposure to different pathogens.
The humoral immune response is sometimes called B cell immunity or antibody immunity because it relies on the action of B cells that make antibodies specific to the invading antigen.
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 infected cells in the body.
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, bacteria, or toxins produced by bacteria). Cell-mediated immunity is effective against intracellular pathogens, an example of which is a host cell infected by a virus.
Key Term: Cell-Mediated Immunity
Cell-mediated immunity is the part of the adaptive immune response that involves cytotoxic T cells targeting infected cells, cancer cells, or foreign cells.
Example 1: Contrasting Cell-Mediated Immunity and Humoral Immunity
What is a difference between cell-mediated and humoral (antibody-mediated) immunity?
- All the immune cells involved in humoral immunity are B cells, while those in cell-mediated immunity are all T cells.
- Cell-mediated immunity is rapid, while humoral immunity is a more delayed but sustained response.
- Humoral immunity involves a specific response to an antigen, but cell-mediated immunity does not.
- Clonal selection occurs in humoral immunity but not in cell-mediated immunity.
- Humoral immunity responds to extracellular pathogens, while cell-mediated immunity responds to intracellular pathogens.
Adaptive immunity is also called specific, or adaptive, immunity. The adaptive immune system handles infections that are not prevented or completely cleared by the innate immune system. Our adaptive immune system is often described in two divisions, humoral immunity and cell-mediated immunity.
The humoral immune response is sometimes called B cell immunity or antibody immunity because it relies on the action of B cells that make antibodies specific to the invading antigen. Humoral immunity is only effective against extracellular pathogens (for example, viruses in the blood, bacteria, or toxins produced by bacteria).
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 infected cells in the body. Cell-mediated immunity is effective against intracellular pathogens, an example of which is a host cell infected by a virus.
Using this information, we can conclude that the difference between cell-mediated immunity and humoral (antibody-mediated) immunity is that humoral immunity responds to extracellular pathogens, while cell-mediated immunity responds to intracellular pathogens.
Cell-mediated and humoral immune responses occur simultaneously and interact closely with each other. Even though they are often described separately, humoral immunity and cell-mediated immunity work together in our adaptive immune system to fight infection.
Cytotoxic T cells are effector T cells that have the ability to recognize antigens present on the surface of a host cell and kill that cell. They can also recognize other abnormal cells, such as cancerous cells that are rapidly dividing, and destroy those as well. This function is important because the humoral immune system alone does not have the ability to destroy cells that are infected with a virus.
A virus is a pathogen that consists of genetic material, either DNA or RNA, inside of a protein coating called a capsid. The virus can enter the cell by fusing its capsid with the cell membrane of the host cell and releasing its genetic material into the cytoplasm. Once inside, the genetic material will take over the cell’s functions, forcing it to make more viruses.
Almost every cell in the body possesses a protein called MHC. MHC stands for “major histocompatibility complex” and presents antigens on the surface of the cell. Once inside the cell, the viral proteins are processed to form antigen molecules. These can then combine with MHC to form the MHC–antigen complex. The MHC bonded with the antigen moves to the outside of the cell membrane where it is known as an MHC–antigen complex, as shown in Figure 2.
Key Term: MHC (Major Histocompatibility Complex)
MHC is a protein that functions to bind antigens and display them on the cell surface for recognition by immune cells.
The MHC–antigen complex is recognized by the T cell receptors on the surface of naive cytotoxic T cells, also called CD8+ T cells due to the presence of the CD8 cell surface protein on their cell membrane. CD stands for “cluster of differentiation” and different types of cells have different combinations of these proteins on them that carry out different functions and also distinguish certain cell types from each other.
Key Term: Cytotoxic T Cell
A cytotoxic T cell is a type of immune cell that can kill certain cells, including foreign cells, cancer cells, and cells infected with a virus. Cytotoxic T cells express the CD8 cell surface protein.
The CD8 protein not only distinguishes cytotoxic T cells from other types of cells but also works together with the T cell receptor (TCR) to help recognize and bind with the MHC–antigen complex, as shown in Figure 3. This is the first step in activating a naive cytotoxic T cell.
A T cell receptor, or TCR, is similar to a B cell receptor in that different T cells have different receptors that are generated randomly through a special type of genetic recombination.
Only a cytotoxic T cell with a certain type of TCR will recognize and attach to a particular MHC–antigen complex on an infected cell.
Only some T cells will be activated by a particular antigen, and others will not, much like the activation of B cells. We call this process clonal selection, and it is illustrated in Figure 4.
Key Term: T Cell Receptor (TCR)
A T cell receptor is a protein found on the surface of T cells that binds with a specific, complementary antigen.
Key Term: Clonal Selection
Clonal selection is the process by which T cells and B cells with receptors that bond with specific antigens are selected to multiply and proliferate.
Cell-mediated immunity also requires the activation of helper T cells. These are sometimes called CD4+ T cells or even T4 cells because they possess the CD4 cell surface membrane. The CD4 cell surface protein also helps the helper T cell to bind its TCR with a complementary MHC–antigen complex.
Helper T cells are usually activated in a different way than cytotoxic T cells. Instead of recognizing the MHC–antigen complex on the surface of an infected host cell, they are usually activated by cells called antigen-presenting cells.
Key Term: Helper T Cell (T-Helper Cell)
A helper T cell is a type of T cell that recognizes foreign antigens and secretes cytokines that activate cytotoxic T cells and B cells. Helper T cells express the CD4 cell surface protein.
When a pathogen invades the body, it is engulfed by phagocytic cells that “eat” the pathogen as a part of the innate immune response. Many of these cells are antigen-presenting cells, or APCs. Without becoming infected themselves, the APCs break apart the pathogen and bind the processed antigen to MHC.
The APCs then move this processed MHC–antigen complex from inside the cell to the surface of the cell membrane. This is how antigen-presenting cells “present” the antigen to other cells of the immune system. A diagram of an antigen-presenting cell interacting with a helper T cell is shown in Figure 5.
Key Term: Antigen-Presenting Cell (APC)
An antigen-presenting cell is a type of immune cell that facilitates an immune response by showing processed antigens on its surface to other cells of the immune system.
APCs can then travel throughout the body within the lymphatic system to the lymph nodes where they will come in contact with many other B and T cells. One of the most important APCs in the immune system is the macrophage.
The CD4 cell surface protein on the cell membrane of the helper T cell recognizes the MHC–antigen complex on the surface of the macrophage. It helps the TCR to bind with the antigen on the MHC–antigen complex, which is a part of the complex process that activates a helper T cell.
Once activated, the helper T cells live up to their name. They begin to release different cytokines that have various functions. Some act as chemotaxis factors to recruit macrophages and other APCs. They also produce interleukins. Inter- means “between” and -leukin refers to white blood cells. Interleukins are a type of cytokine that helps white blood cells to communicate with each other.
The interleukins released by the helper T cells activate B cells. This initiates the humoral immune response. A diagram illustrating the role of helper T cells in humoral immunity and cell-mediated immunity is shown in Figure 6.
The interleukins released by helper T cells also activate cytotoxic T cells. The cytotoxic T cells require two signals to become activated, as shown in Figure 7. The first signal comes from their TCR binding with a compatible MHC–antigen complex on an infected cell. The second signal is from the interleukins released by the activated helper T cells.
Key Term: Interleukin
An interleukin is a type of cytokine that regulates immune responses.
Example 2: Recalling the Type of Cells Involved in Both Cell-Mediated and Humoral Immune Responses
Complete the sentence: cells are involved in both cell-mediated and humoral (antibody) responses.
- Cytotoxic T
- Natural killer (NK)
The cell-mediated and humoral immune responses are both mechanisms of the adaptive immune system. The adaptive immune system adjusts and generates an immune response targeting a specific pathogen. The cell-mediated and humoral immune responses are often described separately, but they interact closely and occur simultaneously.
The humoral immune response is effective against extracellular antigens and is facilitated by antibodies made by B cells that have differentiated into plasma cells. The cell-mediated immune response is effective against intracellular antigens and is facilitated by cytotoxic T cells.
When a pathogen enters the body, it must first reach a certain threshold before the adaptive immune response is activated. The adaptive immune system also takes time to initiate a response. In this time, the innate immune system fights the pathogen. The innate immune system is different from the adaptive immune system in that it fights every pathogen using the same techniques. The innate immune system involves the inflammatory response. It also involves the action of phagocytic cells, like macrophages, neutrophils, and natural killer cells.
Helper T cells can become activated by macrophages. They, in turn, activate the B cells and cytotoxic T cells that are the main effector cells of the adaptive immune response.
Which means we can conclude that T-helper cells are involved in the cell-mediated and humoral responses.
The activated T cells begin to multiply. The helper T cells proliferate by mitosis and continue to produce cytokines that activate cytotoxic T cells and also activate B cells. The activated cytotoxic T cells also proliferate and are able to destroy infected host cells that they come into contact with. Proliferation of activated T cells is called clonal expansion, and it is illustrated in Figure 8.
Effector cells is a term used for cells that are active in carrying out a response to a stimulus. Activated cytotoxic T cells are considered effector cells within the immune system because they are able to destroy infected and abnormal cells.
The TCR recognizes antigens presented on infected cells in the MHC–antigen complex and binds to it with the help of CD8. The T cell is then able to kill the infected cell by secreting a protein called perforin. The perforin perforates, or creates “pores,” in the cell membrane of the infected cell, which ultimately lyses the cell, breaking it open and killing it, as shown in Figure 9. Activated, mature cytotoxic T cells can also trigger programmed cell death, or apoptosis, in infected or abnormal cells.
Our immune system has the ability to recognize abnormal host cells that are rapidly dividing and may become cancerous. It can also distinguish the cells in a transplanted organ from the host’s cells and potentially mount an attack, damaging and rejecting the transplanted organs. The action of CD8+ cytotoxic T cells is responsible for both these immune system functions.
Example 3: Recalling the Role of Cytotoxic T Cells
What would not be a target for a cytotoxic (killer) T cell?
- A cancerous body cell
- A cell from a transplanted kidney
- An epithelial cell infected with COVID-19
- A toxin released by a bacterium
Cytotoxic T cells are the main effector cells in the cell-mediated immune response. The cell-mediated immune response is a part of the adaptive immune system. Cytotoxic T cells become activated by helper T cells. Their activation also requires exposure to an MHC–antigen complex on the surface of an infected host cell.
When a cell is infected by a pathogen, such as a virus like COVID-19, there are proteins called MHC that function to attach to antigens from that pathogen and then present the antigens on the outside of the cell membrane. This allows other cells not only to recognize that something is wrong within the cell but also to be able to tailor a response to the specific pathogen posing a threat.
Activated cytotoxic T cells are able to multiply and expand their population through the process of clonal expansion. These mature cytotoxic T cells then attack and destroy any infected host cells by secreting a protein called perforin that creates holes in the infected cell’s cell membrane, destroying it. Cytotoxic T cells also have the ability to trigger apoptosis, or programmed cell death, in infected target cells.
Cytotoxic T cells not only destroy cells infected with viruses but also recognize other abnormal cells, such as cells dividing too rapidly that may become cancerous, and destroy them using the same methods. Cytotoxic T cells can also become activated by recognizing the cells of a transplanted organ; they will then attack them, causing damage to the organ and possible rejection of the organ by the host.
So, the agent that would not be a target for a cytotoxic T cell is a toxin released by a bacterium.
This reaction between antigen-presenting cells, helper T cells, and cytotoxic T cells is how cell mediated immunity fights infection. When the infection is cleared, another type of T cell deactivates the immune system and returns it to a resting state.
Suppressor T cells are the cells responsible for shutting down the immune system after an infection has been taken care of, or cleared. As shown in Figure 10, suppressor T cells deactivate or kill activated helper T cells, cytotoxic T cells, B cells, and others. Suppressor T cells can do this by direct contact with these cells or by secreting inhibitory lymphokines, which are a type of cytokine produced by lymphocytes. The immune system has a potent effect on the body and can be dangerous if left unchecked.
Key Term: Suppressor T Cells (T Suppressor Cells, Regulatory T Cells)
A suppressor T cell is an immune cell that can inhibit the activity of immune cells.
Example 4: Recalling the Role of a Suppressor T Cell
Complete the sentence: cells are involved in shutting down the immune response after infection.
- T suppressor (regulatory)
- Natural killer (NK)
- Cytotoxic T
Our immune system is dangerous if left unchecked. An uncontrolled immune response can lead to injury, autoimmune disorder, or even death. One of the most important functions of the immune system is its ability to become activated when a threat is present and then to return to a resting or dormant state when the pathogen is cleared. Natural killer cells are involved in the innate immune response and are able to recognize and destroy infected or abnormal cells without the need to develop antigen specificity. T-helper cells activate other immune cells like B cells that differentiate into plasma cells and cytotoxic T cells that destroy cells infected with a specific pathogen. A plasma cell is a type of differentiated B cell that secretes antibodies into the body fluids to help fight infection. When the infection is cleared, none of these cells are needed any longer and so are shut down or destroyed by the action of cells called T suppressor cells or regulatory T cells. These cells perform the essential function of keeping the immune system under control.
Using this information, we can conclude that T suppressor cells are involved in shutting down the immune response after an infection.
Special cells called memory cells persist in the immune system after the suppressor T cells have done their job. These cells live for a long time and remain dormant in the immune system organs, waiting to become activated if our bodies encounter the same pathogen again.
Memory cells include B cells with antibodies specific to a particular antigen, memory cytotoxic T cells, and helper T cells. These cells are needed to quickly activate the B cells and cytotoxic T cells, rapidly triggering both the humoral and cell-mediated adaptive immune responses. This memory component of adaptive immunity prevents us from constantly becoming ill from the same infection. It is also why immunizations, also called vaccinations, are effective at preventing illness. A graph of the action of T cells in an immune response is shown in Figure 11.
Cell-mediated immunity and humoral immunity are closely intertwined components of the adaptive immune system. Humoral immunity relies on antibodies made by B cells. Cell-mediated immunity relies on the action of cytotoxic T cells. Both these immune responses are necessary, and they work simultaneously to allow our bodies to efficiently fight infections. Both humoral immunity and cell-mediated immunity generate immune memory so that our bodies can recognize a recurrence of an infection and mount a response much more quickly.
Let’s summarize what we have learnt about cell-mediated immunity.
- The adaptive immune system includes humoral immunity and cell-mediated immunity.
- The cell-mediated immune response is sometimes called T cell immunity because it relies on the action of helper and cytotoxic T cells.
- A cytotoxic T cell is a type of immune cell that can kill certain cells, including foreign cells, cancer cells, and cells infected with a virus.
- Helper T cells assist in this process by activating cytotoxic T cells.
- A suppressor T cell is an immune cell that can inhibit the activity of B cells and other T cells and shut down an immune response.
- The cell-mediated immune response is effective against intracellular pathogens, while the humoral immune response is more effective against extracellular pathogens.