Cytotoxic T cells (AKA killer T cells) are important lymphocytes of the adaptive immune system. Like helper T cells, they are activated by antigen-presenting cells in the lymph nodes. While helper T cells mediate the activity of other immune cells against a pathogen, cytotoxic T cells attack infected host cells directly and destroy them.

How do cytotoxic T cells kill infected cells?
Cytotoxic T cells use cytotoxic granules to kill infected cells

What is a cytotoxic T cell?

Cytotoxic T cells and helper T cells are the two main types of T lymphocytes in the human immune system. Both come from stem cells in the bone marrow before they migrate to the thymus, where they mature and differentiate CD4 + and CD8 + T cells.

Express all T cells T cell receptors (TCRs) on their surface, and they also express CD4 or CD8 co-receptors, depending on their function. Helper T cells express CD4 receptors (and can be referred to as CD4 + T cells) and cytotoxic T cells express CD8 receptors and are also known as CD8 + T cells.

Helper T cells “help” coordinate the adaptive immune response by activating other cells of the immune system, while cytotoxic T cells directly kill infected cells.

Cytotoxic T cells develop from stem cells in the bone marrow
T cells differentiate into helper T cells and cytotoxic T cells

Activation of cytotoxic T cells

All T cells are considered “naive” until they encounter their specific antigen. Like helper T cells, cytotoxic T cells are specific for only one type of antigen. However, they cannot bind to their antigen directly; Instead, they rely on support from Antigen presenting cells (APCs).

APCs (like dendritic cells, macrophages, and B cells) find and engulf invading pathogens before digesting them into protein fragments. Some of these fragments appear on their surface as part of a structure known as the Major Histocompatibility Complex (MCH) and T cells presented in the lymph nodes. When a cytotoxic T cell encounters its specific antigen on the surface of an APC, its TCR binds to the MHC and the T cell is activated.

A cytotoxic T cell is activated by an antigen presenting cell
Cytotoxic T cells are activated by antigen presenting cells

There are two types of major histocompatibility complexes found on the surface of APCs. these are MCHI and MCHII. The main difference in activation of helper T cells versus cytotoxic T cells is that they each bind to a different type of MCH receptor. Cytotoxic T cells bind to MHCI complexes, while helper T cells can only bind to MHCII complexes.

Once a naive T-cell is presented with its antigen, it divides quickly and cytotoxic T-cells begin to migrate to areas of infection in the body.

Function of cytotoxic T cells

Cytotoxic T cells are also known as “killer” T cells because of their role in destroying infected cells, pathogens, and tumor cells. The main method is the transfer of cytotoxic granules to infected target cells, which kill the cell and any pathogens it contains.

Cytotoxic T cells attack and kill abnormal cells
Cytotoxic T cells attack infected cells and cancer cells

Secretion of cytotoxic granules

Cytotoxic T cells and natural killers (NK cells) use a very similar mechanism to destroy virus-infected cells and pathogens.

Like NK cells, cytotoxic T cells contain cytotoxic granules that contain so-called proteins Perforin and Granzyme, that work together to destroy target cells. When they encounter an infected cell, cytotoxic T cells bind to the MHCI via their TCR receptors and release their cytotoxic granules. Perforin creates holes in the cell membrane of the target cell, and granzymes enter the cell through these pores. Once inside, the Granzyme begins Apoptosis (programmed cell death), which kills the cell and all pathogens it contains.

Cytotoxic T cells release cytotoxic granules that contain perforin and granzyme
Cytotoxic T cells use perforin and granzyme to destroy target cells

Cytotoxic T cells typically target virus infected cells, so this method of killing benefits the host in that it contains and destroys the viruses in the cell. If the cell were simple lysed, The viruses could leak out of the cell and migrate to other parts of the body.

The main difference between the action of NK cells and cytotoxic T cells is how they recognize their targets. Natural killer cells are stimulated to attack by the lack of MHCI, which is typically lost from the surface of tumor cells and cells infected with pathogens. However, cytotoxic T cells recognize their targets by the presence of specific antigens in the MCHI complex. Both cytotoxic T cells and NK cells are “serial killers” and can bind to and attack multiple target cells.

Secretion of cytokines

The secretion of perforin and granzyme is the main weapon of the cytotoxic T cell, but not its only function. Cytotoxic T cells are also eliminated Cytokinesthat contribute to the adaptive immune response in a number of ways.

One of these cytokines (IFN-γ) directly inhibits virus replication, which helps slow the spread of the infection in the body. IFN-γ also activates macrophages, causing them to migrate to sites of infection, where they function as both effector cells (when they engulf and destroy pathogens) and antigen-presenting cells.

Cytotoxic T cells also secrete cytokines
Cytotoxic T cells secrete cytokines to stimulate other immune cells

Regulation of cytotoxic T cells

Cytotoxic T cells play a key role in the adaptive immune response and are highly effective in removing infected cells from the body. However, if left unchecked, cytotoxic T cells can contribute to an excessive immune response, resulting in damage to healthy host cells and tissues.

In most cases this is prevented by an event reported as Contraction phase, This takes place a few weeks after the initial infection. T cell cytotoxic activity typically peaks about 7 days after initial infection. In the days and weeks after the peak of cytotoxic T cell activity, the contraction phase begins and up to 95% of the cells die. The remaining 5-10% become memory T cells that remain in the body for a long time after the infection is cleared.

What is a cytotoxic T cell in memory?

Memory cytotoxic T cells are the small percentage of cytotoxic T cells that remain in the body after the contraction phase. These cells remain in the immune system for a long time and, in the event of renewed infection, quickly recognize and start an attack against the pathogen.

Memory T cells stay in the body for a long time
Some cytotoxic T cells become memory T cells

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