Name: how immune cells trigger cell death
Uploaded: 2023-04-30T10:28:11.000Z
Duration: 1 min 17 s
Channel: JoVE

The extrinsic apoptotic pathway is activated through extracellular death signals from immune cells.
These immune cells recognize dangerous cells, such as diseased ones, through homotrimeric ligands that bind to death receptors on the target cell membrane.
The death receptors belong to the tumor necrosis factor or TNF superfamily, which includes TNF receptor 1 and the Fas receptor.
In the Fas signaling pathway, the Fas ligand expressed on the surface of immune&#160; cells binds to Fas receptor on the target cell, causing activation of the receptor death domain.
The activated death domain recruits an adaptor protein, Fas-associated death domain, which then binds to initiator procaspase-8 to form the death-inducing signaling complex or DISC.
Inside DISC, procaspase-8 molecules dimerize and self-cleave to form active caspase-8, which is released into the cytosol.
Caspase-8 activates executioner procaspase-3 to form caspase-3 that cleaves cellular proteins, resulting in apoptosis.

the extrinsic apoptotic pathway

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate their apoptotic pathway. The extrinsic apoptotic pathway is vital in removing cancerous cells or virus-infected cells.
Another example of external apoptotic signaling occurs during T-cell development in the thymus to eliminate self-reactive T-cells. T-cells are immune cells that bind foreign macromolecules and particles and target them for destruction by the immune system. In order to prevent the immune system from attacking the body&#39;s own cells, T-cells do not target &#8220;self&#8221; proteins (proteins of the same individual). Immature T-cells, or thymocytes, undergo a screening process to determine whether or not they bind self-proteins. If the T-cell binds to self-proteins, it is signaled for apoptosis, thus preventing an autoimmune response.
<h4>Inhibiting Apoptosis</h4>
Anti-apoptotic regulators are proteins that can inhibit the extrinsic apoptotic pathway in cells. The FLICE inhibitory protein, or c-FLIP is one of the master anti-apoptotic regulators that binds to FADD (Fas-associated death domain protein), and caspases such as caspase-8. This binding prevents the formation of the death-inducing signaling complex (DISC), thus preventing the apoptotic pathway.
Some portion of this text is adapted from <a href="https://openstax.org/books/biology-2e/pages/9-3-response-to-the-signal">Openstax, Biology 2e, Section: 9.3</a>

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed ...

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JoVE Core

Cell Biology

Unit 1

Cell Death

KEY TERMS AND CONCEPTS

how immune cells trigger cell death

The extrinsic apoptotic pathway is a cell death process started by signals from outside the cell. In this pathway, extracellular death signals such as specific cytokines activate death receptors on the cell surface. Natural killer cells, or NK cells, and cytotoxic T-lymphocytes help carry out this response.

NK cells are part of the innate immune response, while cytotoxic T-lymphocytes belong to the adaptive immune response. These cells recognize receptors on altered cells and activate apoptosis, the controlled process of cell death. This pathway helps remove cancerous cells and virus-infected cells.

External apoptotic signaling also plays a role in T-cell development in the thymus. During this screening step, immature T-cells, called thymocytes, are tested to see whether they bind self-proteins. If they do, they are signaled to undergo apoptosis so the immune system does not attack the body’s own cells and trigger an autoimmune response.

Some proteins can stop the extrinsic apoptotic pathway. One key anti-apoptotic regulator is c-FLIP, also called the FLICE inhibitory protein. It binds to FADD and caspases such as caspase-8 and blocks formation of the death-inducing signaling complex, or DISC.

How Immune Cells Trigger Cell Death

overview of cell death

Cell Death Pathways in Cells

Cell death pathways help the body remove old or damaged cells. Cell growth and cell death must stay balanced. If this balance is disrupted, it may contribute to cancer or autoimmune diseases. Cell death was first noticed in the early 19th century, but experimental proof came later. In 1842, Carl Vogt described cell death in a metamorphic toad. At that time, the process was not yet called cell death. Scientists identified separate cell death pathways in the 20th century after advances in...

apoptosis

Apoptosis and Cell Survival Control

Apoptosis is a controlled form of cell death that helps keep tissues healthy. The term comes from two Greek words, apo and ptosis, which mean separation and falling off. Hippocrates used the word to describe gangrene caused by bandaging fractured bones. Apoptosis was separated from necrosis in 1970 after John Kerr described its distinct shape changes. In one experiment, loss of blood supply to liver tissue caused the tissue to shrink. Under an electron microscope, Kerr saw that hepatocytes had...

caspases

Caspases in Apoptosis and Immunity

Caspases are cysteine proteases that help control cell death and immune defense. They act as effectors in apoptosis, which is the process of programmed cell death. The ced-3 gene in C. elegans was first linked to apoptosis, and it encodes a caspase similar to the interleukin-1-beta converting enzyme, or ICE, in mammals. Caspases also have a role in inflammation. Inflammatory caspases activate pro-inflammatory cytokines, which help recruit immune cells and stop pathogens from replicating inside...

The extrinsic apoptotic pathway is a cell death process started by signals from outside the cell. In this pathway, extracellular death signals such as specific cytokines activate death receptors on the cell surface. Natural killer cells, or NK cells, and cytotoxic T-lymphocytes help carry out this response. NK cells are part of the innate immune response, while cytotoxic T-lymphocytes belong to the adaptive immune response. These cells recognize receptors on altered cells and activate...

the intrinsic apoptotic pathway

How Cells Trigger Apoptosis from Damage

Intrinsic apoptosis is the cell’s built-in death response to internal stress. Cell injury, hypoxia, and DNA damage can start this process. The B-cell lymphoma 2, or Bcl-2, family of proteins is the main regulator of this pathway. When DNA is damaged, checkpoint proteins such as Ataxia Telangiectasia Mutated, or ATM, and Checkpoints Factor-2, or Chk2, become active. They phosphorylate p53, a protein that helps control cell survival. p53 then turns on pro-apoptotic proteins such as Bax, Bak,...

phagocytosis of apoptotic cells

How Apoptotic Cells Are Cleared

Apoptotic cells must be cleared quickly so they do not cause inflammation, autoimmune disease, or necrosis. During apoptosis, cells break into apoptotic bodies that are then removed by phagocytosis, the process in which other cells engulf and digest them. Professional phagocytes, such as macrophages and immature dendritic cells, handle this job most effectively. Some non-professional phagocytes, including epithelial cells and fibroblasts, can also take part, but they are less efficient. Normal...

autophagic cell death

Autophagy and Cell Death Pathways

Autophagy is a cell cleanup process that can also lead to cell death. Christian de Duve discovered autophagy, in which cell parts are enclosed in membrane-bound sacs called autophagosomes. These autophagosomes then fuse with lysosomes, which digest the material inside. In many cells, autophagy helps prevent cell death. When damage becomes too severe to repair, however, the process can shift toward cell death. Autophagy can connect to apoptosis, necroptosis, and autosis, so it sits at an...

necrosis

Necrosis and Other Cell Death Pathways

Necrosis is an accidental form of cell death that ends in cell lysis, or cell bursting. Rudolf Virchow first used the term in 1859 in his book Cell Pathology to describe advanced tissue breakdown. In high school biology, necrosis is often used to compare damaged cells with other ways cells can die. Necrotic cells can look different depending on the tissue and the cause of injury. In coagulative necrosis, cells lose their nuclei but keep their basic shape because the enzymes that digest cell...

key terms and concepts

Explore how NK cells and cytotoxic T-lymphocytes trigger extrinsic apoptosis, remove infected or cancerous cells, and help prevent autoimmunity.

How Immune Cells Trigger Cell Death | JoVE K12

cell biology

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How Immune Cells Trigger Cell Death

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