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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Innate and adaptive immune response to apoptotic cells
Yufeng Peng1, David A Martin, Justin Kenkel
1Division of Rheumatology, 1959 NE Pacific Avenue, Box 356428, Seattle, WA 98195, USA.
Journal of Autoimmunity
|September 25, 2007
Summary
Efficient clearance of dying cells by phagocytes prevents autoimmune disease. Proper apoptotic cell removal by macrophages and dendritic cells maintains immune tolerance, while failed clearance triggers inflammation and self-antigen responses.
Area of Science:
- Immunology
- Cell Biology
- Autoimmunity
Background:
- The immune system encounters dying cells during central tolerance and from circulating immune cells.
- Phagocytes, such as macrophages and dendritic cells, are crucial for clearing these apoptotic cells under homeostatic conditions.
Purpose of the Study:
- To elucidate the mechanisms of apoptotic cell clearance and its role in maintaining immune tolerance.
- To understand how failed clearance contributes to autoimmune responses and inflammation.
Main Methods:
- The study reviews the process of apoptotic cell recognition, uptake, and ingestion by phagocytes.
- It discusses the role of natural antibodies and serum opsonins in facilitating this process.
- Mechanisms of T cell tolerance, including anergy, deletion, and regulatory T cell induction, are examined in the context of self-antigen exposure.
Main Results:
- Apoptotic cell removal by phagocytes promotes an immunosuppressive environment, preventing inflammatory responses to self-antigens.
- Constant exposure to self-antigen, particularly by immature dendritic cells, induces T cell tolerance through various mechanisms.
- Failure in apoptotic cell clearance, especially when cellular contents leak (necrosis), can trigger immune responses to self-antigens.
Conclusions:
- Effective clearance of apoptotic cells is essential for preventing autoimmunity and maintaining immune homeostasis.
- Dysfunctional apoptotic cell clearance can lead to the breakdown of self-tolerance and the development of inflammatory autoimmune diseases.
- Inflammatory responses can be initiated by the release of intracellular components, activating pattern recognition receptors like Toll-like receptors and inflammasomes.
Related Concept Videos
01:17Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
01:17The 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...
01:28Cells of the Innate Immune Response
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:31The Intrinsic Apoptotic Pathway
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01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...