Apoptosis signaling pathways
Richard M Siegel1, Michael J Lenardo
1National Institute of Allergy & Infectious Diseases, Bethesda, Maryland, USA.
Abstract:
In the past few years much has been learned about the molecular signals governing apoptosis, or programmed cell death, in lymphocytes and other cells of the immune system. Two major pathways, active and passive apoptosis, have been identified and are discussed in this overview. Active apoptosis, also termed propriocidal cell death or antigen-induced cell death, occurs when cells are stimulated through a family of TNF-related receptors termed death receptors. These receptors are up-regulated in activated lymphocytes and trigger apoptosis chiefly in effector cells that have been recently stimulated through the antigen receptor. Passive or lymphokine withdrawal apoptosis occurs when activated lymphocytes are deprived of essential growth cytokines and does not require death receptors. Cell death initiated by either pathway is carried out by a unique family of intracellular cysteine proteases, the caspases. Defects in each of these pathways produce distinct pathologies.
Insights
Programmed cell death (apoptosis) in immune cells occurs via active or passive pathways. Active apoptosis uses death receptors, while passive apoptosis involves cytokine withdrawal. Both pathways utilize caspases for cell death execution.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Apoptosis, or programmed cell death, is crucial for immune system regulation.
- Recent advancements have elucidated molecular signals governing lymphocyte apoptosis.
Purpose of the Study:
- To provide an overview of the two major pathways of apoptosis in immune cells.
- To discuss the molecular mechanisms and implications of these pathways.
Main Methods:
- Literature review and synthesis of current research on apoptosis.
- Identification and description of active and passive apoptosis pathways.
Main Results:
- Two primary apoptosis pathways identified: active (death receptor-mediated) and passive (lymphokine withdrawal).
- Active apoptosis is triggered by TNF-related death receptors, primarily in activated effector lymphocytes.
- Passive apoptosis occurs upon deprivation of essential growth cytokines and does not require death receptors.
Conclusions:
- Both active and passive apoptosis pathways are executed by caspases, a family of intracellular cysteine proteases.
- Defects in either apoptosis pathway lead to distinct pathologies, highlighting their critical roles in immune homeostasis.
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