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The Extrinsic Apoptotic Pathway01:17

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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...
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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...
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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. 
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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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...
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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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Surface code--biophysical signals for apoptotic cell clearance.

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Apoptotic cell clearance prevents inflammation and autoimmune disease. Phosphatidylserine (PS) acts as an

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Area of Science:

  • Immunology and Cell Biology
  • Molecular and Cellular Biology

Background:

  • Apoptosis, or programmed cell death, is a physiological process crucial for development and tissue homeostasis.
  • Unlike necrosis, apoptosis is anti-inflammatory, mediated by specific molecular signals.
  • Efficient clearance of apoptotic cells prevents secondary necrosis and the release of inflammatory signals.

Purpose of the Study:

  • To review current findings on apoptosis-inducing pathways.
  • To elucidate key players in apoptotic cell recognition and clearance.
  • To explore the role of membrane remodeling in phagocytic engulfment.

Main Methods:

  • Review of existing literature on apoptosis and cell clearance mechanisms.
  • Analysis of molecular signals ('find-me', 'eat me', 'tolerate me') involved in the process.
  • Examination of the role of phosphatidylserine (PS) exposure and recognition.

Main Results:

  • Apoptotic cells release 'find-me' signals attracting phagocytes and 'stay away' signals deterring granulocytes.
  • Phosphatidylserine (PS) exposure on apoptotic cells serves as a primary 'eat me' signal, recognized by phagocyte receptors.
  • PS also functions as a 'tolerate me' signal, inducing anti-inflammatory cytokine release, and its lateral mobility aids phagocyte recognition.

Conclusions:

  • Effective apoptotic cell clearance is vital for preventing inflammation and autoimmune diseases like systemic lupus erythematosus.
  • Phosphatidylserine (PS) plays a multifaceted role in apoptotic cell engulfment and immune tolerance.
  • Understanding these mechanisms is key to managing inflammatory and autoimmune conditions.