Lecture on Apoptosis

Definition

• Apoptosis, also known as programmed cell death, is a regulated process.
• Involves production of enzymes degrading nuclear and cytoplasmic material.
• Results in formation of apoptotic bodies that are phagocytosed.

Triggers of Apoptosis

• Pathological triggers:
  • Infections, especially viral.
  • Protein misfolding due to mutation.
  • DNA damage caused by mutation, radiation, hypoxia, and free radicals.
• Homeostatic mechanism:
  • Regulates cell populations by removing unnecessary cells.

Morphological Changes

• Cell shrinkage and compaction of cytoplasm and organelles.
• Pycnosis: Shrinking and condensation of nucleochromatin.
• Karyorexis: Disintegration and fragmentation of chromatin.
• Appearance under microscope:
  • Shrunken cells with dense eosinophilic cytoplasm.
  • Small clumps of hematoxyphilic chromatin.
• Blebbing: Surface blebs and formation of apoptotic bodies.

Inflammation

• Apoptosis does not cause inflammation due to intact plasma membranes of apoptotic bodies.
• Quick recognition and removal by phagocytes.

Pathways of Apoptosis

• Intrinsic Pathway:

  • Triggered by mitochondrial leakage of cytochrome C.
  • Anti-apoptotic proteins (BCL2, BCLX) maintain mitochondrial integrity.
  • BH3 only proteins (BIM, BID, BAD) inhibit BCL2/BCLX under stress.
  • Activation of BACs/BAC creates channels for cytochrome C leakage.
  • Formation of apoptosome complex activates caspase 9, leading to caspase 3 & 6 activation.

• Extrinsic and Granzyme-Perforin Pathways:

  • Extrinsic Pathway:
    • Involves Fas-ligand and Fas-receptor interaction.
    • FAS-associated death domain adaptor protein activates caspase 8.
    • Caspase 8 activates caspases 3 & 6.
  • Granzyme-Perforin Pathway:
    • T cells release perforins, forming pores for granzymes entry.
    • Granzymes activate executioner caspases or cleave DNA.

Executioner Caspases

• Caspases 3 & 6 lead to chromosomal DNA degradation and cytoskeletal protein breakdown.
• Cause nuclear fragmentation and cell shrinkage.

Recognition and Phagocytosis

• Apoptotic bodies coated with phosphatidylserine recognized by phagocytes.
• May also be coated with opsonins like IgG or complement proteins for phagocytosis facilitation.

Summary

• Apoptosis is a crucial biological process for regulating cell populations and removing damaged cells without causing inflammation.