APOPTOSIS
Plan
1. Objectives
2. Definition
3. Causes
4. Mechanism
5. Morphology
6. Clinicopathological aspects
7. Summary
Objectives
Apoptosis is responsible for maintaining the regular
functions & activities of cells, the failure of which
may contribute the various clinical manifestations
like cancer, autoimmune disorders.
Definition
Apoptosis is a pathway of cell death that is induced
by a tightly regulated suicide program in which cell
destined to die activate intrinsic enzymes that degrade
the cells own nuclear DNA & nuclear and
cytoplasmic proteins.
Causes
1. Physiological
2. Pathological
Physiological Conditions
1. During embryogenesis
2. Involution of hormone dependent tissue upon
hormone withdrawal
3. Cell loss in proliferating cell populations
4. Acute inflammatory & immune response
Pathological Condition
1. DNA damage
2. Accumulation of misfolded proteins
3. Infections
4. Pathological atrophy in parenchymal organs after
duct obstruction
Mechanisms
1) The Intrinsic (Mitochondrial) Pathway
2) The Extrinsic (Death Receptor Initiated)
Pathway
• Caspase enzyme activation is important step
2 Phases
Initiation phase – Caspase become enzymatically
active
Execution phase – Caspase trigger the degradation of
critical cellular components
Anti-
apoptotic
Pro-apoptotic Sensors
1. BCL2
2. BCL-XL
3. MCL-1
1. BAX
2. BAK
1.Bad
2.Bim
3.Bid
4.Puma
5.Noxa
Morphological features
1. Cell shrinkage
2. Chromatin condensation
3. Formation of cytoplasmic blebs
4. Apoptotic bodies
5. Phagocytosis of apoptotic cells or cell
bodies
Clinicopathological Correlations
1. Growth Factor Deprivation
2. DNA damage
3. Protein misfolding
4. Apoptosis induced by the TNF Receptor Family
5. Cytotoxic T lymphocyte-mediated apoptosis
Disorders Associated with Dysregulated
Apoptosis
Defective apoptosis
- Cancer
- Autoimmune disorders
Increased apoptosis
- Neurodegenerative diseases
- Ischemic injury
- Death of virus-infected cells
Summary
1. Pathway of cell death
2. Suicidal programme
3. Physiological & Pathological condition
4. Two pathways
5. Clinical aspects
Apoptosis (2)

Apoptosis (2)

  • 1.
  • 2.
    Plan 1. Objectives 2. Definition 3.Causes 4. Mechanism 5. Morphology 6. Clinicopathological aspects 7. Summary
  • 3.
    Objectives Apoptosis is responsiblefor maintaining the regular functions & activities of cells, the failure of which may contribute the various clinical manifestations like cancer, autoimmune disorders.
  • 4.
    Definition Apoptosis is apathway of cell death that is induced by a tightly regulated suicide program in which cell destined to die activate intrinsic enzymes that degrade the cells own nuclear DNA & nuclear and cytoplasmic proteins.
  • 5.
  • 6.
    Physiological Conditions 1. Duringembryogenesis 2. Involution of hormone dependent tissue upon hormone withdrawal 3. Cell loss in proliferating cell populations 4. Acute inflammatory & immune response
  • 7.
    Pathological Condition 1. DNAdamage 2. Accumulation of misfolded proteins 3. Infections 4. Pathological atrophy in parenchymal organs after duct obstruction
  • 8.
    Mechanisms 1) The Intrinsic(Mitochondrial) Pathway 2) The Extrinsic (Death Receptor Initiated) Pathway
  • 9.
    • Caspase enzymeactivation is important step 2 Phases Initiation phase – Caspase become enzymatically active Execution phase – Caspase trigger the degradation of critical cellular components
  • 10.
    Anti- apoptotic Pro-apoptotic Sensors 1. BCL2 2.BCL-XL 3. MCL-1 1. BAX 2. BAK 1.Bad 2.Bim 3.Bid 4.Puma 5.Noxa
  • 13.
    Morphological features 1. Cellshrinkage 2. Chromatin condensation 3. Formation of cytoplasmic blebs 4. Apoptotic bodies 5. Phagocytosis of apoptotic cells or cell bodies
  • 15.
    Clinicopathological Correlations 1. GrowthFactor Deprivation 2. DNA damage 3. Protein misfolding 4. Apoptosis induced by the TNF Receptor Family 5. Cytotoxic T lymphocyte-mediated apoptosis
  • 16.
    Disorders Associated withDysregulated Apoptosis Defective apoptosis - Cancer - Autoimmune disorders Increased apoptosis - Neurodegenerative diseases - Ischemic injury - Death of virus-infected cells
  • 17.
    Summary 1. Pathway ofcell death 2. Suicidal programme 3. Physiological & Pathological condition 4. Two pathways 5. Clinical aspects