1. Cell Death
Dr. Sadaf Mumtaz
19/12/11

2. Cell Injury Reversible cell injury Irreversible cell injury
‘The functional and morphologic changes are
reversible if the damaging stimulus is removed’
Irreversible cell injury
‘With continuing damage the injury becomes
irreversible, at which time the cell cannot
recover and it dies’

3. Causes of cell injury Oxygen deprivation
Cardiorespiratory failure, anemia, after blood loss
Physical agents
Mechanical trauma, temperature, electric shock
Chemical agents and drugs
Arsenic, cyanide, alcohol, insectisides
Infectious agents
Viruses, bacteria, fungi
Immunological reactions
Autoimmune diseases, microbes and enviromental substances
Genetic derrangements
Sickle cell anaemia
Nutritional imbalances
Vitamin deficiencies, Atherosclerosis

4. Cell Death Necrosis Apoptosis
‘Loss of membrane integrity, enzymatic digestion of cells, leakage of cellular contents and frequently a host reaction’
Apoptosis
‘Nuclear dissolution, fragmentation of cell without
complete loss of membrane integrity and rapid removal
of cellular debris’

5. ‘Programmed cell death’
Apoptosis
‘Programmed cell death’
Process was identified in 1972
Named after the Greek designation for ‘falling off’
Physiological
Pathological
Eliminates cells that are no longer needed and to maintain a steady number of various cell population in tissues
Eliminates cells that are injured beyond repair without eliciting a host reaction, thus limiting collateral tissue damage

6. Apoptosis in physiological and pathological conditions
The programmed destruction of cells during embryogenesis
DNA damage
Involution of hormone dependent tissues upon hormone withdrawal
Accumulation of misfolded proteins
Cell loss in proliferating cell populations
Cell death in certain infections, particularly viral infection, tumors and cellular rejection of transplant
Elimination of potentially harmful self-reactive lymphocytes
Pathological atrophy in parenchymal organs after duct obstruction, such as occurs in pancreas, parotid gland and kidney.
Death of host cells that have served their useful purpose

7. Morphological changes in apoptosis

8. Biochemical features of apoptosis
Activation of caspases
‘C’ refers to ‘cysteine proteases’ and ‘aspase’
refers ‘to the unique ability of these enzymes to
cleave after aspartic acid residues’

9. Biochemical features of apoptosis
DNA and Protein breakdown
Ca2+ and Mg2+ dependent endonucleases

10. Biochemical features of apoptosis
Membrane alterations and recognition by phagocytes
‘Annexin V Staining’
The exposed lipids are detectable by binding of a protein called ‘Annexin V’

11. Mechanisms of apoptosis
C Elegans
Intrinsic or mitochondrial pathway
The extrinsic or death receptor-initiated pathway

12. The Intrinsic (mitochondrial pathway) of apoptosis

13. The extrinsic (death receptor-initiated) pathway of apoptosis
Bid
Activation of mitochondrial pathway
FLIP

14. Removal of dead cells Phospholipids fliping
Release of soluble factors by apoptotic cells
Thrombospondin
Macrophages may themselves produce proteins
Apoptotic cells may be coated with antibodies

15. Disorders associated with dysregulated apoptosis
Defective apoptosis and increased cell survival
Increased apoptosis and excessive cell death
Neurodegenerative diseases
(mutations and misfolded proteins)
Ischemic injury, (MI and stroke)
Death of virus infected cells
Cancers & autoimmune diseases

16. Autophagy Cell eats its own contents
Occurs in times of nutrient deprivation
Autophagic vacuole---Autophagolysosome

17. Laboratory assesments of apoptosis
DNA laddering
Annexin 5 staining
Flow cytometry

18. Thankyou

19. FLIP FLICE like inhibitory protein
‘Fas-associated death domain-like interleukin
1β-converting enzyme’