cell death and apoptosis concepts

1. Cell death
ABDUL RASHEED EBRAHIM
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2. Cell cycle
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New cells are formed
from the existing cell
The cell is produced
by duplicating the
existed one and then
they will divide in to
two
This event is called as
cell cycle

3. Cell death
The body is very good at maintaining a constant number
of cells so there has to exist mechanisms for ensuring
other cells in the body are removed when appropriate
Cell death happens in two forms
◦ Apoptosis – suicide – programmed cell death
◦ Necrosis – killing – decay and destruction
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5. Necrosis
Necrosis is the death of
body tissue. It occurs when
too little blood flows to the
tissue. This can be formed by
injury, radiation, or
chemicals.
Necrosis cannot be
reversible
These are dead cells shows
changes in both cytoplasm
and in the nucleus
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6. Nuclear and cytoplasm
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Cytoplasmic changes Nuclear changes
Increases eosinophilia, glassy
appearace granular or vacuolated
cytoplasm, swellen mitochondria
may also show calcification
Karyolysis - complete
dissolution of chromatins
Karyorrhexis – chromatin is
distributed irregularly
Pyknosis – irreversible
condensation of chromatins

7. Factors
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NECROSIS MAY OCCUR DUE TO
EXTERNAL AND INTERNAL
FACTORS
EXTERNAL FACTORS MAY
INVOLVED
MECHANICAL TRAUMA (
PHYSICAL DAMAGE TO THE BODY
THAT CAUSES CELLULAR BREAK
DOWN)
DAMAGE TO BLOOD VESSELS
(WHICH MAY DISRUPT BLOOD
SUPPLY TO ASSOCIATED
TISSUE)
THERMAL EFFECT (EXTREMELY
HIGH OR LOW TEMPERATURE
CAN RESULT IN NECROSIS DUE
TO DISRUPTION OF CELLS

8. Causes
Internal factors causing necrosis includes
1. Trophoneurotic disorders - injury and paralysis of nerve cells
2. Pancreatic enzyme – are the major cause for the fat necrosis
(lipases)
3. Immunological barriers – invasion of pathogen through
surface affected by inflammation (intestinal mucosa)
4. Bacterial toxins – activated natural killer cells and peritoneal
macrophages
5. Toxins and pathogens – may cause necrosis toxins such as
venom may inhibit enzymes and cause cell death
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9. Necrotic cell death
LOSS OF METABOLIC FUCTION
LOSS OF INTEGRITY OF THE CELL MEMBRANES
CESSATION OF THE PRODUCTION OF PROTEIN
CELL ORGANELLS SWELL AND BECOMES NON-FUNCTIONAL
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10. Mechanisms of necrosis
Depletion of ATP  leads to breakdown of the cells ion balance
Reduce oxygen level (hypoxia)
Oxidative stress  the presence of the excess oxygen radicals
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11. Types of
necrosis
1. Coagulation Necrosis
2. Liquefactive necrosis
3. Fat necrosis
4. Caseous necrosis
5. Gangrenous necrosis
6. Fibrinoid necrosis
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12. Coagulation
necrosis
This types necrosis is
seen in every tissues
except brain
They occurs due to the
loss of blood
Cell outlines are
preserved and
everything looks red
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13. Liquefaction necrosis
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This type of necrosis occurs as infection in
brain infarcts
Due to lots of neutrophiles around releasing
their toxic contents “liquefying” the tissue
Tissue is liquidly and creamy yellow (pus)
Lots of neutrophils and cell debris

14. Fat necrosis
Fat necrosis that in which the neutral fats in
adipose tissue are split into fatty acids and
glycerol usually affecting the pancreas
Shadowy outline of dead fat cells
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15. Caseous necrosis (lungs)
Cheesy necrosis that in which the tissues is soft dry and
cottage cheese-like :most ofte seen in tuberculosis and
syphilis
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16. Gangrenous necrosis
See this when an entire limb loses blood supply
and dies
Skin looks black and dead:underlying tissues is in
varying stages of decomposition
Dry gangrene Initially there is coagulative
necrosis from the loss of blood supply
wet gangrene If bacterial infection is
superimposed there is liquefactive necrosis
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17. Fibrinoid necrosis
Fibrinoid necrosis is a specific pattern of
irreversible, uncontrolled cell death that occurs
when antigen-antibody complexes are deposited
in the walls of blood vessels along with fibrin
 see this in immune reactions in vessels
Complexes of antigen and antibodies
It appears as too small and visible grossly
Vessel walls are thickened and pinkish red 
fibrinoid
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18. Apoptosis
Programmed cell death
In human body cells were produced every second by mitosis there is a
similar number die by apoptosis
Between 50-70 billion cells die each day in adult
Between 20-30 billion cells die each day in child
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19. Programmed
cell death
It is a form of cell death in which a suicide program is
activated within cells
Which leads to
Fragmentation of the DNA
Shrinkage of the cytoplasm
Membrane changes and cell death without lysis or damage to
neighboring cells
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20. Characteristics
of apoptosis
It is a normal phenomenon occurring frequently in a
multicellular organism
 A cell that undergoes apoptosis dies neatly without
damaging its neighbour cells
The cell will shrink and then condensed
There will be no inflammation in apoptosis
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21. Importance of apoptosis
Programmed cell death is needed to destroy cells that represent a threat to the
integrity of the organism
Examples :
Cells infected with viruses
Cells with DNA damage
Cancer cells (uncontrolled proliferated cells)
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22. Biochemical
feature of
apoptosis
DNA break down in apoptosis
Protein cleavage
Phagocytic
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23. Mechanisms of apoptosis
Apoptosis occurs in two phases :
1. Initiation phase: It happens when apoptotic enzymes are
getting activated
2. Executive phase: activating enzymes are cause cell death
Initiation phase :
1. Extrinsic pathway
2. Intrinsic pathway
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25. Extrinstic pathway
 It is called as death receptor pathways  mediated by death receptor
Caspase  are (cysteine – aspartic acid) specific proteases that mediates the events that are
associated with programmed cell death
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26. Executive phase
it is mediated by caspase 3 and caspase 6
When it is activated they form sequence chain of reaction than can activates caspase 3 and 6
They break down cytoskeleton protein and neuclear matrix that result in the breaking of the
nucleus
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27. Difference in Necrosis & Apoptosis
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28. Autophagy
•Physiological conditions
Aging
Exercise
Pathological
Various disease
cancer
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29. Basic concept in mechanism
Cellular stress  activates autophagy pathway
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Phagophore
formation
• Isolation membrane
• Derived from endoplasmic recticulum plasma membrane or mitochondria
Autophagos
ome
• Formation of vesicles
autophago
lysosome
• Fusion with lysosome

30. mechanism
Autophagy related genes  which encodes protein called ATG protein
 ATG proteins  needed for the formation of autophagosomes
Depletion of growth factors activates 
This ULK1 complex is called as initiation complex so this complex initiates the
process of autophagy
This forms preautophagosomal structure
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ATG101
ATG13
ULK1

31. Mechanism
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ATG14L
VPS15
BECLIN 1
VPS34
That ULK1 complex activates 
This complex is called as PI3K complex
This stage is called as nucleation
This activation of PI3K complex results in nucleation and formation of phagophore
Phagosome formation

32. Elongation and maturation
 This has to elongate and fuse to form Autophagosome
For that they need a set of proteins called as ubiquitin like conjugation system
The function of ubiquitin is identifying proteins to be degraded by the proteasome,
but ubiquitination can play a role in other processes such as endocytosis and other forms
of protein trafficking, transcription and transcription factor regulation, cell signaling,
histone modification, and DNA repair.
Ubiquitin like system covalently links lipid in phosphatidylethanolamine to the
microtubule-associated protein light chain 3 (LC3) results in elongation and the fusion to
form autophagosome
During the process of autophagosome the cellular content will be trapped inside
autophagosome
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33. Degradation
Lysosome comes near
autophagosome and
then fuses to form
autophagolysosome
Lysosomal contents
enters into
autophagosome and
degradation of cells
happens
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34. Benefits of
autophagy
Its is a survival mechanism under stressful conditions
It maintains the integrity of cells by recycling essential
metabolites and clearing intracellular debris
Intracellular debris occurs in  aging , under stress and in
diseased state
When such cell unable to cope the cell which is already in
autophagy so autophagy itself trigger death
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35. Roles of autophagy
IN CANCER :
In cancer cells, autophagy suppresses tumorigenesis by inhibiting
cancer-cell survival and inducing cell death, but it also facilitates tumorigenesis
by promoting cancer-cell proliferation and tumor growth .the mechanism of the
autophagic process is controlled by a series of proteins
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36. ROLES OF AUTOPHAGY
ROLE OF AUTOPHAGY IN NEURODEGENARATIVE DISEASE
 Increasing evidence suggests that dysregulation of autophagy results in the
accumulation of abnormal proteins and/or damaged organelles, which is
commonly observed in neurodegenerative diseases, such as Alzheimer,
Huntington's, and Parkinson's diseases (Banerjee et al
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