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1. CELL DEATH
LECTURE 7

2. CONTENTS
◦ Cells death. Apoptosis and necrosis.
◦ The concept of stem cells,
◦ types and use in modern cell technologies.

3. CELL DEATH

4. 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.

5. General characteristics of apoptosis
◦ It is normal phenomenon, occurring frequently in a multicellular organism
◦ A cell that undergoes apoptosis dies without damaging it’s neighbors. The cell shrinks and
condenses.
◦ There is no inflammation in apoptosis.
◦

6. Apoptosis/ Programmed cell death
◦ Form of cell death, in which a “suicide” program is activated within the cell, leading to:
◦ A. Fragmentation of the DNA
◦ B. Shrinkage of the cytoplasm
◦ C. Membrane changes and cell death without lysis or damage to neighboring cells.

7. APOPTOSIS- changes which take
place in the cell
◦ 1. Apoptosis is a mode of cell death that occurs under normal physiologic
conditions.
◦ 2. STEPS
◦ DNA fragmentation
◦ Decrease in cell volume
◦ Loss of mitochondrial function
◦ Membrane blebbing
◦ Formation of apoptotic bodies

10. ◦ Tissue homeostasis mainly depends on the balance between cell proliferation and cell
death.
◦ Programmed cell death or apoptosis is an intrinsic death program that occurs in various
physiological and pathological situations .
◦ Apoptosis or self-destruction is necessary for normal development and homeostasis of
multicellular organisms.
◦ Apoptosis plays a major role in many diseases like cancer, AIDS and neurodegenerative
disorders.

11. CELL DEATH
◦ Cell die by one of two mechanisms-
◦ Necrosis - Death By Injury
◦ Apoptosis -
◦ Apoptosis and necrosis have different characteristics

12. NECROSIS
◦ occurs when cells are damaged by harmful
factors
◦ contents leak out through holes in the plasma
membrane.
◦ causes inflammation in the tissue surrounding
the dead cell.
◦ 1. COAGULATIVE NECROSIS
◦ Caused by vascular occlusion
◦ 2. Liquefactive necrosis

13. Liquefactive necrosis
◦ Characterised by softening of the necrotic tissue caused by hydrolytic
lysosomal enzymes released from dead cells and neutrophils.

14. FAT NECROSIS
◦ Occurs after enzymatic and traumatic injury.

15. DIFFERENCE
BETWEEN
APOPTOSIS &
CELL DEATH
◦ 1. NECROSIS
◦ Accidental cell death
◦ occurs when cells are exposed to an
unfavorable physical or chemical
environment
◦ Two characteristic features- rapid cell
swelling & cell lysis
◦ 2.APOPTOSIS
◦ Cells that are no longer needed are
eliminated
◦ It is characterized by controlled
autodigestion, which maintains cell
membrane integrity

18. NEED OF
APOPTOSIS
◦ Apoptosis is needed for proper development
◦ Examples: The formation of the fingers and toes
of the fetus
◦ The formation of the proper connections
between neurons in the brain
◦ Apoptosis is needed to destroy cells
◦ Examples: Cells infected with viruses Cells with
DNA damage Cancer cells

20. WHAT
MAKES A
CELL
UNDERGO
APOPTOSIS
◦ For cells to undergo apoptosis, there should be:
◦ Balance between:
• 1. the withdrawal of positive signals; that is, signals
needed for continued survival, and
2. the receipt of negative signals.

23. MECHANISM
OF APOPTOSIS
◦ 1. INTRINSIC PATHWAY( mitochondrial)
◦ 2. EXTRINSIC PATHWAY ( death activators)
◦ 3. EXECUTION PHASE
◦ 4. REMOVAL OF DEAD CELLS

24. INTRINSIC
PATHWAY
◦ Stress signals, DNA
damage signals, and
defects in signaling
pathways are processed.
◦ Mitochondria is used as
a central component
for activation
of apoptosis
◦ Release of cytochrome
C from mitochondria,
activation of initiator
caspase 9
◦ Control of this pathway
is by apoptotic proteins
such as Bcl-2

33. EXTRINSIC PATHWAY

39. Role in diseases
◦ 1. Too much apoptosis:
◦ Tissue atrophy
◦ 2. Too little apoptosis
◦ Cancer, atherosclerosis

40. DISEASES WHERE APOPTOSIS IS
INHIBITED
◦ 1.Cancer
◦ Colorectal cancer ,Glioma, Liver, Lymphoid malignancies ,Neuroblastoma ,Prostate cancer ,Follicular
lymphomas Carcinomas with p-53 mutations
◦ 2. Autoimmune disorders -Mysthenia gravis ,Systemic lupus erythematous
◦ 3 Inflammatory disease- Bronchial asthma, Inflammattory bowel disease, Pumonary inflammation,
◦ 4 Viral infections- Herpesviruses ,Poxviruses ,Adenoviruses , Cowpox

41. Apoptosis and cancer
◦ There are mutations that alter the cell ability to undergo apoptosis and allow transformed cell to keep
proliferation rather than die.
◦ Eg: translocation of Bcl-2 gene in lymphomas that prevents apoptosis , oncogene products

42. Apoptosis and immune system
◦ Autoimmune lymphoproliferative syndrome or ALPS.
◦ a mutation in the gene for Fas
◦ Features:
• an accumulation of lymphocytes in the lymph nodes and spleen greatly enlarging them.
◦ the appearance of clones that are autoreactive; that is, attack "self" components producing such autoimmune
disorders as
• hemolytic anemia
• thrombocytopenia
• the appearance of lymphoma — a cancerous clone of lymphocytes

43. STEM CELLS

45. TYPES
◦ 1. TOTIPOTENT STEM CELLS- eg zygote
◦ 2. PLURIPOTENT STEM CELLS eg Embryonic stem cells
◦ 3. MULTIPOTENT STEM CELLS eg mesenchymal stem cell (MSC).
◦ 4. OLIGOPOTENT STEM CELLS eg myloid stem cell
◦ 5. UNIPOTENT STEM CELLS. Eg dermatocyte

48. IMPORTANCE OF STEM CELLS
◦ 1. Adult stem cell therapy
◦ 2.Embryonic Stem Cell (ESC) Therapies
◦ 3. Induced Pluripotent Stem Cell Therapies

49. REFERENCES
◦ 2015 Junqueira's Basic Histology Text and Atlas,
15th Edition, pages 67