Apoptosis and Necrosis Flashcards
What is apoptosis?
Programmed cell death
Apoptosis is a cellular process in which a defined and programmed sequence of intracellular events leads to the removal of a cell without the release of products harmful to surrounding cells
When does a cell know to apoptose?
When DNA damage occurs within the cell via base alteration or cross linkage
Which protein detects DNA damage?
P53
What could happen if there is a mutation in the P53 gene?
Cancer
Where is there a lack of apoptosis?
In cancer
Where is there too much apoptosis?
HIV - HIV virus can induce apoptosis. It can induce apoptosis in CD4 helper cells which reduces their num- bers enormously to produce an immunodeficient state.
What is necrosis?
Necrosis is traumatic cell death which indices inflammation and repair
What are regulators of apoptosis? (Inhibitors)
Inhibitors:
Growth factors
Extracellular cell matrix
Sex steroids
What are regulators of apoptosis? (Inducers)
Inducers:
Glucocorticoids
Free radicals
Ionising radiation
DNA damage
What is the intrinsic pathway for apoptosis?
-Uses pro- and anti-apoptotic members of the Blc-2 family
-Bax forms Bax-Bax dimers which enhance apoptotic stimuli
-The Bcl-2:Bax ratio determines the cell’s susceptibility to apoptotic stimuli
-Responds to growth factors and biochemical stress
-p53 gene induces cell cycle arrest and initiates DNA damage repair
-If damage is difficult to repair, p53 can induce apoptosis
What is the extrinsic pathway for apoptosis
-Ligand-binding at death receptors on the cell surface
-Receptors include TNFR1 and CD95
-Ligand-binding results in the clustering or receptor molecules on the cell surface and the initiation of signal transduction cascade
-Caspases are activated, triggering apoptosis
-This pathway is used by the immune system to eliminate lymphocytes
What is necrosis in general?
It is the the wholesale destruction of large numbers of cells by some external factor
What is coagulative necrosis?
Most common type
Can occur in most organs
Cause by ischaemia
What are some clinical examples of necrosis?
- Infarction due to loss of blood supply e.g. myocardial
infarction, cerebral infarction - Frostbite
- Toxic venom from reptiles and insects
- Pancreatitis
What is liquefactive necrosis
Occurs in the brain due to its lack of substantial supporting stroma
What is caseous necrosis
Causes a ‘cheese’ pattern
TB is characterized by this form of necrosis
Important - remember this -
Gangrene
Necrosis with rotting of the tissue
Affected tissue appears black due to deposition of iron sulphide (from degraded haemoglobin
Why is apoptosis important?
It is an important process in normal
cell turnover in the body which prevents cells with accumulated genetic damage from dividing and producing cells
which might eventually develop into cancer cells.
How does a cell apoptose?
The cell triggers a series of proteins which lead to the release of enzymes within the cell
which eventually autodigest the cell. Many of these enzymes are caspases.
Why is apoptosis important in health?
Development - removal of cells during development e.g.
interdigital webs
* Cell turnover - removal of cells during normal turnover
e.g. cells in the intestinal villi at the tips, to be replaced
by cells from below
