Apoptosis And Necrosis Flashcards
Apoptosis
Programmed cell death
Necrosis
A series of morphological changes during cell death after lethal damage
-staged cell death due to unintended damage
Physiological apoptosis
- During embryonic development
2. During immune system development
Pathological apoptosis
- Triggered by immune system cells in response to cell infection
- Self induced due to defective function, developing cytotoxicity
Can necrosis be physiological and pathological?
No, it’s always pathological
Necrosis involves
- disruption of the metabolic process
- cellular component desaturation
- loss of membrane integrity and release of cellular components to surroundings
Apoptosis during embryonic development
Phylogenic organism development programs use programmed cell death as a means of removing unwanted cells: tissue between fingers and toes
Apoptosis during immune system development
- T cells are tested against ‘self antigens’ and if they recognize and bind self antigens, they undergo apoptosis to remove their own lineage
- if they did not ‘self-destruct’ they would kill normal cells upon activation leading to autoimmune disorders
Apoptosis triggered by immune system cells
When a harmful/compromised cell is identified, innate immune cells trigger that cell’s apoptosis program
After the cells innate immune cells trigger apoptosis what happens
- infected cells display ‘non-self antigens’
- transformed ‘cancer’ cells display unusual attributes
- damaged cells or cells developing characteristics of damage
Self induced apoptosis
-cells that surpass specific thresholds acceptable for survival can self induce apoptotic programming. This may include slight metabolic defects or the accumulation of toxic substances such as aggregating proteins
Intrinsic apoptotic pathways
Initiated by interior signaling die to irreparable, irreversible DNA damage
What can cause a cell to undergo intrinsic apoptotic pathway?
- severe stress
- pro-apoptotic proteins from the nucleolus and mitochondria activate the CASPASE CASCADE
- caspases destroy proteins and other molecules with in the cell
- cell begins to bleb into vesicles
- phagocytes cells engulf and digest the ‘blebbed’ vesicles
Extrinsic apoptotic pathway
Initiated by exterior signals due to indications of damage or infection
What could cause extrinsic apoptotic pathway?
- T cell or TNFa induced activation of death domain proteins
- activation of capsase cascade
- capsases destroy proteins and other molecules with in the cell
- cell begins to bleb into vesicles
- phagocytes cells engulf and digest the ‘blebbed’ vesicle
AIF-apoptosis inducing factor
A capsase independent form of apoptosis
What is AIF initiated by?
Damage to the mitochondrion and release of material from the mitochondrial inner membrane space to the cytosol
AIF leaving the mitochondrial
Passes through the cytosol to the nucleus where it causes chromosome condensation
What happens once the chromosomes are condensed in AIF?
The DNA is chopped up
The over all effect of AIF
Results in the compete depletion of energy stores in the cell, no production of new proteins or metabolites, cell ‘blebbing’, and a quiescent cell death similar to apoptosis utilizing caspases
What is the difference between intrinsic/extrinsic and AIF
Extrinsic and intrinsic involve capsases
Which forms of apoptosis is considered quiescent?
All of them
What could be some unintended damage that would cause staged cell death (necrosis)?
- trauma
- infection
- radiation
- toxins
- ischemia
- heat/cold
Usually environmental in nature
What does necrosis involve?
- disruption of the metabolic process
- cellular component denaturation
- loss of membrane integrity and release of cellular components
Disruption of the metabolic process in necrosis
- Loss of TCA and ETS
- glycolysis drives formation of lactic acid.
- rely totally on glycolysis, build up of lactic acid
Cellular component denaturation in necrosis
Increasing lactic acid drives pH down denaturing proteins
Loss of membrane integrity and release of cellular components In necrosis
-complete loss of all cellular function results in the release of many cellular components that will cause problems in cells/tissues surrounding it
Overview of apoptosis
Form of cell death that is regulated and results in the formation of ‘blebbed’ vesicles containing the partially digested contents of the cell. This is considered a quiescent death and does not negatively impact the surrounding cells
Necrosis overview
Results in the complete breakdown of cellular organization. Lysosomal enzymes are released to conduct autolysis and heterolysis when the cell ruptures. Enzymes and materials released cause damage to surrounding interstitial and cells, perpetuating the damage. Opportunistic microbes may benefit. Inflammatory response occurs
-after extensive clean up, tissue repair and scar tissue forming fibroblasts must be activated
