What happens in accidental damage?
Damage to DNA= cell lysis
It leads to inflammation and initiates regulated cell death in neighbouring cells.
2 Programmed cell death examples:
Apoptosis (tidy) - requires ATP
Necrotic cell death (messy) - doesn’t require energy = for emergency
Lysis triggers what
Inflammation (recruits immune cells)
Apoptosis function:
- Essential for normal development: 50B die each day.
- Replaces damage / worn-out (senescent) cells
- Visible as cells stay INTACT
Examples of apoptosis
Eg. Ultraviolet light
: sun burn is gradually replaced by stem cells.
: in utero, fingers are webbed, and apoptosis replaces/remvoes webbing.
Apoptosis is triggered by:
- Extracellular signalling eg. FasL (fast ligand) binds to death receptors on cell membrane.
- Loss of survival signals eg. growth factors
- Detachment from ECM = Anoikis
- Oxidative stress (ROS) or ER stress.
- Microtubule / DNA damage
In the process of apoptosis, name if they’re PROapoptotic or ANTIapoptotic:
1. Stress activated mitochondria:
2. Smac inhibiting IAP:
3. When macrophages decrease TNF:
4. and the increase transforming growth factor beta (TGFB) is:
- PROapoptotic
- ANTIapoptotic
- PROapoptotic
- ANTIapoptotic
Is apoptosis a inflammatory or non-inflammatory process?
non-inflammatory
Apoptotic bodies are coated with Phosphotidyl serine (PS). What is this?
‘eat me’ signals
Once apoptotic bodies have been eaten, what do macrophages decrease and increase?
Decrease TNF (PRO-inflammatory) and increase transforming growth factor beta (TGFB) (ANTI-inflammatory)
What happens if phagocytes are overwhelmed?
Membrane of apoptotic cells can disintegrate, leak cellular contents and generate inflammation.
Inadequate apoptosis example diseases:
autoimmune disease: self reactive lymphocytes are not eliminated
cancers: suppresion of apoptosis leads to cell accumulation.
Excessive apoptosis disease examples:
acute ischemic injury to the heart (myocardial infarcts) and brain (stoke).
chronic heart failure (cardiomyocytes) and neurodegeneration - Aheimer’s (memory), Parkinson’s diease (motor).
Features of necrotic cell death:
- Membrane permeabilisation and cell lysis
- Visible cell swelling ==> oncosis (acute intracellular oedema)
- Leakage of intracellular components: more K+ outside the cell.
- Repair of damaged tissue by scarring.
Messy –> leads to inflammation and necrosis.
Necrosis:
Structural change that follows large scale cell death - formation of pores and leakage of the cellular components drive inflammation.
(No ATP required) used for emergency
3 forms of necrotic death:
Necroptosis
Pyroptosis
Ferroptosis
Causes of necrosis:
Autophagy
Self eating (intracellular process)
: Used to degrade intracellular pathogens, proteins aggregates and damaged organelles.
Autophagy process:
- Membrane bound vacuoles form and enclose the content.
- These fuse with lysosomes, which contain acidic hydrolases
- They become degraded (packaged away form other cells so there isn’t any damage to surrounding components)
Cells use autophagy when they are straved of nutrients –> to degrade disposable contents to generate energy and metabolites for essential protein synthesis.
Oncosis:
Cell swelling
