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Why is slime mold often used as a model organism for investigating multicellularity and cell death?
Under stress the single-celled organisms come together to form a ‘slug’ which acts as a multicellular organism. The cells have different cell fates, some becoming spore cells and some undergoing apoptosis.
What are the four types of signaling between cells?
Paracrine (acting locally), endocrine (via blood), neuronal, and contact-dependent
What are some examples of very proliferative cells in the adult body?
The skin, the lining of the intestine, and the bone marrow (haematopoietic cells)
What are some examples of the least proliferative cells in the adult body?
Neurons, skeletal muscle and adipose tissue (substantial cell size changes possible without division), and liver (though the liver can reenter the cell cycle and rapidly regenerate following damage)
What is meant by apoptosis?
‘Programmed’ cell death (PCD)
Give some examples of apoptosis during normal development
A tadpole losing its tail
Degeneration of the webs between the fingers of a human embryo
Replacement of gut lining every 5-7 days
Removal of damaged or cancerous cells
How many cells are there in the body of an adult human?
30 trillion
How many cells undergo apoptosis per second in an adult human body?
1 million
Give three examples of disorders of cell accumulation (ie. not enough apoptosis)
Cancer, autoimmune diseases such as lupus, viral infections such as herpes, pox and adenovirus
Give some examples of disorders of cell loss (too much apoptosis)
AIDS, neurodegeneration (Alzheimer’s, Parkinson’s), ischemic injury (stroke, myocardial infection), toxin-induced liver disease (ie from alcohol), myelodysplastic syndrome
What is myelodysplastic syndrome?
Accumulation of immature RBCs due to loss/apoptosis of some stem cells which should give rise to correct cell types. Too much apoptosis in a particular type of stem cell in the blood, leading to too many of the other type!! (nb. seems like a disorder of too much apoptosis but is actually a case of not enough.)
Why is apoptosis required in immune system development?
To get rid of immune cells that would otherwise attack the host
What is the ‘bad kind’ of cell death called?
Necrosis
What causes necrosis?
Unregulated cell death resulting from trauma or injury (infection, toxins, hot and cold burns)
What are the observable differences between a cell that has ‘died’ due to apoptosis and one that has ‘died’ by necrosis?
In apoptosis the nucleus and cell fragment without exposing the contents. In necrosis the cell membrane bursts and the contents leak. This is what causes inflammation.
In apoptosis, what are the leftover fragments of the cell called?
Apoptotic bodies
What are the observable differences between a the contents of cells that have died by apoptosis vs necrosis on a gel electrophoresis experiment?
Necrosis looks like a long smear, apoptosis has a ‘laddered’ look due to the action of endonucleases cutting the DNA into fragments of particular lengths
How many cells are there in the body of a fully-formed nematode worm?
1090
How many cells undergo apoptosis during normal development of a nematode worm?
131
How many genes in a nematode worm are involved in apoptosis and clearance?
13
What are caspases?
What is the caspase cascade?
What is nucelar lamin?
An intermediate filament that lines the nucleus. Its cleavage results in destruction to nucleus morphology.
In which two ways can initiator caspases be activated?
Intrinsic or extrinsic pathway
Describe the difference between intrinsic and extrinsic apoptosis
How are apoptotic cells recognised and cleared?
A healthy cell does not have much PS (phosphatidylserine) exposed on its outer leaflet, but an apoptotic cell does. PS is recognised by phagocytes using a PS receptor (PSR).
What happens to mice without PSR?
They die as a result of not being able to perform apoptosis. The cells lining the airways are not cleared away, meaning the mice cannot breathe properly.