cell death

Question 1

what happens to the cell during reversible cell injury?

what occurs during cell death?

Answer 1

There is reversible cell injury in which cells become hydropic (filled with water) Depending on the extent of injury, the cellular response may be adaptive and where possible, homeostasis is restored.
- plasma membrane bleb
- disaggregated ribosomes
- dilated vesicular endoplasmic reticulum
- increased intracellular volume
- aggregated cytoskeletal elements
- mitochondrial swelling and calcification

Question 2

what occurs in cell death?

what is the role of the mitochondria in the cell cycle?

what are free radicals?

Answer 2

1. pumps stop working and water continues to leak into the cell which dilutes reactions and expands the cell, stopping it’s functions and biochemistry and as cell bursts, the cell contents induce an inflammatory response as they are inflammatory
2. mitochondria are regulators which determine whether injury is reversible or if it persists and leads to irreversible death - mitochondria produces ATP and provides this energy to active pumps to keep concentrations stable
3. oxygen free radicals are species with a single spare electron derived from oxygen metabolism

Question 3

1. what is necrosis?
2. what does it induce
3. what causes it?

Answer 3

1. necrosis is death of tissues following bioenergetic failure and loss of plasma membrane integrity
2. it induces inflammation and tissue repair (including fibrosis and new blood vessels and collagen being laid down)
3. it is usually caused by ischaemia (no blood supply or no oxygen in blood supply) :
   - stroke = diminished oxygen supply to brain
   - myocardial infarction = diminished blood supply to the myocardium/cardiovascular disease

Question 4

what are the 6 types of necrosis?

which one occurs in protein rich tissue?
which occurs in fat rich tissue?
which one occurs in the presence of many macrophages?
which one occurs along side putrefaction?
which one occurs in blood vessles?
which one occurs when the peritoneum is affected?

Answer 4

coagulative necrosis - cardiac cells

colliquative necrosis - brain cells

caseous necrosis - slow process of tissue destruction

gangrenous necrosis - usually follows vascular occlusion or certain
infections and appears black

fibrinoid necrosis - Blood vessels affected due to hypertension causing
fibrin activation

fat necrosis

Question 5

what is the definition of apoptosis?

give examples of apoptosis

Answer 5

definition: single cells undergo an active genetically regulated process of a deliberate controlled death (fragmentation of tissue)

examples of apoptosis:
- in embryology: lumen of tubes
- response to growth signals: menstrual cycle
- inflammation - resolution, death of neutrophils (in order to keep acute inflammation going, there has to be continued cell recruitment)
- immune defence - T cells induces apoptosis and natural killer responses
- tumour prevention - apoptosis prevents mutations
- autoimmune disease - self destruction through apoptosis
- HIV AIDs - HIV kills helper T cells so there is no immune system which works and so there is immunosupression

Question 6

what does apoptosis involve?

what are apoptopic bodies? and what occurs if they are not removed?

how are apoptopic bodies removed?

Answer 6

• Apoptosis usually involves DNA fragmentation, as everything in the cell fragments. This is an active genetically regulated process. this usually fragmentation occurs between nuclear proteins.
• ‘Apoptopic body’ (fragments) require energy to be removed. if they are not removed, these fragments explode and leak their cell contents which are inflammatory and therefore inflammation occurs.
• These apoptopic bodies are recognised by macrophages and non-professional phagocytes. Clearance of apoptopic cells by macrophages requires reorganisation of phosphatidylserine (in which the outer leaflet and inner leaflet swap so they can be recognised)

Question 7

1. what are the two major types of apoptosis pathways?
2. what are the steps involved in the extrinsic pathway?
3. give three examples of signals which cause the receptor mediated extrinsic pathway of apoptosis, give three more in which T cell mediated pathway is used

Answer 7

1. The two major types ofapoptosis pathways
   - “extrinsic pathways,” where a cell receives a signal to start apoptosis from other cells in the organism.
   - “intrinsic pathways,” where a cell receives a signal to destroy itself from one of its own genes or proteins due to detection of DNA damage
2. the external signal is receptor mediated or T cell mediated
3. receptor interaction
4. cytoplasmic signals (downstream activation)
5. caspase cascade (family of enzymes which fragment the cell (fragmentation))
6. TNF family (Tumor necrosis factor)
   Fas CD95
   Inflammation

viral infection
transplantation reaction
tumor cell destruction

Question 8

what are the triggers for the intrinsic pathway?

what are the two options which start intrinsic apoptosis?

what are the steps for each?

Answer 8

Intrinsic pathways: starts within the cell and is caused by:
- stress
- metabolism
- DNA damage and p53

1. mitochondria is affected:
   if mitochondria is affected, cristae of mitochondria contain cytochrome C (cyt C) which holds oxygen. If mitochondria is damaged cyt C leaks into the cytoplasm and forms a complex which is called an apoptasome which is a factory which activates the caspases (endogenous activation)
2. DNA is damaged:
   DNA damage (e.g. through radiation) - p53 protein (which is mutated in cancers) senses DNA damage and triggers a response in the mitochondria to cause apoptosis

^each trigger the activation of caspases which cause fragmentation

Question 9

1. what are the Bcl2 family’s function?
2. how does Bcl2 sometimes contribute to cancer?
3. what is another regulator of apoptosis?

Answer 9

1. • they are regulators of apoptosis and acts as a control mechanism aka. sanity check for the cell - do you want to do this - checkpoint
     - this regulates the threshold for apoptosis
2. • however abnormal Bcl2 expression can contribute to cancer:
   • if there is to much Bcl2, the lymphocyte which should be removed by apoptosis does not get removed as there are too many heterodimers/dimers
   • therefore very difficult to remove
3. IAPs (inhibitors of apoptosis proteins)

Question 10

1. define caspases and why are they important for phenotype changes in cells?
2. what are phenotype changes
3. give 4 examples of caspases and what they do

Answer 10

1. caspases:
   - c: cysteine in the active site
   - asp: cleavage after aspartate
   - ase: protease

• for phenotypic changes in cells require cleavage of cellular proteins by caspases (done by caspase activation: an enzyme cascade which therefore amplifies the signal)

2. phenotypic changes:relating to the observable characteristics of an individual resulting from the interaction of its genotype with the environment
3. • cleave ICAD - destroy genetic information
   • cleave PARP - prevents DNA repair
   • cleave lamin - break down nuclear architecture
   • cleave keratin - break down cytoplasmic architechture

Question 11

what is carcinogenesis

Answer 11

Carcinogenesis, also called oncogenesis or tumorigenesis, isthe formation of a cancer, whereby normal cells are transformed into cancer cells

Question 12

what do survival factors do?

Answer 12

it is a general term sometimes used to indicate that certain cytokines or growth factors can maintain cells in culture for extended periods of time without essentially providing a growth stimulatory signal
- they process works through checks and balances for apoptosis to actually occur

Question 13

how does calorie restriction lengthen lifespan?

Answer 13

Moreover, since calorie restriction generally results in weight loss, less energy overall is needed to maintain the reduced body mass. As a result of this reduction of metabolic rate, it is hypothesized that calorie restriction could extend lifespansby decreasing the rate of free radical damage.

Question 14

when does apoptosis go wrong?

Answer 14

1. autoimmune disease
2. cancer
3. neurodegeneration