Lecture 33 Comparative Cell Biology

Front 1

What is the definition of apoptosis?

Back 1

- a process seen in multicellular organisms, by which specific cells are killed and removed for the benefit of the organism

Front 2

Programmed cell death is essential for embryonic development. How?

Back 2

- sculpting of limbs

- neuronal development

- negative selection of T cell lymphocytes that recognise self;

Front 3

Why is PCD important for neuronal development?

Back 3

- excessive production of neurons at first;

- signals from target tissue promote neuronal survival

Front 4

Why is PCD important for negative selection of T cell lymphocytes?

Back 4

- immune cells are made in embryonic thymus gland;

- receptors on T cells recognise abnormal proteins/pathogens;

- during embryogenesis variety of T cells generated recognising normal and abnormal proteins

Front 5

PCD is used after development for removal of redundant structures?

Back 5

- there is an increased number of milk secreting cells formed in pregnancy - PCD after

- metamorphosis

Front 6

PCD is important for regulation of cell numbers. Problems with it lead to pathogenic conditions?

Back 6

- degenerative disorders - Alzheimers or autoimmune diseases

- diseases of over-proliferation - cancer

Front 7

PCD also limits collateral tissue damage by eliminating specific cells that are damaged beyond repair as result of:

Back 7

- DNA damage (when repair mechanisms cannot cope)

- accumulation of misfolded proteins (causes ER stress and cell death; linked with neurodegenerative disorders)

- cells infected by certain viral agents (limits spread of infection)

Front 8

What is the difference between necrosis and apoptosis?

Back 8

- Necrosis is always pathological

- Apoptosis can be pathological but is usually physiological (but has the same morphological features in either case)

Front 9

What are the reversible morphological features of necrosis?

Back 9

- cell swelling

- plasma membrane alterations (blebbing, loss of microvili)

- mitochondrial changes (swelling, formation of small amorphous densities)

- ER dilation (polysome formation)

- Nuclear changes (disaggregation of fibrils)

Front 10

What are the irreversible morphological features of necrosis (due to severe injury)?

Back 10

- Extensive cell swelling and loss of plasma membrane integrity

- mitochondrial changes (marked swelling, formation of large amorphous densities)

- dilation of organelles

- myelin formation (phospholipid masses)

- nuclear changes (pyknosis, karyorrhexis)

Front 11

What are the initial morphological features of apoptosis?

Back 11

- cell shrinkage (dense cytoplasm, organelles are tightly packed)

- minor membrane blebs

- chromatin condensation (peripheral aggregation of dense chromatin mass under nuclear membrane; various shapes (crescent or circular dense mass)

Front 12

What are the morphological features of apoptosis?

Back 12

- extensive membrane blebbing

- cell fragments via blebbing into apoptotic bodies (membrane-bound portions of cytoplasm and organelles; with or w/o nuclear fragments)

- phagocytic ingestion and degradation

Front 13

What are the biochemical features of apoptosis (3)?

Back 13

- activation of caspases

- DNA and protein breakdown

- membrane alteration and recognition by phagocytes

Front 14

What are caspases?

Back 14

- found in animals

- suicide proteases

- cysteinyl-aspartate-specifc proteases

Front 15

What are the features of caspases?

Back 15

- cysteine at the active site

- cleaves target proteins at specific aspartic acids

- synthesised as inactive procaspase

- activated by proteolytic cleavage at own aspartic residues to generate 2 subunits

- 2 released subunits associate with another 2 subunits to form the active tetrameric caspase

Front 16

What domains do initiator caspases contain?

Back 16

- CARD - caspase recruitment domain

- DED - death effector domain

Front 17

How are initiator caspases activated?

Back 17

- exist as monomers

- interact with adaptor/scaffold protein causing procaspases to aggregate

- procaspase form posses some proteolytic activity

- activation through proximity or conformational change

- released subunits from active tetrameric protease and activate effector caspases

Front 18

How are initiator caspases activated (image)?

Back 18

Front 19

How are effector caspases activated?

Back 19

- exist as inactive dimers

- cleaved by active initiator caspases

- released subunits form active tetrameric proteases

- execute the proteolysis seen during the demolition phase of apoptosis by targeting a range of cellular proteins

Front 20

How are effector caspases activated (image)?

Back 20