4C: apoptosis

necrosis

unregulated cell death

cause of necrosis

disease, injury, failure of blood supply

process of necrosis

• damage to plasma membrane → flow in of fluid = swell and burst

  • burst material spreads over adjacent tissue, causes inflammation

apoptosis diagram

cell balance

normal tissue cells = rate of production + death → balanced

reproduction exceeds

• growth / cancer

reproduction less

• tissue wasting diseases / autoimmune diseases

balance regulated by…

regulator proteins

why does apoptosis occur?

• maintenance

  • e.g. body continually makes + replaces RBC as they become damaged while squeezing across capillaries

• removing damaged + dangerous cells

  • cells with damaged DNA and mutations

  • cells that have been infected by viruses

  • cells that attack self-cells as part of the immune function

• normal development

  • e.g. as foetus develops, apoptosis = part of digit + limb development

apoptotic pathways

• internal / intrinsic / mitochondrial activated pathway

• external / extrinsic (death receptor protein on cell membrane) activated pathway

extrinsic pathway

• death chemicals (often called ligands, released by WBC) that are external to the cell bind to membrane death receptors (proteins) on the cell membrane

triggers of extrinsic pathway

when cells are recognised are:

• malformed

• infected

• in excess

example of extrinsic pathway

Cytotoxic T cell (WBC) can bind to a cancer cell

• release death signal

• binds to death receptors (protein) → apoptosis

triggers of intrinsic pathway

• triggered by internal stressors, such as:

  • cell damage by virus

  • DNA damage

    • may be caused by UV, radiation

  • chemotherapy / radiation

process of apoptosis (1/2)

1. pre-apoptotic signal received by the cell

2. activation of apoptotic enzymes (caspases) within the cell

3. degradation of the nucleus, shrinkage of the cell, blebbing of the cell into apoptotic bodies

4. apoptotic bodies engulfed by phagocytes

process of apoptosis (2/2)

1. caspases (enzymes) activated

2. cell and nucleus shrinks

3. breaking down of cell contents, including organelles + DNA

4. cytoskeleton broken and the membrane starts blebbing

5. cells forms membrane enclosed vesicles called apoptotic bodies

6. engulfed by phagocytes

blebbing

bulging of plasma membrane to form separate apoptotic bodies

apoptotic bodies

vesicle containing cell contents that are released from a dying cell during apoptosis and eventually engulfed by phagocytes

phagocyte

a group of WBC responsible for the endocytosis and destruction of pathogens and foreign material

caspase

enzymes that cleave / cut specific intracellular proteins in apoptosis

role of caspase enzymes

• cleavage / cutting of DNA into fragments

• degrading / breaking down nuclear proteins

• cleave / cutting of proteins in nuclear membrane

• dismantling of the cell’s cytoskeleton - forms blebs

• breakdown of proteins in cytosol

• breakdown of organelles

tumours

uncontrolled cell division b/c apoptotic failure

benign tumour

relatively slow, trapped in tissue of origin, trapped in capsule = prevents invading other tissues, non-cancerous

malignant tumours

bengign tumour spread / invaded other tissue types, cancerous