apoptosis

1. 5.1 intrinsic

1.1. caused by intracellular signals

1.2. triggered by irreparable AND irreversible DNA damage

1.3. lead to activation of ATM

1.3.1. which Activates P53

1.4. P53 activate protein BAX

1.5. BAX forms bores in the outer membrane of mitochondria

1.6. Calcium, hydrogen ions & cytochrome leak out

1.7. cytochrome C binds to procaspase 9

1.7.1. which activates it

1.8. Active caspase 9 cleaves additional caspases initiating the so called caspase cascade.

1.9. Caspase 9 also destroys many other proteins.

2. 1 It's a programed cell death

2.1. is a pathway of cell death that is induced by a tightly regulated suicide program in which cells destined to die, activate enzymes capable of degrading the cells' own nuclear DNA and nuclear and cytoplasmic proteins.

3. 2 physiologic causes

3.1. detraction of cells during embrygenesis

3.2. Involution of hormone-dependent tissue

3.3. cell loss in proliferating

3.4. cells that have served there purpes

3.5. eliminating harmful self-reactive lymphocytes,

4. 3 pathologic causes

4.1. elimination of cells that are genetically altered or injured with out sever host reaction

4.2. loss of cells DNA

4.2.1. radiation. cytotoxic anticancerdruges,etc

4.3. cell injury in infections

4.4. pathologic atrophy in parenchmal organs after duct obstruction :such as pancreas, parotid and kidney

5. 4 important

5.1. Morphogeneisi

5.1.1. the fingers

5.2. selection

5.2.1. kill non functional cells

5.3. immunity

5.3.1. kill dangerous cells

5.4. maintain organs size + function

5.5. EX: apoptosis during the metamorphosis of a tadpole to a frog

6. 5 Initiation

6.1. pathway

6.1.1. mitochondrial (intrinsic)

6.1.2. death receptor (extrinsic)

6.1.3. both are activated by CASPASE 3

7. 5.2 extrinsic

7.1. coused by extracellular signals

7.2. the most popular is tumour necrosis factor alpha "TNFa"

7.3. TNFa is secreted by many cells Eg. T-killer cells

7.4. it binds to TNF receptor at outer membran

7.5. death domin recepto is activated

7.6. procaspase 8 + hydrolysis = activate caspase 8

7.7. Caspase 8 dissociates from the receptor & initiates the caspase cascade.

8. 6 execution

8.1. def. : Comprises cleavage of DNA & cleavage of cytoskeleton.

8.2. 6.1 cleavage of DNA:

8.3. casepase 3 activate DNase

8.4. DNase cleaves DNA at 180 base pairs

8.5. 6.2 cleavage of the cytoskeleton:

8.6. Caspase 3 cleaves proteins of the cytoskeleton destroying the cell structure.

8.7. The cell collapses into vesicles called apoptotic blebs.

8.8. No leakage of cellular contents, therefore no inflammatory response.

9. 7 phago-cytosis

9.1. Phagocytosis:

9.2. Execution causes significant alteration of

9.3. the outer membranes of cells & blebs.

9.4. The intact modified membrane structure

9.5. allows their removal by macrophages.

9.6. Inside the macrophages the blebs are

9.7. digested by lysosomal enzymes.