AIDS acquired immune deficiency syndrome: A set of conditions in which the affected individual suffers opportunistic infectionsas a result of a depleted immune response

Apoptosis cell death by suicide, following a well-defined sequence of events ‘built in’ to the cell

Bleb a bubble-like structure on the cell surface, containing the remains of broken–down organelles

Cancer a condition resulting from a loss of control of orderly cell division

Extrinsic ‘from outside’ : A process or structure occurring outside the cell

Intrinsic ‘from within’ : A process or structure occurring inside the cell

PCD programmed cell death: Another name for apoptosis, emphasising that the sequence of events leading to cell suicide is‘built in’ to the cell’s genetic programme.

Phagocyte a white blood cell which may remove target materials by ingestion within temporary vacuoles; the formation of vacuolesin this way is phagocytosis.

Receptor a molecule, often on a cell surface, able to recognise and bind to a complementary molecule. This complementarymolecule may then act as a signal for an intracellular process.

Bio Factsheet

1

Number 221www.curriculum-press.co.uk

Apoptosis

IntroductionCells do not live forever – eventually each one of them dies. Cells may be made to commit suicide – this is known as apoptosis orprogrammed cell death.Most cells undergo about 50 mitotic divisions (known as the Hayflick constant) before apoptosis. Cells which die by committingsuicide do so in a well-organised manner (Fig.1):• They shrink• The DNA and protein in the nucleus is degraded (broken down)• The mitochondria are degraded• ‘Blebs’ develop on the cell surface• The ‘blebs’ are engulfed by phagocytes• The phagocytes release signals to inhibit inflammation

Fig 1 : Simple outline of apoptosis

Nucleus

Blebs

Apoptotic body

Phagocyte (i.e. macrophages)engulfs apoptotic bodies

Nucleus fragmenting

1. Cell 'programmed' for apoptosis

2. 'Signal'received

3. Nucleus condenses and cell shrinks

Nucleus condensing

4. Nucleus fragments. 'Blebs' collected by phagocyteif phagocyte recognises cell for apoptosis

Definitions

Bio Factsheet

2

www.curriculum-press.co.uk221 Apoptosis

Why do cells commit suicide?There are two reasons for this.• It may be part of the body’s defences against pathogens or dangerous, damaged cells.• It may be part of the normal developmental process for the organism.

Fig 2 : Reasons for apoptosis

During metamorphosisThe reabsorption of the tail of a tadpole as itdevelops into a frog depends on apoptosisas the cells of the tail must be broken downbefore their components can be reabsorbed.

Development of an organism

Synapse formationDuring development of the nervous systemapoptosis removes surplus cells so thatsynaptic connections can be made correctlybetween the appropriate cells needed in aparticular nerve pathway.

‘Trimming’ and shapingThe formation of fingers and toes on handsand feet needs the surplus tissue betweenthem to be removed by apoptosis.

During menstruationThe endometrium (the inner lining of theuterus) is shed at the beginning of themenstrual cycle as apoptosis removes cellswhich hold the lining in place.

Threats to an organism

AutoimmunityCell-mediated immune responses become lessextensive as the challenge to the immunesystem is removed. There is a danger that theactive immune cells could attack the body ofthe host organism, so cytotoxic T-lymphocytesset off the process of apoptosis in each other(and even in themselves!). If this process doesnot work effectively, the immune cells maycause autoimmune diseases, such asrheumatoid arthritis, in which body tissuescan be severely damaged. This autoimmuneresponse can be fatal.

Infected cellsCytotoxic T-lymphocytes (white blood cellsinvolved in defence against disease) kill virus-infected cells by making them undergoapoptosis. Some infecting viruses may usetheir own protection system to prevent thishappening! One of the HPV (Human PapillomaViruses) implicated in causing cervical cancerdoes this by producing a protein that binds toand inhibits the p53 promoter of apoptosis.

Damage to DNADamage to the DNA in a cell may make that cellbecome cancerous, or it may affect its normalpathway of development and cause birth defects.Cells with DNA damage produce large quantitiesof a protein, p53, which acts as a powerful inducerof apoptosis. It is interesting that many cancerouscells have mutations in the gene producing thiscompound, and so cannot be made to ‘commitsuicide’.

Cancer cellsSome forms of radio and chemotherapy set offapoptosis in cancer cells, so that the cancer cellsdestroy themselves and the threat to the wholeorganism is overcome. Some very severe andaggressive forms of cancer can prevent thishappening. For example, melanoma (the mostdangerous form of skin cancer) cells avoidapoptosis by inhibiting the formation of one ofthe proteins that starts the process of breakingdown cell proteins. Some lung cancer cellsprevent lymphocytes from recognisingdangerous dividing cells by producing a decoymolecule on their surface so that the lymphocytecannot bind and begin apoptosis.

Bio Factsheet

3

www.curriculum-press.co.uk221 Apoptosis

Control of ApoptosisApoptosis is controlled by a wide range of signals, some of which come from inside the cell (intrinsic factors) and some of which come fromoutside the cell (extrinsic factors).

Whether or not a cell commits suicide depends on a balance between two sets of signals: positive signals (such as growth factor forneurones and interleukin for mitosis of lymphocytes) which are needed for the cell to continue to survive, and negative signals (such ashigh levels of oxidants (e.g. peroxide ions), cytokines, nitric oxide, harmful radiation, accumulation of incorrectly-shaped proteins anddeath activators that bind to specific receptors on the cell surface) which signal the start of apoptosis.

Apoptosis and AIDSDuring AIDS the numbers of CD4 T cells in the affected individual fall dramatically, and this individual cannot then mount an effectiveimmune response. CD4 T cells are infected by the HIV (Human Immunodeficiency Virus), but it isn’t these particles that kill off the CD4cells. It seems that these cells are killed by apoptosis because they produce too much of a receptor (called FAS) which can bind to a deathactivator, causing the cells to commit suicide.

Practice Questions1. Why is apoptosis important to living organisms? (8 marks)

2. Complete the following account of apoptosis by filling in the gaps.

Apoptosis is also known as ..........................................................., because the ability to commit suicide appears to be ‘built in’ to every cell.

Cells undergoing apoptosis can be recognised because they ................................ in size, the ............................. condenses and organelles

such as ................................... break down and become enclosed in extensions of the cell surface membrane called ...................... .

The signals for apoptosis may be internal (.............................. ) or external ( ............................ ). A common internal signal is the presence of

high levels of oxidants such as ....................................… Both internal and external signals eventually result in the destruction and removal

of the cell by ...................................... . (9 marks)

Answers1.defence against pathogens/with examples (max 3 marks);

development of organism/with examples (max 4 marks);in disease management e.g. targeting of tumour cells (1 mark).

2.programmed cell death;decrease/shrink;nucleus;mitochondria;blebs;intrinsic;extrinsic;peroxide ions/superoxide ions;phagocytes;

Acknowledgements:This Factsheet was researched and written by Ron Pickering.Curriculum Press, Bank House, 105 King Street, Wellington, Shropshire, TF1 1NU.Bio Factsheets may be copied free of charge by teaching staff or students, provided that their school is a registered subscriber. No partof these Factsheets may be reproduced, stored in a retrieval system, or transmitted, in any other form or by any other means, without theprior permission of the publisher. ISSN 1351-5136