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B io Factsheet

www.curriculum-press.co.uk Number 221

Apoptosis
Definitions
AIDS acquired immune deficiency syndrome: A set of conditions in which the affected individual suffers opportunistic infections
as 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 vacuoles
in this way is phagocytosis.
Receptor a molecule, often on a cell surface, able to recognise and bind to a complementary molecule. This complementary
molecule may then act as a signal for an intracellular process.

Introduction
Cells do not live forever – eventually each one of them dies. Cells may be made to commit suicide – this is known as apoptosis or
programmed cell death.
Most cells undergo about 50 mitotic divisions (known as the Hayflick constant) before apoptosis. Cells which die by committing
suicide 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

1. Cell 'programmed' for apoptosis 4. Nucleus fragments. 'Blebs' collected by phagocyte


Nucleus if phagocyte recognises cell for apoptosis

Nucleus condensing Nucleus fragmenting

2. 'Signal'
received

Blebs

Apoptotic body
3. Nucleus condenses and cell shrinks
Phagocyte (i.e. macrophages)
engulfs apoptotic bodies

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221 Apoptosis Bio Factsheet
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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

Threats to an organism Development of an organism


Infected cells
Cytotoxic T-lymphocytes (white blood cells Synapse formation
involved in defence against disease) kill virus- During development of the nervous system
infected cells by making them undergo apoptosis removes surplus cells so that
apoptosis. Some infecting viruses may use synaptic connections can be made correctly
their own protection system to prevent this between the appropriate cells needed in a
happening! One of the HPV (Human Papilloma particular nerve pathway.
Viruses) implicated in causing cervical cancer
does this by producing a protein that binds to
and inhibits the p53 promoter of apoptosis.

Autoimmunity
‘Trimming’ and shaping
Cell-mediated immune responses become less
The formation of fingers and toes on hands
extensive as the challenge to the immune
and feet needs the surplus tissue between
system is removed. There is a danger that the
them to be removed by apoptosis.
active immune cells could attack the body of
the host organism, so cytotoxic T-lymphocytes
set off the process of apoptosis in each other
(and even in themselves!). If this process does
not work effectively, the immune cells may
cause autoimmune diseases, such as
rheumatoid arthritis, in which body tissues
can be severely damaged. This autoimmune
response can be fatal.

Damage to DNA
During menstruation
Damage to the DNA in a cell may make that cell
The endometrium (the inner lining of the
become cancerous, or it may affect its normal
uterus) is shed at the beginning of the
pathway of development and cause birth defects.
menstrual cycle as apoptosis removes cells
Cells with DNA damage produce large quantities
which hold the lining in place.
of a protein, p53, which acts as a powerful inducer
of apoptosis. It is interesting that many cancerous
cells have mutations in the gene producing this
compound, and so cannot be made to ‘commit
suicide’. During metamorphosis
The reabsorption of the tail of a tadpole as it
Cancer cells develops into a frog depends on apoptosis
Some forms of radio and chemotherapy set off as the cells of the tail must be broken down
apoptosis in cancer cells, so that the cancer cells before their components can be reabsorbed.
destroy themselves and the threat to the whole
organism is overcome. Some very severe and
aggressive forms of cancer can prevent this
happening. For example, melanoma (the most
dangerous form of skin cancer) cells avoid
apoptosis by inhibiting the formation of one of
the proteins that starts the process of breaking
down cell proteins. Some lung cancer cells
prevent lymphocytes from recognising
dangerous dividing cells by producing a decoy
molecule on their surface so that the lymphocyte
cannot bind and begin apoptosis.

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221 Apoptosis Bio Factsheet
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Control of Apoptosis
Apoptosis is controlled by a wide range of signals, some of which come from inside the cell (intrinsic factors) and some of which come from
outside 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 for
neurones and interleukin for mitosis of lymphocytes) which are needed for the cell to continue to survive, and negative signals (such as
high levels of oxidants (e.g. peroxide ions), cytokines, nitric oxide, harmful radiation, accumulation of incorrectly-shaped proteins and
death activators that bind to specific receptors on the cell surface) which signal the start of apoptosis.

Apoptosis and AIDS


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

Practice Questions
1. 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)

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

in disease management e.g. targeting of tumour cells (1 mark).


development of organism/with examples (max 4 marks);
1. defence against pathogens/with examples (max 3 marks);
Answers

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 part
of these Factsheets may be reproduced, stored in a retrieval system, or transmitted, in any other form or by any other means, without the
prior permission of the publisher. ISSN 1351-5136
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