Download Biofactsheet Apoptosis

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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
Nucleus
4. Nucleus fragments. 'Blebs' collected by phagocyte
if phagocyte recognises cell for apoptosis
Nucleus condensing
Nucleus fragmenting
2. 'Signal'
received
Blebs
Apoptotic body
3. Nucleus condenses and cell shrinks
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Phagocyte (i.e. macrophages)
engulfs apoptotic bodies
Bio Factsheet
221 Apoptosis
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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
Development of an organism
Threats to an organism
Infected cells
Synapse formation
Cytotoxic T-lymphocytes (white blood cells
involved in defence against disease) kill virusinfected cells by making them undergo
apoptosis. Some infecting viruses may use
their own protection system to prevent this
happening! One of the HPV (Human Papilloma
Viruses) implicated in causing cervical cancer
does this by producing a protein that binds to
and inhibits the p53 promoter of apoptosis.
During development of the nervous system
apoptosis removes surplus cells so that
synaptic connections can be made correctly
between the appropriate cells needed in a
particular nerve pathway.
Autoimmunity
‘Trimming’ and shaping
Cell-mediated immune responses become less
extensive as the challenge to the immune
system is removed. There is a danger that the
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.
The formation of fingers and toes on hands
and feet needs the surplus tissue between
them to be removed by apoptosis.
Damage to DNA
During menstruation
Damage to the DNA in a cell may make that cell
become cancerous, or it may affect its normal
pathway of development and cause birth defects.
Cells with DNA damage produce large quantities
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’.
The endometrium (the inner lining of the
uterus) is shed at the beginning of the
menstrual cycle as apoptosis removes cells
which hold the lining in place.
During metamorphosis
The reabsorption of the tail of a tadpole as it
develops into a frog depends on apoptosis
as the cells of the tail must be broken down
before their components can be reabsorbed.
Cancer cells
Some forms of radio and chemotherapy set off
apoptosis in cancer cells, so that the cancer cells
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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Bio Factsheet
221 Apoptosis
www.curriculum-press.co.uk
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)
2. programmed cell death;
decrease/shrink;
nucleus;
mitochondria;
blebs;
intrinsic;
extrinsic;
peroxide ions/superoxide ions;
phagocytes;
1. 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).
Answers
Acknowledgements:
This Factsheet was researched and written by Ron Pickering.
Curriculum Press, Bank House, 105 King Street, Wellington, Shropshire, TF1 1NU.
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