Jacqueline McDermolt and Richard Grencis

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Most people know that white blood cells protect the body against
infection. Fewer people know that they also provide a defence
against cancer. This article explains their protective function.

cquired immunodeficiency syndrome (AIDS) a subset of lymphocytes whose role is to coordinate the
is caused by the human immunodeficiency immune responses. They are a bit like the conductor of
virus (HIV). Since the virus was first recog- an orchestra. Without them, as we see with AIDS, the
nised in
1981. it has caused over 25 million immune system cannot function and death ensues. We
deaths worldwide. Today. there are estimated to be will look at T cells in more detail later in this article.
about 19 million people infected with HIV and two-
thirds of these people live in sub-Saharan Africa (see White bNood cells
Figure l). The World Health Organization (WHO) White blood cells (leucocytes) are cells of the immune
describes AIDS as a major medical emergency. Only system and they are produced in the bone marrow.
20'k of. those infected are currently receiving drug They are not white
treatment. Those who receive treatment will require - we call them that to distinguish
them from red blood cells. They need to be stained
drugs for life. before they can be seen under the light microscope (see
Why is HIV such a destructive virus? The answer is Figure 2). The two major types of white blood cell are
because it targets the very cells required to fight the phagocytes and lymphocytes.
infection. HIV enters a particular type of white blood
Phagocytes
cells, called T helper cells, via receptors on their plasma
There are two types of phagocytes, neutrophils (see
membrane (see Box I ). The virus incorporates itself into
Figure 3) and monocytes. They engulf and destroy
the cell's DNA, instructing the cell to make and then
bacteria and unwanted foreign material. Neutrophils are
release virus particles. Infected cells die either because of
the most common white blood cells in the circulation
the accumulation of viruses inside them or because they
(60-70%). They are also called granulocytes because of
are killed by other uninfected T cells. The destruction of
the numerous granules in their cytoplasm (see Figure 3).
T helper cells leaves infected individuals unable to
Key words
lmmunity defend themselves against other infections or the
White blood cells
Infection
growth
HIV
of cancer celis (see Box 2).
has shown the important role of T helper
BOX I ,,u infects r hetpercetts
Ca ncer
cells ln the surveillance and destruction of both HIV uses a glycoprotein, 9p120, found on its external
microorganisms and cancer cells. T helper cells are envelope to attach to cells. The plasma membrane of
T helper cells contains CD4 molecules and it is these
that 9p120 recognises and binds to. The virus enters
Adult population
the cell and either remains latent or replicates. Viral
with HIV/%
replication kills infectedT helper cells and viruses are
::i:''i No data
,-. 0.0-0.1 released.
'' 0.1-0.5
- 0.5-1.0

w
'W
s-ts
CD4 molecule
15+

T helper cell

Figure I Global prevalence of HIV infection.

34 BIOLOGICALSCIENCES ?FV E\ "

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zf
Coloured
scanning electron
t micrograph of
macrophages
(blue) attacking a
foreign body
(centre). x7500

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F

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o
z

Monocytes, rvhich nrake up around 10% of white blood
cells, are important Lrecanse they not only engulf
microorganisms ancl un\vanted material but they are
able to Dresent tl-ris nraterial to T cells and activate them.
Lymphocytes
There are two major tlpes of lymphocytes (see Figure 4).
Together they comprise 20% of circulating white blood
cells, and like all leucocytes originate from the bone
marrow. One group matures in the bone marrow before
joining the circulation
- B lymphocytes; the other
group moves to the thymus gland and matures there
before joining the circulation. These are known as
T lymphocytes. B and T lymphocytes circulate around
the body, passing through lymph nodes where they may
be activated by antigen-presenting cells. B cells produce
antibodies which protect against bacteria and viruses.
T cells can be divided into silbsets. T helper cells, as we
have already seen, control the immune response; and
cytotoxic (ce1l-killing) T cells are important in the
defence against viruses and cancer. Lymphocytes are
part of the adaptive immune response and provide long-
lived immunological memory (see Bror-ocrcal Scmlcrs
Rrwrw, Vol. 16, No. 3, pp. )l-)5).
Other white blood cells
The blood also contains rarer white blood cells.
Eosinophils are granulocytes and are involved in allergic
responses, such as hayfever and asthma, and help
protect us against parasitic worm infections such as
roundworms (see Brorocrcar Screucrs Revrrw, Vol. 19,
No. 2, pp. 2-6).In past times, almost everybody would
have had worm infections and it is believed that the
rise in allergy and asthma in the 'developed'world may
in part be due to the fact that people no longer have t*
worms. Dendritic cells are essential in initiating immune -
responses by presenting antigens to T cells in lymph x
nodes and so forming a bridge between innate and
Figure 2
I
adaptive immunity (see Brorocrcar ScrENcps RevrEw, Peripheral blood
Vol. 18, No. I, pp. 2-6 and this issue pp. l4-17). Natural film showing red
killer cells are important in killing virally infected cells cells and white
and cancer cells. cells. x750

BOX p o,r""r"s associated with AIDS

When T helper cell numbers drop below a certain
level, peopie with HIV are at risk of acquiring these
infections and tumours.
lnfections
Candidiasis o'oesophagus and airways (frngal
infection)
P n e u mocysti s carinli pneumonia
Tuberculosis
*
Toxoplasmosis of brain (orotozoan infection)
Salmonella septicaemia (bacterial infection)
Cytomegalovirus
Cancers
Kaposi's sarcoma
,.'*$h*l,l
Burkitt's lymphoma

APRIL 2OO7 35

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 K&K S ,n"go.rrosisof bacteria by
neutrophils

\\\
The neutrophil cell membrane r'7?a=^
surrounds a bacterium.

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lQ"cX\
I
The bacterium is engulfed
within the cell. lt is now inside
a phagosome. k"gJ
os,7
\
v
A lysosome fuses with the
phagosome, releasing its
nrnta^l\/tra an7\/mae @"€.')
a

z
\ @av/
Y
Figure 3 Frotcetion agaimst nirulses and bacteria 4 The bacrerium is oestroyed
Coloured

\ry
/e'@.\
Neutrophils ingest bacteria and destroy them insidc hv erzvmes and o-hcr toxic
transmission
enzyme-rich vesicles (see Box 3). They engulf bacteria products, including hydrogen
electron
micrograph of a more readily if the organism is coated with antibody or peroxide and nitric oxide.
neutrophil - the complement proteins (produced by the liver and found
most common ir-r blood plasma Brorocrcar ScrrNcrs Rnvrnw,
type of white Vol. lB, No. l, pp. 2-6). This process is called opsoni- who have genetic disorders of the intntune syslem
blood cell. x9000 sation. Neutrophils are short-lived cells, and dead or (immunodeficiencies). Without the growth factor treat-
dying neutrophils make up a large component of pus. ment, many of these people have recurrent bacteriai
Neutrophils are produced in the bone marrow. infections, either because they have so lew neutrophils
Leukaemias are cancers of the bone marrow. During or because their ner-rtrophils are deiective.
cancer therapy the diseased bone marrow is first Macrophages are longer-lived phagocyres found in
destroyed by anti-cancer drugs and is then replaced with tissues. They are derived frorn monocytes in Lhe blood.
Figure 4 Diagram
showing the healthy bone marrow from a donor. After transplant- Monocytes move through the capillary walls intct the
different types of ation the patient is susceptible to bacterial infection until tissues whe re they matur e into macrophages. These cells
white blood cells. the new bone marrow'takes'. Neutrophil growth factors engulf bacteria and use similar killing n-rechanisms to
can be given to the patient neutrophils. Macrophages present conlponents of the
- these
lnduce the bone marrow cells to make ingested bacteria on their plasma membranes. These
millions of new neutrophils. This 'bacterial bits' can be recognised by T cells, rvhich can in
therapy can also be used for people turn stimulate B cells to make antibodies soecific to the
invading microorganism (see Figure 5). Anti-
bodies are an important weapon against
pathogenic
pathoge. microorganisms: they opsonise
(._,,) bacteria, mal'ing it casicr l,'r llr.rgoc) rcs r,,
bactcria,
/e."lrr\ engulf tt
thern; they neutralise bacter ial toxins;
, stem cells (make
they bin
bind to virlrscs and prevent them frclm
\ ,/ /\ Etibodi? invading cells; and they bind
invadinl to virus-
Lymphoid
infected cells, allowing thern to be killed by
cells
natural Ikiller cells.
natr-rral
Granul \,/ Unlikke most bacteria, vituses can onl1,
T cells replicate.e inside the cells of the host. There-
Mast cells {ore, wh hite blood cells have to tackie viruscs
Neutrophils
(phagocytes)
(defence against in a diflcrent way l0 batrcria.
worms) When a cell is infected with a

4",0",..")
(control immune
6"-*r*)
'(defence against
virus, before il is killed, it displays
Iragnrt'nts ol the r irus on il:
\ viruses and plasrna nrern[rrane. These Irag-

{'0"""7 \ancer)-rl
ments arc recognised by specific
T cells called cytotoxic T cells.

JO BIOLOGICAL SCIENCES Rt , It\

BOX fl.r,o,oric r cells killtumour
cells
:: :. i-'-crr- antigens on their cell
= -,.)' sed by cytotoxic T cells as
,.
. :-':-:a sk1l theabnormal cell by
'3 e3S ^l :-- '' - :^'.. ^,ng granules (containing
psl u: l
.= :: ..--'2 ^ :le target cell membrane.
Tha nnrp ; - .'):c!c T cells to pump n
aaa\lmo
v,,Ly",v vv -'=.-
aa - - . ;'.^ - es, which eventually kill the
cell.

They will kill the inlccte d ccll using special cell surface
receptors, or b-v pr-nrching a hole in the cell and injecting
the cell with toxic t.r'tolecules. Some viruses have
adapted to tl'lese tncchanisms. They are able to hide
from the T cells b1' stopping the infected cell from
displaying bits of thcr.nselves on the plasma membrane.
However, the imnune system has adapted too and *
natural killer cells are able to recognise and kill cells ii
,t
containing'hidden' virttses.

Killing cancer cells

The process of cell division is carefully controlled and if
El
mistakes are ntade during the replication of DNA, there celis and destroy them have shoru-r us how critical these Figure 5
cells are for maintaining good health. Scanning x
are a number of mechanisms that exist to repair the *
electron
faulty strand. Every so often the repair mechanisms fail micrograph of K
and the nlltation is passed on; this usually results in Dr Jacqueline McDermott is a Research Associate in helminth n
uncontrollable cell division and the development of a immunology and Richard Grencis is Professor of (browny red)
tumolrr. Cancer cells are different from normal cells and immunology at the University of Manchester. Therr main surrounded by
they ofter.r display different (tr-rmour) antigens on their research interest is the immune response to intestlnal neutrophils
(blue) and
cell surface. Tumour antigens are recognised as worm infection.
eosinophils
abnormal by cytotoxic T cells and natural killer cells. (yellow with red
These cells circulate around the body, hunting down
cancer cells and kiiling them (see Box 4). With
KEYpoint, lumps). x1200

increasing age, both the DNA repair and the tumour
recognition processes become less efficient, which is
why cancer is more common in older people.
Sulmrnary
\\'hite blood cells are crucial in our defence against
::rr irlinc, I)athogens. They are also necessary to protect
r-r:,r!.rirrrt (crnCer. Phagocyies cngull and destroy
batirIr.r. So]lrc itf thcm activaLe specific lymphocytes.
T ccils L(rulr(rl lhc ittrtnLtne response and kill virally
infccte d cclls; 13 cclls ltroclltcc antibodies. The activation
ol lyn'rphootes alLirts the development of long-lived
memory ce lls, n'hich frote ct r-ts against future infection.
Eosinophils provicle a defcnce against parasites but can
also be harmlul to us dr-rring allergic responses. HIV and
other infective microorganisms that target white blood
c White blood cells give the body protection against
infection caused by microorgantsms.
s White biood cells also help to protect against the
development of cancers.
* There are ditferent types of white blood cells with
different roles to plav.
e Phagocytes engulf and destroy 'foreign' material
Thev form the basis of the initial non-specific
response to the detection of the foreign antigens.
o Lymphocytes form the basis of acquired immunity
specific to a particular pathogen, e.g. measles.
-
* All lymphocytes come from the bone marrow.
B lymphocytes mature there while T lymphocytes
mature in the thymus gland.

APRIL 2OO7 37