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Immunology

Chapter 11

Parasites and pathogensInectious diseases are ones that we can catch

rom someone else, such as a cold, TB, malariaand HIV/AIDS. These diseases are caused by

pathogens. A pathogen can be dened as a

microorganism that causes disease.

Pathogens are a kind o parasite. A parasite is

an organism that lives in a very close relationship

with another organism, called its host, and does it

harm. The parasite gains rom the relationship. So

all pathogens are parasites, but not all parasites are

pathogens. For example, you might have lice living

in your hair, but they are not causing a disease so

they are not pathogens.

A well-adapted parasite or pathogen does not

kill its host. The parasite or pathogen is most likely

to survive, and produce ospring that can move

to a new host, i its host survives long enough or

this to happen. Most o the inectious diseases that

have been around or a long time, such as colds,

measles and TB, either do not kill us or do not

kill us quickly.

Pathogens belong to one o our dierent groups

o microorganisms viruses, bacteria, ungi and

protozoa. (Some may argue that viruses are notorganisms at all.) Table 11.1 lists some examples o

diseases caused by each o these groups.

The immune responseWe have numerous deences against invasion o

our bodies by pathogens. The rst line o deence

is to stop them getting in at all. I they do gain

access, then the immune system comes into action.

The way in which white blood cells respond when

pathogens enter the body is called the immune

response.

Several types o white blood cells (leucocytes)

are able to recognise oreign cells or molecules

that enter the body. In other words, they can

distinguish sel rom non-sel. The immune

response is the way in which the immune system

responds to the presence o non-sel cells or

molecules in the body.

By the end o this chapter you should be able to:

a describe the mode o action o phagocytes;

b describe the roles o mast cells and histamine

production, complement, and phagocytes as

antigen-presenting cells;

c dene the term immune response;

d compare the origin and maturation o B- and

T-lymphocytes, including the types o T-cells

and their unctions, and B-cells and theirunctions;

e distinguish between the humoral and the cell-

mediated immune responses;

explain the role o T- and B-memory cells in

long-term immunity;

g relate the molecular structure o a typical

antibody molecule to its unction, including

specicity;

h distinguish between active and passive

immunity, natural and articial immunity;

i explain the role o vaccination in providing

immunity;

j state what is meant by a monoclonal antibody;

k describe the use o monoclonal antibodies in

diagnosis and treatment, including pregnancy

testing, and the anticancer drug MabThera.

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Chapter 11: Immunology

222

Pathogen Type o microorganism Disease caused

human immunodeciency virus

(HIV)

virus acquired immune deciency

syndrome (AIDS)

adenovirus virus colds

Mycobacterium bacterium tuberculosis (TB)

Tinea pedis ungus athletes oot

Plasmodium protozoan malaria

Table 11.1 Causes o some inectious diseases.

The best line o deence against pathogens is to

prevent them rom getting established in

the body.

Skin is impermeable to most pathogens,

although there are a ew viruses, such as the ones

that cause warts, that can penetrate unbroken

skin. We have our own ora o harmless

bacteria that live on healthy skin, but most

pathogenic bacteria cannot survive there, partly

because lactic acid and atty acids secreted rom

sweat glands and sebaceous glands provide a pH

that is too low or them. However, the common

bacterium Staphylococcus aureus can thrive even

on undamaged skin, and it oten inects hair

ollicles and sebaceous glands.The normal bacterial ora living on our body

suraces can help to prevent inection by other

microorganisms. For example, the bacteria that

normally live in the vagina keep the pH low by

secreting lactic acid. I a person takes antibiotics,

these bacteria may be killed. Then the pH

o the vagina rises, and this may allow other

microorganisms, such as the ungus that causes

thrush, Candida, to multiply to a much greater

population density than usual.

I skin is damaged or example, by cutsor extensive burns then the way is open or

bacteria to get into the underlying tissues. Blood

clotting helps to seal wounds rapidly, until a

more permanent repair is produced by mitosis

o the cells surrounding the wound. A blood

clot orms when soluble, globular brinogen is

Primary lines o deence

converted to the insoluble, brous protein brin.

This orms a mesh o strands across the wound

in which platelets stick and red blood cells get

trapped, thus preventing urther loss o blood or

entry o pathogens.

Moist body suraces, such as the surace o

the eyes and mouth, are bathed in uids which

have some bactericidal action. An enzyme called

lysozyme is present in saliva and tears, and this

enzyme can damage and destroy many bacteria.

Semen contains a bactericide called spermine;

milk contains a bactericidal enzyme called

lactoperoxidase. The hydrochloric acid secreted

into the stomach is very eective in destroying

bacteria and other pathogens ingested in ood.Mucus helps to protect the digestive and

respiratory tracts rom inection. It acts as a

barrier so that bacteria cannot make contact with

the epithelial cells lining the walls o the tubes.

Mucus is produced by goblet cells, which are part

o the epithelium. A layer o cells containing

goblet cells is sometimes known as a mucous

membrane (but dont conuse this membrane

with a plasma membrane o a cell). In the trachea

and bronchi, the mucus is swept upwards to the

back o the throat by cilia and then swallowed.Coughing and sneezing help to expel mucus

containing microorganisms rom the trachea and

bronchi. I the mucus is swallowed, the acid and

enzymes in the stomach destroy any bacteria

trapped in it.

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Phagocytes

I pathogens do get through the bodys outer

deences, they may be destroyed by patrolling

phagocytic white blood cells. The types o white

blood cells known as neutrophils and macrophages

are phagocytes. They engul and digest oreign

particles o almost any type or size (Figure 11.1).

They crawl around within almost every part o the

body or example, over the suraces o the alveoli

in the lungs.

Neutrophils are ound in the blood, where

they make up about 60% o the white blood cells.

They do not live very long, oten dying ater they

have taken in and destroyed bacteria, and so new

neutrophils are constantly being made in the

bone marrow. They move around actively, and

requently leave the blood and patrol parts o thebody where invaders may be ound.

Macrophages also leave the blood. (Indeed,

when they are actually in the blood they are given

a dierent name monocytes.) They are present

in especially large numbers in the liver, where they

are known as Kuper cells. They also line the

passages through which lymph ows inside lymph

nodes and are ound on the inside o the alveolar

walls. Unlike neutrophils, they are quite long-lived,

tending to survive ater taking in oreign particles.

They break the particles up into their component

molecules and place some o these molecules in

their plasma membranes. Cells that do this are

called antigen-presenting cells. By doing this, they

display the molecules to other cells o the immune

system, helping these cells to identiy the invaders

and be able to destroy them. This role is described

more ully on pages 226228.

For phagocytosis to take place, the

microorganisms must rst adhere to the plasma

membrane o the phagocyte. This process is helpedby a group o proteins called complement (page

228) which are always present in the blood plasma,

and also by chemicals called cytokines, which are

produced by other white blood cells in response

2 Phagocytosis takesplace. 3 Lysosomes join with the

vacuole (phagosome) andthe pathogen is killed anddigested.

4 Any chemicals that arenot absorbed into thecell are egested.

1 Phagocytic white blood cellmoves towards a pathogen.

Figure 11.1 Phagocytosis.

phagosomelysosome

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224

to the presence o particular antigens. Cytokines

make phagocytes more efcient at killing any

microorganisms that they have enguled.

The way in which phagocytes deal with invading

cells or other oreign material is a non-specic

response. Each phagocyte can attack and destroy

any type o non-sel material.

Lymphocytes

Lymphocytes are relatively small white blood

cells. They are o two types, B-lymphocytes and

T-lymphocytes. These two types look identical,

and dier only in their unctions. B-lymphocytes

are so-called because they develop in the bone

marrow, while T-lymphocytes need to spend time

in the thymus gland during a persons childhood

to become properly developed. This gland is oundin the neck. It disappears by the time a person

becomes a teenager.

Lymphocytes are stimulated into action

when they come into contact with molecules

called antigens. Invading bacteria and viruses

are recognised as oreign because they carry or

produce antigens that are dierent rom any o our

own molecules. Antigens may be ree or they may

be part o a bigger structure, such as the cell wall

o a bacterium.

We have a huge number o dierent kinds olymphocytes in our blood. Each one is capable

o recognising and responding to one particular

antigen. The response o lymphocytes to non-sel

molecules is thereore known as a specic response.

As they mature, lymphocytes produce small

quantities o particular glycoproteins called

antibodies (page 233). We have perhaps a million

dierent kinds o lymphocytes, each kind

producing an antibody which is slightly dierent

rom other antibodies. At this stage, the antibodies

are placed into the plasma membranes o the

lymphocytes (Figure 11.2). Here, the antibodies act

as receptors, able to bind with a particular antigen

i this should appear in the body.

I bacteria enter the body, there is a good chance

that some o the lymphocytes will have receptors that

bind with antigens on the surace o the bacteria. I

so, then a response is triggered. B-lymphocytes and

T-lymphocytes respond dierently.

How B-lymphocytes respond to antigens

Most B-lymphocytes will spend all their liveswithout anything happening to them at all, because

they never meet their particular antigen. But i a

B-lymphocyte does encounter an antigen which

binds to the receptors in its plasma membrane,

it is triggered into action. It could simply meet

this antigen in the blood, or it could meet it as

it is being displayed in the plasma membrane

o an antigen-presenting cell (APC) such as a

macrophage (Figure 11.3).

You can imagine the macrophages sitting in

the lymph channels inside a lymph node, holdingout the antigens they have discovered so that the

lymphocytes will see them as they pass by.

The B-lymphocyte responds by dividing

repeatedly by mitosis. A large number o

genetically identical cells is ormed a clone o the

stimulated lymphocyte.

The process o the B-lymphocyte binding

with its specic antigen is sometimes called

clonal selection, and its division to orm a clone

o genetically identical cells is called clonal

prolieration or clonal expansion.

Some o these cells dierentiate into plasma

cells. These cells develop extra protein-making

machinery more endoplasmic reticulum, more

ribosomes and more Golgi apparatus. They

rapidly synthesise more and more molecules o

their particular antibody and release them by

exocytosis. It has been estimated that a plasma cell

can produce and release more than 2000 antibody

One type o antibody is held in theplasma membrane acting as areceptor or a specic antigen.

The same antibodycan be secreted rom

the cell in quantity.

Figure 11.2 A lymphocyte can produce one

specic type o antibody.

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molecules per second. Perhaps as a direct result o

this tremendous rate o activity, plasma cells do

not live long, mostly disappearing ater only a ew

weeks.

The antibodies are secreted into the blood and

so are carried to all parts o the body. They bindwith the antigens on the invading bacteria, which

results in the destruction o the bacteria as we

shall see on pages 232 233.

Other cells in the clone produced by the original

B-lymphocytes division do not secrete antibodies.

Instead, they remain as memory cells. These cells

live or a long time, and remain circulating in the

blood long ater the invading bacteria have all been

destroyed. They are capable o responding very

quickly i the same type o bacterium enters the

body again.

How T-lymphocytes respond to antigens

T-lymphocytes, like B-lymphocytes, are activated

i and when their particular antigen binds with the

specic glycoproteins that are held in their plasma

membranes. T-lymphocytes, however, normally

only respond to their antigen i they nd it in the

plasma membrane o another cell. This could

be a macrophage that is displaying some o the

molecules rom a pathogen that it has taken up.

Or it could be molecules on a body cell that has

been invaded by a virus, and has placed virus

particles in its plasma membrane as a help signal

(Figure 11.4).There are several types o T-lymphocytes,

including T-helper cells and T-killer cells. A

particular T-helper cell with the complementary

receptor binds to the antigen that it has ound. It

then divides to orm a clone o itsel. The cloned

T-helper cells then begin to secrete chemicals called

cytokines. These chemicals stimulate other cells to

ght against the invaders. For example, they may

stimulate macrophages to carry out phagocytosis,

or they may stimulate B-lymphocytes specic to

this antigen to divide rapidly and become plasma

cells. They also help to stimulate appropriate

T-killer cells.

T-killer cells actually destroy the cell to which

they have become bound. A body cell displaying

virus particles will be destroyed by T-killer cells.

This is the only way o destroying the viruses it

cant be done without destroying the cell in which

they are multiplying. The T-killer cells destroy

bacterium

phagocytosis by an antigen-presentingcell (APC), e.g. macrophage

antigen processedand displayed

The B-lymphocytedisplays an antibodyspecic to the antigenon the bacterium.

The B-lymphocyte meetsits specic antigen eitheron a macrophage or onthe bacterium.

The B-lymphocytedivides to producemany plasma cells,which all secreteantibodies.

Figure 11.3 B-lymphocyte response to antigen.

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226

A macrophage(APC) ingests,processes anddisplays an antigen.

The T-lymphocytemeets the specicantibody on amacrophage oranother APC.

The T-lymphocytedivides.

The T-helper or T-killerlymphocyte displays onits plasma membranean antibody specic tothe antigen.

T-killer cells kill thecells they attach to.

A cell inected byvirus displays theantigen on its surace.

T-helper cells secretecytokines to stimulatephagocytic cells andB-lymphocytes.

T-helper cells

T-killer cells

Figure 11.4 T-lymphocyte response to antigen.

the inected cell by secreting chemicals such as

hydrogen peroxide. The T-killer cells are our main

deence against viral diseases.

We have seen that T-lymphocytes, likeB-lymphocytes, divide to orm clones when they

meet their own particular antigen (Figure 11.5).

While most o these cells act as helper cells or

killer cells, some o them remain in the blood as

memory cells. These, like the memory cells ormed

rom B-lymphocytes, help the body to respond

more quickly and eectively i this same antigen

ever invades again.

SAQ

1 With reerence to the way in which they respond

to antigens, suggest why T-lymphocytes are

more eective than B-lymphocytes in dealing

with inection by a virus.

SAQ

2 Match each o these words with its denition

below.

antibody,antigen, pathogen, parasite,

B-lymphocyte, neutrophil, macrophage

a a type o white blood cell that divides

to produce plasma cells, which secrete

antibodies

b a phagocytic white blood cell with a

multilobed nucleus and granular cytoplasm

c a molecule that is recognised by lymphocytes

as being oreign to the body

d an organism that lives in close association

with a host, and does it harm.

e a microorganism that causes disease

a glycoprotein secreted by some white blood

cells, which binds to specic antigens

g a phagocytic white blood cell that is

relatively large, and which tends to be ound

in tissues such as the lungs, rather than in

the blood

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Specic bindingB-lymphocyte with antibodyin its plasma membranebinds to complementaryantigen.

antigen

Antigen presentationAn APC (macrophage)ingests, processes andpresents antigen.

Clonal selection and prolierationStimulated B-lymphocyte dividesmany times.

Specic bindingT-helper lymphocyte orT-killer lymphocyte binds tocomplementary antigen onan APC.

Memory cellsThese survive ora long time.

Plasma cellsThese secrete largeamounts o antibody.

T-killer lymphocytesThese bind to cellspresenting thecomplementary antigen.

T-helper lymphocytesThese secrete cytokineswhich stimulatephagocytic cells andother lymphocytes.

I antigen appears later,the memory cells arestimulated, divide andproduce many plasmacells very quickly.

T-killer cells bindto cells presentingthe complementaryantigen and kill them.

cell killed

Clonal selection andprolierationOne clone is stimulatedand this T-lymphocytedivides many times.

Figure 11.5 Summary o B-lymphocyte and T-lymphocyte actions.

B-cells T-cells

either

memorycells

memorycells

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228

Complement

Complement is a collection o small proteins (more

than 25 dierent ones) that are always present

in the blood plasma. It was rst discovered in

1895, and was given this name because it helps,

3 To answer this question, you will need to think

back to your work on cells.

Anexperiment was carried out to ollow what

happens inside plasma cells as they make and

secrete antibodies. Some cells were cultured in

a solution containing amino acids which had

been labelled with a radioactive marker. The

radioactivity in the Golgi body, endoplasmic

reticulum and ribosomes was then measured

over the next 40 minutes. The results are shown

in the graph.

SAQ

a In which order did the amino acids move

through the three organelles? Use the results

shown in the graph to justiy your answer.

b Using your own knowledge, describe what

happened to the amino acids in each organelle.

c Suggest why the peak values or the

radioactivity in the ribosomes and the

endoplasmic reticulum are the same, whereas

the peak value or the Golgi body is lower.

(There may be more than one possibility.)

d Suggest how the amino acids would have been

taken up into the cell at the beginning o the

experiment.e Describe how the antibody molecules would

be secreted rom the cell.

or complements, the activity o antibodies and

phagocytes. Complement is very important in

ghting bacterial inections.

Many o the proteins that make up complement

are precursors o enzymes. When a piece o their

molecule is removed, they become active. Once one

o them has been activated in this way, it acts as a

catalyst or the activation o another complement

protein. This becomes a cascade process, in which

one small action (whatever activates the rst

protein) ends up having a very large eect on a

large number o protein molecules (Figure 11.6).

There is more than one way in which the cascade

can be initiated. Firstly, when an antibody binds

to an antigen, one o the complement proteins can

bind to the antibody. This changes the shape o the

complement protein, activating it and setting othe cascade. Alternatively, a dierent complement

protein can bind directly with a pathogen (or any

other non-sel surace). Once again, this changes

its shape and starts o the cascade. The result

o either o these events is the production o

various proteins that can help to destroy invading

microorganisms. There are three ways in which

they do this.

Opsonisation Some o the proteins produced

when the complement cascade is activated bind

to the surace o bacteria, coating them witha layer o protein called opsonin. Phagocytic

cells have receptors which bind to opsonin, and

this stimulates them to engul and destroy the

coated bacterium.

Attracting macrophages and other cells tothe site o inection Some o the newly

produced complement proteins drit away rom

the place where they were ormed, into the

tissue uid and blood. Their presence attracts

phagocytes and other white blood cells, which

move towards the site. (Cell movement in the

direction o a chemical stimulus is an example

o chemotaxis.) This is important in the

inammatory response.

Destroying oreign cells A third kind o

complement protein directly destroys the cells

that stimulated its production, by making holes

in their plasma membranes.

30

cisternae oendoplasmicreticulum

Golgi body

ribosomes

Time / minutes

Radioactivity/arbitrar

yunits

0 10 20 30 400

10

20

40

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The infammatory response

I a pathogen gets into a particular area o your

body and begins to multiply, it is no use having

your phagocytes and lymphocytes spread all over

the body you need them to be concentrated in the

danger area. The process that brings this about is

called the infammatory response, and it results in

inammation (Figure 11.7).Imagine, or example, that a thorn has

penetrated deep under your skin. Bacteria on the

thorn begin to multiply. The presence o antigens

on the bacteria, and your own damaged tissues,

activate the complement system. Chemicals are

released that increase the blood supply to the area

and make the capillaries more permeable. This

brings more phagocytes and lymphocytes to the

inected tissues. Phagocytes are attracted to the

area by the chemicals, and they crawl out o the

blood into the inected tissues.

The extra blood supply makes the area look red,

and the leakage o uid rom the blood makes it

swollen. I all goes well, your body will win the

battle against the pathogens, and the swelling and

redness will subside as the inection is brought

under control. Sometimes, a thick white mixture o

dead bacteria, lymphocytes and phagocytes builds

up, known as pus.

Figure 11.6 Complement.

Mast cells

Mast cells are cells that are ound in all tissues,

generally lying close to the walls o blood vessels

and nerves. Their cytoplasm is packed ull o

granules (Figure 11.8), which contain numerous

chemicals, especially histamine and heparin.

We know a lot about mast cells because they are

very much involved in allergies and auto-immunediseases. Both o these result rom the immune

system behaving inappropriately, causing illness.

However, it is also thought that mast cells do

have a useul role to play, probably in helping the

immune system to ght intestinal worms and other

parasites.

Mast cells must be activated beore they begin to

do anything. There are three main ways in which

this happens.

They may respond directly to injury. This could

be physical, or it could be caused by toxic

chemicals such as alcohol.

The membranes o mast cells have receptorsthat bind tightly to a type o antibody called

IgE, so each mast cell is completely coated

with IgE molecules. I the protein that ts

into the IgE molecule binds with them, the

IgE molecules become linked together, and

this activates the mast cell. Unortunately, this

Complement is a group o short-lived soluble proteinsalways present in blood plasma. Complement is activatedby contact with antibody bound to antigen, or with aoreign surace. Activation o complement triggers acascade which results in the production o active proteins. Opsonins coat a oreign

cell which encouragesphagocytosis.

a complementprotein

Phagocytes areattracted to thearea by activecomplement protein.

The active proteins help destroy oreign cells.

activation

inactive enzyme

inactive enzyme

inactivecomplementprotein

activecomplementprotein

active enzyme

active enzyme

Foreign cells aredestroyed by activecomplement protein.

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230

oten happens not in response to a potentially

dangerous pathogen, but to a harmless antigen

such as a protein in the surace o a pollen

grain, or on a cell in a peanut. These substancesthat should be harmless, but that act as antigens

and bring about a strong and inappropriate

immune response, are known as allergens.

Activated complement proteins can also activate

mast cells.

An activated mast cell releases the contents o

its granules. These include histamine and several

cytokines. These cause an acute inammatory

reaction, in which blood vessels dilate, smooth

muscle in airways contracts, rashes appear on the

skin and tissues swell as uid accumulates in them.

In a severe allergic reaction, mast cells all over

the body release their contents at the same time,

causing a massive inammatory response that can

be lie-threatening.

Several diseases are the result o a misdirected

attack o the immune system on a persons own

tissues, and these are known as auto-immune

diseases. Mast cells are known to play a major part

Figure 11.7 Inammation.

Figure 11.8 A coloured electronmicrograph o a

mast cell (12 000).

Clotting and immune responses are activated.

In an infammation, blood supply to an injured or inected areais increased. Capillaries in the area become more permeableallowing more chemicals to leave the blood plasma and enterthe area. White blood cells crawl out o the capillaries bychemotaxis.

tissue damaged by a cut

Tissue damage andthe presence oantigens rom bacteria,or example, act as astimulus.

There is greater leakageo plasma containingsoluble substances e.g.complement, clottingactors, antibodies.

infammation

Activities taking place at the site oinjury may include: blood clotting,antibody-antigen interaction,phagocytosis and killing opathogens.

White blood cells are attractedto the area and leave throughholes in the capillary wall.capillary

Arterioles supplying capillariesdilate, increasing blood fowinto capillaries. This causes thecapillaries to dilate.

vesicles (granules)that contain histamine

mitochondrianucleus

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in many o these, including rheumatoid arthritis

(in which the joints become inamed) and multiple

sclerosis (in which the myelin sheaths o neurones

are destroyed). Despite much research, there is

still no clear picture o what causes these diseases

to develop. There does seem to be some genetic

component, because auto-immune diseases may

have a tendency to run in amilies. However, there

is also an environmental component, because the

development o an auto-immune disease oten

seems to ollow inection by a virus.

Humoral and cell-mediated responses

Early studies o the immune system suggested

that the body had two dierent ways o attacking

pathogens. One involved cells the phagocytes and

T-lymphocytes and was called the cell-mediatedresponse. The other involved chemicals, especially

antibodies produced by B-lymphocytes, and was

called the humoral response. It is now known

that, in reality, there are constant and complex

interactions between cells and chemicals, as you

will have appreciated rom what you have read

earlier in this chapter.

HIV/AIDS and the immune system

The human immunodeciency virus inects a

particular group o T-helper cells called CD4+cells, and also some types o macrophages. In the

disease AIDS, the presence o the virus causes

a reduction in the numbers o CD4+ cells. This

can be because the virus itsel destroys the cell as

it reproduces inside it and bursts out rom it; or

because other T-lymphocytes recognise that the

CD4+ cell is inected, and attack and destroy it.

The reduction in numbers o the CD4+ cells

greatly weakens the ability o the immune system

to respond to inection, and it is this that causes

the symptoms o AIDS.

AntibodiesAntibodies are glycoproteins. Their molecules

contain chains o amino acids, and also sugar

units. Figure 11.9 shows the structure o an

antibody molecule.

Antibodies are also known as immunoglobulins.

There are several dierent kinds o them, given

names such as IgG and IgA.

Each antibody contains a variable region that

can bind specically with a particular antigen. We

have millions o dierent antibodies with dierent

variable regions. The particular part o the antigen

that is recognised by the immune system, and to

which the antibody attaches, is called an epitope.

When an antibody molecule meets its specicantigen, it binds with it. The eect that this has

depends on what the antigen is, and on what type

o immunoglobulin has bound to it.

Some antibodies directly neutralise the antigen

or example, by binding with a toxin produced

by a bacterium. Others may encourage phagocytes

to destroy the pathogen, sometimes by making the

pathogens clump together. Yet others may stop

pathogens getting a oothold on body suraces, by

preventing them rom attaching to cells or tissues

(Figure 11.10 and Figure 11.11).

How immunity developsWhen a pathogen rst enters the body, there will be

only a ew lymphocytes with receptors that t into

its antigens. It takes time or these lymphocytes

to encounter and bind with these pathogens. It

takes more time or them to divide to orm clones,

and or the B-lymphocytes to secrete enough

polypeptides

polysaccharidechains

heavy chain

disulphidelinks

lightchain

Figure 11.9 The structure o an antibodymolecule.

hingeregion

epitope

constantregion

variableregion

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232

antibodies to destroy the pathogens, or or enough

T-lymphocytes to be produced to be able to

destroy all the cells that are inected by them.

During this delay, the pathogens have the

opportunity to divide repeatedly, orming large

populations in the body tissues. The damage that

they cause, and toxins that they may release, can

make the person ill. It may be several days, or even

weeks, beore the lymphocytes get on top o the

pathogen population and destroy it.

However, i the body survives this initial attack

by the pathogen, memory cells will remain in the

blood long ater the pathogen has been destroyed.

I the same pathogen invades again, these memory

cells can mount a much aster and more eectiveresponse. More antibodies can be produced more

quickly, usually destroying the pathogen beore it

has caused any illness.

The response to the rst invasion o the

pathogen is called the primary response

(Figure 11.12). Subsequent invasions generate a

secondary response. You can see that the secondary

response happens more quickly, and produces

many more antibodies. This is why we usually

become immune to a disease i we have had it once.

Active and passive immunity

The kind o immunity described on the previous

pages is a type oactive immunity. The immune

system has been stimulated to make a particular

type o antibody, and can produce this same one

more quickly and in larger quantity i it is exposed

to the same pathogen again. The immunity has

developed naturally, so it is a type onatural

immunity.

Another way in which active immunity can

develop is by vaccination. This involves injecting

the antigen into the body (page 224). It may, or

example, be in the orm o viruses that have been

made harmless, or as an inactivated toxin rom a

bacterium. The body responds in the same way

as it would i invaded by the living pathogen,

producing memory cells which will make the

person immune to the disease i they should

ever encounter it. This way o acquiring active

Figure 11.10 How antibodies neutralise bacteria and bacterial toxins.

antibody

Toxins releasedby pathogens canbe neutralised byantibodies.

An antibody can neutralise abacterium i the antibody bindsto a chemical necessary orpathogenicity.

Antigen binding

stimulates phagocyticwhite cells to ingest andkill the bacterium.

pathogenicbacteria

toxin producedby bacteria

Figure 11.11 How antibodies agglutinate

bacteria.

antibody with severalsites that can bind toantigen

The antibody makes the bacteriaclump together (agglutinate).

Agglutinated bacteria don't movearound as much and are morereadily ingested by phagocyticwhite cells.

pathogenicbacterium withantigens on its surace

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immunity is not natural, so it is a orm oarticial

immunity (Figure 11.13).

A young babys immune system takes time

to develop. In the uterus, the oetus obtains

antibodies rom the mothers blood, across the

placenta. Ater birth, the baby will continue to

receive them in the mothers milk, i she decides

to breasteed. These ready-made antibodies help

the baby to ght o pathogens. The baby has

immunity to the same diseases as the mother.Because the babys body has received ready-made

antibodies, rather than making them itsel, this

is said to be passive immunity. It has happened

naturally, so it is an example o natural immunity

too.

Passive immunity can also be provided by

injections. This is not a natural way o gaining

immunity, so it is another example o articial

immunity. For example, i someone goes to the

emergency department o a hospital with a cut that

may have dirt in it, they may need to be protected

against the bacterium that causes tetanus,

Clostridium tetani. It is too late or a vaccination,because by the time the persons immune system

responds, the bacterium could have multiplied

and caused the atal illness tetanus. Instead, the

Concentrationofantibo

dyintheblood

Concentrationofantibo

dyintheblood

Primary response Secondary response

0 1 2 0 1 2 3Time / weeks Time / weeks

weeks oryears later

inection inection

Figure 11.12 Primary and secondary responses to antigen.

Figure 11.13 Active and passive immunity.

Active immunityImmunity developed ater contactingpathogens inside the body.

Articialinjection o live orattenuated pathogen

Naturalinection

Passive immunityImmunity provided by antibodies orantitoxins provided rom outside the body.

Naturalantibodies rom amother in breast milkor across the placenta

Articialinjection o antibodiesor antitoxin

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234

person will be given an injection o antitoxin. The

antitoxin will bind to the toxin produced by the

bacteria, rendering it harmless. Antitoxins can also

be given in this way to destroy toxins introduced

into the body through bites rom poisonous

animals, such as spiders or snakes.

Passive immunity does not last as long as active

immunity. No lymphocytes have been stimulated

to make clones o themselves, so no memory cells

have been ormed. Passive immunity lasts only as

long as the antibodies or antitoxins last. The body

actually sees them as being oreign, and they will

be removed and destroyed quite quickly by cells in

the liver and spleen.

Vaccination

Vaccination is an excellent way o preventing aperson rom acquiring an inectious disease. The

larger the proportion o people who are vaccinated

in a population, the lower the chance that anyone

even those who have not been vaccinated will get

that disease. This is called herd immunity. For most

diseases, at least 8085% o the population need to

be vaccinated to achieve herd immunity.

Vaccination involves giving a person a dose o

a preparation that will cause the immune system

to react as though an antigen rom a pathogenic

organism has entered the body. Most vaccinationsare given by injection, but the polio vaccine

is given by mouth. Many vaccines contain an

attenuated (weakened) orm o the bacterium or

virus that causes the disease, while others contain a

modied toxin produced by them.

When the vaccine enters the body, lymphocytes

that recognise the antigen respond to it as i

they had encountered live bacteria or viruses.

They orm clones o plasma cells, which secrete

antibodies, and also memory cells. In most cases, a

second booster dose o the vaccine is given later

on. This raises the antibody level much higher than

the rst dose, and helps to ensure that protection

against the antigen lasts or some time (Figure

11.14).

Monoclonal antibodiesWe have seen that there is a huge number o

dierent antibodies that can be made by humanB-lymphocytes, and that each lymphocyte can

make only one kind. In the 1970s, researchers

wanted to be able to obtain large amounts o one

particular antibody at a time, so that they could

study it without intererence rom all the other

antibodies that are usually present in a mammals

blood. Their aim was to produce a large clone o

a particular type o B plasma cell, all secreting

identical antibodies, known as monoclonal

antibodies.

There is one problem in achieving this B-lymphocytes that divide to orm clones o

plasma cells do not secrete antibodies, and plasma

Figure 11.14 Antibody levels ater vaccination.

rst vaccination

booster vaccinationa ew weeks later

Levelofantibody

protective level

booster vaccination at somepoint in the uture

Time / months Time0 2 4 6 8

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Figure 11.15 Monoclonal antibody production.

cells that secrete antibodies do not divide. In 1975,

a technique was developed to get around this

problem (Figure 11.15). B-lymphocytes were used

with cancer cells, which unlike other body cells

go on dividing indenitely. The product o this

usion is called a hybridoma cell. The hybridoma

divides repeatedly to orm a clone o cells that

secrete monoclonal antibodies.

When this technique was rst invented, no-

one really knew what uses might be made o it.

Since then, many applications have been ound

or monoclonal antibodies, both in research and

in various areas such as medical diagnosis and

treatment. Their uses derive rom the act that

any particular monoclonal antibody binds very

specically to a particular molecule.

Using monoclonal antibodies or

diagnosis

Monoclonal antibodies can be used to help to

diagnose a particular condition, or to nd out

where particular types o cells are present in

the body.

Monoclonal antibodies can be used to locate

places where blood clots have ormed in the body

o a person suspected o suering rom deep-vein

thrombosis (a blood clot in a vein, oten in the

leg). First, a mouse is injected with human brin,a protein ound in blood clots. The brin acts as

an antigen in the mouse. Mouse B-lymphocytes

with the antibody or human brin prolierate,

especially in the spleen. Ater a month or so,

the spleen contains large quantities o these

lymphocytes.

The mouse spleen cells are then mixed with

cancer cells to orm hybridomas, which are

checked to see which antibody they secrete.

Hybridomas secreting the anti-brin antibody are

selected and cultured in a ermenter, so that large

amounts o the antibody are made. The antibody

can be labelled by attaching it to a radioactive

chemical that produces gamma radiation.

The labelled antibodies are then introduced into

the patients blood. As they are carried around

the body in the blood stream, they bind to brin

molecules. A gamma camera can be used to detect

the position o the antibodies, an thereore o any

blood clots, in the patients body.

A very dierent diagnostic application is in

testing or pregnancy. Any couple who are trying

or a baby will want to know as soon as possible

i the woman has become pregnant. There are

now many dierent pregnancy testing kits on

the market which can be used at home. Most o

them use monoclonal antibodies to test or the

presence o a hormone called human chorionic

gonadotrophin (HCG) in her urine. This hormone

is only secreted during pregnancy.

Monoclonal antibodies are made, using mouse

lymphocytes, that will bind specically with HCG.

In one type o pregnancy-testing kit, these HCG-

specic antibodies are bound to atoms o gold.

The antibodygold complexes are then used to

coat the end o a dipstick (Figure 11.16). Anothertype o monoclonal antibody is also made, which

antigen injection

spleen cells cancer cells

mixed andtreated to causecell usion

hybridoma cells

Tiny samples are taken so thatonly one cell is present in awell. The wells are tested tond a hybridoma cell producingthe required antibody.

The hybridoma cell which produces the requiredantibody is allowed to divide and produce a clone.These cells can be cultured in ermenters, wherethey will secrete monoclonal antibody.

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236

will specically bind with HCGantibodygold

complexes. These antibodies are impregnated into

a region urther up the dipstick, called the Patient

Test Result region.

To use the dipstick, it is dipped into a urine

sample. Any HCG in the urine will bind to the

antibodies at the end o the stick, which will be

carried upwards as the urine seeps up the stick.

As the HCGantibodygold complexes reach the

test result region o the stick, they bind with the

antibodies there and are held rmly in position.

As more and more gold atoms arrive there, a

pink colour (or another colour, dependent on the

brand) builds up.

The stick also contains an area called the

Procedural Control Region, which contains yet

another type o immobilised monoclonal antibody.

These are rom goats, and they are anti-mouse

antibodies. They bind with the antibodygold

complexes even i these have not encountered any

HCG in the urine sample. This strip thereore goes

pink even i the test result is negative.

Other uses are or producing reagents used

to determine a persons blood group, the

identication and location o some types o cancer

and ollowing the progression o an HIV inection.

Procedural ControlRegion (antibodiesspecic to theantibodies at theend o the stick)

antibodies specic toHCG bound to gold

Patient Test Region(immobilised antibodyspecic to HCG)

1 The stick is dippedinto urine to the line.

2 HCG-specicantibodies bound togold are carried up.I there is any HCGpresent, it binds to theantibodies and is alsocarried up.

3 I the stick is working, apink line always appearsin the Procedural ControlRegion HCG-specicantibody bound to goldis carried upwards andcaptured by antibodyspecic to it, which wasimmobilised here.

The design o the dipstick How the pregnancy dipstick works

4 I the urine contains HCG,it binds to the HCG-specicantibody and gold at the endo the dipstick and is carriedupwards. When this meetsimmobilised HCG-specicantibody, it is bound and a pinkline appears. This shows theperson is pregnant.

Figure 11.16 How one type o pregnancy-testing kit works.

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Using monoclonal antibodies or

treatmentThe anticancer drug MabThera is a monoclonal

antibody. MabThera is a trade name or the drug

rituximab.

Rituximab is a monoclonal antibody that binds

to a protein called CD20. This protein is ound

only on the surace o B-lymphocytes. When

rituximab binds to these lymphocytes, it destroys

them, although the exact mechanism by which it

does this is not yet understood.

SAQ

4 Suggest the purpose o the Procedural Control

Region on the pregnancy test dip stick.

Rituximab is used to treat a cancer called

non-Hodgkin lymphoma, in which it is the

B-lymphocytes that are the cancerous cells,

dividing out o control and producing very large

numbers in the body. They orm tumours in the

lymph nodes. The drug kills both the abnormal

(cancerous) B-lymphocytes and also any normal

ones, because all o them have CD20 on their

suraces. However, the body continues to produce

new B-lymphocytes which are usually normal,

rather than cancerous, ones.

Rituximab is also used to treat some

auto-immune diseases in which overactive

B-lymphocytes are implicated, such as rheumatoid

arthritis.

Summary

The bodys immune system responds to the presence o non-sel cells or molecules by attacking theoreign material. This is done by various white blood cells (leucocytes), including phagocytes and

lymphocytes. This response is called the immune response. A molecule that initiates an immune

response is called an antigen.

Phagocytes are mobile cells that are ound in almost all parts o the body. They engul and digestoreign cells or other materials. They include neutrophils and macrophages. Phagocytes oten act as

antigen-presenting cells, placing antigens rom the oreign cells they have enguled in their plasma

membranes, where other cells o the immune system may come into contact with them.

Lymphocytes are cells that exist in many dierent varieties. Unlike phagocytes, each individuallymphocyte is able to respond only to one particular antigen.

When a B-lymphocyte meets its specic antigen, it responds by dividing to orm a clone ogenetically identical plasma cells. These all secrete antibodies that bind to the antigen.

When a T-lymphocyte meets its specic antigen on the surace o an antigen-presenting cell, itresponds by dividing to orm a clone o T-helper cells or T-killer cells. T-helper cells bind to the

antigen and secrete cytokines, which stimulate other cells to attack the antigen. T-killer cells also

bind to the antigen, and then destroy the cell on which the antigen is present.

Both B-lymphocytes and T-lymphocytes also orm clones o memory cells, which remain in the body

and are able to mount a rapid attack i the same antigen invades the body again.

The blood plasma contains numerous small protein molecules which together orm complement.When antigens are present in the body, the complement system is activated. The shape o one o

the proteins is altered, causing it to become active as an enzyme and remove part o the molecule o

another o the complement proteins. This activates the second protein, and so on down the chain,

eventually producing large quantities o proteins that help to destroy invading pathogens.

continued ...

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238

Mast cells contain granules o substances such as heparin and histamine. When activated, theyrelease their granules and this causes inammation to occur. The inammatory response involves

the dilation o blood vessels, bringing more lymphocytes and phagocytes to the area. Although mast

cells may have a useul role to play, they are involved in inappropriate immune responses to harmless

substances, called allergens. They are also involved in some auto-immune diseases.

HIV invades a particular type o T-lymphocyte called CD4+ cells. This eventually destroys these cells,

weakening the immune system and allowing other pathogens to prolierate in the body.

Antibodies are glycoproteins. They are also known as immunoglobulins. Most o them are Y-shapedmolecules, with binding sites or specic antigens at the tips o the Y.

Active immunity develops when a persons body has responded to the presence o an antigen, and

has produced a clone o memory cells that can react promptly i the same antigen invades again.

This can be achieved through natural exposure to the antigen (natural active immunity) or through

vaccination (articial active immunity).

Passive immunity develops when antibodies rom elsewhere are introduced into the body. Babies

acquire antibodies rom their mother through the placenta and in breast milk (natural passive

immunity). Antibodies may also be injected into the body (articial passive immunity). Passive

immunity does not last as long as active immunity, because there are no memory cells involved.

Monoclonal antibodies are identical antibodies produced rom a clone o hybridoma cells. These are

produced by using a lymphocyte with a cancer cell. Monoclonal antibodies can be used in diagnosis

(e.g. in pregnancy tests) or in the treatment o diseases (e.g. MabThera or the treatment o non-

Hodgkin lymphoma and rheumatoid arthritis).

Questions

Multiple choice questions

1 The ollowing are the steps involved in the process o phagocytosis o a bacterium by a macrophage.

I recognition and attachment o bacterium to the phagocyte

II attraction o the bacterium and movement o the phagocyte by chemotaxis

III intracellular killing and digestion o bacterium

IV egestion o epitopes and antigen presentation

V usion o lysosome with a vesicle produced by endocytosis (phagosome)

VI engulment o the bacterium by phagocyte

Which o the ollowing shows the correct sequence o the process o phagocytosis?

A III III IVVVI

B IIIII I IVVVI

C IVII IIIIVIV

D IIIVIV III IV

continued ...

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continued ...

2 An immune response is best dened as:

A a deensive reaction by the immune system.

B a bodily deence reaction which recognises an invading substance and produces a range o

cellular and chemical agents directed at the substance.

C a reaction which recognises an invading substance.

D the bodys reaction to inection.

3 The diagram shows the origin and maturation o B and T-lymphocytes.

Which o the ollowing correctly identies cells I, II, III and IV?

I II III IV

A T-cells B-cells plasma cells memory cells

B plasma cells memory cells B-cells T-cells

C B-cells T-cells plasma cells memory cells

D memory cells plasma cells B-cells T-cells

4 Which o the ollowing parts o statements are correct about cell-mediated and

humoral immunity?

Cell-mediated Humoral

A involves T-killer cells involves B-cells

B involves B-cells involves T-killer cells

C produces antibodies produces antibodies

D does not involve cell-to-cell interaction involves cell-to-cell interaction

bone marrowstem cell

lymphoid

precursor cell

matures in bone marrowmatures in thymus

I

II III IV

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240

continued ...

5 Why is passive immunity eective or only a short time?

A Memory cells are produced.

B Antibodies are broken down rapidly.

C Antigens enter the body.

D Plasma cells are stimulated.

6 Students in a class were exposed to the chicken pox virus by an inected student. What type o

immunity would the students obtain i they also became inected?

A articial active immunity

B articial passive immunity

C natural active immunity

D natural passive immunity

7 Which o the ollowing is not true about antibodies? They:

A neutralise toxins.

B bind to specic antigens.

C activate the complement system.

D are eective only when attached to the T-cells.

8 Immune responses may be specic or non-specic. Which response is a specic immune response?

A capillaries becoming leaky

B phagocytosis

C release o histamines

D production o memory cells

9 Any o the highly specic antibodies produced in large quantity by the clones o a single hybrid cell

ormed in the laboratory by the usion o a B cell with a tumour cell are known as:

A IgG antibodies.

B monoclonal antibodies.

C IgM antibodies.D IgA antibodies.

10 Monoclonal antibodies are used in all o the ollowing except: A blood typing or transusions.B the identication o the location o some types o cancer.

C the stimulation o the immune system.

D ollowing the progression o HIV inection.

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continued ...

11 a i What do you understand by the term non-specic immunity? [1 mark]

ii Give two examples o non-specic immunity. [2 marks]

b The diagram below shows the events occurring during a non-specic response.

Structured questions

i Name the substance produced by the mast cell. [1 mark]ii What are the unctions o the substance identied in b i? [2 marks]

iii Identiy cells 1, 2 and 3. [2 marks]

iv Explain the role o the complement system in non-specic immunity. [3 marks]

v I the inection lasts or a while the specic immune system is stimulated.

What do you understand by the term specic immunity? [1 mark]

vi Explain the role o cell 3 in stimulating the specic immune system. [3 marks]

bacteria in cut skin

capillary

mast cell

cell 1

cell 2

cell 3

producessubstance

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242

continued ...

12 The diagram below shows the structure o an antibody.

a Name the type o cell that produces antibodies. [1 mark]

b Copy the diagram above and label the ollowing parts o an antibody:

binding site, variable region, constant region, disulphide bonds, light chain,heavy chain, hinge region [3 marks]

c State one unction or each o the ollowing parts: hinge region and disulphide bonds. [2 marks]

d Explain why a variable region is necessary in the structure o the molecule. [1 mark]

e Vaccines contain the antigens o pathogens. There are two types o polio vaccine.

The Salk vaccine contains dead viral particles while the Sabin vaccine is made o a live

attenuated polio virus. The Sabin vaccine replaced the Salk vaccine.

i What do you understand by the term antigen? [1 mark]

ii State one advantage o using living attenuated viruses to make a vaccine. [2 marks]

The graph below shows the concentration o antibody in the blood o a baby ater the

rst oral vaccine and booster shot or polio.

0 10 20 30 40

Time / days

Concentrationofantibodyinblood

rst oralvaccine

second oralvaccine

primaryresponse

secondaryresponse

delay0 10 20 30 40

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i Why is there a delay between the time o the rst oral vaccine and the rst

appearance o antibodies in the blood? [2 marks]

ii State two ways in which the immune systems primary response diers rom the

secondary response. [2 marks]

iii Explain the dierences shown between the primary and secondary responses. [2 marks]

13 a Distinguish between:

i natural and articial immunity

ii active and passive immunity. [4 marks]

b Copy and complete the table below to indicate the type o immunity attained in

each case.

Example Type o immunity

baby eeding on breast milk

child exposed to a riend with chicken pox

receiving the MMR vaccine as a child

receiving the H1N1 vaccine as an adult

getting an emergency tetanus injection ater

stepping on a rusty nail

[5 marks]

c Describe how an eective vaccine can provide long-term immunity. [4 marks]

d Explain how passive immunity provides protection to a person who has been

bitten by a snake. [2 marks]

Essay questions

14 a Describe the mode o action o phagocytes. [3 marks]

b Dene the term immune response. [2 marks]c i Describe the origin and maturation o T-lymphocytes. [2 marks]

ii Describe the changes that occur to T-lymphocytes during an immune response. [3 marks]

d i Describe how B-lymphocytes are involved in the immune response. [3 marks]

ii Describe the importance o B memory cells in immunity. [2 marks]

15 a i Dene the term antibody. [1 mark]

ii Make an annotated schematic drawing o an antibody molecule. [4 marks]

iii Describe how an antibody acts on bacteria. [2 marks]

b i What are monoclonal antibodies? [2 marks]

ii Monoclonal antibodies are used or diagnosis and treatment. Identiy two examples

o each use. [2 marks]

iii Describe the use o monoclonal antibodies in pregnancy kits. [4 marks]

16 a Distinguish between humoral and cell-mediated immunity. [3 marks]

b Draw a ow diagram to illustrate the stages o the immune response to an

invading pathogen. [7 marks]

c Explain what is meant by clonal selection and clonal expansion. [5 marks]

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