Faculty of Health and Life Sciences

School of Allied Health Sciences

Module Handbook
BIOM 2004
Inflammation and
Immunobiology
for Biomedical Science
BIOM 2904
Studies in Inflammation and
Immunobiology for Biomedical
Science

Name of Student
Student E-mail address

CONTENTS
Welcome to
BIOM2004/2904
...3
1. Introduction to the
Module
...3
1.1. Module
characteristics
..3
1.2. Contact details of
staff
5
2. Module specific
information
.6
2.1. Learning
outcomes
.6
2.2. Hand-in
dates
.7
2.3. Module
calendar
...8
2.4. Marking
system
..9
2.5. Late submission of assignments.
..13
3. Referencing
guide
.14
3.1. Guide to Turnitin and the Virtual Learning
Environment..14
3. 2. WHERE TO START YOUR FIRST HOMEWORK!
.................16
3.3. Textbooks..
...16
3.4. Websites and
journals
..17
3

4. Student feedback from previous

years...17
Appendix 1. Safety
declaration.......................
........18
Appendix 2. Learning material for your
start19

WELCOME TO BIOM2004/2904
Welcome to the BIOM2004/2904 Inflammation and Immunobiology
module which will introduce you to our immune system and how it
battles to repair our body and protect it from the attack of
threatening external invaders!
Throughout the module, together we will delve into the world of
systems and molecules, looking at the mechanisms used to
maintain human defenses and combat diseases. The course will give
a detailed account of the individual components of the immune
system and how they interact, and the mechanisms involved in the
aethiology and treatment of disease states in autoimmunity,
hypersensitivity, immunodeficiency and malignancy. Your studies of
these areas will also extend into the final year of the degree
programme as BIOM3003/3903 Immunopathology module.

Using this opportunity I would like to wish you to get fascinated with
this subject and develop an in-depth understanding of how the body
recognises and responds to self, as well foreign agents. Be
enthusiastic, creative, curious and positive during your studies, be
enlightened and enlighten your colleagues,
Have a great time!
Dr Ruta Furmonaviciene
Programme Leader for BSc. (Hons) Biomedical Science
Senior Lecturer in Biomedical Sciences / Immunology
BIOM2004/2904 Module Leader

1. INTRODUCTION TO THE MODULE

1.1. MODULE CHARACTERISTICS
This module introduces learners to basic immunolobiology and
inflammatory processes, preparing them for the study of
immunopathology during the Sandwich Placement Year (if this
discpline is chosen) and at Level 3. Inflammatory mechanisms,
humoral and cellular immune responses and the development of the
immune system are all addressed.
The major topic areas to be covered include:
Structure and function of the immune system
Cellular and humoral components of the immune system
Antigen and antibody interactions
Tolerance and immunological memory
Immunity of aging
Within each topic area you will be expected to demonstrate that you
can:
Identify and define the component parts of that topic.
Identify the basic immunological mechanisms associated with the
topic area,
Relate component parts of the topic to information delivered in
other modules.
Associate the topic area with named examples of immunological
processes and clinical laboratory practice.
Undertake comparative discussion of the components in the topic
area, with illustrative examples.
Show further reading, at a primary source level.
5

Lecture handouts may be provided at the discretion of the

Lecturer: if so, will be given out at the lecture and will
supplement and not replace the Reading List.
Practicals for BIOM2004 are designed as a sequence of the following
laboratory based sessions:
Practical No 1 Bradford Assay And Size Exclusion Chromatography
Practical No 2 ELISA Immuno Explorer
Detailed instructions as well as supplementary learning
material for the practicals can be found on the Blackboard.
At the end of your practical, you will submit your results in the form
of a laboratory report. The laboratory reports will be presented in a
formal style, with introduction, materials and methods, results,
discussion and conclusion. A reference list and full citation must be
made. The Introduction should discuss the case to a point that
fully explains the rationale for the laboratory investigation. The lists
of laboratory materials represent those materials that will be made
available to you in the laboratory. The Materials and methods of
your report should, with a reasoned series of statements outlining
the rationale and explaining the principles, present a full set of
standard operating procedures and the available materials. The
Results section should contain a full annotation of the data
obtained and the analysis and assessment of that data. The results
should be clearly presented and their significance outlined. The
Discussion should be based on your results, their full interpretation
and their link with your lecture themes. Your discussion should be
based on primary literature sources.

1.2. CONTACT DETAILS OF STAFF

The staff members will very much appreciate if all your
queries related to the module could be directed to the
module leader in the first instance.

Dr Ruta Furmonaviciene (Module Leader)

Senior Lecturer in Biomedical Sciences / Immunology,
Hawthorn building, Room H 1.18
e-mail: rfurmonaviciene@dmu.ac.uk

Dr Umakhanth Venkatraman Girija

Lecturer in Biomedical Science / Immunology
Hawthorn building, Room H 1.10
e-mail: umakhanth.venkatramangirija@dmu.ac.uk

Dr Carika Weldon
PT Lecturer in Biomedical Sciences
e-mail: Carika.Weldon@dmu.ac.uk

2. MODULE SPECIFIC INFORMATION

2.1. LEARNING OUTCOMESFor BIOM2004 Inflammation

and Immunobiology: 1 To describe basic aspects of

immunology and inflammation at the molecular and systemic
level.2 - To execute simple laboratory techniques
addressing immune function.3 -To describe and evaluate
experimental results clearly and concisely.4 - To present
the above in the form of essays, laboratory reports and oral
presentations.For BIOM2904 Studies in Inflammation and
Immunobiology:

1To describe basic aspects of immunology and inflammation at

the molecular and systemic level.
2To present the above in the form of essays and oral
presentations.

Full-time students are expected to attend two

practical sessions, tutorial session
lecture sessions!

and all

Studies students are expected to attend one of

the
practicals (please contact module leader for
more
information)!

IVP and IC students are expected to attend

lecture sessions only!

2.2.ASSESSMENTS AND HAND-IN DATES

Assessments for Full-time students:

Practical 1 (in-class report) Week 5
8

Practical 2 (in-class report) Weeks 16-18

(depending on your group)
Essay (computer Lab assignment) - Week 9
tutorial session
Formative assessments (short answers in
writing) during lectures

Assessments for Studies students:

Practical 1 (in-class report) Week 5
Essay (computer Lab assignment) - Week 9
Formative assessments (short answers in writing)
during lectures
Assessments for IVP and IC students:
Essay (please ask module leader for details)
Formative assessments (short answers in writing)
during lectures
Please check Blackboard VLE daily for the most
current instructions and announcements!

2.3. MODULE CALENDAR

Weekly lecture topics are listed bellow:
9

Week
1
2
3
4
7
8
9
10
11
15
16
17
18
19
20
21
23
24

Lecture Title
Introduction to the module
Innate Immunity
Adaptive Immunity
Humoral Immunity, B cell activation, antibodies
Complement in Immunity
Major Histo Compatibility (MHC)
Mucosal Immunology 1
Mucosal Immunology 2
Hypersensitivity
Cellular Immunity: neutrophils and phagocytes
Dendritic cells and Ag presentation
T cell activation
Flowcytometry
Immune system of newborns
Immune system of the elderly
Clinical Immunology lab
Mock exam
Mock exam feedback

Staff
RF
RF
RF
RF
UVG
UVG
UVG
UVG
UVG
RF
RF
RF
RF
RF
RF
RF
RF
RF

List of study topics is can change in cases of emergencies, please follow

the Blackboard daily for most current information.

Practicals are listed bellow:

Week

Title

_______________________________________________________________
5
16-18

Practical No 1 Bardford Assay

Practical No 2 ELISA Immuno Explorer

2.4. MARKING SYSTEM

Assessments of Biomedical Science Students:
2hr Examination
Coursework

= 70% of Module Mark

= 30% of Module Mark

Breakdown of Coursework:
10

Practical 1:
=10%
Practical 2:
=10%
Essay
10%

Assessments of Biomedical Studies Students:

2hr Examination
Coursework

= 70% of Module Mark

= 30% of Module Mark

Breakdown of Coursework:
Essay:
Practical
=15%

=15%

Assessments of IVP and IC Students:

2hr Examination
Coursework

= 70% of Module Mark

= 30% of Module Mark

Breakdown of Coursework:
Essay:

=30%

Assessment rationale: Generic Regulations of De Montfort

University apply.

THE END OF YEAR EXAMINATION

There are two sections in the paper (sections A and B).
11

Section A
Candidates should attempt four (4) questions out of a total of six (6)
questions from section A (each worth 12.5 %). These are short
questions.
Section B
Candidates should attempt two (2) questions out of a total of four
(4) questions from section B (each worth 25%). These are longer,
essay type questions.
REVISION
Background material required for answering the questions are
contained in the lecture notes. So you should begin to identify
discrete sections within the notes and compose essay plans around
them. Essay plans should be no longer then half a side of A4 and
contain a few points (10-15) which are easy to remember. Then
begin to revise by writing essays. You cannot expect to score well in
an essay question if you have not tried writing essays as part of
your revision. The very act writing the essay helps you to remember
the facts and what should be mentioned where.

MARK DESCRIPTORS
Each component of the written coursework within the module will be
given a grade or % mark as follows:
These descriptors are inter-related: with regard to marks of 40 and
above there is an assumption that in awarding marks in one band
work will have met the requirements of the previous band; with
regard to marks of 39 and below there is an assumption that in
awarding marks in one band work will NOT have met the
requirements of the previous higher band.
When marking an individual piece of work there is an expectation
that it will clearly demonstrate most of the criteria within each
band:

Mark
Range
90100%

Criteria
Responds to all of the assessment criteria for the
task.
Displays exceptional degree of originality.
Exceptional analytical, problem-solving and/or
12

80-89%

70-79%

60-69%

50-59%

creative skills
No fault can be found with the work other than
very minor errors, for example minor typographical
issues
Responds to all of the assessment criteria for the
task.
Work of outstanding quality, evidenced by an ability
to engage critically and analytically with source
material.
Likely to exhibit independent lines of argument.
Highly original and/or creative responses.
Extremely wide range of relevant sources used
where appropriate
Responds to all of the assessment criteria for the
task.
An extremely, well developed response showing
clear knowledge and the ability to interpret and/or
apply that knowledge.
An authoritative grasp of the subject, significant
originality and insight,
Significant evidence of ability to sustain an
argument, to think analytically, critically and/or
creatively and to synthesise material.
Evidence of extensive study, appropriate to task.
Responds to most of the assessment criteria for the
task.
A detailed response demonstrating a thorough grasp
of theory, understanding of concepts, principles,
methodology and content.
Clear evidence of insight and critical judgement in
selecting, ordering and analysing content.
Demonstrates ability to synthesise material, to
construct responses and demonstrate creative skills
which reveal insight and may offer some originality.
Draws on an appropriate range of properly
referenced sources.
Responds to most of the assessment criteria for the
task.
An effective response demonstrating evidence of a
clear grasp of relevant material, principles and key
concepts
An ability to construct and organise arguments.
Some degree of critical analysis, insight and
creativity.
Demonstrating some conceptual ability, critical
analysis and a degree of insight.
Accurate, clearly written/presented
13

40-49%

30-39%

20-29%

10-19%

0-9%

Responds to some of the assessment criteria for the

task.
A response demonstrating an understanding of basic
points and principles sufficient to show that some of
learning outcomes/assessment criteria have been
achieved at a basic level.
Suitably organised work demonstrating a reasonable
level of understanding
Covers the basic subject matter and is appropriately
presented but is rather too derivative and
insufficiently analytical.
Demonstrates limited conceptual ability, levels of
evaluation and demonstration of creative skills.
Demonstrates adherence to the referencing
conventions appropriate to the subject and/or task.

Overall insufficient response to the

assessment criteria.
A weak response, which, while addressing
some elements of the task, contains significant gaps
and inaccuracies.
Indicates an answer that shows only weakly
developed elements of understanding and/or other
skills appropriate to the task.
May contain weaknesses in presentation
that constitute a significant obstacle in
communicating meaning to the assessor.
Overall insufficient response to the
assessment criteria.
A poor response, which falls substantially
short of achieving the learning outcomes.
Demonstrates little knowledge and/or other
skills appropriate to the task
Little evidence of argument and/or coherent
use of material
Overall insufficient response to the
assessment criteria.
A very poor response demonstrating few
relevant facts
Displays only isolated or no knowledge
and/or other skills appropriate to the task.
Little adherence to the task
Overall insufficient response to the
assessment criteria.
Displays virtually no knowledge and/or other skills
appropriate to the task.
Work is inappropriate to assessment task given
14

Please find below some more information about these descriptors.

YOUR GUIDE TO THE UNIVERSITY UNDERGRADUATE MARK
DESCRIPTORS (2010)
The University has a set of mark descriptors which can be found in
the Undergraduate Regulations and in the Academic Registry part of
the University website. These descriptors have been designed to fit
all undergraduate programmes but individual programmes and
faculties are also encouraged to produce their own versions of these
which meet the specific needs of their own students. You are
advised to talk with your tutor about this to find out more.
The full range of marks, from 0-100% have been split into bands.
The descriptors have been designed to be cumulative. This means
that in being awarded marks in one band you have already met the
requirements of the previous band.
The final mark awarded to a piece of work will be informed by its
predominant character. In each mark band the criteria indicate the
quality of the work. Within each band it is possible for a piece of
work to have some flaws provided that such weaknesses are
sufficiently compensated by the quality of the remainder of the
work. These principles apply to all formally assessed work with
some differences in emphasis for assessments completed in
different circumstances. For example, the standards for English and
referencing are likely to be higher for coursework than for
examinations.
Markers are encouraged to use the full range of marks from 0-100%.
They will signal excellent responses to the assignment task
by awarding marks above 70% and marks above 80% will be
used to indicate outstanding work.
Conversely, marks below 40% will indicate a Fail grade (shown
in the mark descriptors by the shaded boxes) and will be awarded
for answers that fail to demonstrate a satisfactory achievement of
the assessments learning outcomes. For example, an answer that
indicates a complete ignorance of the relevant subject content will
fail, even if it is presented in the correct format.
Modules generally use a range of assessment methods designed to
monitor your progress and to find out whether or not you have
achieved the intended module learning outcomes. It would be
unusual for all learning outcomes to be tested in a single
assessment. Therefore, you should note that the marking criteria
will be adapted to suit the requirements of particular assessments.
It is your responsibility to ensure that you understand the
15

criteria being applied in any particular assessment and to

seek clarification from your tutors if necessary.
FEEDBACK
Feedback on formal assessments would be linked to the marking
criteria. This feedback can take different forms, including generic
oral feedback to a whole class or individual comment sheets. The
aim of the feedback is to help you develop the knowledge and skills
needed for successful completion of the module.
Informal feedback from tutors is used to inform you of your progress
and may take place through individual meetings, classroom
discussions and other means such as online exchanges. Peer
feedback between students may be encouraged through group
meetings, seminars, class discussions and the use of social
networking sites on the internet. You should make use of all these
different forms of feedback to evaluate your learning and identify
further appropriate learning activities.

2.5. LATE SUBMISSION OF ASSIGNMENTS

The following regulations will apply for all BIOM module assessments
handed in late:
o

40% cap for work submitted unauthorised up to 7 actual days

after original submission date.

0% for work submitted unauthorised more than 7 actual days

after original submission date.

Assessments may be handed in late by prior arrangement with the

module leader. To do this you must have:
i)
ii)

a valid reason for the report to be handed in late.

an Extension to Coursework Application available from the
Student Advice Centre. Bring this with you when you see the
module leader to request an extension, which must be before
the deadline date.

An extension date can then be agreed upon between the student

and module leader should the circumstances warrant this.

3. REFERENCING GUIDE
16

3.1. GUIDE TO TURNITIN AND THE VIRTUAL

LEARNING ENVIRONMENT
What are plagiarism and collusion?
In your second year you will keep up the good practice of citing and
referencing the work of others. Failure to do so and passing of the
work of others as your own is known as plagiarism. Copying work
from fellow students is known as collusion. These are both treated
as academic offences and further details are found in the University
regulations document General Regulations and Procedures
Affecting Students, chapter 4 Academic Offences [see:
http://mle.dmu.ac.uk/regulations/general/].
To learn about citation and referencing, the Library has a number of
self-study booklets including Information Citation and Plagiarism
which
are available
on-line
and
in
the
library.
[See
http://www.library.dmu.ac.uk/Support/Selfstudy/index.php?
page=89]. These will enable you to improve your academic skills.
Your module team will also have support materials to help you, and
along with your personal tutor will be able to provide you with
specific guidance.
What is Turnitin?
Turnitin is a web-based plagiarism detection tool widely used in UK
universities and schools/colleges. It searches the current and
archived internet documents, and papers submitted by other
students, and identifies any similarities between text. This tool is
available through Blackboard to help detect plagiarism in text
assignments.
You will receive an introduction to Blackboard and Turnitin, and there
is information available through the Student Advice Centre. Again,
module staff can provide you with further information.
How will Turnitin be used on this module?
You will initially use Turnitin as a formative exercise, that is, you will
be able to submit drafts of your work and have full access to Turnitin
and its results (originality report) to help you to improve your
academic practice, such as evaluating and referencing the work of
others.
You will then be advised on which assignments Turnitin will be used
to detect plagiarism and collusion. If plagiarism and collusion is
identified, your module staff will discuss this with you, and academic
conduct procedures will be followed as per University regulations.
You will be advised how to submit your work to Turnitin through
Blackboard by module staff.

17

Concluding remarks
You must not copy text, diagrams, figures or even strings of ideas
from any source printed texts, the world-wide-web, CD-ROMs or
from colleagues.
You must be aware of the current regulations regarding plagiarism
offences. Please read carefully the University leaflet Plagiarism &
Fabrication of Results which is available from the Student Advice
Centre, Hawthorn Building.

Blackboard VLE
General lecture information, pre-lecture reading/assignments,
changes to the timetable and other announcements concerning the
module are all placed onto a dedicated university website called
Blackboard (Bb) (https://vle.dmu.ac.uk/index.htm) and every
BIOM2004 student has access to it. Bb is an example of what is
currently known as a virtual learning environment (VLE). This is
essentially a way to place module information on a web-based
format for access to anyone who is able to use a web browser. As a
DMU student, you are automatically put on the system to be able
to access Bb. You will be able to access all modules (known as
course in Bb) which you are enrolled on (but remember not all
modules may have a Bb site, it depends on the module leader).
As with many websites, it is difficult to write an instruction sheet
for you to learn how to use Bb. By far the best way is just to access
it and have a play around, you can then see what is available. In
addition it is good idea if you read the tutorial on how to use
blackboard which can be found from the DMU Blackboard website. It
is your responsibility to familiarise yourself with the
software during your first days of the module and to check
blackboard regularly throughout the academic year!

3. 2. WHERE TO START YOUR FIRST HOMEWORK

18

For your start, especially if you have never studied

immunology before, you can explore the learning
material in Appendix 2 this will give you A level
background in the subject.
3. 3. TEXTBOOKS
At Honours Level you are expected to be working from refereed
Journal articles wherever available. Current text books, however,
provide a foundation on which to build the knowledge you require,
therefore you should use the following textbooks:
The main module textbook
David Male, Jonathan Brostoff, David B Roth and Ivan Roitt.
Immunology, Mosby, 2012, 8th edition.
Recommended reading
Abul K Abbas, Andrew H Lichtman and Shiv Pillai. Cellular and
molecular Immunology, Elsevier, 2014, 8th edition.
Anthony L DeFranco and Richard M Locksley. Immunity,
Associates Incorporated, 2015.

Sinauer

Helen Chapel, Mansel Haeney, Siraj Misbah and Neil Snowden.

Essentials of Clinical Immunology,
Wiley-Blackwell, 2014, 6 th
edition.
John Playfair and Gregory Bancroft. Infection and Immunity, Oxford
University Press, 2013, 4th edition.
Roderick Nairn and Matthew Helbert. Immunology for medical
students, Elsevier, 2007, 2nd edition.
Thomas J Kindt, Richard A Goldsby and Barbara A Osborne.
Immunology, Palgrave, 2006, 6th edition.
Further reading
Arthur M Lesk. Introduction to Protein Architecture: the Structural
Biology of Proteins, Oxford University Press, 2001.
Debbie Holmes, Peter Moody and Diana Dine. Research Methods for
the Biosciences, Oxford University Press, 2010.
Graeme D Ruxton, Nick Colegrave. Experimental Design for the Life
Sciences, Oxford University Press, 2010.

19

3.4. WEBSITES AND JOURNALS

Useful Immunology websites:
Immunology and Microbiology Online from the University of South
Carolina
http://www.microbiologybook.org/
Merck Manual. Online Medical Library
http://www.merckmanuals.com/professional/SearchResults?
query=immunology
Journals:
Please refer to the subject journal and textbook list for Biomedical
Science available in DMU Library (ask your subject librarian in
Kimberlin Library).

4. STUDENT FEEDBACK FROM PREVIOUS

YEARS
In case of a problem during your studies or a query, please contact
the Module Leader instantly using the following e-mail:
rfurmonaviciene@dmu.ac.uk. You can also get advice and help
from the Student Advice Center and your Personal Tutor.
Please participate constructively in feedback questionnaires
as your feedback helps to improve the design of the course
and specifically tailor the delivery to current auditorium.
Previous student feedback helped to shape current learning
outcomes of the module and improve the structure of lectures and
clarify the criteria of assessment.
It is due to your constructive feedback and participation in
discussions about Immunology and learning in general, we
can together build a course that can be truly fulfilling to our
students as some quotations from student e-mails below indicate:
I actually enjoyed the exam today!
Thanks again for everything; your time, your patience and all your
help.
I would like to express my gratitude and sincere thanks for all the
help you have provided during my course (Year 2 & 3). I really do
20

appreciate all the assistance in Immunology. It really made me

enlightened and made me look forward to specialize in the course.

21

APPENDIX I.

Safety Declaration
Detach and give to the Lecturer in charge at the beginning of the
first practical period

I have read and understood the requirements

under the following sections of the DMU
General Regulations and Procedures
Affecting Students
http://dmu.ac.uk/dmu-students/the-studentgateway/academic-support-office/studentregulations.aspx

Chapter 2, Student discipline

Chapter 9, Health and Safety Policy

Name (BLOCK CAPITALS: ____________________________________

Student Number: ___________________________

Signature:_______________________________________
Date: ______________

Students not signing and submitting the Safety Declaration to the

Laboratory Supervisor will not be allowed admittance to the laboratory
area.

22

23

APPENDIX 2.
LEARNING MATERIAL FOR YOUR START

IMMUNITY AND HEALTH

This booklet has been adapted from Immunity and Health issued
by the Animals in Medicine Research Information Council (AMRIC).
It is designed to provide a very basic knowledge of immunology for
students with a general biology background.

The Immune System

Disease-causing bacteria, viruses, parasites and fungi are around

us all the time. So why don't we become ill more often? Why do
we recover from infections? What keeps pathogens (diseasecausing organisms) under control? Our bodies have an immune
system to defend us against pathogens. The immune system has
cells and chemicals which work with the body's physical barriers
to stop most pathogens getting inside us. If they do get in, this
fighting force battles against the pathogens. Sometimes it loses
and infections can kill. But, luckily for us, it usually wins and we
recover. Often we do not even realise there was a struggle. Day to
day skirmishes are a normal part of the process by which the
immune system keeps the body healthy.

1.1 A Few Central Concepts

Key points

the immune system is a body system that provides immunity

immunity prevents disease
immunity occurs as a result of infection

1.1.1 The immune system is a body system that provides

immunity.
The immune system, like the nervous system or the digestive system, is
a set of cells, tissues and organs that work together to carry out a
specialised function within the body. The digestive system breaks down
food so that we can use it to gain energy; the immune system provides us
with immunity.
Immunity, however, is a condition rather than a physical end product. We
feel the ill-effects of an infection and we can recognise our immune

24

system's efforts to resist and overcome colds, flu and food poisoning, for
example, but when we are well we tend to think that our immune system
has lapsed into inactivity. In fact, nothing is further from the truth.
We cannot talk about the immune system without talking about the
usually microscopic organisms that are probably the reason for its
existence. Here the word 'pathogens' is used as the general term for
infectious organisms or agents that cause disease.

1.1.2 Infection is different from disease: immunity prevents

disease
It is important to distinguish between infection (the entry of a pathogen
into the body) and disease (the damaging effects of the pathogen on the
body). Immunity prevents disease: it might also prevent infection, though
infection frequently occurs but is dealt with so quickly by the immune
system that we never know it happened.

1.1.3 Immunity Occurs As A Result Of Infection

It is important to understand that much of our most important immunity is
gained through exposure to infection. We know this because many
infections do not occur more than once in the same person. In fact, as will
be described later, a first infection can actually make the immune system
work much better.
Infections by bacteria and viruses are usually dealt with very well,
although some can cause serious and even fatal illnesses. (Today we have
the help of medicines such as antibiotics to deal with persistent or lifethreatening bacterial infections.) In general, the immune system has more
trouble with fungi, worms and protozoa. Fungi have tough cell walls
that prevent attack by the immune system while parasitic worms and
protozoa have evolved extremely clever ways to side-step the best
attempts of the immune system to fight them.

1.2 How the Immune System Is Organised

The immune system is a complex network which is difficult to classify
simply. We can categorise the different T-cell types that carry out various
functions and we can also classify according to the overall functions
themselves, most of which involve different types of cell working together.
We have tried to summarise both approaches briefly in this section.

Key points

immune cells are uniquely mobile

cells of the immune system have special and different functions
the immune system provides non-specific and specific immunity

1.2.1 Immune Cells are Uniquely Mobile

25

The immune system is made up of cells which make up the immune

tissues. Many of these cells can also wander about the body. The mobility
of its cells is a unique and important property of the immune system: it
allows young cells to move from their site of origin to different parts of the
body, as and when they are most needed.
The vital role that cell mobility plays in immunity is illustrated in people
who have a genetic defect that affects cell movement through the body:
such people always have seriously damaged immune systems.

1.2.2 Cells of the Immune System Have Special and Different

Functions
The different cells of the immune system have many different functions.
Individual cells are specialised to do particular jobs and this is necessary
for the system to deal with the many different pathogens and the many
different ways they use to infect and damage us.
Many books on immunology attempt to teach important concepts using
the analogies of battles and war. The danger is that the analogy itself may
mean different things to different people, so we will try to keep the
analogies simple to avoid confusion. For example it is quite useful to think
of the cells of the immune system working together as an army - most
people are aware that an army is made up of many different specialists.
In the immune system the specialist cells have become this way partly
because they were born to it and partly because they learn, or are
educated, to do certain things. They protect us and maintain the internal
environment of our bodies.
In the classification of the cells of the immune system throughout this
book (starred in the glossary), all the cell types and their descendants that
occur in the blood are included, with one exception; the red blood cells.
The cells of the immune system are therefore primarily the lymphocytes
and phagocytes. These cells can interact with many - perhaps all - other
cells in the body.

1.2.3 The Immune System Provides Non-Specific and Specific

Immunity
The immune system provides two main sorts of immunity. First, there is
natural, innate, or non-specific immunity that works against all
pathogens, irrespective of what they are. Non-specific immunity
encompasses the physical and chemical barriers that prevent entry of
pathogens into the body and also the general reactions that the body
makes to pathogens that invade the body. Second, we have the
protective, adaptive or specific immunity that occurs as a result of
infection or intentional immunisation and which is specific for particular
pathogens.

26

Keeping Pathogens Out

Our skin forms a strong physical barrier to stop pathogens getting

inside our bodies. It is also a chemical barrier; the surface of the
skin is acidic and is covered in enzyme-rich sweat. These enzymes
can kill pathogens.
It is easier for pathogens to enter the body at its openings; the
nose, ears, eyes and mouth, for example. Because of this we have
defences at all the body's openings. Sticky mucus in the nose and
wax in the ear are good traps for pathogens. Tears and saliva
have enzymes to hill bacteria.
The body also makes good use of friendly bacteria. These live in
the gut, vagina and urethra and help keep pathogens out.

2.1 Non-Specific Immunity: Physical And Chemical

Barriers
Key concepts

the body has physical and chemical barriers to prevent

pathogens
getting in
the skin is a tough physical barrier which works in combination
with
the chemicals in sweat
mucous membranes which line the lungs, gut and other body
entrances
have special techniques to prevent entry of pathogens
we make use of non-harmful bacteria to prevent growth of
pathogens
in the gut.

2.1.1 The Body Has Physical and Chemical

Prevent the Entry of Pathogens

Barriers

to

The physical and chemical barriers of the body are the first line of defence
against pathogens. They occur at the surface of the body (the skin), at its
openings (mouth, eyes, ears, nose, rectum, vagina, urethra) and at
internal sites which are nevertheless exposed constantly to the external
environment (the different parts of the respiratory system and the
alimentary canal).

27

The body's physical and chemical barriers provide innate immunity: the
immunity with which we are born. It is also called non-specific or natural
immunity, for obvious reasons, and it has two important features. First, it
is effective against a wide range of microbes, irrespective of their type.
Second, its effectiveness does not change with experience of infection
(see below). This sets it apart from adaptive immunity, which is dealt with
in greater detail later.

2.1.2 The Skin Is a Tough Physical Barrier which Works

Combination with the Chemicals in Sweat

in

The skin normally provides a very efficient physical barrier to stop

pathogens getting into the body. The hard outside layer of the skin is
made up of dead cells which are rich in keratin, a protein that gives the
skin some of its physical strength. The secretions of the skin usually spell
bad news for unwelcome invaders as well. Sweat is acid, in which some
bacteria can't survive, and it also contains enzymes that can digest
bacteria. The ears and eyes need special protection: the ears secrete wax
which has special anti-microbial properties and the tears are particularly
rich in anti-bacterial enzymes (especially lysozyme).

2.1.3 Mucous Membranes Which Line the Lungs, Gut and

Other Body
Entrances Have Special Techniques to
Prevent Entry of Pathogens
The linings of the respiratory, digestive and urinary and genital systems
are also external surfaces of the body. Because they have evolved to do
the important jobs of absorption and secretion they lack a tough,
protective covering but instead have delicate membranes called mucous
membranes. Their clever defence is to make mucus and secrete acids,
enzymes and other chemicals that work together to prevent pathogens
getting through into the body. Sticky mucus traps microbes, the cilia in the
airways beat and wash them away and chemicals digest and kill them. All
these actions prevent microbes attaching themselves to the membrane,
an achievement that is necessary to enable them to actually penetrate the
body tissues.

2.1.4 We Make Use of Non-Harmful Bacteria to Prevent

Growth of Pathogens In the Gut, Urethra and Vagina
Further inside the body, in the urethra and vagina and also in the lower
gut or large intestine, we make use of the non-harmful bacteria that live
there quite happily without causing us problems most of the time. (It's a
staggering fact that the healthy human body is made up of about 10 15
[one thousand million million] human cells and its large intestine is home
to about 100 times this number of bacteria.)
These commensal bacteria compete with invading bacteria for nutrients
and also make natural substances (antibiotics) that can limit the growth of
invading pathogens. We know how important these non-harmful bacteria
are, because if someone loses them, they can develop severe health

28

problems. Babies of all mammals are born without commensal bacteria

and their gut becomes colonised with them in the early days of life.

3
What Happens if Pathogens Manage to
Invade?
Sometimes the first line of defence is overcome and pathogens
get into the body. When this happens the body sends extra blood
to the site of infection and the area becomes red, swollen, hot
and painful. This process is called inflammation. It sends out
distress signals to tell white blood cells to hurry to the scene.
Specialised white cells called phagocytes grab and then digest
bacteria and pieces of damaged tissue. This 'eating' process is
known as phagocytosis.
The body also uses its all-purpose chemical weapons. They help
the phagocytes to eat pathogens and they also kill bacteria
directly by punching holes in their cell walls.
These early defences are non-specific - they are used against any
invading pathogen. Sometimes they are all the body needs to deal
with the infection. At other times non-specific defences keep the
infection under control until specific defences can be called up.
Specific immunity takes longer for the body to arrange because it
is tailor-made to kill one type of pathogen only.

3.1

Non-Specific Immunity: Inflammation and Phagocytosis

When microbes do penetrate tissues, the body deals with them using all
the methods available. Non-specific immunity does not only include the
physical defences.
This section describes some of the activities of chemicals and cells of the
immune system which act inside the body against any invading pathogen.
The next section ('Designer Defence') goes on to look at the specific
immune system in detail.

Key points

inflammation is part of a healthy response when pathogens get

into the
body, millions of cells come to fight them
phagocytes (cells that eat) and their important role in immunity

29

other cells have special roles in non-specific immunity

some cells are killers: they attack microbes directly
cells also make chemicals which help the fight against disease

3.1.1 Inflammation is Part of a Healthy Response

Inflammation is a rapid response to tissue damage. This can be caused by
a cut, insect bite or a heavy blow such as a sports injury or by an infection.
This is a very important reaction which deals with the infecting organisms
in the place where they have entered the body.
The features of inflammation are:
redness:
blood flow to the
heat:

caused by the extra blood flow.

swelling:
and allows
site of infection.
pain:

blood vessels in the area enlarge (dilate) to increase

area.

the extra blood forces fluid into the damaged tissues

immune cells from the blood to get to the

swollen tissues press on receptors and nerves and chemicals

produced by cells in the area cause pain.

Inflammation is triggered by damaged cells. In addition to ruptured local

cells, certain cells (mast-cells and basophils) release 'alarm' chemicals
such as histamine and kinins. These substances cause the enlargement of
blood vessels, or vasodilation that leads to the classic signs of
inflammation. They also attract other cells from the blood to the area.
Neutrophils, monocytes and macrophages (collectively known as
phagocytes) accumulate to increase the rate at which bacteria and
debris can be dealt with by phagocytosis.

3.1.2 When Pathogens Get Into the Body, Millions of Cells

Come To Fight Them
Most of the time we are unaware that our environment is teeming with
bacteria, viruses and fungi. Most of them are not harmful but there are
some which can quickly and aggressively invade the body, if they get the
chance. Many bacteria, for example, live naturally on our skin without
harming us but a small cut or prick in the skin can very easily become
septic. By this we mean that it is infected, usually with the bacteria that
have taken the opportunity of the cut to invade the body's tissues. Some
of the symptoms are caused by the bacteria damaging the body; some are
due to the body reacting to the infection by making a protective response.
Pus, the yellow goo which is the hallmark of a septic wound, is actually
made up of the dead bodies of millions of our own special immune cells
that have migrated into the wound from the blood. These cells feed on,

30

and destroy the bacteria which multiply rapidly in the wound, using the
process of phagocytosis (see below). Although and it can be a painful and
unpleasant reaction, and its presence obviously indicates that something
undesirable has occurred, it is valuable because it contains the infection,
hopefully preventing it from spreading throughout the body and causing
much more serious damage.

3.1.3 Phagocytes (Cells That Eat) and Their Important Role in

Immunity
At the centre of the internal non-specific immune mechanisms that deal
with invading microbes are phagocytes, cells that can 'eat' foreign
materials, including microbes, and digest them. The 'eating' process is
called phagocytosis.
There are two major types of phagocyte:
- mononuclear phagocytes (usually known as monocytes while in the
blood and
as macrophages when they are in the tissues)
- neutrophils (these also go by the name of polymorphonuclear
leucocytes)
Both share some important properties: they are descendants of special
cells in the bone marrow called stem cells; they are produced
continuously throughout life and they are found in the blood.
Neutrophils have a short life span and are designed for a very rapid
response to a local infection, such as when bacteria enter the skin through
a cut. The site of infection becomes inflamed and sends out chemical
signals that attract neutrophils into the wound area. Once on the scene,
these cells ingest and (hopefully) destroy the bacteria.
Mononuclear phagocytes also come from bone marrow stem cells but they
are longer living cells. Newly produced cells of this type circulate in the
blood as monocytes, and enter the tissues where they mature into
macrophages. Macrophages are generally much better phagocytes than
monocytes.
This migration of monocytes into tissues is a natural event to ensure an
adequate supply of phagocytes everywhere in the body. Like neutrophils,
they enter sites of inflammation to eat microbes but they also form a
'clean-up committee' which polishes off the dying neutrophils that have
themselves fed on bacteria. The combined actions of these two types of
phagocyte can deal with a large number and also a wide range of different
microbes.
As you might imagine, children who are born with very few, or with
ineffective neutrophils have terrible problems with infections caused by
pus-forming bacteria. However, no case of someone being born without
macrophages has ever been reported and so we conclude that this
condition is lethal to the growing embryo. This might be partly because
macrophages have other roles in the body in clearing up dead self tissues
and in the modelling of tissues during development.
31

3.1.4 Other
Immunity

Cells

Have

Special

Roles

in

Non-Specific

Neutrophils have some near relatives that look similar, but which have
different protective jobs. Eosinophils are important in protection against
some parasitic worms, and also have a special role in allergies such as hay
fever. Mast-cells and basophils are other relatives of the neutrophils
which live in tissues close to mucous membranes (such as those that line
the lungs and the gut), and are important for dealing with parasites that
invade through the gut and lungs. However, they too are involved in
allergies.

3.1.5 Some Cells Are Killers

Lymphocytes have an important role in specific immunity, (described
below in "Designer Defence") but the body has a very important set of
cells that are close relatives of lymphocytes but which provide important
non-specific immunity. Natural killer, or NK, cells are large cells with a
granular appearance under the microscope (this has given them the name
of large granular lymphocytes). They can kill many different types of
cells and they do other things too. They help in anti-viral immunity, in antitumour immunity and, surprisingly, in controlling the production of cells in
the bone marrow.
NK cells can kill cells very easily without needing special activation first
and so form an important first line of defence against invading pathogens.
They are always available in the body to do this and are an important part
of the non-specific immune response to infection.
Because of their ability to kill some tumour cells in-vitro, research into new
cancer treatments is looking at boosting the activity of NK cells with
selected cytokines (see interferons below).

3.1.6 Cells Also Make

Against Disease

Chemicals

Which Help

the Fight

Although some immune cells themselves interact 'face- to-face' with

pathogens, many of them manufacture and secrete special substances
that then lock onto pathogens, or which arm other cells to do the attack.
The complement system includes more than 20 proteins which circulate
in the blood. These proteins are made by macrophages and work together
in a cascade to deal with microbes in various ways. Some of the
complement proteins, for example, coat bacteria and make them 'more
appetising' to macrophages. Several of the complement proteins also work
together to form a sort of 'hole-punch', which jabs holes in the cell walls
and membranes of bacteria and parasites. This spells bad news for the
pathogens as they become leaky and soon die as a result.
There is also a large collection of so-called acute phase proteins that
circulate in the blood and are made, as their name implies, in the early
and acute phase of inflammation that accompanies an infection. These

32

proteins can coat invading pathogens to prevent them infecting tissue

cells or to make them more likely to be eaten by phagocytes.
Interferons are made by cells infected with viruses. They inhibit the
growth of viruses in other cells, so can be useful in preventing the spread
of viruses through the body. Interferons belong to a large family of proteins
called cytokines. Interferons are being investigated for their potential to
control NK cells.

Designer Defence

To fight some pathogens, our bodies use specially designed

defences. These are provided by two different types of white
blood cells, called B-cells and T-cells.
B-cells
B-cells
weapons called
pathogens, particularly
by:

which

are

factories that make chemical

antibodies. Antibodies target
bacteria,

sitting on the surface of the bacteria and

attracting special proteins, some of
punch holes in them.

coating the bacteria, making them sticky and easier for the
phagocyte to
grab.
Most of the antibody factories die soon after the infection has
been stopped but a few will live on and remember the pathogen if
they meet it again.
These 'B-memory cells' will then swiftly make more antibodies
which will kill the invaders before they have time to make us ill.
This 'immune memory' explains the success of immunisation.
T-cells
Viruses and some bacteria live inside cells where antibodies
cannot get to them, but T-cells can target the infected cells. They
stick on to these infected cells and kill them. T-cells also tell other
cells in the immune system what to do and when to do it.
There are four main types of T-cell

antibodies.

Helper T-cells - help B-cells to make efficient

They also tell other T-cells what to do.

33

by
ordering

Killer T-cells - kill body cells that have been infected

viruses using direct, cell-to-cell combat or by
them to self-destruct.

down

Regulator T-cells - tell the immune system to wind

when an infection is over.

the
quickly to it

Memory T-cells - (like memory B-cells) remember

pathogen so that the body can react more
the next time.

4.1 An Overview of the Specific Immune System

Key points

non-specific immunity cannot cope alone

specific immunity is specific for particular pathogens
lymphocytes are the key to specific immunity
lymphocytes recognise specific antigens and remember them
lymphocytes have receptors to help them recognise antigens

4.1.1 Non-Specific Immunity Cannot Cope Alone

The mechanisms of non-specific immunity act quickly in response to a
great range of different infections. They are, however, not designed to
deal specifically with one particular microbe, nor are they made more
effective by repeated use. In fact, important as they are, they are not
enough on their own. We also need the other face of the immune system,
the specific immune system which can recognise particular pathogens,
react to them very effectively and remember them for next time.

34

4.1.2 Specific Immunity is Specific for Particular Pathogens

At the heart of protective immunity - the term we use to describe the
resistance to infection we develop from being exposed to it - are cells
called lymphocytes. These cells provide us with a designer defence
which can accurately target many different microbes. Individual
lymphocytes can respond specifically to the particular invading microbe
and they also remember the microbes they are specific for. We know
specificity and immunological memory exist because people who have
chicken-pox only get it once, but their chance of catching a cold doesn't
change. These properties of the specific immune system are manipulated
by immunisation (see below) when a specific vaccine tricks the immune
system into thinking it has encountered a real infection.
4.1.3 Lymphocytes (T-Cells and B-Cells) are the Key to Specific
Immunity
A healthy human has more than a million million (10 12) lymphocytes in
their body, and half of these are closely associated with areas just
underneath mucous membranes. These surfaces are a very important
route of entry for microbes. Lymphocytes are organised into various
lymphoid tissues or organs, but they also move around the body, so we
find them in the blood and in small numbers almost everywhere else. We
can think of these circulating cells surveying the body for infection, or for
other odd changes like the start of tumours. This is the concept of
immune surveillance.
Lymphocytes start their life in the bone marrow where they are produced
by stem cells that divide repeatedly. The daughter cells produced go on to
change into mature lymphocytes. We start life with rather few
lymphocytes and so are not able to fight every kind of infection but the
breach is filled very effectively by the passive immunity provided by the
antibodies in colostrum and breast milk. We run out of these stem cells in
very old age and lose the ability to go on making new lymphocytes to
replace those that have died naturally. This is one of the reasons why very
elderly people are particularly vulnerable to infections.
Lymphocytes migrate from the bone marrow to populate the lymph nodes
and spleen, and these so-called secondary lymphoid tissues are where
lymphocytes make immune responses. Lymphocytes grow up to become
one of two types: B-cells or T-cells. B-cells complete their development in
the bone marrow itself before they settle down elsewhere. T-cells, on the
other hand, need to mature in the thymus (hence the T in their name)
before they go to join the B-cells in the secondary lymphoid tissues.
Because the bone marrow and thymus are the factories where
lymphocytes are made they are known as the primary lymphoid
tissues. Without a thymus or without bone marrow, life is impossible.
People who have been exposed to high doses of radiation lose the cells in
their bone marrow, something which was first realised after the atomic
explosions in World War II. Today, assuming sufficiently well-matched
donors can be found, people with damaged bone marrow can be given a
bone marrow transplant. In some cases of leukaemia, a patient's bone
marrow is intentionally destroyed by drugs or radiation and healthy stem

35

cells from another person are transplanted to replace the marrow. Some
children have a rare mutation that prevents the thymus from developing
and they have to be isolated in a sterile environment to protect them from
infection. They too can now be helped by a transplant of healthy thymus
tissue.

MORE INFORMATION ON LYMPHOCYTES

Lymphocytes have receptors to help them recognise
antigens
In order for a lymphocyte to be turned on to do its protective work
it needs to recognise a pathogen. The way in which lymphocytes
react to an antigen (from a pathogen) depends absolutely on the
very useful receptors for antigen that lymphocytes have on their
cell surfaces. These proteins are called the T-cell receptor

(TCR) on T-cells and the B-cell receptor (BCR) on the Bcells.

The latter is known as Immunoglobulin (Ig) or antibody
(Ab).
There are several thousand receptor molecules on the surface
of each lymphocyte.
When an antigen
receptor molecule

36

(on the surface of

a lymphocyte)
bind to an antigen
(on a pathogen),
a signal is sent
from the receptors
to the cell nucleus.
This instructs
lymphocyte to

the
turn

on the genes that

it needs to read to
produce protective proteins. If the lymphocyte is a B-cell, the
protein produced is an antibody; if it is a T-cell, the protein is a
cytokine.
an

Of course, complicated as this may sound, this is very much

oversimplification. Other signals are needed to make sure the
cell is correctly activated. However, the crux of the whole
reaction is the interaction of the receptor on the lymphocyte

with
the antigen from the pathogen.

4.1.4 Lymphocytes
Remember Them

Recognise

Specific

Pathogens

and

B-cells and T-cells have many features in common, but they also differ in
important ways. Before we consider their individual properties, it would be
helpful to describe some things they have in common, because these
properties will help to explain how specific immunity is created and used
by the body.
Lymphocytes react to foreign substances by making immune responses. A
substance which stimulates lymphocytes to make immune responses is
called an antigen. Almost anything can provoke a specific immune
response. Antigens are very varied in their structure and lymphocytes can
discriminate very small differences between different antigens. We get
colds throughout our lives because cold symptoms are caused by
infections due to many different types of rhinovirus: specific immunity that
results from an infection with one pathogen does not protect against an
infection caused by a different pathogen.
It makes sense for the immune system to attack antigens which do not
form part of the body (we term body antigens self-antigens). The
immune system has developed powerful mechanisms of selection that
destroy lymphocytes that wrongly react with self-antigens. But as we shall
see later, there are situations where the immune system does react
against tissues in the body, leading to autoimmune disease.

37

4.1.5 Lymphocytes Have Receptors To Help Them Recognise

Antigens
Lymphocytes have proteins actually on their cell surface membranes
which are called receptors. These receptors help lymphocytes to recognise
pathogens by binding to antigens on the pathogen's surface. This is
explained in detail above:

4.2 The Role of B-Cells

Key points

B-cells can recognise and react to specific antigens

B-cells make antibodies which combine with antigens specifically
different types of antibodies are found in different places and
they do
different things
antigen activates a B-cell and it makes a clone
some activated B-cells produce antibody: others become
memory cells
the body's genes have a clever trick that allows millions of types
of
different antibodies to be made

4.2.1 B-Cells Can Recognise and React to Specific Antigens

When a B-cell meets the antigen to which it is programmed to react, it
becomes activated. The cell starts to make antibodies which combine
chemically with molecules of the same antigen that stimulated the B-cell
in the first place. This selective activation of lymphocytes by antigen is the
basis of immune specificity. A very important fact to remember at this
stage is that there are millions of different antigens and therefore
everyone can make millions of different B-cells, but one B-cell can only
recognise and react to one antigen.

4.2.2 B-Cells Make Antibodies Which Combine with Antigens

Specifically
Antibodies were the first molecules of the immune system to be
discovered and to have their biochemical structure analysed in detail.
They come in several different forms, but they all have a similar basic
structure. Every antibody molecule is Y-shaped with two arms at the end of
a tail. At the end of each arm are special sites that combine with antigen.
The tail end does not bind antigen, but does bind to other things that
determine the function of that particular antibody.

38

Antibodies bring about the ultimate destruction of the microbe in a

number of different ways. A central function of antibody is to promote
phagocytosis. Phagocytes have receptors on their surface for the tails of
antibodies. The tails stick out all over the microbe, providing handy targets
to which phagocytes can attach themselves. So a phagocyte can recognise
and then engulf a microbe coated in antibody much more easily than an
uncoated pathogen. This enhancement of phagocytosis is called
opsonisation.

bind
This
release
attract more
the site, so
effectiveness of
It also forms the
'hole-punch' which
the pathogen,
the inside out and the

The tails of antibodies also

with complement proteins.
binding event causes the
of chemicals which
phagocytes to
enhancing the
inflammation.
complement
jabs holes in
letting
outside in.
When antibodies bind to the
outer proteins of a
prevent
it

virus, they can

attaching itself to a
body cell. This limits virus replication and so slows the spread of the
virus through the body. Antibody can also bind to the flagellae of bacteria.
This stops them swimming around and clumps them together, making
them sitting targets for phagocytes.

4.2.3 Different Types of Antibodies Are Found in Different

Places and They Do Different Things
One feature of antibodies deserves a special mention. You have heard that
there are slightly different types of antibody. All these types have the
same bits that combine with antigen but they have different tails and this
means that they do different things. These are important because
microbes have a myriad of different ways of attacking us and evading the
attentions of our immune systems. There is for us an advantage in having
a big diversity of immune mechanisms to deal with infection and this is a
theme that will recur throughout this booklet. Antibodies of these different
types also tend to be associated with different tissues. It is easiest to
present these in a table as follows:

39

Type
of Location
antibody
IgG
Blood and body

IgM
IgA

IgE
IgD

Special functions

Deal with bacteria in

tissues and viruses
anywhere
in
the
body
Blood mostly
Quick resistance to
bacteria in the blood
Secreted
across
mucous Protects
against
membranes
viruses and other
microbes
in
gut,
lungs etc.
On mast cells and basophils in Resistance to worm
the body but especially near infections
and
mucous membranes
agents of allergy
Mostly on B-cells
Antigen receptor on
B-cells

4.2.4 Antigen Activates a B-Cell and it Makes a Clone

We will use B-cells to explain what happens when a lymphocyte is
activated by antigen and what follows applies in general to T-cells as well.
One B-cell makes one antibody, and during B-cell development (before
they have ever met an antigen) individual cells become programmed to
make just that antibody. When it is turned on by its corresponding antigen,
a B-cell produces many copies of itself (clones) and makes a lot of its own
very special and specific antibody.
One of the real beauties of producing clones of identical cells is that it is
very economic: it is a way of expanding just that bit of the immune system
that is needed. When the body is threatened by a particular pathogen with
its own unique antigens, it makes sense for the body to put most of its
energy into producing cells which react to those specific antigens.

4.2.4 Some Activated B-Cells

Become Memory Cells

Produce

Antibody:

Others

When an antigen enters the body it gets into, say a lymph node, where
there are many different B-cells. The antigen binds to the surface
receptors (BCRs) of only those lymphocytes that can recognise it. The
activated B-cell goes through a burst of growth. It literally gets bigger, and
then divides in two, producing two daughters identical to itself. This
multiplication process is repeated many times producing the clone that we
mentioned earlier.
Some of the daughter cells then make enormous amounts of 'free
antibody' which goes off throughout the body and does its job of getting
rid of the pathogen. These cells have become so specialised, and so
productive that they wear out and die after a few days. Others, however,
secrete much less antibody but survive in the lymph node to await another
encounter with the same antigen.

40

4.3 The Role of T-Cells

Key points

T-cells
T-cells
T-cells
cells
T-cells
T-cells

have a great range of functions in specific immunity

react to antigens and produce clones
form sub-sets: helper T-cells, killer T-cells and regulator Tcan remember too, just like B-cells
recognise antigens in a different way to B-cells

4.3.1 T-Cells Have a Great Range of Functions in Specific

Immunity
T-cells are like B-cells in many ways, but they do quite different jobs. Bcells, as we have seen, make antibodies that bind with antigen. B-cells do
little else in providing protection against infection. T-cells, on the other
hand, can secrete important molecules and they also interact 'face-toface' with other immune cells. As we saw earlier, T-cells originate from
stem cells in the bone marrow and, after maturing in the thymus, they
enter the secondary lymphoid tissues (lymph nodes and spleen) where
they lay in wait for antigen to be brought to them.

4.3.2 T-Cells React to Antigens and Produce Clones

Like a B-cell, a T-cell also changes when it meets its specific antigen - it
multiplies itself to form a clone directed against the specific antigen. One
T-cell recognises only one antigen but, unlike B-cells, T-cells can form quite
distinct sub-sets which we identify by their possession of special molecules
on their surface called either CD4 or CDS. These types of cell have distinct
roles to play in the immune system.

4.3.3 T-Cells Form Sub-Sets: T-Helper Cells, T-Killer Cells and

T-Regulator Cells
T-Helper Cells
Exactly as their name implies, T-helper cells (CD4T-cells) help other cells of
the immune system to do their jobs more effectively. B-cells need the help
of T-cells to make antibodies that are efficient at binding to antigen. This is
a good example of cell co-operation - it is a very important concept in
immunology that cells work together to achieve something that neither
can do on its own.

41

Think about a particular microbe; say a bacterium, inducing a response.

Specific T-cell and specific B-cell clones become activated by result of the
co-operation between the two cell types. The B-cell interacts with the Tcell through cell-to-cell contact and this helps to turn on the T-cell. The
activated T-cell then returns the favour by sending back similar messages
via soluble molecules called cytokines which it releases into the
surroundings.
T-helper cells also activate macrophages and promote inflammation. To do
this the cells make cytokines, but different ones from those that help Bcells. Remember how important macrophages are in protection, so here is
another example of how specific cells that provide specific immunity cooperate with cells important in non-specific immunity. Macrophages
activated by T-cell cytokines are much better at phagocytosis and
digesting the microbes they have engulfed. An interesting example is the
tubercle bacillus that causes tuberculosis: this lives inside macrophages
which, without activation by T-cells, find it impossible to fight the
bacterium effectively.
T- Killer Cells
T-killer cells (CD8 T-cells) can kill other cells of the body. At first, this does
not sound sensible, but they have a vital role in protection against virus
infections. You will understand this when you think that viruses have to
live inside cells in order to multiply. Antibodies are no help because they
cannot get into cells to kill the virus. But T-cells are different. The T-killer
cell recognises if a cell contains a specific virus because little bits of telltale viral protein are expressed on the surface of the infected cell. Then
the T-killer cell really goes to work. A single T-killer cell can kill many
virus-infected cells.
T-cells kill in a fascinating way. It involves two mechanisms. In the first, the
killer cell punches holes in the membrane of the target cell, causing its
contents (including incomplete virus particles) to leak out. In the second,
the killer cell activates the mechanism that causes the cell to selfdestruct! It has been realised only quite recently that all cells are probably
genetically programmed to self-destruct under certain circumstances: this
is just part of the good maintenance of the body. What T-killer cells do is to
activate this programmed cell death. The self-destruction process is really
clever because not only does it destroy the home of the virus (the cell that
it has infected), the destruction machinery also destroys the virus itself.
Regulator T-Cells
Both CD4 T-cells and CD8 T-cells also regulate immune responses - they
can suppress other cells. Exactly which T-cells do this and how they do it
has puzzled immunologists for many years. At one time, it was fashionable
to talk about T-suppressor cells, but the majority view now is that
suppression is a property of several different types of T-cell. Nonetheless it
is an important concept that the immune system can suppress itself
through the action of specific T-cells. You can imagine that, once the
antigen has been dealt with, it is more helpful to the body to turn off the
immune response than to allow it to carry on.

42

Regulation in some cases reflects a balance between the actions of

different types of help provided by T helper cells - those that work with Bcells on the one hand and those that activate macrophages on the other.
There are also types of T-cells that regulate each other. T killer and helper
cells interact as well. So, you can see that interactions between different
types of T-cell are central to the normal functioning of the immune system.
T-Cells Can Remember Too
We talk about T-cells in a general sense as providing memory in just the
same way as B-cells do. They survive quietly for many years in lymph
nodes just waiting for the same microbe to come along again. We believe
that a T-helper cell, for example, when it is re-awakened by another
encounter with its specific antigen, goes on being a helper cell again - but
it is just possible that particular T-cells can subtly change their functions in
later immune responses.

MORE ON T-CELLS AND B-CELLS

T-cells recognise antigens in a different way from B-cells.
T-cells are similar to B-cells in several respects, but they do not
react to
antigens in the same way. T-cells can only react to protein antigens
that
have been broken down into fragments called peptides inside
infected
body cells or activated immune cells. Body cells push these
peptides
out to their cell surface, presenting them in such a way that other
immune cells can easily recognise them. They do this by binding the
'foreign' peptides to important cell-to-cell recognition molecules
called
Major Histocompatability Complex (MHC) molecules. A useful
analogy is to think of the MHC molecule as a sort of flag which
carries
a message along the lines of "Help: under attack!"
The binding of T-cell receptors to the MHC-peptide assembly can
bring
about the activation of that T-cell. This is a complex process: for
example, with T-killer cells the CD8 molecules on their surface
engage
MHC Class I molecules with peptide in them on the presenting cell.
Helper T-cells, on the other hand have a CD4 molecule on their
surface
which engages an MHC Class II molecule on the presenting cell.
Now, MHC Class I molecules only present bits of proteins that were

43

made inside the presenting cell. Class II molecules only present bits
of
proteins made outside the cell that were then taken up by the
processing cell. All cells have Class I molecules, so when infected
with
virus they are all able to be identified as fit for destruction by CD8
cytotoxic cells.
Class II molecules are much more limited in the cells that express
them,
so only some cells have the presenting ability to activate the
helping or
amplifying cells of the immune system.
A good idea when you think about it. For their efforts in unravelling
this marvellous machinery, Rolf Zinkernagel and Peter Doherty
were
awarded the Nobel Prize in 1996.
MORE ON ANTIGENS
After you have read the sections on B-cells and T-cells you may like
to
know a bit more about antigens and how the lymphocytes interact
with
them. It may help to expand a little on what antigens are.
First, the term is functional: anything that can evoke a specific
immune
response is usually called an antigen. We know that substances in
all
classes of chemicals can work in this way: proteins, carbohydrates,
nucleic acids, lipids, organic and inorganic substances have this
property. So it is not just the proteins on the outside of a bacterium
that can function as antigens, but also things inside the cells and
substances in our environment.

We know a lot about protein antigens, and it is reactions against

them that are at the heart of protective immunity.
There are important differences about the way that T-cells and Bcells recognise antigens. The BCR of Ab binds to small areas,
called antigenic determinants, on the surface of the protein.
Because the sequence of a particular protein does not usually
repeat itself, different determinants have different structures.
Thus, B-cells of different fine specificity can react to different
determinants on the same cell. One antigen therefore can
activate several different clones of B-cells.
The same is basically true of T-cell specificity, but whereas B-cells

44

recognise determinants on intact proteins, T-cells need the

protein to be broken down and presented to them in a very
particular way in order to be recognised.

Stimulating Immunity

A great deal of effort is put into medical research to try to find ways of
stimulating our immune system to work even better than it does. Our
immune system is beautifully designed - most of the time we are unaware
of how well it works - but there is a war going on with the microbes and
parasites around us. Some of these pathogens are dangerous and
infection can kill before protective immunity can build up.
Key points

immunisation mimics infection without producing disease

some vaccines are tremendously successful: smallpox was
eradicated
through mass immunisation
vaccines must be safe as well as protective
some pathogens mutate, making immunisation difficult
new vaccines are under development
animal vaccines are widely used and are very effective

5.1 Immunisation
Immunisation gives the immune system advance information
about a pathogen so that it can be ready to do battle if necessary.
Today, in the UK we are usually immunised against diphtheria,
whooping cough, polio, measles, tetanus, mumps, rubella and TB.
In an unimmunised person these illnesses can cause permanent
damage and, in some cases, death.
When we are immunised against an infectious disease like
measles, our immune system is pushed into action. The vaccine
(the substance that we are immunised with) activates B-cells and
T-cells in the same way as a real infection would do. In fact, the
vaccine looks like the real measles virus but it has been changed
so that it is not dangerous.
The end result is that our immune system forms memory cells. If
we are exposed to the real measles virus later, our body will be
able to destroy it before it harms us.

5.1.1 Immunisation
Disease

Mimics

Infection

Without

Producing

45

One of the most important tools in the fight against these pathogens is
immunisation. The principles of immunisation are very simple. (The term
differs from 'vaccination' in that immunisation is the looked-for result of
vaccination.) The body is given an altered form of a pathogen which tricks
the immune system into responding to it as if it were a real infection.
Immunity to the pathogen forms and when the real pathogen is met later
in life, the body is able to mount a massive and very effective response.
Some acquired immunity is permanent but some not. To be effective, the
immunity produced by immunisation should be as good and as longlasting as that induced by a real infection. It's also important that the
vaccine does not cause the serious disease of the natural infection and
that it does not have damaging effects on the person being immunised
and is as safe as it possibly can be.
Some vaccines are tremendously successful: smallpox was eradicated
through mass immunisation. Smallpox, a viral disease, was completely
eradicated during the late 1970s as a result of mass immunisation with a
hugely successful vaccine. The development of an effective vaccine for
smallpox began two hundred years ago. Edward Jenner knew nothing of
viruses, but he observed that milkmaids who caught cowpox, a trivial
infection in humans, never got smallpox, the terrible disease that
disfigured many and killed about 25% of its victims. Jenner's experiment
was to inject some pus from a cowpox scab into a small boy and then to
show that when the boy was later injected with smallpox pus, he did not
get smallpox.
Jenner had confidently predicted the successful outcome of his
experiment. Think what we like about the ethics of that experiment (which
would never be permitted today), it was a landmark in the fight against
disease which formed the basis of vaccination with vaccinia virus and the
world-wide eradication of smallpox. The hope is that diseases like polio
and measles might also be soon eradicated through mass global
immunisation.
Eradication of a disease depends on two vital factors. The first, which is
very much under human control, is the number of people immunised. You
don't usually have to immunise absolutely everybody, but a high
proportion must be protected to prevent the infection being transmitted. If
this is achieved, then the virus could, like smallpox, become extinct,
providing man is the only host of the infectious organism. (Remember,
other animals carry many of the same pathogens.) The second factor, not
under human control, is that the target pathogen must be very stable. This
means that it does not mutate and change itself so that people immunised
remain permanently protected against infection. We are all familiar with
the way the influenza viruses mutate and give rise to epidemics. The
spread of these can be predicted accurately by scientists who examine the
virus type involved in a new outbreak. This is why flu vaccines with the
current strains need to be given to people at risk every year.

5.1.2 Vaccines Must be Safe as Well as Protective

Disease-causing pathogens must be changed before they can be used as
vaccines so that do not cause the disease itself. By repeatedly growing a

46

pathogen outside of the body or by treating it with chemicals, it can

become attenuated (weakened). It is still able to infect and stimulate an
immune response, but it is unable to cause disease. At the beginning of
this book the distinction was made between infection and disease - an
attenuated vaccine should induce immunity but not disease.
We have a variety of successful bacterial vaccines against whole bacterial
cells or the toxins they produce. Some of the most effective virus vaccines
are made of attenuated live virus but dead virus particles can also make
effective vaccines (i.e. hepatitis, rabies and polio). But the success of
vaccines made of these dead particles depends on their ability to provoke
a strong immune response because the particles are too feeble to infect
cells as the real virus would. This is an 'only sometimes successful'
strategy which puts the system on alert without properly mimicking
infection. The search is on for safe versions of viruses that can be used in
vaccines
In the early years of vaccine development, inexperience in vaccine
production led to serious problems and some deaths. In the 1950s for
instance, at a time of major polio epidemics, a batch of killed polio virus
particles was not properly inactivated. Today, we understand that such
potential dangers exist - one of the reasons why the research and
development of vaccines is such a slow process. Public confidence in
vaccine safety is very important, not least to countries' health
departments, because vaccines are given for the good of both the
individual being immunised and the wider good of a society that wants to
rid itself of dangerous infectious diseases. In the UK, children are usually
immunised against diphtheria, tetanus and pertussis, polio and
Haemophilus influenzae B (HiB, a form of meningitis) in the first year of
life, and measles, mumps and rubella in the second. Other vaccines can
be given later or when there is a known risk of exposure.

5.1.3 Some Pathogens Mutate, Making Immunisation Difficult

The problems when viruses mutate are very real. The human
immunodeficiency virus (HIV) is a good example: it keeps mutating its
protein antigens so that as soon as effective immunity has been generated
against it, the antigen changes and the immune system has to start all
over again. Scientists would like to find a vaccine that uses a bit of a
protein of HIV that does not change and which will induce good protective
immunity.
The same problem of mutation occurs in some parasites that cause
serious disease throughout the world.
Trypanosomiasis, or African
sleeping sickness, is caused by a protozoan (a unicellular organism) that
keeps on changing its coat proteins, thoroughly confusing the immune
system of the infected host. This is one example of evasion by parasites:
there are others in which, for example, parasites change their antigens
during their complicated life cycles and hide inside cells of the host for
most of the time. Plasmodium, the malaria parasite, evades the immune
system in this way

5.1.4 Animal Vaccines are Widely Used and are Very Effective

47

We should remember that immunisation is quite widely used for animals

as well because they have their own health problems, in addition to many
they share with humans. Feline enteritis and canine distemper are
examples of life threatening diseases that can now be vaccinated against.
Obviously good health is important in companion and farm animals: and
the vaccines used are designed to protect animals from serious disease, to
maintain healthy farm animals for food, and to prevent catastrophic
financial loss for farmers whose animals may suffer these diseases. It's
worth noting that vaccines for animal diseases are developed through the
same research process as are vaccines for human diseases.

6
AIDS
(Acquired
Syndrome)

Immune

Deficiency

In an 'immunodeficiency' the immune system does too little. AIDS

is an immunodeficiency condition caused by the 'HIV virus. People
do not always know they have been infected with the virus
because it is usually years before symptoms of AIDS appear. The
precise reason for the gap between the initial HIV infection and
serious illness is not clear.
What is clear is that the virus gets into some of the cells of the
immune system and disables them. Eventually the natural
defences of the body are no longer able to cope and people with
AIDS become unable to fight off other infections.
Medicines can now deal with some of the infections and also hold
the virus at bay for a time, so people can live with HIV and AIDS
much longer. But we need to find medicines both to kill the virus
more effectively and to help the immune system defend itself.

6.1 Immunodeficiency
Immunodeficiency is the term used to describe a breakdown in the
immune system. This can happen for various reasons including genetic
problems, irradiation, cancer and infection by pathogens such as the
Human Immunodeficiency Virus (HIV), the virus which leads to Acquired
Immune Deficiency Syndrome (AIDS).
Key points

AIDS is a syndrome caused by HIV

HIV infection precedes AIDS
the symptoms of AIDS vary but AIDS allows other pathogens to
infect
the body and tumours also increase
much progress has been made to find new treatments for AIDS
which
is still a big challenge
48

AIDS is not the only cause of immunodeficiency

6.1.1 Aids Is a Syndrome Caused by HIV

A syndrome is a complex condition with multiple symptoms, presenting
itself in different ways in different people. AIDS, to give it its shortened
name, is a syndrome in which a person's immune system essentially
becomes ineffective - they become immunodeficient. When the immune
system ceases to function as well as it should we become susceptible to
all sorts of infections that would usually be uncommon or trivial.
Over the years since AIDS was first recognised, better treatment for AIDS
related illnesses has been increasing life expectancy. Until very recently
however, AIDS has been thought by most medical scientists to be
invariably fatal. Now, new treatments aimed at the virus itself are helping
many people to return to good health, often with a viral load so low as to
be undetectable. It's too early to say whether some people taking these
treatments will remain well and have a normal lifespan. For now at least,
they are making a big difference and new treatments are being developed.

6.1.2 HIV Infection Precedes Aids

It is now certain that the human immunodeficiency virus (HIV, for short) is
the sole cause of AIDS.
The first sign of HIV infection is usually no more than a mild fever which
subsides after a few days. There may be no outward signs after this for a
long time, more than fifteen years in some cases. During this time the
virus survives inside cells of the immune system (mostly T helper cells and
macrophages) and the infected person's immune system reacts repeatedly
to the virus to try to keep the infection under control.
This period of HIV infection can be diagnosed because the body makes
antibodies to the proteins of HIV, and virus antigen can be found in the
blood. Hence people who have been infected but are otherwise perfectly
healthy are said to be HIV positive. For reasons that are not entirely
understood, the effective control of the virus eventually breaks down and
the cells of the immune system are slowly destroyed. The loss of T helper
cells is one important part of this, and it means that making effective
immune responses becomes progressively more difficult.
HIV is a very resourceful virus which finds new ways to avoid the barriers
put in its path. To make it harder for the virus to do this, combinations of
medicines (generally three) which use different strategies to obstruct the
virus are now used together. The idea is both to harm the virus and to foil
its efforts to take evasive action - thereby so weakening the virus's ability
to take over immune cells that the immune system is not further
compromised and can even recover and fight effectively again.
The 'triple therapy' regime is more effective for some people than for
others. Also, it's very complicated to stick to and all medicines can have
side effects. So not everyone gets on well with the treatments. Even with
successful combination therapy, eventual drug resistance is possible. So

49

the development of new medicines remains an urgent priority. But

scientists are optimistic that AIDS will soon become, if not curable, at least
a manageable illness.
Exactly when and where HIV first appeared is a matter for heated
argument, like many other aspects of AIDS biology, but the general view is
that it is a fairly recent arrival amongst viruses that infect humans. It
probably arose as a version of a virus that infected a wild animal, an
African chimpanzee, it is now thought. Many animal species have their
own versions of immunodeficiency virus that cause their own speciesspecific version of AIDS. Research into these related animal diseases has
given scientists important insight into how HIV infiltrates and then hijacks
the cells of the immune system.

6.1.3 The Symptoms of Aids Vary but by the Time Someone

Has Aids, Other Pathogens Have Been Able to Infect
the Body and Tumours also Increase
As the immune system becomes deficient, so the symptoms of AIDS
appear. These can include such things as Kaposi's sarcoma, a cancer that
is otherwise uncommon. The main feature in most people with AIDS is the
continued development of all sorts of infections that are otherwise
uncommon or much less serious in healthy people. A serious form of
pneumonia, from the normally harmless pneumocystis organism, and
tuberculosis are the main causes of severe infection. These infections
need aggressive treatment with antibiotics. Cytomegalovirus, a virus
infection, and fungal infections that usually wouldn't be a serious problem
can be life-threatening and so need prompt and powerful treatment.
Patients eventually die from infection or tumour, so it is the AIDS-related
illness that actually kills, not the HIV virus and not the state of
immunodeficiency itself.

6.1.4 Finding Effective Treatments for AIDS is still a Big

Challenge
The newer AIDS therapy is costly and needs careful management so is
unavailable to many people, particularly in developing countries. One
great challenge to medical science posed by AIDS is to find a vaccine that
will protect against infection, but this has proved to be elusive so far.
There are many reasons for this but a major one is that the virus changes
its antigens very easily, so the patient's immune system is repeatedly
fooled by the appearance of 'new' versions of the virus against which no
effective immunity has been developed.
An added problem for
researchers is that, although animals have been crucial in the
understanding of the immune system and the nature of HIV as well as in
the development of treatments for people with AIDS, the infection in
animals is not identical. These factors have made vaccine research slow
and difficult.

6.1.5 A Very Small Number of People Seem to be Naturally

Resistant to HIV

50

Everyone is aware of AIDS as a big public health problem and it receives

intense coverage because it causes premature death in otherwise healthy
and young people. This has dispelled many of the misconceptions about
AIDS which existed a few years ago and it has also brought to scientist's
attention some individuals who seem to be resistant to HIV infection even
though they are exposed repeatedly to HIV. Study of such populations is
undoubtedly important to help us unravel the genetic influences involved
in resistance to HIV.

6.2 HIV Is Not the Only Cause of Immunodeficiency

There are many other sources of immunodeficiencies. Some children are
born without an immune system which works properly. These people have
primary deficiencies, but these are relatively uncommon. More frequent
are acquired (or secondary) deficiencies, AIDS being just one example.
Some medicines can cause immunodeficiency for example those used to
treat cancers or prevent graft rejection may have these effects, but this
can usually be controlled by getting the dose at just the right balance.
Even without medicines that might have this effect, some cancers seem to
induce deficiencies.
Mice and rats also have a great range of well studied immunodeficiencies
and have been vital in unravelling the role of different lymphoid tissues
and cells in specific immunity.

Suppressing Immunity

7.1 Autoimmune Diseases

Like any other body system, the immune system can become
faulty. Sometimes the body's cells and chemicals which normally
deal with pathogens, turn against the body itself. This can cause a
variety of illnesses known as 'autoimmune diseases'.
Rheumatoid Arthritis (RA) - In this disease the body starts to
attack its own joints which become inflamed and may be badly
damaged. It can affect young people as well as older people.
Although many people with RA can be helped by medicines, some
become very disabled.
Diabetes - In the type of diabetes young people get, the body
damages special cells in its own pancreas. These cells normally
make insulin, a hormone which is needed by the body to turn

51

carbohydrates into energy. People with 'juvenile onset' diabetes

must have regular injections of insulin to stay alive.
Multiple Sclerosis (MS) - A disease where white blood cells enter
the brain and damage the coating on nerves, causing loss of
function. Someone with MS may become disabled.
Key points

a healthy immune system can recognise self

autoimmunity can lead to serious illness
autoimmunity might be genetic or it could result from infection
autoimmune disease can be difficult to treat but there are
effective medicines and research into novel therapies is in
progress

7.1.1 A healthy Immune System Can Recognise Self

While lymphocytes are developing, cells are created that have the ability
to react against self (antigens that form part of our own body), rather than
non-self foreign antigens. Obviously, these cells could do serious damage,
so there is an ingenious selection system that destroys those that react
too strongly against self. Not all are killed, however, and some do escape
to populate the lymphoid tissues. Here they are controlled by other
lymphocytes and by the fact that they usually cannot get to the self
antigens to which they are specific (lymphocytes cannot get into healthy
living cells).
It was the traditional view that autoimmunity had to be avoided by the
immune system at all costs - it was what the famous pathologist Erlich
called "horror autotoxicus" (the fear of self intoxication!). Well, we now
understand, more than he could ever have done, how in the right
circumstances, this self reactivity is actually a useful thing. After
wounding, burns or surgery, for example, material escapes from damaged
tissue and the inside of cells: we make antibodies against this junk and
they bring about its effective clearance by phagocytes. This is part of the
healing process. The antibodies are not made any more after the damaged
self has been dealt with. These antibodies tend to be made by B-cells
without the help of T-cells.

7.1.2 Autoimmunity can Lead to Serious Disease

If T-cells do become activated to self antigens, then there can be severe
consequences. We call this autoimmune disease. There are many different
autoimmune diseases, and in the UK probably more than 5% of the
population lives with one or another at some stage in their life. They differ
in their severity, but many are severely debilitating and can be fatal after
often prolonged illness.

52

Autoimmune disease can involve a single organ or tissue, as in diabetes,

or several as in rheumatoid arthritis (really a syndrome) which affects
not only joints but also blood vessels, skin, tendons among other tissues.
Aside from these two the other diseases that are best known and most
common are thyroid disease (goitre, thyroiditis), multiple sclerosis
which affects the brain and spinal cord, systemic lupus erythematosus
('lupus') affecting kidneys, skin and brain and pernicious anaemia
affecting the intestine. There are also autoimmune versions of liver
disease and there are several blood diseases such as autoimmune
haemolytic anaemias that are medically important too. Many cases of
blindness in adults result from an autoimmune reaction against the eye.
These diseases present us with a real challenge: they are frequent and
cause tremendous morbidity. This is a big cost to the person with the
illness, their family and society in general. Patients may need to take a
variety of medicines to control the illness and its symptoms for many
years and may become relatively immobile and unable to work, for
example.

7.1.3 Some Cases of Autoimmunity Are Genetic, Some Result

from Infection
We do not yet really understand why autoimmune diseases arise in the
first place. We know that susceptibility may be inherited in some diseases
but there are obviously many factors that need to converge for one
individual to become ill. Infection is probably crucial in many, but there is
almost certainly not going to be a virus that causes, for example,
rheumatoid arthritis but rather a range of related infections that
precipitate in susceptible people a chain of events that lead to T-cells
becoming switched on by some self antigens. In some diseases, we don't
really know what the crucial antigens are.

7.1.4 Autoimmune Disease is Difficult to Treat But There Are

Effective Medicines and Research Into Novel Therapies is in
Progress
Treatment varies considerably according to the illness and its severity.
Firstly, we have medicines which correct the imbalance or replace the
substances that cannot be made by the tissue that has been damaged by
the autoimmunity, here insulin for diabetes and thyroxin for thyroiditis are
fairly well known examples. Secondly, we also frequently use medicines to
damp down - turn off or suppress - the immune system. Very fine
judgment is needed to get the dose just right: it needs to be high enough
to suppress the autoimmune condition without shutting down the whole
immune system to make the patient susceptible to all sorts of unwanted
infections.
There is intense research into autoimmune disease aimed at
understanding the mechanisms behind the development of the disease
and how it damages self tissues. New therapies based upon feeding self
antigens (an unexpected idea at first sight, but one which induces
suppression of responses to antigens) were first studied in rodents and are
now being tested in human clinical trials in multiple sclerosis, rheumatoid
arthritis, uveitis (the major cause of sudden adult blindness) and diabetes.

53

7.2 Allergies
An allergy is an exaggerated immune response. In asthma,
inflamed narrowed airways create breathing problems. The
condition is usually caused by underlying allergy.
Hay fever is an allergy to pollen. When someone with hay fever
breathes in pollen particles, the pollen reacts with special white
cells, called mast-cells that line the nasal passages. Crucial
experiments in animals have shown that these cells then burst
open. They release chemicals, including histamine, which produce
an immediate inflammation. This leads to a streaming nose, runny
eyes and sneezing.
Why do some people have allergies? The main reason is that, in
people with allergies, the mast-cells are coated with a special sort
of antibody which reacts with allergens. This reaction makes the
mast-cells open. Other people don't make these special
antibodies.
Key points

an allergy is a condition where an immune response to a foreign

antigen causes incidental damage to the body
allergies involve mast-cells and a special class of antibody
the allergic response has several stages
food allergy and intolerance can be severe
allergies happen when the immune system does too much
the incidence of asthma seems to be increasing

7.2.1 An Allergy Is a Condition Where an Immune Response

to a Foreign Antigen Causes Incidental Damage to the
Body
Most people are familiar with the idea that we can be allergic to things in
our environment such as cat fur, house dust, pollens, food or chemicals these are called allergens. The word allergy is sometimes used very
loosely to describe all sorts of reactions to environmental substances, but
it has a very precise meaning to immunologists. Allergies are conditions
where an immune response to a foreign antigen (the allergen) causes
problems for the body.
Typically, the allergy sufferer becomes immunologically sensitised to cat
fur, for example, which acts as a powerful antigen. When the same
material is again encountered later on, a reaction occurs that is
unpleasant in its effects and can be very dangerous in some cases.

54

The reactions may involve an asthmatic attack, a skin rash or vomiting

and diarrhoea. Exposure to allergens often happens through mucosal
membranes of the respiratory tract or gut, hence the symptoms
associated with these systems.

7.2.2 Allergies Involve Mast-Cells and a Special Class of

Antibody
The critical component of allergies of this sort is a special type of antibody
known as IgE which has the unique property of sensitising mast-cells. In
fact, the presence of IgE antibodies against the foreign antigen (the
allergen) is used to actually diagnose allergy. Mast-cells are normally
associated with mucous membranes, so allergies very often involve the
lungs and gut.
When mast-cells meet the antigen that binds to the IgE antibodies on their
surface, these cells burst open releasing many natural compounds that
cause the mucous membranes to swell and become inflamed: histamine is
one of the substances, hence the use of anti-histamines and similar
medicines in allergy. The sensitisation is usually initiated by breathing or
eating the material.
Why do some people become allergic to particular substances while
others, who live in the same environment, do not? Undoubtedly there is a
genetic element that makes some susceptible, and there are individuals
who have an obviously heightened tendency to be allergic to many
different things, they are said to be atopic.

7.2.3 The Allergic Response Has Several Stages

If we take sensitivity to pollen as an example, we can see distinct stages
to the allergic response. The first reaction is, as anyone who has hay fever
will know only too well, quite quick and involves tickling in the mouth and
nose, sneezing, running eyes and coughing. Remember too that these are
protective reactions designed to get rid of the offending substance (pollen
in the case of hay fever). However, this is only partly effective and a later
phase to the reaction appears after a few hours. This involves
inflammation and serious constriction of the airways, and this is potentially
much more dangerous than the initial symptoms. The late phase depends
on other cells called eosinophils and on T-cells, so it is for this reason
that immunosuppression of T-cell activity is needed in people with severe
respiratory allergy. This is the point of longer-term asthma medicines that
are used to keep day-to-day inflammation under control.

7.2.4 Food Allergy

There are many examples of food allergy that depend upon the same
mechanism as hay fever. Childhood allergies to things like the protein of
egg white are common: they cause nausea and can be avoided by not
eating the offending food. Fortunately, this type of allergy usually clears
up within a few years. There are, however, sometimes very dangerous
reactions to foods in sensitised people, and in recent years there has been
a great increase in nut, particularly peanut, allergies.

55

Within a matter of minutes of exposure to the allergen, an allergic person

can experience massive constriction of the airways which could suffocate
them without treatment. (It's worth noting that many people are intolerant
to certain foods for reasons other than allergy e.g. lactose intolerance.)

7.2.5 Protective Immunity and the Origins of Allergies

Allergy happens when the immune system does too much: we term this
situation hypersensitivity. There are many different allergies, involving
antibodies of other sorts of T-cells making inflammatory cytokines. They
can have unpleasant or dangerous side effects and they are all ways in
which the immune system reacts to foreign or invading antigens in an
attempt to get rid of them. Often, there are complex reactions involving
more than one mechanism working together. An important point is that
these adverse reactions are, in reality, expressions of the machinery that
has evolved to protect us from infectious diseases.
Why then do these conditions arise? We don't know for certain, but we do
know that the cells and mediators involved in our hay fever example are
those that are needed to deal with infections of parasitic worms that infest
the gut or lungs. In Europe, such parasites are rare, and it may be that the
unused capacity of our immune system gets misdirected to dealing with
other substances in our environment to which we just cannot avoid
exposure.
Given the high incidence of allergy, the development of anti-allergy
medicines is now a very important quest. Animals, like humans, make IgE
antibodies against inhaled antigens, so their use is very important in
analysing the mechanisms of allergy and in testing new medicines.

7.2.6 The Incidence of Asthma Seems to be Increasing

The incidence of asthma in children has risen quite alarmingly in recent
years. Many people feel it is a consequence of the polluted environment of
our towns and cities. However, the incidence has risen just as much in
New Zealand which has a much cleaner environment than the UK, so
pollution alone is not an adequate explanation. There is suggestive
research in mice, however, that pollutants like diesel exhaust particles can
work to promote sensitisation to antigens that are inhaled. The relatively
closed-up environment of the modern home also encourages a
concentration of house dust, for example, and this may also be a
contributing factor.

7.3 Organ Transplants

Today many people can lead active lives because they have had a
kidney, lung or liver transplant.
As we might expect, putting an organ from one person into
another person so that person recovers and goes on to lead a
normal life, is not easy. Normally, the immune system of the

56

person with a transplanted organ would attack and destroy the

'intruder' organ. We describe this as the organ being rejected.
To give the best chance of success, donors and receivers of
organs are carefully matched using tissue typing techniques. But
this is not enough. Medicines are needed to damp down the
immune system.
There are medieval references to transplantation of limbs but it is only in
the twentieth century that transplantation has become a practical reality.
Against widespread indifference and resistance, groups of doctors
throughout the world persevered with experimental surgery and showed,
in the 1960s and 1970s, how kidneys, lungs, hearts and livers could be
transplanted from one individual to another. Success rates have increased
significantly since then: kidney transplants, for example, are now highly
successful.

Key points

the techniques for transplanting organs and tissues are very

advanced but we still face immunological problems
graft rejection can be prevented using tissue typing and
immunosuppressive medicines
there are not enough organs to supply all the people who
desperately need transplants
xenotransplantation (using animal organs) might be an answer
to
the organ supply problem
bone marrow grafts and stem cells are a special case

7.3.1 The Techniques for Transplanting Organs and Tissues

Are Very Advanced But We Still Face Immunological
Problems
Organ transplants have saved many thousands of lives. Unfortunately,
very large numbers of people die prematurely throughout the world from
kidney failure, heart, respiratory and liver diseases. The surgical problems
of transplanting organs have been very much overcome, and high
standards of patient care have increased success rates. But doctors are
still battling against underlying immunological problems.

57

Transplants of cells, tissues or organs between different individuals are

recognised as foreign by the recipient's immune system and are rejected.
The antigens on the transplanted organ that matter most are the
molecules of the MHC - these molecules are on all cells and tissues and
their real job is to control T-cell activation in response to foreign antigens.
They were obviously not put there to frustrate transplant surgeons, but the
fact is they do. Because we all have slightly different MHC molecules, the
T-cells of the host react very strongly to the MHC molecules of the donor.
The ensuing immune response destroys the graft or transplant. As in
allergy and autoimmunity, the mechanisms that have evolved to protect
us from pathogens are actually those that do harm.
Years of careful research in laboratory animals have given us a great
understanding of why and how grafts are rejected. In the discussion of
kidney or heart grafting it is too easy to forget that transplantation has
actually been going on very successfully with other tissues. Blood
transfusion is a form of transplantation. It is comparatively easy to match
blood group antigens to ensure that transfused blood is not destroyed by
the recipient. But transfused red blood cells are not expected to survive
indefinitely, and in any case, they cannot because they have a limited life
span. Corneal transplantation has been a routine medical treatment for
years. The cornea is unusual in that lymphocytes do not normally have
access to it, so rejection is not a great problem.

7.3.2 Graft Rejection Can Be Prevented Using Tissue Typing

and Immunosuppressive Medicines
Dealing with graft rejection is complex. Finding suitable donors can be
difficult because they must be as genetically similar as possible to the
recipient, so that the recipient's immune system does not see the organ as
foreign. Because the MHC is so very varied in the human population (we
say it is highly polymorphic), the chances of finding a perfectly matched
donor for a particular recipient are practically non-existent. So, the best
tissue match possible is usually used. This can sometimes involve using a
living related donor, a parent donating a kidney to a child for instance.
Unrelated people who have died suddenly, most often in road traffic
accidents are the main source of organs for transplantation. To maximize
the chance of finding a matched organ and to ensure that available organs
are used most effectively, there are national and international agencies to
act as information centres to flash the tissue type of newly available
organs across the country, or even across the world.
Along with a good tissue match, immunosuppressive therapy is needed to
overcome rejection. There is now a variety of medicines used, but one,
ciclosporin, revolutionised transplantation. This is because of its ability to
suppress immune response in very specific ways but, crucially, with
relatively little effect on the rest of the immune system - enabling the
body to accept the transplant while avoiding the problems immune
suppression could invite. Ciclosporin was discovered during a screening of
natural compounds. Studying this particular compound in mice, a sharpeyed scientist noted that it suppressed specific immune responses. It was
then tested in autoimmune conditions and alleviated those too, and was
shown to be very good at preventing graft rejection in a range of species.
This gave the confidence for clinical trials in humans that were successful.

58

7.3.3 There Are Not Enough Organs to Supply All the People
Who Desperately Need Transplants
Without doubt, transplantation of organs saves many lives but the supply
of donor tissues is a great problem. In spite of the willingness of many
people to donate their organs after death, there is a long waiting list of
seriously ill people hoping for transplants. The list is growing at about 15%
a year. Even with concerted efforts to encourage more people to agree to
donate their organs, there would not be anywhere near enough kidneys,
hearts and lungs available. For this reason, there is intense interest in
artificial and mechanical transplants. These can work very well when the
transplant involves bone, as in hip replacement. There are no immune
problems here: the new joint is metal and plastic and therefore not
antigenic. However, artificial hearts do not match the exquisite natural
version.

7.3.4 Xenotransplantation (Using Animal Organs) Might Be

the Answer to the Organ Supply Problem
Research today is looking at the alternative of using animals as donors.
Normally, such a transplant would be immediately rejected by a rapid
immune attack above and beyond that which would occur in a human-tohuman transplant. But there is confidence that this 'hyperacute rejection'
can be overcome by genetically modifying donor animals, and then
breeding them, so that they carry a small piece of human DNA - much less
than 1% of the genome - which selectively inhibits the attack by
complement. This is a system of proteins in the blood which would, if
activated, cause the hyperacute rejection. This should allow animal organs
to be accepted by the human body. Of course, even if this is successful,
the normal rejection problem would still need to be overcome with
medicines.
Grafts from other species, xenografts, raise ethical and scientific issues.
Individuals will have their own views on the ethics of xenotransplantation
but given the seriousness of the illnesses with which potential recipients
are living and high standards of animal welfare, it is likely that people
would accept these organs if safety questions are able to be satisfactorily
answered. Pigs appear to be the best choice because their organs are of
comparable size to human organs but we need to know more about the
potential risks of infection by animal viruses that might be carried by the
donor. It is encouraging to think, however, that pig skin and other cells and
tissue have been used in humans for many years.

7.3.5 Bone Marrow Grafts and Stem Cells Are a Special Case
Bone marrow transplants have received a lot of attention: partly because
they are used to treat leukaemia in children and partly because of much
publicised efforts to match donors. The mechanical process of
transplanting marrow from one person to another is now straightforward.
But the immunological problems are even greater than in other
transplants, as marrow cells are especially sensitive to immune damage.

59

Very good tissue type matching is vital, and even then the graft can, under
some circumstances, attack and damage the recipient. This is graftversus-host disease and can be very serious. People with particular forms
of leukaemia receive transplanted bone marrow, having first received
aggressive chemotherapy to effectively destroy their own faulty marrow.
Although there are potentially serious risks, the success rate is now very
high giving the patient back a healthy immune system.
Despite improvements in bone marrow transplants there is a much more
exciting prospect which might make bone marrow transplants a thing of
the past. It turns out that normal blood contains stem cells, admittedly in
tiny numbers, and these can now be purified, concentrated and used to
repopulate the marrow of patients. Better than adult blood, the blood in
the veins of umbilical cords has much larger numbers of stem cells and
these are now being used in a few places with great success.
This is a marvellous use of human tissue that otherwise is mostly
discarded. One thing for sure, there is an enormous supply of cords and
they give us few medical and ethical problems.

Animals and Research

Improving our biological understanding and our ability to

immunise against, diagnose and treat illness depends on a variety
of research methods including research in animals.
Here are examples where animals have been necessary in
research in the immune system:

it was discovered that T-cells and B-cells are important in

immunity because of research in mice and chickens

the discovery of the mechanisms which lead to graft

rejection depended on research in rats and mice. The ability
to suppress the immune system in mice and subsequent
research in dogs led to effective anti-rejection medicine
which made organ transplantation successful

antibodies, mainly raised in rabbits and mice, are used to

diagnose disease.
Animals help us find out how the body defends itself against
infection and how autoimmune diseases develop. Diabetes,
multiple sclerosis and rheumatoid arthritis are all examples where
the study of animals has suggested new ways to prevent and
treat these diseases in humans. And potential new medicines,
which look promising on computer and in the test tube, need to
be studied in animals before they can be tested and used in
people. Of course, the use of animals should be avoided wherever
possible.
We tend to think of medical advances in terms of tangible progress - new
medicines, surgical procedures and medical devices. But underpinning
these advances is much more basic research which probably doesn't make

60

gripping reading to non-scientists but which can add enormously to,

sometimes even radically change, what researchers know about how, for
instance, the immune system functions.
Biologically, humans are very like other animals in so many important
ways. This means that what we can observe in animals will be useful in
understanding what is going on in humans. This is especially true of
immunity and resistance to infection. We know from many years of study
that we, as humans, react to infections in very similar ways to mice, rats,
dogs, horses and so on. It follows that, by looking at the body's immune
system in animal studies, we can derive important benefit for humans.
There are many examples of immunological discoveries in animals that
have greatly helped the understanding, diagnosis and treatment of human
illness, and several examples have been mentioned already.
Much of our fundamental understanding of the cells and mechanisms of
immunity comes from research in animals. For example, the study of mice
that naturally lack a thymus taught us about the crucial role this organ
plays in T-cell development and in particular how it destroys most of those
cells that might cause autoimmune damage. Similarly, the role of the
Bursa of Fabricius, a lymphoid organ in birds, in dictating the development
of B-cells taught us that there are also critical events in their life history.
This knowledge has been applied in many ways including, for example, to
the understanding of the origins and nature of some tumours of lymphoid
cells.
The fundamental discovery that lymphocytes are the actual agents of
protective immunity came from experiments in animals where
lymphocytes were transferred between genetically identical individual
mice - and with the lymphocytes, it was found, came the immunity. This
was a crucial discovery. It also paved the way to identifying the myriad
and complex migration pathways that these cells follow in the normal
course of their lives in providing protection against infectious disease. It is
hard to overestimate the importance of fundamental discoveries such as
these: they not only have shaped our understanding of the functioning of
the immune system but they contribute to giving us a rational (that is,
logical) basis upon which to design medicines to affect immune function.
The genetic reasons for the rejection of transplants were elucidated first in
animals, and methods to keep transplants from being rejected were
developed in animals. These same studies also led to a significant
advance in understanding how our genes selectively control immune
responses in a general way and this has proved absolutely invaluable in
research on autoimmune disease and allergy, to give only two examples.
These are examples where animal research has not only enabled
experiments and analysis that would be impossible in humans, but it has
also greatly speeded up the rate of discovery of important facts.
Modern methods of genetic modification are used to add specific genes to
or to delete them from individual mice and rats, for example. From these
transgenic animals we learn very quickly about the importance of
particular genes in immunity. Thus, through providing important basic
information both about how the body maintains good health and the

61

nature of disease processes, ways are opened to develop new therapies

for otherwise intractable diseases.
Autoimmune diseases are a special challenge because we know so little
about many of them. Even so, the study of diseases mainly in mice and
rats, and also veterinary research into immune-related problems of our
companion animals, have given us great insights into the origins and
mechanisms of the diseases themselves.
From this, many scientists have been able to examine the potential of new
medicines or special treatment approaches for their effectiveness before
using them in humans. Newer approaches to treatment of diseases like
rheumatoid arthritis, multiple sclerosis and diabetes which use natural
products of the body have come directly from experiments in laboratory
rodents. In the same way, new insights and potential new treatments for
asthma and allergy are being developed from animal studies.
Another area that has depended on animals is the identification of
pathogens and other cell types and in the diagnosis of disease. Pathogens
cannot usually be identified simply by examining blood samples. But
pathogens (and also some tumours for instance) express tell-tale
substances and these can be detected by tests which use antibody.
To obtain 'monoclonal' antibody for use in hospitals and laboratories,
antibody first needs to be raised in animals (mainly mice) by immunising
them with the relevant antigen. Their antibody producing (lymphoid) cells
can then be used as the basis for antibody production in vitro. The ability
to do this in vitro, after the initial animal cells have been obtained, is quite
recent because it depends on modern laboratory techniques to first
'immortalise' these otherwise short-lived cells and then clone them to
ensure that they are specific to a single antibody only; hence, the term
'monoclonal' antibodies. 'Polyclonal' antibodies, raised in rabbits for
example, recognise a broader range of antigenic structures, and so are
used where the target antigen is unknown or where there are a variety of
antigens that could be relevant.

8.1 Why
Are
Medicines?

Animals

Needed

to

Develop

A statement from the Animals in Medicines Research Information Centre

(AMRIC) Project Sponsor:
All new medicines that doctors prescribe are developed with the help of
information from animal studies. This is also the case for vaccines. It's
simply not yet possible to adequately investigate the range of effects a
medicine may have using computers and in vitro methods alone, before
going into human testing. All new medicines must be studied in people
before they can be licensed but only after doctors and scientists have
learned enough about a medicine to feel confident that they can do so
without undue risk.
We recognise that many people find animal research hard to accept. Some
may believe that there is no justification for using animals for any reason,

62

no matter how important, and regardless of the attention paid to animal

welfare. Some others may accept, in theory, the use of animals for
medical purposes but find it difficult to understand why today, given rapid
advances in technology, all the research cannot be done in other ways.
In fact, much of that research is done in other ways it stands to reason
that pharmaceutical companies use the most modern technology they
can. But replacing all animal research, if achievable, is going to be a long
slow process. The reason is that medicines can affect and be affected by
countless interactions between all the cells, organs and systems in the
body - actions and reactions that, in many areas, we are only just barely
beginning to understand. Computers make theoretical models based on
the information they are given. By its very nature, cell culture looks at bits
of our biology in isolation. Some questions can only be addressed in the
whole living body - first in animals and then in people.

8.2 Balancing Human and Animal Life

Of course, there are differences between humans and other animals but
these are small compared to the similarities. Most of those potential
effects of medicines that cannot yet be investigated outside the living
body can be predicted on the basis of carefully designed and conducted
animal studies. Without these preliminary tests, studying potential new
medicines in people would put those individuals at considerable risk.
Even with strong feelings about our responsibilities to respect and protect
animal life, most of us would feel it wrong to risk causing harm to people
in order to avoid harming animals. Recognising this, government
departments of health around the world demand information from animal
tests before they will allow medicines to be tested and used in patients. At
the same time, governments also recognise that animals used in research
should be protected from unnecessary use and ill-treatment. In the UK this
is done through the Animals (Scientific Procedures) Act 1986.
Decisions about the research methods to be used at any given stage of
drug development are not taken arbitrarily. They are based on the nature
of the information that is needed. Using animals when other methods
could, realistically, provide the required information would not make
sense. Quite apart from the ethical issues involved, newer non-animal
methods are almost always cheaper and faster than animal studies they
replace.

8.3 More About Computers and Cell Culture

Today, terms like 'molecular modelling' are part of everyday conversation
in medicines research organisations. Because of the whole new field of
molecular biology coupled with new technology, we can do things on
computer today that would not have been possible in the past. For
instance, if it is known that, to block a particular enzyme, a molecule
would have to have a particular structure (as was the case for protease
inhibitors used in HIV treatment); computers can rapidly design thousands
of molecular variations of that structure. In addition, features known to be
associated with unwanted activity can be designed out.

63

But just to underline the point, it was only possible to do this on computer
because researchers already knew the structure they needed. In most
cases, computers still fill a more conventional role of allowing people to
work more quickly and efficiently than would otherwise be remotely
possible. Also, remember that 'designing' a molecule is not the same as
'testing' it.
Equally, cell culture work has progressed enormously. Advances in our
understanding of cell biology mean that we can grow a wide range of cells
and keep them alive, enabling researchers to study the direct effects of
test compounds on specific cells, whether for the desired biological
activity or for safety. This allows some work that used to have to be done
in animals to be done in-vitro.

8.4 High-Throughput Screening

There are also activity screens in which antibodies are used in a variety of
ways in state of the art robotic systems to search collections of
compounds for any that might have a particular activity. Using these
systems, research organisations can screen literally thousands of
compounds overnight and pinpoint ones that may have value as a new
medicine i.e. ones that react with a particular protein involved in a
particular illness. In these systems, the desired protein may be
manufactured by cells that have been genetically programmed to do so
and then drawn out of these cells by antibody specific to that protein.
This is a good example of how new technology and advances in biological
knowledge work together. Advances in robotics have added the speed. It
was the development of our understanding of genetics and how the
information in DNA can be harnessed to do specific jobs, coupled with
existing knowledge of the use of antibody that allowed robotics to be used
in this way. Not only has this spared animal life at the 'drug discovery'
stage (though some animals are needed to raise antibody) but it has
allowed pharmaceutical companies to investigate a vastly increased
number of compounds than would otherwise be possible.

8.5 The Whole Body

Medicines may have indirect effects on the body (such as raising blood
pressure or putting a strain on kidney function) for reasons that may be
unpredictable and so not programmable into a computer or identifiable in
cell culture. Developing a medicine is a long process of both information
gathering and elimination. Only a fraction of those compounds which go
through preliminary screens will go on to be studied in animals and only a
fraction of those will go on to be studied in people.
Animal research does not, nor do researchers expect that it would, give
final answers about the usefulness of a potential new medicine. Even after
extensive clinical trials involving thousands of patients, a new medicine

64

may still cause unexpected problems in some people, particularly when

very large numbers of people are taking it. But doctors and scientists have
to do the best they can to avoid causing harm to people.
The use of animals in research is not an easy or a comfortable subject. It
would certainly be preferable if all the necessary research could be done
in other ways.
Immunology is an area which has both contributed to and benefited from
advances in in-vitro technologies but animals are still needed.
Clearly, animals should only be used where necessary and always with
care. But illness caused by underlying problems in the immune system think of asthma, diabetes, rheumatoid arthritis and AIDS to name a few affect vast numbers of people.

8.6 The Future

Much of what we know about the intricacies of the immune system and of
what can go wrong, has only been recently discovered. Translating this
basic knowledge into treatments for people living with related medical
problems is a long uncertain process. But already real progress is being
made. New treatments for HIV and AIDS are making a dramatic difference.
Many people receiving the new medicines for multiple sclerosis have, for
the first time, a treatment that makes a major impact on their quality of
life.
There are new approaches to vaccination, such as DNA vaccines
mentioned in the book, and 'therapeutic' vaccines (which should be able
to harness the power of the immune system to help deal with a condition
once it is diagnosed). New vaccines are thought likely to make a huge
impact on medicine in future.
New approaches to the treatment of diabetes are being explored, some
well-advanced in the pharmaceutical industry pipeline. Increased
understanding of the genetic basis and underlying mechanisms involved in
other autoimmune conditions such as rheumatoid arthritis, asthma, and
allergy give real hope for prevention, improved treatment and cure in the
future. Even now, new ways to treat the inflammatory aspect of these
conditions are in development. There are developments in transplantation,
including the possibility that in the future, animal organs may be able to
used, saving many lives every year.
The list of possibilities, even in the next few decades, is too long to try to
cover here. Researchers build on the knowledge gained from the work that
has gone before them, adding to it their own experience and original
ideas. They use a combination of the best available research methods,
including the use of animals where necessary, to understand how our
bodies function in both health and disease and to find ways to prevent,
treat and cure illness.

65

GLOSSARY
Acute Phase Proteins They coat
invading tissue cells and

Made in the early stages of inflammation.

invading pathogens to prevent them
aid attack by phagocytes.

Adaptive immunity -

Another term for specific acquired immunity.

Allergens -

Substances that induce allergy.

Anaemia -

Condition in which the number of red blood cells are

reduced.

Antibodies Each

Protein molecules produced by the immune system.

antibody is specific for its own antigen.

Antigen immune

An antigen is a substance which stimulates an

response.

Antigen presenting
cells (APC) their

Specialised cells of the immune system that process

antigens from pathogens and then stick them on

antigens
Antigenic determinant or a T-cell

surface. T-cells find it easier to recognise foreign

that are presented in this way.
The part of a foreign antigen that an antibody
binds to.

66

Atopic -

Subject to multiple allergies.

Attenuated in
the disease it is

Weakened. Viruses are attenuated before being used

vaccines so that the vaccine does not cause
trying to prevent.

B-cell receptor (BCR) antigen.

A receptor on the surface of a B-cell that binds

Bacteria cause
species

Simple, single-celled microscopic organisms that can

disease. Example: Neisseria meningitidis, one of the
of bacteria that can cause meningitis.

Basophil * -

A type of white cell.

Commensal bacteria in the gut for

and help to
foothold.

Bacteria usually found on or inside the body,

example. These bacteria do not cause disease
prevent pathogenic bacteria getting a

Complement system activated, the proteins

infected body cells, killing

A protein cascade in the blood. When

can punch holes in bacteria and
them.

Ciclosporin -

Drug which damps down the immune system. Used

primarily for transplant patients.

Cytokines -

Soluble protein made by T-cells.

Dendritic cell *cells.

A specialised cell that presents antigens to T-

Diabetes blood

Disease in which the body is not able to control its

sugar levels.

Eosinophil * -

A type of white cell.

Fungi have their own

Organisms from the Kingdom Fungi. These

characteristics and are not plants.

Gene segments -

Small parts of DNA.

Genome cell.

The complete genetic information contained within a

Helper T-cell * body's immune

A Lymphocyte that helps to regulate the

response.

Human Immunodeficiency Virus (HIV) -

The virus which causes AIDS.

Hypersensitivity over the

Term used to describe an immune response that is

top.

IgE-

A sub-type of antibody important in allergy.

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Immune response foreign

Immune surveillance detect foreign
quickly.
Immune system infection.
Immunisation artificially by giving
or a modified form of a

Action by the immune system against material that is

to the body.
The immune system maintains a system to
antigens and react to them very
The body system that responds protectively to
Same as vaccination. Inducing immunity
a person an extract, a purified antigen
pathogen.

Immunity -

Resistance to infection.

Immunoglobulin -

Antibody. There are several subtypes: IgA, IgG, IgE,for

example. Each type has its own function in

the body.
Immunological memory the body.
Immunosuppressive response.

The capacity of the immune system to remember and

recognise a pathogen next time it gets into
Something which damps down the immune

Infection Infection

Invasion of the body by another living organism.

does not always lead to disease.

Innate -

In-born. Another term applied to natural immunity.

Interferons inhibit

Proteins made by cells infected with viruses. They

growth of viruses in other cells.

Killer (cytotoxic) T-cell*activated by a

bacteria or infected

One type of killer cell, a lymphocytes that is

specific antigen and which then attacks
body cells.

Large granular
Also known as natural killer (NK) cell. Can kill
different types lymphocyte * (NK) of cells and help in anti-viral and antitumour immunity.
Lymphocyte * -

A white cell. Either B-cell or T-cell.

Lymphoid tissues -

See primary and secondary lymphoid tissues.

Macrophages * -

Large white cells which carry out phagocytosis.

Major Histocompatibility

An important antigen recognition system that

regulates Complex (MHC) - immune
responses.

Mast-cell * packets of

Large cells which degranulate, releasing

histamine in response to an allergen.

Monocytes * -

See mononuclear phagocytes.

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Mononuclear phagocytes * -

Usually known as monocytes. Made from bone

marrow stem cells. Circulate in blood and
mature into macrophages when they enter
tissues.

Morbidity -

The state of being diseased.

Mucous membrane -

The delicate membranes which line the inner

surfaces of the
entrances to the body.

Multiple sclerosis -

An autoimmune disease where white blood

cells enter the brain and damage the coating
on the nerves.

Mutation -

A change in the base sequence of nucleic

acids leading to production of different
proteins.

Natural killers cells *-

See large granular lymphocytes.

Neutrophil * -

Also known as a polymorphonuclear

leucocyte. Short lived phagocyte, which
provides a very rapid response to local
infection.

Non-specific immunity -

Works against all pathogens and includes

physical and chemical barriers and general
reaction of the body towards pathogens.

Opsonisation -

The enhancement of phagocytosis by

antibody attachment to a microbe.

Pathogens -

Disease-causing organisms.

Peptides -

Small length or fragment of protein chain.

Pernicious anaemia -

An autoimmune disease that affects the

intestine and the blood.

Phagocytes * -

Cells which engulf particles in the process of

phagocytosis.

Phagocytosis -

The process by which white cells engulf and

clear dead bacteria and other cell debris from
the body.

Polymorphic -

Can be very varied within a population.

Polymorphonuclear
leucocyte * -

See neutrophil.

Primary deficiencies works properly.

Born without an immune system that

Primary lymphoid tissues -

The bone marrow and thymus, lymphocytes

are made here.

Programmed cell death to self destruct

All cells are probably genetically programmed

under certain conditions.

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Protective immunity -

The resistance we develop to infection by

being exposed to it.

Protozoa -

Single-celled organisms such as Plasmodium

that causes malaria.

Pus -

Sticky yellow discharge that results from a

bacterial infection. Consists of dead bacteria
and dead white cells.

Rejected attacked by the

Foreign tissue (usually transplanted tissue)

hosts immune system.

Rheumatoid arthritis -

An autoimmune disease, that is one where the

bodies
immune system attacks the
body itself, in this case the tissues of the
joints.

Secondary lymphoid

Lymph nodes and spleen where lymphocytes

make immune tissues - responses.

Self-antigens -

Antigens that are part of the body.

Septic -

Putrefaction following infection.

Specific immunity -

Only works against particular invading

microbes, associated with T and B-cells.

Specificity -

The ability of lymphocytes to respond to only

one particular type of invading microbe.

T-cell receptor -

A site on the T-cell which can bind to the MHC

and bring about activation of that T-cell.

Thymus -

A lobulated gland found just below the larynx.

Thyroiditis -

Inflammation of the thyroid gland.

Tissue match -

Selection of donor tissue that is as genetically

similar as possible to the recipient tissue to
minimise rejection.

Transplantation -

Transfer of an organ or tissue from one person

to another. Organs commonly transplanted
include: kidney, heart, liver and lungs.

Uveitis -

An autoimmune disease which causes

inflammation in the eye and may lead to
blindness.

Vasodilation -

Increase in the size of blood vessels to

facilitate increased blood flow.

Viruses -

A large group of infectious agents whose

structure can only be seen in detail with an
electron-microscope.

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Worms -

Parasitic worms, which can develop strategies

to side step the immune system.

Xenograft -

A graft in which the donor tissue comes from a

different species of animal from the recipient.

*Cells of the immune system

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