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Herausgeber: John Wiley & Sons
Kategorie: Fachliteratur
Serie: At a Glance
Sprache: Englisch

Beschreibung

Immunology at a Glance provides a user-friendly overview of the body’s defence mechanisms. Ideal from day one of a medical, biomedical or life science course, the text begins with a basic overview of both adaptive and innate immunity, before progressing to applied immunological concepts, which look at what happens when things go wrong, and how, in clinical medicine, each body system can be affected by immunity.

Each double-page spread corresponds to a typical lecture and diagrammatically summarises core concepts in immunology, through accessible schematic diagrams on left-hand pages, with key points concisely summarised on the right-hand page. There are also self-assessment essay questions so you can test your knowledge.

New for this 10th edition:

Thoroughly updated and reorganised chapters offer greater clarity and easier understanding for those new to the subject
New chapters on cytokine receptors and ‘Immunology in the Laboratory’
A completely re-written section on autoimmunity
A brand new companion website featuring self-assessment questions and PowerPoint slides of images from the book, ideal for teaching and revision at www.ataglanceseries.com/immunology

Immunology at a Glance is the ideal companion for anyone about to start a new course in immunology and will appeal to medical and biomedical science students. Perfect for exam preparation, it provides the concepts and frameworks you need to succeed in your exam.

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Table of Contents

Cover

Companion website

Title page

Preface

Acknowledgements

Note on the tenth edition

How to use this book

Further reading

List of abbreviations

Immunity

1 The scope of immunology

2 Innate and adaptive immune mechanisms

Innate immunity

Adaptive immunity

Interactions between innate and adaptive immunity

3 Recognition and receptors: the keys to immunity

Innate immune system

Cell-associated recognition

Some other receptor systems

Adaptive immune system

4 Cells involved in immunity: the haemopoietic system

A note on terminology

Innate immunity

5 Receptors of the innate immune system

6 Complement

Classic pathway

Alternative pathway

MBL and other pathways

Lytic pathway

Complement inhibitors

7 Acute inflammation

8 Phagocytic cells and the reticuloendothelial system

9 Phagocytosis

Adaptive immunity

(i) The molecular basis

10 Evolution of recognition molecules: the immunoglobulin superfamily

11 The major histocompatibility complex

12 The T-cell receptor

13 Antibody diversification and synthesis

14 Antibody structure and function

(ii) The cellular basis

15 Lymphocytes

16 Primary lymphoid organs and lymphopoiesis

Yolk sac

Bursa

Liver

Bone marrow

Thymus

17 Secondary lymphoid organs and lymphocyte traffic

Lymph node

Spleen

Mucosa-associated lymphoid tissues

(iii) The adaptive immune response

18 Antigen processing and presentation

The class I pathway

The class II pathway

19 The antibody response

20 Antigen – antibody interaction and immune complexes

Antigen – antibody interaction

Immune complexes

21 Cell-mediated immune responses

(iv) Regulation

22 Tolerance

23 Cell communication and cytokines

24 The cytokine network

25 Immunity, hormones and the brain

Central nervous system

Autonomic nervous system

Endocrine system

Immune system

Immunity and psychological illness

Potentially useful immunity

26 Antimicrobial immunity: a general scheme

27 Immunity to viruses

Viruses

Atypical organisms

28 HIV and AIDS

29 Immunity to bacteria

Bacteria

30 Immunity to fungi and ectoparasites

Ectoparasites

31 Immunity to protozoa

32 Immunity to worms

Roundworms (nematodes)

Flukes (trematodes)

Tapeworms (cestodes)

Undesirable effects of immunity

33 Immunodeficiency

Defects affecting several types of cell

Defects predominantly affecting T cells

Defects predominantly affecting B cells

Defects of complement

Defects affecting myeloid cells

Receptors of innate immunity

Secondary immunodeficiency

34 Harmful immunity: a general scheme

Innate immune damage

Types of hypersensitivity (Gell and Coombs’ classification)

35 Allergy and anaphylaxis

Mediators

Inhibitors

Non-IgE triggering

Allergic diseases

36 Immune complexes, complement and disease

Immune complex diseases

Haemolytic disease of the newborn

37 Chronic and cell-mediated inflammation

Granulomas

Granulomatous diseases

38 Autoimmune disease

Self-tolerance and self-reactivity

Autoimmune diseases

Treatment of autoimmunity

Altered immunity

39 Transplant rejection

Typing and matching

Rejection

Immunosuppression

40 Immunosuppression

Non-specific immunosuppression

Specific immunosuppression

41 Immunostimulation and vaccination

Passive immunization

Active immunization (‘vaccination’)

Immunity in health and disease

42 Cancer immunology

Non-specific immunotherapy

Specific immunotherapy

43 Immunity and clinical medicine

44 Investigating immunity

Investigating immunodeficiency

Investigating allergy

Investigating autoimmunity

Tissue typing and transplantation

Tumours of immunological cells

45 Immunology in the laboratory

46 Out of the past: evolution of immune mechanisms

Unicellular organisms

Invertebrates

Vertebrates

Plants

47 Into the future: immunology in the age of genomics

Self-assessment

Self-assessment questions

Answers

Appendices

Appendix I

Comparative sizes

Comparative molecular weights

Appendix II

Landmarks in the history of immunology

Some unsolved problems

Appendix III

CD classification

Index

Companion Website

This book has a companion website at:

www.ataglanceseries.com/immunology

The website includes:

95 interactive test questions

All figures from the book as PowerPoints for downloading

This edition first published 2013

Previous editions: 1979, 1982, 1984, 1987, 1992, 1996, 2001, 2005, 2009

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Library of Congress Cataloging-in-Publication Data

Playfair, J. H. L.

Immunology at a glance / J.H.L. Playfair, B.M. Chain. – 10th ed.

p. ; cm. – (At a glance series)

Includes bibliographical references and index.

ISBN 978-0-470-67303-4 (pbk. : alk. paper) – ISBN 978-1-118-44745-1 (eBook/ePDF) – ISBN 978-1-118-44746-8 (ePub) – ISBN 978-1-118-44747-5 (eMobi)

I. Chain, B. M. II. Title. III. Series: At a glance series (Oxford, England)

[DNLM: 1. Immune System Phenomena. QW 540]

616.07'9–dc23

2012024675

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover image: courtesy of Science Photo Library

Cover design by Meaden Creative

Preface

This is not a textbook for immunologists, who already have plenty of excellent volumes to choose from. Rather, it is aimed at all those on whose work immunology impinges but who may hitherto have lacked the time to keep abreast of a subject that can sometimes seem impossibly fast-moving and intricate.

Yet everyone with a background in medicine or the biological sciences is already familiar with a good deal of the basic knowledge required to understand immunological processes, often needing no more than a few quick blackboard sketches to see roughly how they work. This is a book of such sketches, which have proved useful over the years, recollected (and artistically touched up) in tranquillity.

The Chinese sage who remarked that one picture was worth a thousand words was certainly not an immunology teacher, or his estimate would not have been so low! In this book the text has been pruned to the minimum necessary for understanding the figures, omitting almost all historical and technical details, which can be found in the larger textbooks listed on the next page. In trying to steer a middle course between absolute clarity and absolute up to dateness, we are well aware of having missed both by a comfortable margin. But even in immunology, what is brand new does not always turn out to be right, while the idea that any form of presentation, however unorthodox, will make simple what other authors have already shown to be complex can only be, in Dr Johnson’s heartfelt words, ‘the dream of a philosopher doomed to wake a lexicographer’. Our object has merely been to convince workers in neighbouring fields that modern immunology is not quite as forbidding as they may have thought.

It is perhaps the price of specialization that some important aspects of nature lie between disciplines and are consequently ignored for many years (transplant rejection is a good example). It follows that scientists are wise to keep an eye on each others’ areas so that in due course the appropriate new disciplines can emerge – as immunology itself did from the shared interests of bacteriologists, haematologists, chemists and the rest.

J.H.L. PlayfairB.M. Chain

Acknowledgements

Our largest debt is obviously to the immunologists who made the discoveries this book is based on; if we had credited them all by name it would no longer have been a slim volume! In addition we are grateful to our colleagues at UCL for advice and criticism since the first edition, particularly Professor J. Brostoff, Dr A. Cooke, Dr P. Delves, Dr V. Eisen, Professor F.C. Hay, Professor D.R. Katz, Dr T. Lund, Professor P.M. Lydyard, Dr D. Male, Dr S. Marshall-Clarke, Professor N.A. Mitchison and Professor I.M. Roitt. The original draft was shown to Professor H.E.M. Kay, Professor C.A. Mims and Professor L. Wolpert, all of whom made valuable suggestions. We would like to thank Dr Mohammed Ibrahim (King’s College Hospital), Dr Mahdad Noursadeghi (UCL) and Dr Liz Lightsone (Imperial College) for help with the new chapters in the ninth edition. Edward Playfair supplied a useful undergraduate view of the first edition. Finally, we would like to thank the publishing staff at Wiley-Blackwell for help and encouragement at all stages.

Note on the Tenth Edition

Since the last edition in 2009 every chapter has needed some updating, but the major advances concern the innate immune system, whose cells, molecules and receptors continue to attract enormous attention from immunologists. We have added a new chapter on cytokine receptors, and completely rewritten the chapter on autoimmunity. Some chapters have been moved to fit better into the sequence of a typical undergraduate course – for example AIDS and evolution, and the clinical section has been expanded to include a brief survey of methods in use in the immunology lab. Self-assessment now includes online MCQs as well as the essay-type questions at the end of the book.

J.H.L. PlayfairB.M. Chain

How to Use This Book

Each of the figures (listed in the contents) represents a particular topic, corresponding roughly to a 45-minute lecture. Newcomers to the subject may like first to read through the text (left-hand pages), using the figures only as a guide; this can be done at a sitting.

Once the general outline has been grasped, it is probably better to concentrate on the figures one at a time. Some of them are quite complicated and can certainly not be taken in ‘at a glance’, but will need to be worked through with the help of the legends (right-hand pages), consulting the index for further information on individual details; once this has been done carefully they should subsequently require little more than a cursory look to refresh the memory.

It will be evident that the figures are highly diagrammatic and not to scale; indeed the scale often changes several times within one figure. For an idea of the actual sizes of some of the cells and molecules mentioned, refer to AppendixI.

The reader will also notice that examples are drawn sometimes from the mouse, in which useful animal so much fundamental immunology has been worked out, and sometimes from the human, which is after all the one that matters to most people. Luckily the two species are, from the immunologist’s viewpoint, remarkably similar.

Non-Self

A widely used term in immunology, covering everything that is detectably different from an animal’s own constituents. Infectious microorganisms, together with cells, organs or other materials from another animal, are the most important non-self substances from an immunological viewpoint, but drugs and even normal foods, which are, of course, non-self too, can sometimes give rise to immunity. Detection of non-self material is carried out by a range of receptor molecules (see Figs 5, 10–14).

Infection

Parasitic viruses, bacteria, protozoa, worms or fungi that attempt to gain access to the body or its surfaces are probably the chief raison d’être of the immune system. Higher animals whose immune system is damaged or deficient frequently succumb to infections that normal animals overcome.

External Defences

The presence of intact skin on the outside and mucous membranes lining the hollow viscera is in itself a powerful barrier against entry of potentially infectious organisms. In addition, there are numerous antimicrobial (mainly antibacterial) secretions in the skin and mucous surfaces; these include lysozyme (also found in tears), lactoferrin, defensins and peroxidases. More specialized defences include the extreme acidity of the stomach (about pH 2), the mucus and upwardly beating cilia of the bronchial tree, and specialized surfactant proteins that recognize and clump bacteria that reach the lung alveoli. Successful microorganisms usually have cunning ways of breaching or evading these defences.

Innate Resistance

Organisms that enter the body (shown in the figure as dots or rods) are often eliminated within minutes or hours by inborn, ever-present mechanisms, while others (the rods in the figure) can avoid this and survive, and may cause disease unless they are dealt with by adaptive immunity (see below). These mechanisms have evolved to dispose of pathogens (e.g. bacteria, viruses) that if unchecked can cause disease. Harmless microorganisms are usually ignored by the innate immune system. Innate immunity also has a vital role in initiating the adaptive immune response.

Adaptive Immune Response

The development or augmentation of defence mechanisms in response to a particular (‘specific’) stimulus, e.g. an infectious organism. It can result in elimination of the microorganism and recovery from disease, and often leaves the host with specific memory, enabling it to respond more effectively on reinfection with the same microorganism, a condition called acquired resistance. Because the process by which the body puts together the receptors of the adaptive immune system is random (see Fig. 10), adaptive immunity sometimes responds to harmless foreign material such as the relatively inoffensive pollens, etc., or even to ‘self’ tissues leading to autoimmunity.

Vaccination

A method of stimulating the adaptive immune response and generating memory and acquired resistance without suffering the full effects of the disease. The name comes from vaccinia, or cowpox, used by Jenner to protect against smallpox.

Grafting

Cells or organs from another individual usually survive innate resistance mechanisms but are attacked by the adaptive immune response, leading to rejection.

Autoimmunity

The body’s own (‘self’) cells and molecules do not normally stimulate its adaptive immune responses because of a variety of special mechanisms that ensure a state of self-tolerance, but in certain circumstances they do stimulate a response and the body’s own structures are attacked as if they were foreign, a condition called autoimmunity or autoimmune disease.

Hypersensitivity

Sometimes the result of specific memory is that re-exposure to the same stimulus, as well as or instead of eliminating the stimulus, has unpleasant or damaging effects on the body’s own tissues. This is called hypersensitivity; examples are allergies such as hay fever and some forms of kidney disease.

Immunosuppression

Autoimmunity, hypersensitivity and, above all, graft rejection sometimes necessitate the suppression of adaptive immune responses by drugs or other means.

Innate and Adaptive Immune Mechanisms

Just as resistance to disease can be innate (inborn) or acquired, the mechanisms mediating it can be correspondingly divided into innate (left) and adaptive (right), each composed of both cellular (lower half) and humoral elements (i.e. free in serum or body fluids; upper half). Adaptive mechanisms, more recently evolved, perform many of their functions by interacting with the older innate ones.

Innate immunity is activated when cells use specialized sets of receptors (see Fig. 5) to recognize different types of microorganisms (bacteria, viruses, etc.) that have managed to penetrate the host. Binding to these receptors activates a limited number of basic microbial disposal mechanisms, such as phagocytosis of bacteria by macrophages and neutrophils, or the release of antiviral interferons. Many of the mechanisms involved in innate immunity are largely the same as those responsible for non-specifically reacting to tissue damage, with the production of inflammation (cover up the right-hand part of the figure to appreciate this). However, as the nature of the innate immune response depends on the type of infection, the term ‘non-specific’, although often used as a synonym for ‘innate’, is not completely accurate.

Adaptive immunity is based on the special properties of lymphocytes (T and B, lower right), which can respond selectively to thousands of different non-self materials, or ‘antigens’, leading to specific memory and a permanently altered pattern of response – an adaptation to the animal’s own surroundings. Adaptive mechanisms can function on their own against certain antigens (cover up the left-hand part of the figure), but the majority of their effects are exerted by means of the interaction of antibody with complement and the phagocytic cells of innate immunity, and of T cells with macrophages (broken lines). Through their activation of these innate mechanisms, adaptive responses frequently provoke inflammation, either acute or chronic; when it becomes a nuisance this is called hypersensitivity.

The individual elements of this highly simplified scheme are illustrated in more detail in the remainder of this book.

Innate Immunity

Interferons

A family of proteins produced rapidly by many cells in response to virus infection, which block the replication of virus in the infected cell and its neighbours. Interferons also have an important role in communication between immune cells (see Figs 23 and 24).

Defensins

Antimicrobial peptides, particularly important in the early protection of the lungs and digestive tract against bacteria.

Lysozyme (Muramidase)

An enzyme secreted by macrophages that attacks the cell wall of some bacteria.

Complement

A group of proteins present in serum which when activated produce widespread inflammatory effects, as well as lysis of bacteria, etc. Some bacteria activate complement directly, while others only do so with the help of antibody (see Fig. 6).

Lysis

Irreversible leakage of cell contents following membrane damage. In the case of a bacterium this would be fatal to the microbe.

Mast Cell

A large tissue cell that releases inflammatory mediators when damaged, and also under the influence of antibody. By increasing vascular permeability, inflammation allows complement and cells to enter the tissues from the blood (for further details of this process see Fig. 7).

PMN

Polymorphonuclear leucocyte (80% of white cells in human blood), a short-lived ‘scavenger’ blood cell whose granules contain powerful bactericidal enzymes. The name derives from the peculiar shapes of the nuclei.

MAC

Macrophage, a large tissue cell responsible for removing damaged tissue, cells, bacteria, etc. Both PMNs and macrophages come from the bone marrow, and are therefore classed as myeloid cells.

DC

Dendritic cells present antigen to T cells, and thus initiate all T-cell-dependent immune responses. Not to be confused with follicular dendritic cells, which store antigen for B cells (see Fig. 19).

Phagocytosis (‘Cell Eating’)

Engulfment of a particle by a cell. Macrophages and PMNs (which used to be called ‘microphages’) are the most important phagocytic cells. The great majority of foreign materials entering the tissues are ultimately disposed of by this mechanism.

Cytotoxicity

Macrophages can kill some targets (perhaps including tumour cells) without phagocytosing them, and there are a variety of other cells with cytotoxic abilities.

NK (Natural Killer) Cell

A lymphocyte-like cell capable of killing some targets, notably virus-infected cells and tumour cells, but without the receptor or the fine specificity characteristic of true lymphocytes.

Adaptive Immunity

Antigen

Strictly speaking, a substance that stimulates the production of antibody. However, the term is applied to substances that stimulate any type of adaptive immune response. Typically, antigens are foreign (‘non-self’) and either particulate (e.g. cells, bacteria) or large protein or polysaccharide molecules. Under special conditions small molecules and even ‘self’ components can become antigenic (see Figs 18–21).

Specific; Specificity

Terms used to denote the production of an immune response more or less selective for the stimulus, such as a lymphocyte that responds to, or an antibody that ‘fits’ a particular antigen. For example, antibody against measles virus will not bind to mumps virus: it is ‘specific’ for measles.

Lymphocyte

A small cell found in blood, from which it recirculates through the tissues and back via the lymph, ‘policing’ the body for non-self material. Its ability to recognize individual antigens through its specialized surface receptors and to divide into numerous cells of identical specificity and long lifespan makes it the ideal cell for adaptive responses. Two major populations of lymphocytes are recognized: T and B (see also Fig. 15).

B Lymphocytes

secrete antibody, the humoral element of adaptive immunity.

Antibody

is a major fraction of serum proteins, often called immunoglobulin. It is made up of a collection of very similar proteins each able to bind specifically to different antigens, and resulting in a very large repertoire of antigen-binding molecules. Antibodies can bind to and neutralize bacterial toxins and some viruses directly but they also act by opsonization and by activating complement on the surface of invading pathogens (see below).

T (‘Thymus-Derived’) Lymphocytes

are further divided into subpopulations that ‘help’ B lymphocytes, kill virus-infected cells, activate macrophages and drive inflammation (see Fig. 21).

Interactions between Innate and Adaptive Immunity

Opsonization

A phenomenon whereby antibodies bind to the surface of bacteria, viruses or other parasites, and increase their adherence and phagocytosis. Antibody also activates complement on the surface of invading pathogens. Adaptive immunity thus harnesses innate immunity to destroy many microorganisms.

Complement

As mentioned above, complement is often activated by antibody bound to microbial surfaces. However, binding of complement to antigen can also greatly increase its ability to activate a strong and lasting B-cell response – an example of ‘reverse interaction’ between adaptive and innate immune mechanisms.

Presentation

of antigens to T and B cells by dendritic cells is necessary for most adaptive responses; presentation by dendritic cells usually requires activation of these cells by contact with microbial components (e.g. bacterial cell walls), another example of ‘reverse interaction’ between adaptive and innate immune mechanisms.

Help

by T cells is required for many branches of both adaptive and innate immunity. T-cell help is required for the secretion of most antibodies by B cells, for activating macrophages to kill intracellular pathogens and for an effective cytotoxic T-cell response.

Recognition and Receptors: The Keys to Immunity

Before any immune mechanism can go into action, there must be a recognition that something exists for it to act against. Normally this means foreign material such as a virus, bacterium or other infectious organism. This recognition is carried out by a series of recognition molecules or receptors. Some of these (upper part of figure) circulate freely in blood or body fluids, others are fixed to the membranes of various cells or reside inside the cell cytoplasm (lower part). In every case, some constituent of the foreign material must interact with the recognition molecule like a key fitting into the right lock. This initial act of recognition opens the door that leads eventually to a full immune response.

These receptors are quite different in the innate and the adaptive immune system. The innate system (left) possesses a limited number, known as pattern-recognition receptors (PRRs), which have been selected during evolution to recognize structures common to groups of disease-causing organisms (pathogen-associated molecular patterns, PAMPs); one example is the lipopolysaccharide (LPS) in some bacterial cell walls (for more details see Fig. 5). These PRRs act as the ‘early warning’ system of immunity, triggering a rapid inflammatory response (see Fig. 2) which precedes and is essential for a subsequent adaptive response. In contrast, the adaptive system has thousands of millions of different receptors on its B and T lymphocytes (right), each one exquisitely sensitive to one individual molecular structure. The responses triggered by these receptors offer more effective protection against infection, but are usually much slower to develop (see Figs 18–21).

Linking the two systems are the families of major histocompatibility complex (MHC) molecules (centre), specialized for ‘serving up’ foreign molecules to T lymphocytes. Another set of ‘linking’ receptors are those by which molecules such as antibody and complement become bound to cells, where they can themselves act as receptors.

Innate Immune System

Soluble Recognition Molecules

Complement

A complex set of serum proteins, some of which can be triggered by contact with bacterial surfaces (for details see Fig. 6). Once activated, complement can damage some cells and initiate inflammation. Some cells possess receptors for complement, which can assist the process of phagocytosis (see Fig. 9).

Mannose-Binding Lectin (MBL)

binds the surface of bacteria and fungi, and can activate complement or act directly to assist phagocytosis.

Acute Phase Proteins

Another complex set of serum proteins. Unlike complement, these proteins are mostly present at very low levels in serum, but are rapidly produced in high amounts by the liver following infection, where they contribute to inflammation and immune recognition. Several acute phase proteins also function as PRRs.

Cell-Associated Recognition

PRR

Pattern-recognition receptors have now been described for every type of pathogen, and more are being discovered all the time. They can broadly be divided in terms of cellular localization, e.g. cell membrane, endosome/phagosome and cytoplasm. Although they are represented by a bewildering variety of types of molecules, their common functional feature is they regulate the innate immune response to infection. Note that not all PRRs are found on all types of cell, the majority being restricted to macrophages and dendritic cells (MAC, DC in figure). Further details of PRR types are given in Fig. 5.

Some Other Receptor Systems

Receptors feature in a number of other biological processes, many of them outside the scope of this book. Here are a few that are relevant to immunity.

Virus Receptors

To enter a cell, a virus has to ‘dock’ with some cell-surface molecule; examples are CD4 for HIV (see Fig. 28) and the acetylcholine receptor for rabies.

Cytokine Receptors

Communication between immune cells is largely mediated by ‘messenger’ molecules known as cytokines (see Figs 23 and 24). To respond to a cytokine, a cell needs to possess a receptor for it.

Hormone Receptors

In the same way as cytokines, hormones (e.g. insulin, steroids) will only act on cells carrying the appropriate receptor.

Adaptive Immune System

Antibody

Antibody molecules (for details see Figs 13, 14, 19 and 20) can act as both soluble and cell-bound receptors.

1 On the B lymphocyte, antibody molecules synthesized in the cell are exported to the surface membrane where they recognize small components of protein, carbohydrates or other biological macromolecules (‘antigens’) and are taken into the cell to start the triggering process. Each B lymphocyte is programmed to make antibody of one single recognition type out of a possible hundreds of millions.

2 When the B lymphocyte is triggered, large amounts of its antibody are secreted to act as soluble recognition elements in the blood and tissue fluids; this is referred to as the ‘antibody response’. Antibody in serum is often referred to as immunoglobulin (Ig).

3 Some cells possess ‘Fc receptors’ (FcR in figure) that allow them to take up antibody, insert it in their membrane, and thus become able to recognize a wide range of antigens. This can greatly improve phagocytosis, but can also be responsible for allergies (see Fig. 35).

T-Cell Receptor (TcR in Figure)

T lymphocytes carry receptors that have a similar basic structure to antibody on B lymphocytes (for further details see Figs 12 and 18) but with important differences:

1 They are specialized to recognize only small peptides (pieces of proteins) bound to MHC molecules (see below);

2 They are not exported, but act only at the T-cell surface.

MHC Molecules

These come in two types. MHC class I molecules are expressed on all nucleated cells while class II MHC molecules are normally found only on B lymphocytes, macrophages and dendritic cells. Their role is to ‘present’ small antigenic peptides to the T-cell receptor. The class of MHC and the type of T cell determine the characteristics of the resulting immune response (see Figs 11 and 18). Their name comes from their important role in stimulating transplant rejection (see Fig. 39).

NK Cell Receptors

Natural killer cells share features of both lymphocytes and innate immune cells. They are specialized for killing virus-infected cells and some tumours, and they possess receptors of two opposing kinds.

1 Activating receptors are analogous to PRRs, recognizing changes associated with stress and virus infection.

2 Inhibitory receptors recognize MHC class I molecules, preventing NK cells killing normal cells. The final result thus depends on the balance between activation and inhibition (for further details see Figs 10, 15 and 42).

Cells Involved in Immunity: The Haemopoietic System

The great majority of cells involved in mammalian immunity are derived from precursors in the bone marrow (left half of figure) and circulate in the blood, entering and sometimes leaving the tissues when required. A very rare stem cell persists in the adult bone marrow (at a frequency of about 1 in 100 000 cells), and retains the ability to differentiate into all types of blood cell. Haemopeoisis has been studied either by injecting small numbers of genetically marked marrow cells into recipient mice and observing the progeny they give rise to (in vivo cloning) or by culturing the bone marrow precursors in the presence of appropriate growth factors (in vitro cloning). Proliferation and differentiation of all these cells is under the control of soluble or membrane-bound growth factors produced by the bone marrow stroma and by each other (see Fig. 24). Within the cell these signals switch on specific transcription factors, DNA-binding molecules which act as master switches that determine the subsequent genetic programme, in turn giving rise to development of the different cell types (known as lineages). Remarkably, recent studies have shown that it is possible to turn one differentiated cell type into another by experimentally introducing the right transcription factors into the cell. This finding has important therapeutic implications, e.g. in curing genetic immunodeficiencies (see Fig. 33). Most haemopoietic cells stop dividing once they are fully differentiated. However, lymphocytes divide rapidly and expand following exposure to antigen. The increased number of lymphocytes specific for an antigen forms the basis for immunological memory.

A Note on Terminology

Haematologists recognize many stages between stem cells and their fully differentiated progeny (e.g. for red cells: proerythroblast, erythroblast, normoblast, erythrocyte). The suffix ‘blast’ usually implies an early, dividing, relatively undifferentiated cell, but is also used to describe lymphocytes that have been stimulated, e.g. by antigen, and are about to divide.

Bone Marrow

Unlike most other tissues or organs, the haemopoetic system is constantly renewing itself. In the adult, the development of haemopoetic cells occurs predominantly in the bone marrow. In the fetus, before bones develop, haemopoeisis occurs first in the yolk sac and then in the liver.

Stroma

Epithelial and endothelial cells that provide support and secrete growth factors for haemopoiesis.

S

Stem cell; the totipotent and self-renewing marrow cell. Stem cells are found in low numbers in blood as well as bone marrow and the numbers can be boosted by treatment with appropriate growth factors (e.g. G-CSF), which greatly facilitates the process of bone marrow transplantation (see Fig. 39).

LS

Lymphoid stem cell, presumed to be capable of differentiating into T or B lymphocytes. Very recent data suggest that the distinction between lymphoid and myeloid stem cells may in fact be more complex.

HS

Haemopoietic stem cell: the precursor of spleen nodules and probably able to differentiate into all but the lymphoid pathways, i.e. granulocyte, erythroid, monocyte, megakaryocyte; often referred to as CFU-GEMM.

ES

Erythroid stem cell, giving rise to erythrocytes. Erythropoietin, a glycoprotein hormone formed in the kidney in response to hypoxia, accelerates the differentiation of red cell precursors and thus adjusts the production of red cells to the demand for their oxygen-carrying capacity, a typical example of ‘negative feedback’.

GM

Granulocyte–monocyte common precursor; the relative proportion of these two cell types is regulated by ‘growth-’ or ‘colony-stimulating’ factors (see Fig. 24).

Cloning

The potential of individual stem cells to give rise to one or more types of haemopoetic cells has been explored by isolating single cells and allowing them to divide many times, and then observing what cell types can be found among the progeny. This process is known as cloning (a clone being a set of daughter cells all arising from a single parent cell). Evidence suggests that in certain conditions a single stem cell can give rise to all the fully differentiated cells of an adult haemopoetic system.

Neutrophil (Polymorph)

The most common leucocyte in human blood, a short-lived phagocytic cell whose granules contain numerous bactericidal substances. Neutrophils are the first cells to leave the blood and enter sites of infection or inflammation.

Eosinophil

A leucocyte with large refractile granules that contain a number of highly basic or ‘cationic’ proteins, possibly important in killing larger parasites including worms.

Basophil

A leucocyte with large basophilic granules that contain heparin and vasoactive amines, important in the inflammatory response.The above three cell types are often collectively referred to as ‘granulocytes’.

MK

Megakaryocyte: the parent cell of the blood platelets.

Platelets

Small cells responsible for sealing damaged blood vessels (‘haemostasis’) but also the source of many inflammatory mediators (see Fig. 7).

Monocyte

A precursor cell in blood developing into a macrophage when it migrates into the tissues. Additional monocytes are attracted to sites of inflammation, providing a reservoir of macrophages and perhaps also dendritic cells.

Macrophage

The principal resident phagocyte of the tissues and serous cavities such as the pleura and peritoneum (see Fig. 8).

DC (Dendritic Cell)

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