Basic and clinical immunology

374 Pages·2010·118.328 MB·English

by  Peakman, Mark;Vergani, Diego

BASIC AND CLINICAL
IMMUNOLOGY
SECOND EDITION
Commissioning Editor: Timothy Horne
Development Editor: Ailsa Laing
Project Manager: Emma Riley
Designer: Sarah Russell/Kirsteen Wright
Illustration Manager: Kirsteen Wright/Gillian Richards
BASIC AND CLINICAL
IMMUNOLOGY
SECOND EDITION
Mark Peakman
MBBS PhD FRCPath
Professor of Clinical Immunology,
King’s College London;
Honorary Consultant Immunologist,
King’s College Hospital,
London
Diego Vergani
MD PhD FRCPath FRCP
Professor of Liver Immunopathology,
King’s College London;
Honorary Consultant Immunologist,
King’s College Hospital,
London
Illustrated by
Danny J. Pyne Martin Woodward
and
EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO 2009
First Edition © 1997, Elsevier Limited.
Second Edition © 2009, Elsevier Limited. All rights reserved.
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ISBN: 978 0 443 10082 6
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Preface to the second edition
Since the publication of the fifirst edition of Basic and Clinical array of receptors for pathogens, the discovery of which has
Immunology, there have been two main forces driving us changed the way we think about interactions between the
inexorably towards this new edition. ThThe fifirst has been the immune system and the environment. We speculated in the
continuous, and very much appreciated, commentary from fifirst edition about the potential for ‘magic bullet’ monoclonal
our students and peers that Basic and Clinicall was an impres- antibody therapy, but could not have dreamt of the benefifit
sive fifirst effffff ort. It clearly fifilled a gap, as we had intended, now being realised in a number of mainstream clinical set-
between the basic and theoretical immunology found in tings, that include rheumatoid arthritis, lymphoma and
many textbooks, and the advanced clinical immunology breast cancer. ThTh e tools have evolved too — technology for
found in others. By combining the main elements of both, the investigation and imaging of the immune system now
we had created a single text that was usable in biomedical, allows single immune cells to be tracked in vivo. And, inevi-
medical and health schools. ThTh e second driver was the emer- tably, there is a new T helper cell on the block, along with
gence of landmark discoveries in the understanding of the reincarnation of the suppressor T cell (only it is called a
immunity and its application to medicine, which began to regulator). One has the sense that much has happened and
date our fifi rst book all too quickly. much will happen hence.
In 1997 we had devoted just a few lines to dendritic cells;
they are now viewed as the master controllers of adaptive London M.P.
immunity. ThThis potency is achieved through expression of an 2009 D.V.
v
Preface to the fifirst edition
‘Immunology is an invention of the devil.’ dence that immunology was truly demonic, a conversation
with an expert physician, encountered at an international
From the outset, this book was intended as a text combining conference, was recounted in the same article. ‘I hope you
the basic science components required to understand the understand all this stuff ’, he had said to the journalist, ‘they
role of immunity in disease with an account of the major didn’t teach it when I was in medical school and I never
diseases classififi ed under the umbrella of clinical immunol- fifi gured it out.’ We hope that this book goes some way towards
ogy. ThThe book would thus naturally span the curricula of redressing the balance.
most medical or paramedical courses, from basic to applied. It would have been impossible to be authoritative about
From technical, medical, dental and science students at all every aspect of clinical immunology. For this reason, we have
levels, we had both perceived a glaring need for such a text. consulted friends and colleagues with the relevant expertise
But as if any stimulus was required for us to see the project to advise us, and to these we are indebted: Fred Dische,
to completion, an article appeared in a popular news maga- Adrian Eddleston, John Fabre, Jonathan Frankel, Elizabeth
zine for doctors whilst the book was being planned, asking Higgins, Rob Higgins, William Hirst, Giorgina Mieli-Vergani,
several regular contributors for their most hated words. Lindsay Nicholson and Anton Pozniak. We are also grateful
‘Immunology’ made its appearance as ‘an invention of the to colleagues who provided photographic material for illus-
devil, who is making it up as he goes along because he is trations, notably Nat Cary, Fred Dische and Magnus Norman,
not too clear about this stuffff either’. ThTh e article went on Jane Evanson, Stella Knight, Jonathan Frankel, Elizabeth
to compare immunology to a Rube Goldberg or Heath Higgins, Patrick O’Donnell, Bernard Portmann and John
Robinson cartoon: for example, the light is turned on when Salisbury.
you trip over a chair, startling the cat, who leaps against the
door, which swings shut, knocking a picture offff the wall, London M.P.
which strikes the light switch as it falls. And as a fifinal evi- 1997 D.V.
vi
Contents
1
Anatomyy and cells of the immune syystem 1
2
Innate immunityy I: pphyysical and humoral pprotection 11
3
Innate immunityy II: cellular mechanisms 23
4
Acqquired immunityy: antiggen recepptors 35
5
The human leukocyyte antiggens 55
6
Cellular immune respponses I: dendritic cells, macropphagges and B lyympphocyytes 71
Cellular immune responses II: T lymphocytes, antigen presentation and natural
7
killer cells 87
8 The immune response to microbes: an overview 115
9 Tolerance and mechanisms of autoimmunity 121
10 Hypersensitivity reactions and clinical allergy 133
11 Transplantation 151
12 Rheumatic diseases 167
13 Endocrine autoimmune disease 189
14 Liver diseases 203
15 Gastrointestinal diseases 211
16 Immune-mediated nephritis and vasculitis 219
17 Immune-mediated skin disease 239
18 Immune-mediated diseases of the nervous system and eye 249
19 Immunodefifi ciency 265
20 Human immunodefifi ciency virus and AIDS 283
21 Immunological manifestations of haematological disease 293
22 Immune-based therapies 307
23 Immunisation 323
Appendices
1: Commonly encountered CD molecules 334
2: Major cytokines, cells releasing them, targets and functions 342
3: List of class II human leukocyte antigen alleles 346
4: Abbreviations used for amino acids 347
Index 349
vii
Symbols used in the diagrams
LFA-1 ICAM-1 P-selectin E-selectin L-selectin CD8 TCR CD4
molecule molecule
Lymphocyte
AAAAAAAAAPPPPPPCCCCCC
L
Antigen
presenting cell Dendritic cell B-lymphocyte NK cell
B NK
T-lymphocyte
Plasma cell
T
Class I MHC molecule (blue)
with associated peptide (orange)
Macrophage Neutrophil P
and TCR (green)
CD8 CD4
Mast cell
Basophil
CTL
TH1 TH2 Treg
Eosinophil
Class II MHC molecule (red)
with associated peptide (orange)
and TCR (green)
Stimulates/enhances
Inhibits/kills
Becomes
viii
1
Anatomy and cells of
the immune system
the blood. ThTh e granulocytes constitute approximately 65% of
Cells of the immune system 1
all white cells and derive their name from the large numbers
Granulocytes 1
of granules found in their cytoplasm. ThThe appearance of
Monocytes and dendritic cells 1 these granules under the light microscope following conven-
Lymphocytes 2 tional staining provides a further subdivision. Granules with
Natural killer cells 3 intense blue staining are found in basophils, which make up
0.5–1% of granulocytes; red-staining granules are present in
Organs of the immune system 5 eosinophils (3–5%); while neutrophils (90–95%) have gran-
Primary lymphoid organs 5 ules that remain relatively unstained (Fig. 1.2a–c). ThThe term
‘polymorphonuclear cell’, describing the multilobed nuclei
Secondary lymphoid organs 6
of granulocytes, has become synonymous with neutrophils,
which constitute by far the majority of granulocytes, but
eosinophil nuclei may have a similar appearance. Granulo-
ThTh e immune system is like any other organ of mammalian
cytes circulate in the blood and migrate into the tissues par-
physiology — the liver, kidney, thyroid — in being composed
ticularly during inflfl ammatory responses. ThThe exception to
of specialised cells that function within discrete, organised
this rule is the mast cell, which is fifixed in the tissues. Mast
anatomical structures. To understand its role in host defence,
cells and basophils share many common features, yet their
it is necessary fifirst to become familiar with the cells and
derivation is difffffferent: the basophil is of the same lineage as
anatomy of the immune system.
neutrophils and eosinophils, whilst mast cells arise from an
as yet unidentifified precursor possibly in the spleen, thymus
or lymph node.
Cells of the immune system
ThTh e bone marrow is the source of the precursor cells that
Monocytes and dendritic cells
ultimately give rise to the cellular constituents of the immune
system, save for one brief period during foetal life when the
Monocytes form between 5 and 10% of circulating white
liver is also a site of immune cell development. ThThe produc-
blood cells and have a short half-life, spending approximately
tion of immune cells is one component of haemopoiesis, the
24 hours in the blood. ThThey enter the extravascular pool and
process by which all cells that circulate in the blood arise and
become resident in the tissues, where they are termed mac-
mature. An important underlying principle of haemopoiesis
rophages. Whilst each macrophage was thought to derive
is that there is a single precursor cell that is capable of giving
from a single monocyte, there is now evidence that macro-
rise to all blood cell lineages, ranging from platelets to lym-
phages may also arise following division of immature forms
phocytes (Fig. 1.1). ThThis cell is known as the pluripotent
of monocytes. Monocyte and macrophage morphology is
haemopoietic stem cell: it is to the bone marrow what the
highly variable, but in broad terms they are larger than neu-
queen bee is to the hive (Science Box 1.1). Immunology
trophils and lymphocytes, have a single nucleus and abun-
concentrates upon the roles of white blood cells in host
dant granular cytoplasm (Fig. 1.2d). Several specialised forms
defence: these include the granulocytes (neutrophils, eosino-
of the mature cell exist, including alveolar macrophagesin
phils and basophils), monocytes and dendritic cells, and
the lung, Kupffffffer cells in the liver, mesangial cells in the
lymphocytes.
kidney, microglial cellsin the brain, osteoclastsin bone, and
other macrophages lining channels in the spleen and lymph
Granulocytes nodes.
ThTh ere is an additional very small population of immune
ThTh e granulocyte/monocyte lineage gives rise to precursors cells in the peripheral blood, lymph nodes, bone marrow and
that mature within the bone marrow and are released into tissues that have a characteristic appearance of numerous
1