Principles of Immunopharmacology: 3rd revised and extended edition

743 Pages·2011·32.891 MB·English

by  Frank J. T. Staal, Karin Pike-Overzet, Menno C. van Zelm (auth.), F.P. Nijkamp, Michael J. Parnham (eds.)

Principles of
Immunopharmacology
3rd revised and extended edition
Edited by
Frans P. Nijkamp and
Michael J. Parnham
Frans P. Nijkamp Michael J. Parnham
Division of Pharmacology Pharmacological Institute for Life Scientists
Department of Pharmaceutical Sciences J.W. Goethe University
Faculty of Science Frankfurt a.M., Germany;
Utrecht University University Hospital for Infectious Diseases
P.O. Box 80082 “Dr Fran Mihaljevic”
3508 TB Utrecht Migrogojska cesta 8
The Netherlands 10000 Zagreb, Croatia;
and MediMlijeko d.o.o.
10000 Zagreb, Croatia
Bibliographic information published by Die Deutsche Bibliothek
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ISBN: 978-3-0346-0135-1 e-ISBN: 978-3-0346-0136-8
9 8 7 6 5 4 3 2 1
Contents
Preface to the first edition................................................................ xv
Preface to the second edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvi
Preface to the third edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix
Introduction: Altering the chain of command in host defence
Inflammation and host defence............................................................ xxvii
Measuring host defence reactions.......................................................... xxix
Pharmacological modulation of immune responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxix
Selected readings....................................................................... xxxi
A Immunity
A1 Hematopoiesis and lymphocyte development: an introduction
Introduction: Blood cell development and immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Hematopoietic stem cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Lymphocyte development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Specificity: Rearrangement of genes encoding antigen receptors............................. 5
T cell development................................................................ 7
B cell development................................................................ 8
NK cell development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Immunopharmacology and hematopoiesis.............................................. 10
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Selected readings................................................................. 11
Important websites................................................................ 12
References...................................................................... 12
A2 T cell subsets and T cell-mediated immunity
Introduction..................................................................... 15
Biology of the T lymphocyte immune response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Composition of the T cell network.................................................... 16
T cell subset markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Effectors of T cell-mediated immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Mechanisms of T cell activation...................................................... 22
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Selected readings................................................................. 26
vi Contents
A3 Antibody diversity and B lymphocyte-mediated immunity
Antibodies and immunoglobulins..................................................... 29
Structure of immunoglobulins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Generation of antibody diversity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
B cell receptor and signal transduction................................................. 31
B lymphocyte costimulation......................................................... 36
Cytokine regulation and isotype switching.............................................. 37
T cell-independent B lymphocyte activation............................................. 38
Primary and secondary antibody response.............................................. 40
Biological functions of antibodies..................................................... 42
Clinical relevance and future prospects................................................. 45
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Selected readings................................................................. 46
Recommended websites............................................................ 46
References...................................................................... 46
A4 Dendritic cells
Introduction..................................................................... 47
Biology of the DC ................................................................ 47
Mechanisms and pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Pathophysiological relevance ........................................................ 53
Pharmacological implications ........................................................ 55
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Selected readings................................................................. 56
References...................................................................... 56
A5 Cytokines
Introduction..................................................................... 59
Differentiation factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Activation and growth factors of lymphocytes........................................... 63
Mediators of inflammation.......................................................... 66
Pharmacological relevance.......................................................... 69
Regulatory factors of immune reactions................................................ 70
Chemokines..................................................................... 72
Inhibition of cytokines ............................................................. 74
Summary and outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Selected readings................................................................. 78
Recommended website ............................................................ 78
References...................................................................... 78
A6 Innate immunity – Phagocytes, natural killer cells and the complement system
Introduction..................................................................... 81
Phagocytes...................................................................... 81
Natural killer cells................................................................. 91
The complement system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Contents vii
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Selected readings................................................................. 99
References...................................................................... 99
A7 Inflammatory mediators and intracellular signalling
Introduction..................................................................... 101
Eicosanoids...................................................................... 101
Platelet-activating factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Innate immune signalling receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Cytokines....................................................................... 112
Chemokines and their intracellular signalling ............................................ 115
Neuropeptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
Kinins.......................................................................... 117
Nitric oxide...................................................................... 118
Reactive oxygen species............................................................ 122
Amines......................................................................... 122
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
References...................................................................... 125
A8 Immune response in human pathology: Infections caused by bacteria, viruses, fungi, and parasites
Infections....................................................................... 127
Natural resistance................................................................. 127
Specific resistance................................................................. 129
Defence against bacteria, viruses, fungi, and parasites..................................... 130
Pathogenesis of shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Human immunodeficiency virus infection............................................... 135
Vaccines and vaccination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
Infections in the new millennium..................................................... 137
Selected readings................................................................. 138
Important websites................................................................ 138
A9 Immune response in human pathology: Hypersensitivity and autoimmunity
Introduction..................................................................... 139
Hypersensitivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Selected readings................................................................. 147
Important websites................................................................ 147
References...................................................................... 147
A10 Cancer immunity
Introduction: Cancer immunity from a historical perspective ................................ 151
Key players in the immune responses against cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
Expression of targets for the immune system by cancer cells ................................ 155
Immunotherapy of cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Conclusions and future developments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
viii Contents
Selected readings................................................................. 167
Important websites................................................................ 168
References...................................................................... 168
A11 Neuroimmunoendocrinology
Historical background.............................................................. 179
Regulation of the immune system by neuroendocrine hormones............................. 180
Functions of leukocyte-derived peptide hormones in vivo.................................. 187
Regulation of nervous system by immune factors ........................................ 188
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
Selected readings ................................................................ 193
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
References...................................................................... 193
B Immunodiagnosis
B1 Antibody detection
Introduction..................................................................... 201
Basic principle of immunoassays...................................................... 201
Antibody structure................................................................ 202
Clinical relevance of antibody detection................................................ 202
Antibody-detection methods ........................................................ 203
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Selected readings................................................................. 208
References...................................................................... 208
B2 Immunoassays
Introduction..................................................................... 209
Basic principles of assay design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Components of immunoassays....................................................... 211
Selected immunoassays ............................................................ 214
Assay performance and validation .................................................... 216
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
Selected reading.................................................................. 219
References...................................................................... 219
B3 Flow cytometry
Introduction..................................................................... 221
Mechanistic principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Classification/types of assay......................................................... 224
Components/construction of assays................................................... 227
Examples and their application....................................................... 231
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
Suggested readings and website . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
References...................................................................... 234
B4 Microarrays
Introduction..................................................................... 237
Contents ix
Principle of the technology.......................................................... 237
Application of microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
Array data: acquisition, analysis and mining............................................. 244
Examples of microarray experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Selected readings................................................................. 249
Recommended websites............................................................ 249
References...................................................................... 250
C Immunotherapeutics
C1 Vaccines
Introduction..................................................................... 255
Historical background.............................................................. 256
Current vaccine categories.......................................................... 257
Pharmacological effects of vaccination................................................. 262
New developments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Selected readings................................................................. 269
Websites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
References...................................................................... 269
C2 Plasma-derived immunoglobulins
Introduction..................................................................... 271
Antibody structure and effector functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
Glycosylation of immunoglobulins .................................................... 280
Pharmacokinetics of immunoglobulins................................................. 281
Immunoglobulin preparations for medical use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
Indications for immunoglobulins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Adverse reactions to IgG therapy..................................................... 293
Viral safety of immunoglobulins...................................................... 294
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Selected readings ................................................................ 297
Recommended websites............................................................ 297
References...................................................................... 297
C3 Anti-allergic drugs
Introduction..................................................................... 303
Disodium cromoglycate and nedocromil sodium (cromones) ................................ 303
Histamine receptor antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Anti-leukotrienes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
Anti-IgE ........................................................................ 314
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
Selected readings................................................................. 316
References...................................................................... 316