The vast majority of medically important pathogens infect their host across a body surface such as the skin, or across a mucosal tissue such as the respiratory tract or intestines, as these sites are the ones exposed to the external environment. By focusing on immunity at mucosal and body surfaces this book presents a fresh, new approach to the teaching of immunology.
After an introduction to the basic structure of the immune system, the book looks at two important families of signalling molecules: cytokines and chemokines, before covering the workings of the mucosal immune system. It continues by examining immunity against the four major groups of pathogens - viruses, bacteria, fungi and parasites, and concludes by looking at disorders of the immune system, mucosal tumour immunology and the process of vaccination.
- A fresh, new approach to the subject focusing on mucosal and body surfaces.
- Describes the mucosal immune systems of the gastrointestinal, respiratory and urogenital tracts, as well as the skin.
- Details the important roles of cytokines and chemokines in an immune response.
- Separate chapters devoted to immunity against viruses, bacteria, fungi and parasites.
- Includes chapter summaries, boxes with topics of special interest and an extensive glossary.
- Clearly written and well- illustrated in full colour throughout.
Students across a range of disciplines, including biology, biochemistry, biomedicine, medicine and veterinary sciences, will find this book invaluable, both as an introduction to basic immunology and as a guide to mucosal immune defence mechanisms.
Table of Contents
Preface, xvList of Standard Cells and Symbols, xvii
1 Basic Concepts in Immunology, 1
1.1 The immune system, 1
1.2 Tissues and cells of the immune system, 1
1.3 Activation, regulation and functions of immune responses, 4
1.4 Innate versus adaptive immunity, 5
1.5 Primary and secondary immune responses, 6
1.6 Immune cell development, 7
1.7 Mast cells and basophils, 9
1.8 Eosinophils, 11
1.9 Neutrophils, 11
1.10 Monocytes and macrophages, 11
1.11 Dendritic cells, 12
1.12 Natural killer cells, 12
1.13 CD4+ T helper cells, 13
1.14 CD8+ cytotoxic T cells, 14
1.15 B cells, 15
1.16 γδ T cells, 16
1.17 Natural killer T cells, 16
1.18 Anatomy of the immune system, 16
1.19 Lymph nodes, 16
1.20 Spleen, 19
1.21 Summary, 19
2 The Innate Immune System, 20
2.1 Introduction to the innate immune system, 20
2.2 Innate immune receptors and cells, 20
2.3 TLRs and pattern recognition, 22
2.4 TLR signalling in response to LPS, 23
2.5 Peptidoglycan and Nods, 24
2.6 Nod-like receptors recognize PAMPs and DAMPs, 25
2.7 Damage associated molecular patterns (DAMPs), 26
2.8 Complement proteins perform several innate immune functions, 27
2.9 The classical complement pathway, 28
2.10 The lectin and alternative complement pathways, 29
2.11 Biological properties of complement cleavage products, 29
2.12 Opsonization by complement proteins, 30
2.13 Phagocytosis, 31
2.14 Fc receptors induce phagocytosis, 32
2.15 Neutrophil function and the respiratory burst, 32
2.16 ADCC, 33
2.17 NK cells recognize missing self, 35
2.18 Activating adaptive immunity, 36
2.19 Dendritic cells link innate and adaptive immunity, 38
2.20 Summary, 40
3 The Adaptive Immune System, 41
3.1 Introduction to adaptive immunity, 41
3.2 T cells and B cells recognize foreign antigens, 41
3.3 Overview of antibody structure, 42
3.4 Constant region and antibody isotypes, 45
3.5 B cell receptor (BCR) diversity, 46
3.6 Genetic recombination of BCR genes, 46
3.7 Mechanism of VDJ recombination, 47
3.8 Introducing junctional diversity, 48
3.9 Somatic hypermutation and affinity maturation, 49
3.10 Immunoglobulin class switching, 50
3.11 Structure of Fc receptors, 51
3.12 Fc receptor specificity and affinity, 53
3.13 Cross-linking of antibody is necessary for Fc receptor signalling, 53
3.14 Fc receptor immune functions, 54
3.15 T cell receptor diversification, 54
3.16 T cells undergo positive and negative selection within the thymus, 55
3.17 Antigen presentation to T cells, 57
3.18 MHC class II processing pathway, 59
3.19 MHC class I processing pathway, 59
3.20 Activation requires co-stimulation, 60
3.21 Late co-stimulatory signals, 62
3.22 Activation of B cell responses, 63
3.23 CD4+ T helper cell differentiation, 63
3.24 Activation of CTLs, 65
3.25 Generation of memory T cells, 66
3.26 Summary, 67
4 Cytokines, 68
4.1 Introduction to cytokines, 68
4.2 Structure of cytokine families, 69
4.3 IL-1 superfamily, 71
4.4 IL-6 family, 71
4.5 IL-10 family, 72
4.6 Common ?-chain family, 73
4.7 IL-12 family, 74
4.8 Interferons, 75
4.9 TNF ligand superfamily, 75
4.10 Growth factors, 77
4.11 Functional classification Th1 versus Th2, 78
4.12 Th17, immunopathology and regulatory cytokines, 79
4.13 Cytokine receptor signalling, 79
4.14 Type I and type II cytokine receptors, 79
4.15 The JAK/STAT signalling pathway, 80
4.16 IL-2 signalling through the JAK/STAT pathway, 81
4.17 The JAK/STAT pathway is also used by IL-6, 83
4.18 Plasticity in type I cytokine signalling, 83
4.19 Suppressor of cytokine signalling (SOCS), 83
4.20 IFN-? signalling pathway, 84
4.21 TGF-ß and the SMAD signalling pathway, 85
4.22 Type III cytokine receptors and the TNF receptor family, 86
4.23 The IKK complex and the activation of NF-?B, 87
4.24 The IL-1R family of type IV cytokine receptors activate NF-?B, 88
4.25 Soluble cytokine receptors act as decoy receptors, 90
4.26 IL-33 and ST2 signal regulation, 91
4.27 Potential for cytokine therapy, 91
4.28 Summary, 92
5 Chemokines, 93
5.1 Introduction, 93
5.2 Structure and nomenclature of chemokines, 93
5.3 Chemokine receptors, 94
5.4 Expression of chemokines and their receptors, 97
5.5 Chemokines promote extravasation of leukocytes, 97
5.6 Chemotaxis, 99
5.7 Chemokine receptor signalling cascade, 99
5.8 Tissue specific homing, 100
5.9 Lymphocyte migration to secondary lymphoid tissues, 101
5.10 Chemokines involved in lymphoid structure formation, 102
5.11 Chemokines contribute to homeostasis, 104
5.12 Chemokine receptors on T cell subsets, 104
5.13 Redundancy in the chemokine/receptor system, 106
5.14 Chemokines in disease, 108
5.15 Chemokines as new anti-inflammatory drugs, 109
5.16 Summary, 110
6 Basic Concepts in Mucosal Immunology, 111
6.1 Introduction, 111
6.2 What is a mucosal tissue?, 112
6.3 Immune defence at mucosal tissue is multi-layered, 113
6.4 Origins of mucosal associated lymphoid tissue, 114
6.5 Concept of the common mucosal immune system, 115
6.6 How do T and B lymphocytes migrate into mucosal tissues?, 116
6.7 Special features of mucosal epithelium, 117
6.8 Toll-like receptors and NOD proteins in the mucosa, 120
6.9 Antigen sampling at mucosal surfaces, 121
6.10 Mucosal dendritic cells, 122
6.11 Secretory dimeric IgA at mucosal surfaces, 124
6.12 Regulation of J-chain and secretory component expression, 126
6.13 How does the sub-mucosa differ from the epithelium?, 126
6.14 Organized lymphoid tissue of the mucosa, 127
6.15 Cytokines in the mucosa, 128
6.16 Pathogens that enter via mucosal sites, 130
6.17 Immune diseases of mucosal tissues, 130
6.18 Summary, 132
7 Immunology of the Gastrointestinal Tract, 133
7.1 Structure of the gastrointestinal tract, 133
7.2 Development of the gastrointestinal tract, 133
7.3 The digestive tract as a mucosal tissue, 135
7.4 Barrier function, 136
7.5 Defensins and Trefoil factors, 138
7.6 Structure of Peyer’s patches, 139
7.7 Lymphoid follicles and germinal centre formation, 140
7.8 M cells sample the intestinal lumen, 143
7.9 Dendritic cells sample the lumen contents, 143
7.10 Lymphocytes within the epithelium (IELs), 143
7.11 ?d T cells in the GALT, 146
7.12 NKT cells, 147
7.13 T cells in the lamina propria, 148
7.14 Maintenance of T cell homeostasis, 148
7.15 Sub-mucosal B cells and mucosal IgA, 149
7.16 How IgA is produced at intestinal mucosal sites, 150
7.17 Cytokines in the gut, 151
7.18 Chemokines and the homing of lymphocytes to GALT, 152
7.19 Pathogens and immune diseases, 153
7.20 Summary, 154
8 Immunology of the Airways, 156
8.1 The airways as a mucosal tissue, 156
8.2 Development of the respiratory tract, 156
8.3 The structure of the respiratory tract, 158
8.4 Barrier function and the mucociliary elevator, 159
8.5 Mucins and mucociliary clearance, 160
8.6 Defensins and antimicrobial peptides, 160
8.7 Structure of the tonsils and adenoids of the Waldeyer’s Ring, 161
8.8 Local lymph nodes and immune generation, 163
8.9 Structure of the NALT, 165
8.10 Structure of the BALT, 165
8.11 Cells of the lower respiratory tract, 166
8.12 Surfactant proteins, 167
8.13 Immune modulation by airway epithelial cells, 167
8.14 Innate immune response, 168
8.15 Dendritic cells are located throughout the respiratory tract, 168
8.16 Alveolar macrophages maintain homeostasis, 169
8.17 NK cells in the lung, 171
8.18 T cells at effector sites in the lung, 171
8.19 Memory T cell responses within the lung, 172
8.20 Migration of circulating T cell into the lung tissue, 172
8.21 IgA production in the respiratory tract, 173
8.22 Respiratory diseases and pathogens, 174
8.23 Summary, 176
9 Immunology of the Urogenital Tract and Conjunctiva, 177
9.1 The urogenital tract as a MALT, 177
9.2 Epithelial barrier function, 178
9.3 Passive immunity, 181
9.4 Immunoglobulins, 181
9.5 APCs in genital tract mucosa, 182
9.6 NK cells and the semi-allogeneic foetus, 183
9.7 Pre-eclampsia is an immune-mediated disease, 184
9.8 Maintenance of foetal tolerance, 185
9.9 T cells and adaptive immunity, 186
9.10 Sexually transmitted diseases and pelvic inflammatory disease, 187
9.11 Alloimmunization and autoimmune diseases, 189
9.12 The foetal and neonatal immune system, 189
9.13 Immunity in the urinary tract, 190
9.14 Eye associated lymphoid tissue, 191
9.15 Conjunctiva associated lymphoid tissue (CALT), 192
9.16 Immune privilege of the eye, 192
9.17 Immune privilege and inflammation, 193
9.18 Conjunctivitis, 194
9.19 Summary, 195
10 Immunology of the Skin, 196
10.1 The skin as an immune tissue, 196
10.2 Barrier Immune function of the skin, 196
10.3 Cellular immune system of the skin, 198
10.4 Keratinocytes can act as immune cells, 199
10.5 Keratinocytes secrete antimicrobial peptides, 200
10.6 Langerhan’s cells act as immune sentinels in skin, 202
10.7 Dermal dendritic cells and cross-presentation of antigen, 203
10.8 Mast cells and NK cells in the skin, 205
10.9 Intraepidermal lymphocytes in the skin, 206
10.10 Lymphocytes in the dermis, 206
10.11 Skin homing T cells express CLA, 206
10.12 Chemokines and migration, 207
10.13 Initiation of an immune response in the skin, 208
10.14 Cytokines, 211
10.15 Psoriasis, inflammation and autoreactive T cells, 211
10.16 Autoimmune-mediated diseases of the skin, 213
10.17 Systemic diseases that affect the skin, 214
10.18 Infectious diseases of the skin, 215
10.19 Summary, 216
11 Immunity to Viruses, 217
11.1 Introduction, 217
11.2 Structure of viruses, 217
11.3 Classification of viruses, 218
11.4 Viruses replicate within host cells, 218
11.5 Infections caused by viruses, 219
11.6 Certain viruses can infect immune cells, 220
11.7 Virus infection of epithelial cells, 221
11.8 IFN-a response, 222
11.9 NK cell response to viruses, 222
11.10 Viral evasion of NK cell responses, 223
11.11 Macrophages contribute to virus elimination, 225
11.12 TLRs and NLRs recognize virus motifs, 226
11.13 Activation of the inflammasome by viruses, 226
11.14 Dendritic cells present virus antigens to CD8+ CTLs, 227
11.15 T cell responses to viruses, 229
11.16 Evasion of CTL-mediated immunity by viruses, 229
11.17 Bystander effects of immune responses to viruses, 231
11.18 Antibody response to viruses, 232
11.19 Difference between cytopathic and non-cytopathic viruses, 233
11.20 Immune evasion by antigenic shift and drift, 235
11.21 Vaccination and therapies against viral infections, 235
11.22 Summary, 237
12 Immunity to Bacteria, 238
12.1 Introduction to bacterial immunity, 238
12.2 Classification of bacteria, 238
12.3 Structure of the bacterial cell, 240
12.4 Diseases caused by bacteria, 241
12.5 Mucosal barriers to bacterial infection, 241
12.6 Anti-microbial molecules, 242
12.7 Recognition of bacterial PAMPs by Toll-like receptors, 243
12.8 Complement and bacterial immunity, 244
12.9 Neutrophils are central to bacterial immune responses, 245
12.10 Some bacteria are resistant to phagosome mediated killing, 247
12.11 NK cells and ADCC, 248
12.12 The role of antibody in bacterial immunity, 249
12.13 Dendritic cells and immunity to bacteria, 250
12.14 Autophagy and intracellular bacteria, 251
12.15 T Cells contribute to protective immunity, 253
12.16 The DTH response and granuloma in TB, 253
12.17 Th17 cells in bacterial immunity, 254
12.18 Treg cells in bacterial infection, 255
12.19 Unconventional T cells, 256
12.20 Vaccination against bacterial diseases, 256
12.21 Summary, 256
13 Immunity to Fungi, 258
13.1 Introduction, 258
13.2 Morphology of fungi, 258
13.3 Yeasts, 260
13.4 Moulds, 260
13.5 Fungal dimorphism, 261
13.6 Diseases caused by fungi, 262
13.7 Immune response to fungi, 263
13.8 Innate immunity, 263
13.9 Mucosal barriers to fungal infection, 263
13.10 Anti-fungal molecules, 265
13.11 Recognition of fungal PAMPs by Toll-like receptors, 266
13.12 Complement and fungal immunity, 266
13.13 Dendritic cells link innate and adaptive fungal immunity, 268
13.14 DCs provide the adaptive immune response with instructive signals, 270
13.15 Macrophages are important APCs during fungal infection, 270
13.16 Neutrophils participate in the inflammatory response to fungi, 271
13.17 NK cells provide inflammatory signals to macrophages, 271
13.18 Adaptive immunity to fungi, 272
13.19 The DTH response and granuloma formation inhibit fungal dissemination, 272
13.20 The role of antibody in fungal resistance, 273
13.21 Vaccination and immunotherapies, 274
13.22 Fungal immune evasion strategies, 276
13.23 Immuno-modulatory fungal products, 276
13.24 Evasion of phagolysosomal killing, 276
13.25 Modifying the cytokine response, 277
13.26 Summary, 277
14 Immunity to Parasites, 278
14.1 Introduction, 278
14.2 Protozoa are diverse unicellular eukaryotes, 278
14.3 Structure of the protozoan cell, 278
14.4 Life cycle of protozoan parasites, 280
14.5 The life cycle of Trypanosoma brucei, 281
14.6 Life cycle of Leishmania species, 281
14.7 The life cycle of Plasmodium falciparum, 281
14.8 Helminths are multicellular, macroscopic parasites, 282
14.9 Structure of the trematode Schistosoma mansoni, 283
14.10 Life cycle of Schistosoma mansoni, 284
14.11 Structure of the nematode Ascaris lumbricoides, 285
14.12 The life cycle of A. lumbricoides, 286
14.13 Immune responses to parasites, 286
14.14 Innate immunity to trypanosomes, 287
14.15 Adaptive immunity to trypanosomes, 287
14.16 Innate immunity to plasmodium, 288
14.17 Adaptive immunity to plasmodium, 289
14.18 Immunity to Leishmania – Th1 versus Th2, 290
14.19 Immunity to Giardia, 291
14.20 Immunity to schistosomes, 292
14.21 Innate immunity to schistosomes, 292
14.22 Adaptive immunity to schistosomes, 293
14.23 Granuloma formation in schistosomiasis, 294
14.24 Immunity to intestinal nematode worms, 294
14.25 Innate immunity to nematode worms in the gut, 294
14.26 Adaptive immunity to nematode worms in the gut, 295
14.27 Immune evasion strategies of parasites, 296
14.28 Trypanosome variant surface glycoproteins (VSGs), 297
14.29 Plasmodium life cycle contributes to immune evasion, 298
14.30 Leishmania evade phagocytic killing, 298
14.31 Immune evasion strategies of helminths, 298
14.32 Summary, 300
15 Disorders of the Immune System, 302
15.1 Introduction to immune disorders, 302
15.2 Types of allergy, 302
15.3 Sensitization and the acute phase response, 304
15.4 Mast cell degranulation, 305
15.5 Late phase response, 306
15.6 Allergic asthma, 307
15.7 Mast cells and the early phase allergic asthma, 308
15.8 Epithelial cells can trigger allergic asthma, 308
15.9 T cells and the late phase of allergic asthma, 310
15.10 Allergic rhinitis, 310
15.11 Skin allergy and atopic dermatitis, 311
15.12 Food allergies, 311
15.13 T cell subsets in allergy, 312
15.14 Mechanisms of autoimmune disease, 313
15.15 Disregulation of tolerance and autoimmunity, 313
15.16 Inflammatory bowel disease, 316
15.17 Coeliac disease, 317
15.18 Systemic lupus erythematosus, 317
15.19 Other autoimmune diseases, 318
15.20 Immunodeficiencies, 320
15.21 Summary, 321
16 Mucosal Tumour Immunology, 322
16.1 Introduction, 322
16.2 Transformation into cancer cells, 322
16.3 Proto-oncogene activation, 323
16.4 Mutation in the p53 protein, 324
16.5 Mutant Ras proteins enhance proliferation, 324
16.6 Aneuploidy and colorectal cancer, 324
16.7 Tumourigenesis, 324
16.8 Angiogenesis, 326
16.9 Metastasis, 327
16.10 The immune system and cancer, 327
16.11 Immune surveillance, 328
16.12 Immunogenicity of tumour cells, 329
16.13 Recognition of transformed cells, 330
16.14 Tumour associated antigens, 331
16.15 Carcinoembryonic antigen in colorectal cancer, 331
16.16 Melanoma differentiation antigens, 332
16.17 Viral tumour associated antigens, 332
16.18 Effector molecules during tumour immune surveillance, 333
16.19 Dendritic cells modulate anti-tumour immune responses, 333
16.20 Tumour reactive T cells are activated in lymph nodes, 335
16.21 NK cell recognition – missing self, 335
16.22 NKG2D receptor on NK cells, 335
16.23 Macrophages and neutrophils phagocytose tumour cells but support tumour growth, 336
16.24 Immune cells can augment tumour growth, 337
16.25 Immune evasion strategies, 337
16.26 Darwinian selection and tumour cell escape, 338
16.27 Cytokine environment and tumour escape, 339
16.28 Tumours have disregulated MHC expression and antigen presentation, 339
16.29 Tumour escape through Fas/FasL, 340
16.30 Summary, 341
17 Vaccination, 342
17.1 Introduction, 342
17.2 The principles of vaccination, 342
17.3 Passive immunization, 344
17.4 Active immunization, 344
17.5 Processing of the vaccine for immune recognition, 344
17.6 Adaptive Immune response following vaccination, 347
17.7 Vaccine adjuvants, 347
17.8 Alum, 348
17.9 Freund’s complete adjuvant, 348
17.10 Mucosal adjuvants and vaccine delivery, 350
17.11 Prospects in adjuvant design, 350
17.12 Th1/Th2 polarization and vaccine development, 351
17.13 Live-attenuated vaccines, 351
17.14 Inactivated vaccines, 353
17.15 Polysaccharide vaccines, 354
17.16 Peptide vaccines, 354
17.17 DNA vaccination, 355
17.18 Immuno-stimulatory complexes (ISCOMs), 355
17.19 Dendritic cell vaccines, 358
17.20 Mucosal administration of vaccines, 359
17.21 Nasally administered vaccine against genital infections, 360
17.22 New strategies for vaccine development, 360
17.23 Summary, 362
Glossary of Terms, 363
Index, 374
