Immunology: Mucosal and Body Surface Defences

Immunology......Page 3
Contents......Page 7
Preface......Page 17
List of Standard Cells and Symbols......Page 19
1.2 Tissues and cells of the immune system......Page 21
1.3 Activation, regulation and functions of immune responses......Page 24
1.4 Innate versus adaptive immunity......Page 25
1.5 Primary and secondary immune responses......Page 26
1.6 Immune cell development......Page 27
1.7 Mast cells and basophils......Page 29
1.10 Monocytes and macrophages......Page 31
1.12 Natural killer cells......Page 32
1.13 CD4+ T helper cells......Page 33
1.14 CD8+ cytotoxic T cells......Page 34
1.15 B cells......Page 35
1.19 Lymph nodes......Page 36
1.21 Summary......Page 39
2.2 Innate immune receptors and cells......Page 40
2.3 TLRs and pattern recognition......Page 42
2.4 TLR signalling in response to LPS......Page 43
2.5 Peptidoglycan and Nods......Page 44
2.6 Nod-like receptors recognize PAMPs and DAMPs......Page 45
2.7 Damage associated molecular patterns (DAMPs)......Page 46
2.8 Complement proteins perform several innate immune functions......Page 47
2.9 The classical complement pathway......Page 48
2.11 Biological properties of complement cleavage products......Page 49
2.12 Opsonization by complement proteins......Page 50
2.13 Phagocytosis......Page 51
2.15 Neutrophil function and the respiratory burst......Page 52
2.16 ADCC......Page 53
2.17 NK cells recognize missing self......Page 55
2.18 Activating adaptive immunity......Page 56
2.19 Dendritic cells link innate and adaptive immunity......Page 58
2.20 Summary......Page 60
3.2 T cells and B cells recognize foreign antigens......Page 61
3.3 Overview of antibody structure......Page 62
3.4 Constant region and antibody isotypes......Page 65
3.6 Genetic recombination of BCR genes......Page 66
3.7 Mechanism of VDJ recombination......Page 67
3.8 Introducing junctional diversity......Page 68
3.9 Somatic hypermutation and affinity maturation......Page 69
3.10 Immunoglobulin class switching......Page 70
3.11 Structure of Fc receptors......Page 71
3.13 Cross-linking of antibody is necessary for Fc receptor signalling......Page 73
3.15 T cell receptor diversification......Page 74
3.16 T cells undergo positive and negative selection within the thymus......Page 75
3.17 Antigen presentation to T cells......Page 77
3.19 MHC class I processing pathway......Page 79
3.20 Activation requires co-stimulation......Page 80
3.21 Late co-stimulatory signals......Page 82
3.23 CD4+ T helper cell differentiation......Page 83
3.24 Activation of CTLs......Page 85
3.25 Generation of memory T cells......Page 86
3.26 Summary......Page 87
4.1 Introduction to cytokines......Page 88
4.2 Structure of cytokine families......Page 89
4.4 IL-6 family......Page 91
4.5 IL-10 family......Page 92
4.6 Common g-chain family......Page 93
4.7 IL-12 family......Page 94
4.9 TNF ligand superfamily......Page 95
4.10 Growth factors......Page 97
4.11 Functional classification Th1 versus Th2......Page 98
4.14 Type I and type II cytokine receptors......Page 99
4.15 The JAK/STAT signalling pathway......Page 100
4.16 IL-2 signalling through the JAK/STAT pathway......Page 101
4.19 Suppressor of cytokine signalling (SOCS)......Page 103
4.20 IFN-g signalling pathway......Page 104
4.21 TGF-g and the SMAD signalling pathway......Page 105
4.22 Type III cytokine receptors and the TNF receptor family......Page 106
4.23 The IKK complex and the activation of NF-k......Page 107
4.24 The IL-1R family of type IV cytokine receptors activate NF-k......Page 108
4.25 Soluble cytokine receptors act as decoy receptors......Page 110
4.27 Potential for cytokine therapy......Page 111
4.28 Summary......Page 112
5.2 Structure and nomenclature of chemokines......Page 113
5.3 Chemokine receptors......Page 114
5.5 Chemokines promote extravasation of leukocytes......Page 117
5.7 Chemokine receptor signalling cascade......Page 119
5.8 Tissue specific homing......Page 120
5.9 Lymphocyte migration to secondary lymphoid tissues......Page 121
5.10 Chemokines involved in lymphoid structure formation......Page 122
5.12 Chemokine receptors on T cell subsets......Page 124
5.13 Redundancy in the chemokine/receptor system......Page 126
5.14 Chemokines in disease......Page 128
5.15 Chemokines as new anti-inflammatory drugs......Page 129
5.16 Summary......Page 130
6.1 Introduction......Page 131
6.2 What is a mucosal tissue?......Page 132
6.3 Immune defence at mucosal tissue is multi-layered......Page 133
6.4 Origins of mucosal associated lymphoid tissue......Page 134
6.5 Concept of the common mucosal immune system......Page 135
6.6 How do T and B lymphocytes migrate into mucosal tissues?......Page 136
6.7 Special features of mucosal epithelium......Page 137
6.8 Toll-like receptors and NOD proteins in the mucosa......Page 140
6.9 Antigen sampling at mucosal surfaces......Page 141
6.10 Mucosal dendritic cells......Page 142
6.11 Secretory dimeric IgA at mucosal surfaces......Page 144
6.13 How does the sub-mucosa differ from the epithelium?......Page 146
6.14 Organized lymphoid tissue of the mucosa......Page 147
6.15 Cytokines in the mucosa......Page 148
6.17 Immune diseases of mucosal tissues......Page 150
6.18 Summary......Page 152
7.2 Development of the gastrointestinal tract......Page 153
7.3 The digestive tract as a mucosal tissue......Page 155
7.4 Barrier function......Page 156
7.5 Defensins and Trefoil factors......Page 158
7.6 Structure of Peyer's patches......Page 159
7.7 Lymphoid follicles and germinal centre formation......Page 160
7.10 Lymphocytes within the epithelium (IELs)......Page 163
7.11 gd T cells in the GALT......Page 166
7.12 NKT cells......Page 167
7.14 Maintenance of T cell homeostasis......Page 168
7.15 Sub-mucosal B cells and mucosal IgA......Page 169
7.16 How IgA is produced at intestinal mucosal sites......Page 170
7.17 Cytokines in the gut......Page 171
7.18 Chemokines and the homing of lymphocytes to GALT......Page 172
7.19 Pathogens and immune diseases......Page 173
7.20 Summary......Page 174
8.2 Development of the respiratory tract......Page 176
8.3 The structure of the respiratory tract......Page 178
8.4 Barrier function and the mucociliary elevator......Page 179
8.6 Defensins and antimicrobial peptides......Page 180
8.7 Structure of the tonsils and adenoids of the Waldeyer's Ring......Page 181
8.8 Local lymph nodes and immune generation......Page 183
8.10 Structure of the BALT......Page 185
8.11 Cells of the lower respiratory tract......Page 186
8.13 Immune modulation by airway epithelial cells......Page 187
8.15 Dendritic cells are located throughout the respiratory tract......Page 188
8.16 Alveolar macrophages maintain homeostasis......Page 189
8.18 T cells at effector sites in the lung......Page 191
8.20 Migration of circulating T cell into the lung tissue......Page 192
8.21 IgA production in the respiratory tract......Page 193
8.22 Respiratory diseases and pathogens......Page 194
8.23 Summary......Page 196
9.1 The urogenital tract as a MALT......Page 197
9.2 Epithelial barrier function......Page 198
9.4 Immunoglobulins......Page 201
9.5 APCs in genital tract mucosa......Page 202
9.6 NK cells and the semi-allogeneic foetus......Page 203
9.7 Pre-eclampsia is an immune-mediated disease......Page 204
9.8 Maintenance of foetal tolerance......Page 205
9.9 T cells and adaptive immunity......Page 206
9.10 Sexually transmitted diseases and pelvic inflammatory disease......Page 207
9.12 The foetal and neonatal immune system......Page 209
9.13 Immunity in the urinary tract......Page 210
9.14 Eye associated lymphoid tissue......Page 211
9.16 Immune privilege of the eye......Page 212
9.17 Immune privilege and inflammation......Page 213
9.18 Conjunctivitis......Page 214
9.19 Summary......Page 215
10.2 Barrier Immune function of the skin......Page 216
10.3 Cellular immune system of the skin......Page 218
10.4 Keratinocytes can act as immune cells......Page 219
10.5 Keratinocytes secrete antimicrobial peptides......Page 220
10.6 Langerhan's cells act as immune sentinels in skin......Page 222
10.7 Dermal dendritic cells and cross-presentation of antigen......Page 223
10.8 Mast cells and NK cells in the skin......Page 225
10.11 Skin homing T cells express CLA......Page 226
10.12 Chemokines and migration......Page 227
10.13 Initiation of an immune response in the skin......Page 228
10.15 Psoriasis, inflammation and autoreactive T cells......Page 231
10.16 Autoimmune-mediated diseases of the skin......Page 233
10.17 Systemic diseases that affect the skin......Page 234
10.18 Infectious diseases of the skin......Page 235
10.19 Summary......Page 236
11.2 Structure of viruses......Page 237
11.4 Viruses replicate within host cells......Page 238
11.5 Infections caused by viruses......Page 239
11.6 Certain viruses can infect immune cells......Page 240
11.7 Virus infection of epithelial cells......Page 241
11.9 NK cell response to viruses......Page 242
11.10 Viral evasion of NK cell responses......Page 243
11.11 Macrophages contribute to virus elimination......Page 245
11.13 Activation of the inflammasome by viruses......Page 246
11.14 Dendritic cells present virus antigens to CD8+ CTLs......Page 247
11.16 Evasion of CTL-mediated immunity by viruses......Page 249
11.17 Bystander effects of immune responses to viruses......Page 251
11.18 Antibody response to viruses......Page 252
11.19 Difference between cytopathic and non-cytopathic viruses......Page 253
11.21 Vaccination and therapies against viral infections......Page 255
11.22 Summary......Page 257
12.2 Classification of bacteria......Page 258
12.3 Structure of the bacterial cell......Page 260
12.5 Mucosal barriers to bacterial infection......Page 261
12.6 Anti-microbial molecules......Page 262
12.7 Recognition of bacterial PAMPs by Toll-like receptors......Page 263
12.8 Complement and bacterial immunity......Page 264
12.9 Neutrophils are central to bacterial immune responses......Page 265
12.10 Some bacteria are resistant to phagosome mediated killing......Page 267
12.11 NK cells and ADCC......Page 268
12.12 The role of antibody in bacterial immunity......Page 269
12.13 Dendritic cells and immunity to bacteria......Page 270
12.14 Autophagy and intracellular bacteria......Page 271
12.16 The DTH response and granuloma in TB......Page 273
12.17 Th17 cells in bacterial immunity......Page 274
12.18 Treg cells in bacterial infection......Page 275
12.21 Summary......Page 276
13.2 Morphology of fungi......Page 278
13.4 Moulds......Page 280
13.5 Fungal dimorphism......Page 281
13.6 Diseases caused by fungi......Page 282
13.9 Mucosal barriers to fungal infection......Page 283
13.10 Anti-fungal molecules......Page 285
13.12 Complement and fungal immunity......Page 286
13.13 Dendritic cells link innate and adaptive fungal immunity......Page 288
13.15 Macrophages are important APCs during fungal infection......Page 290
13.17 NK cells provide inflammatory signals to macrophages......Page 291
13.19 The DTH response and granuloma formation inhibit fungal dissemination......Page 292
13.20 The role of antibody in fungal resistance......Page 293
13.21 Vaccination and immunotherapies......Page 294
13.24 Evasion of phagolysosomal killing......Page 296
13.26 Summary......Page 297
14.3 Structure of the protozoan cell......Page 298
14.4 Life cycle of protozoan parasites......Page 300
14.7 The life cycle of Plasmodium falciparum......Page 301
14.8 Helminths are multicellular, macroscopic parasites......Page 302
14.9 Structure of the trematode Schistosoma mansoni......Page 303
14.10 Life cycle of Schistosoma mansoni......Page 304
14.11 Structure of the nematode Ascaris lumbricoides......Page 305
14.13 Immune responses to parasites......Page 306
14.15 Adaptive immunity to trypanosomes......Page 307
14.16 Innate immunity to plasmodium......Page 308
14.17 Adaptive immunity to plasmodium......Page 309
14.18 Immunity to Leishmania – Th1 versus Th2......Page 310
14.19 Immunity to Giardia......Page 311
14.21 Innate immunity to schistosomes......Page 312
14.22 Adaptive immunity to schistosomes......Page 313
14.25 Innate immunity to nematode worms in the gut......Page 314
14.26 Adaptive immunity to nematode worms in the gut......Page 315
14.27 Immune evasion strategies of parasites......Page 316
14.28 Trypanosome variant surface glycoproteins (VSGs)......Page 317
14.31 Immune evasion strategies of helminths......Page 318
14.32 Summary......Page 320
15.2 Types of allergy......Page 322
15.3 Sensitization and the acute phase response......Page 324
15.4 Mast cell degranulation......Page 325
15.5 Late phase response......Page 326
15.6 Allergic asthma......Page 327
15.8 Epithelial cells can trigger allergic asthma......Page 328
15.10 Allergic rhinitis......Page 330
15.12 Food allergies......Page 331
15.13 T cell subsets in allergy......Page 332
15.15 Disregulation of tolerance and autoimmunity......Page 333
15.16 Inflammatory bowel disease......Page 336
15.18 Systemic lupus erythematosus......Page 337
15.19 Other autoimmune diseases......Page 338
15.20 Immunodeficiencies......Page 340
15.21 Summary......Page 341
16.2 Transformation into cancer cells......Page 342
16.3 Proto-oncogene activation......Page 343
16.7 Tumourigenesis......Page 344
16.8 Angiogenesis......Page 346
16.10 The immune system and cancer......Page 347
16.11 Immune surveillance......Page 348
16.12 Immunogenicity of tumour cells......Page 349
16.13 Recognition of transformed cells......Page 350
16.15 Carcinoembryonic antigen in colorectal cancer......Page 351
16.17 Viral tumour associated antigens......Page 352
16.19 Dendritic cells modulate anti-tumour immune responses......Page 353
16.22 NKG2D receptor on NK cells......Page 355
16.23 Macrophages and neutrophils phagocytose tumour cells but support tumour growth......Page 356
16.25 Immune evasion strategies......Page 357
16.26 Darwinian selection and tumour cell escape......Page 358
16.28 Tumours have disregulated MHC expression and antigen presentation......Page 359
16.29 Tumour escape through Fas/FasL......Page 360
16.30 Summary......Page 361
17.2 The principles of vaccination......Page 362
17.5 Processing of the vaccine for immune recognition......Page 364
17.7 Vaccine adjuvants......Page 367
17.9 Freund's complete adjuvant......Page 368
17.11 Prospects in adjuvant design......Page 370
17.13 Live-attenuated vaccines......Page 371
17.14 Inactivated vaccines......Page 373
17.16 Peptide vaccines......Page 374
17.18 Immuno-stimulatory complexes (ISCOMs)......Page 375
17.19 Dendritic cell vaccines......Page 378
17.20 Mucosal administration of vaccines......Page 379
17.22 New strategies for vaccine development......Page 380
17.23 Summary......Page 382
Glossary of Terms......Page 383
Index......Page 394