Immunology Mucosal and Body Surface Defences

by Williams, Andrew E.

• ISBN13: 9780470090039
• ISBN10: 0470090030
• Edition: 1st
• Format: Hardcover
• Copyright: 2011-11-30
• Publisher: Wiley

Summary

Immunity: Mucosal Immunology in Health and Disease provides a realistic approach to the teaching of immunology, dealing with immunity at specific sites in the body a novel approach not adopted in current books. This book is the first immunology textbook to focus on the mucosa, the largest immune organ in the body. It discusses basic aspects of immunology together with the main themes of modern mucosal immunology, and provides an integrated approach to describe the immunological events from the moment the antigen enters the body to the immune mechanisms that eradicate it. This textbook covers the following topics so that readers will appreciate that not all sites within the body respond in the same manner: Entry of the antigen/pathogen The structure of the infected site Mechanisms that alert the immune system Cells affected/infected by that antigen Innate and acquired immune mechanisms relevant to that specific site Clearance and/or antigen mediated damage Transmission to other hosts Each chapter in this unique textbook contains boxed areas of text including for example case studies, techniques or recent developments worthy of the public's attention. The book also includes an associated website containing a range of support material for lecturers. Immunity: Mucosal Immunology in Health and Disease is an essential resource for BSc and MSc students and those studying for a PhD degree in departments of biology, biochemistry, biomedicine, medicine, veterinary sciences, and immunology. It has a strong appeal within the pharmaceutical industry.

Author Biography

Dr Andrew E. Williams, Imperial College, London, UK.

Table of Contents

Preface	p. xv
List of Standard Cells and Symbols	p. xvii
Basic Concepts in Immunology	p. 1
The immune system	p. 1
Tissues and cells of the immune system	p. 1
Activation, regulation and functions of immune responses	p. 4
Innate versus adaptive immunity	p. 5
Primary and secondary immune responses	p. 6
Immune cell development	p. 7
Mast cells and basophils	p. 9
Eosinophils	p. 11
Neutrophils	p. 11
Monocytes and macrophages	p. 11
Dendritic cells	p. 12
Natural killer cells	p. 12
CD4+ T helper cells	p. 13
CD8+ cytotoxic T cells	p. 14
B cells	p. 15
¿¿ T cells	p. 16
Natural killer T cells	p. 16
Anatomy of the immune system	p. 16
Lymph nodes	p. 16
Spleen	p. 19
Summary	p. 19
The Innate Immune System	p. 20
Introduction to the innate immune system	p. 20
Innate immune receptors and cells	p. 20
TLRs and pattern recognition	p. 22
TLR signalling in response to LPS	p. 23
Peptidoglycan and Nods	p. 24
Nod-like receptors recognize PAMPs and DAMPs	p. 25
Damage associated molecular patterns (DAMPs)	p. 26
Complement proteins perform several innate immune functions	p. 27
The classical complement pathway	p. 28
The lectin and alternative complement pathways	p. 29
Biological properties of complement cleavage products	p. 29
Opsonization by complement proteins	p. 30
Phagocytosis	p. 31
Fc receptors induce phagocytosis	p. 32
Neutrophil function and the respiratory burst	p. 32
ADCC	p. 33
NK cells recognize missing self	p. 35
Activating adaptive immunity	p. 36
Dendritic cells link innate and adaptive immunity	p. 38
Summary	p. 40
The Adaptive Immune System	p. 41
Introduction to adaptive immunity	p. 41
T cells and B cells recognize foreign antigens	p. 41
Overview of antibody structure	p. 42
Constant region and antibody isotypes	p. 45
B cell receptor (BCR) diversity	p. 46
Genetic recombination of BCR genes	p. 46
Mechanism of VDJ recombination	p. 47
Introducing junctional diversity	p. 48
Somatic hypermutation and affinity maturation	p. 49
Immunoglobulin class switching	p. 50
Structure of Fc receptors	p. 51
Fc receptor specificity and affinity	p. 53
Cross-linking of antibody is necessary for Fc receptor signalling	p. 53
Fc receptor immune functions	p. 54
T cell receptor diversification	p. 54
T cells undergo positive and negative selection within the thymus	p. 55
Antigen presentation to T cells	p. 57
MHC class II processing pathway	p. 59
MHC class I processing pathway	p. 59
Activation requires co-stimulation	p. 60
Late co-stimulatory signals	p. 62
Activation of B cell responses	p. 63
CD4+ T helper cell differentiation	p. 63
Activation of CTLs	p. 65
Generation of memory T cells	p. 66
Summary	p. 67
Cytokines	p. 68
Introduction to cytokines	p. 68
Structure of cytokine families	p. 69
IL-1 superfamily	p. 71
IL-6 family	p. 71
IL-10 family	p. 72
Common ¿-chain family	p. 73
IL-12 family	p. 74
Interferons	p. 75
TNF ligand superfamily	p. 75
Growth factors	p. 77
Functional classification Th1 versus Th2	p. 78
Th17, immunopathology and regulatory cytokines	p. 79
Cytokine receptor signalling	p. 79
Type I and type II cytokine receptors	p. 79
The JAK/STAT signalling pathway	p. 80
IL-2 signalling through the JAK/STAT pathway	p. 81
The JAK/STAT pathway is also used by IL-6	p. 83
Plasticity in type I cytokine signalling	p. 83
Suppressor of cytokine signalling (SOCS)	p. 83
IFN-¿ signalling pathway	p. 84
TGF-ß and the SMAD signalling pathway	p. 85
Type III cytokine receptors and the TNF receptor family	p. 86
The IKK complex and the activation of NF-¿B	p. 87
The IL-1R family of type IV cytokine receptors activate NF-¿B	p. 88
Soluble cytokine receptors act as decoy receptors	p. 90
IL-33 and ST2 signal regulation	p. 91
Potential for cytokine therapy	p. 91
Summary	p. 92
Chemokines	p. 93
Introduction	p. 93
Structure and nomenclature of chemokines	p. 93
Chemokine receptors	p. 94
Expression of chemokines and their receptors	p. 97
Chemokines promote extravasation of leukocytes	p. 97
Chemotaxis	p. 99
Chemokine receptor signalling cascade	p. 99
Tissue specific homing	p. 100
Lymphocyte migration to secondary lymphoid tissues	p. 101
Chemokines involved in lymphoid structure formation	p. 102
Chemokines contribute to homeostasis	p. 104
Chemokine receptors on T cell subsets	p. 104
Redundancy in the chemokine/receptor system	p. 106
Chemokines in disease	p. 108
Chemokines as new anti-inflammatory drugs	p. 109
Summary	p. 110
Basic Concepts in Mucosal Immunology	p. 111
Introduction	p. 111
What is a mucosal tissue?	p. 112
Immune defence at mucosal tissue is multi-layered	p. 113
Origins of mucosal associated lymphoid tissue	p. 114
Concept of the common mucosal immune system	p. 115
How do T and B lymphocytes migrate into mucosal tissues?	p. 116
Special features of mucosal epithelium	p. 117
Toll-like receptors and NOD proteins in the mucosa	p. 120
Antigen sampling at mucosal surfaces	p. 121
Mucosal dendritic cells	p. 122
Secretory dimeric IgA at mucosal surfaces	p. 124
Regulation of J-chain and secretory component expression	p. 126
How does the sub-mucosa differ from the epithelium?	p. 126
Organized lymphoid tissue of the mucosa	p. 127
Cytokines in the mucosa	p. 128
Pathogens that enter via mucosal sites	p. 130
Immune diseases of mucosal tissues	p. 130
Summary	p. 132
Immunology of the Gastrointestinal Tract	p. 133
Structure of the gastrointestinal tract	p. 133
Development of the gastrointestinal tract	p. 133
The digestive tract as a mucosal tissue	p. 135
Barrier function	p. 136
Defensins and Trefoil factors	p. 138
Structure of Peyer’s patches	p. 139
Lymphoid follicles and germinal centre formation	p. 140
M cells sample the intestinal lumen	p. 143
Dendritic cells sample the lumen contents	p. 143
Lymphocytes within the epithelium (IELs)	p. 143
¿¿ T cells in the GALT	p. 146
NKT cells	p. 147
T cells in the lamina propria	p. 148
Maintenance of T cell homeostasis	p. 148
Sub-mucosal B cells and mucosal IgA	p. 149
How IgA is produced at intestinal mucosal sites	p. 150
Cytokines in the gut	p. 151
Chemokines and the homing of lymphocytes to GALT	p. 152
Pathogens and immune diseases	p. 153
Summary	p. 154
Immunology of the Airways	p. 156
The airways as a mucosal tissue	p. 156
Development of the respiratory tract	p. 156
The structure of the respiratory tract	p. 158
Barrier function and the mucociliary elevator	p. 159
Mucins and mucociliary clearance	p. 160
Defensins and antimicrobial peptides	p. 160
Structure of the tonsils and adenoids of the Waldeyer’s Ring	p. 161
Local lymph nodes and immune generation	p. 163
Structure of the NALT	p. 165
Structure of the BALT	p. 165
Cells of the lower respiratory tract	p. 166
Surfactant proteins	p. 167
Immune modulation by airway epithelial cells	p. 167
Innate immune response	p. 168
Dendritic cells are located throughout the respiratory tract	p. 168
Alveolar macrophages maintain homeostasis	p. 169
NK cells in the lung	p. 171
T cells at effector sites in the lung	p. 171
Memory T cell responses within the lung	p. 172
Migration of circulating T cell into the lung tissue	p. 172
IgA production in the respiratory tract	p. 173
Respiratory diseases and pathogens	p. 174
Summary	p. 176
Immunology of the Urogenital Tract and Conjunctiva	p. 177
The urogenital tract as a MALT	p. 177
Epithelial barrier function	p. 178
Passive immunity	p. 181
Immunoglobulins	p. 181
APCs in genital tract mucosa	p. 182
NK cells and the semi-allogeneic foetus	p. 183
Pre-eclampsia is an immune-mediated disease	p. 184
Maintenance of foetal tolerance	p. 185
T cells and adaptive immunity	p. 186
Sexually transmitted diseases and pelvic inflammatory disease	p. 187
Alloimmunization and autoimmune diseases	p. 189
The foetal and neonatal immune system	p. 189
Immunity in the urinary tract	p. 190
Eye associated lymphoid tissue	p. 191
Conjunctiva associated lymphoid tissue (CALT)	p. 192
Immune privilege of the eye	p. 192
Immune privilege and inflammation	p. 193
Conjunctivitis	p. 194
Summary	p. 195
Immunology of the Skin	p. 196
The skin as an immune tissue	p. 196
Barrier Immune function of the skin	p. 196
Cellular immune system of the skin	p. 198
Keratinocytes can act as immune cells	p. 199
Keratinocytes secrete antimicrobial peptides	p. 200
Langerhan’s cells act as immune sentinels in skin	p. 202
Dermal dendritic cells and cross-presentation of antigen	p. 203
Mast cells and NK cells in the skin	p. 205
Intraepidermal lymphocytes in the skin	p. 206
Lymphocytes in the dermis	p. 206
Skin homing T cells express CLA	p. 206
Chemokines and migration	p. 207
Initiation of an immune response in the skin	p. 208
Cytokines	p. 211
Psoriasis, inflammation and autoreactive T cells	p. 211
Autoimmune-mediated diseases of the skin	p. 213
Systemic diseases that affect the skin	p. 214
Infectious diseases of the skin	p. 215
Summary	p. 216
Immunity to Viruses	p. 217
Introduction	p. 217
Structure of viruses	p. 217
Classification of viruses	p. 218
Viruses replicate within host cells	p. 218
Infections caused by viruses	p. 219
Certain viruses can infect immune cells	p. 220
Virus infection of epithelial cells	p. 221
IFN-¿ response	p. 222
NK cell response to viruses	p. 222
Viral evasion of NK cell responses	p. 223
Macrophages contribute to virus elimination	p. 225
TLRs and NLRs recognize virus motifs	p. 226
Activation of the inflammasome by viruses	p. 226
Dendritic cells present virus antigens to CD8+ CTLs	p. 227
T cell responses to viruses	p. 229
Evasion of CTL-mediated immunity by viruses	p. 229
Bystander effects of immune responses to viruses	p. 231
Antibody response to viruses	p. 232
Difference between cytopathic and non-cytopathic viruses	p. 233
Immune evasion by antigenic shift and drift	p. 235
Vaccination and therapies against viral infections	p. 235
Summary	p. 237
Immunity to Bacteria	p. 238
Introduction to bacterial immunity	p. 238
Classification of bacteria	p. 238
Structure of the bacterial cell	p. 240
Diseases caused by bacteria	p. 241
Mucosal barriers to bacterial infection	p. 241
Anti-microbial molecules	p. 242
Recognition of bacterial PAMPs by Toll-like receptors	p. 243
Complement and bacterial immunity	p. 244
Neutrophils are central to bacterial immune responses	p. 245
Some bacteria are resistant to phagosome mediated killing	p. 247
NK cells and ADCC	p. 248
The role of antibody in bacterial immunity	p. 249
Dendritic cells and immunity to bacteria	p. 250
Autophagy and intracellular bacteria	p. 251
T Cells contribute to protective immunity	p. 253
The DTH response and granuloma in TB	p. 253
Th17 cells in bacterial immunity	p. 254
Treg cells in bacterial infection	p. 255
Unconventional T cells	p. 256
Vaccination against bacterial diseases	p. 256
Summary	p. 256
Immunity to Fungi	p. 258
Introduction	p. 258
Morphology of fungi	p. 258
Yeasts	p. 260
Moulds	p. 260
Fungal dimorphism	p. 261
Diseases caused by fungi	p. 262
Immune response to fungi	p. 263
Innate immunity	p. 263
Mucosal barriers to fungal infection	p. 263
Anti-fungal molecules	p. 265
Recognition of fungal PAMPs by Toll-like receptors	p. 266
Complement and fungal immunity	p. 266
Dendritic cells link innate and adaptive fungal immunity	p. 268
DCs provide the adaptive immune response with instructive signals	p. 270
Macrophages are important APCs during fungal infection	p. 270
Neutrophils participate in the inflammatory response to fungi	p. 271
NK cells provide inflammatory signals to macrophages	p. 271
Adaptive immunity to fungi	p. 272
The DTH response and granuloma formation inhibit fungal dissemination	p. 272
The role of antibody in fungal resistance	p. 273
Vaccination and immunotherapies	p. 274
Fungal immune evasion strategies	p. 276
Immuno-modulatory fungal products	p. 276
Evasion of phagolysosomal killing	p. 276
Modifying the cytokine response	p. 277
Summary	p. 277
Immunity to Parasites	p. 278
Introduction	p. 278
Protozoa are diverse unicellular eukaryotes	p. 278
Structure of the protozoan cell	p. 278
Life cycle of protozoan parasites	p. 280
The life cycle of Trypanosoma brucei	p. 281
Life cycle of Leishmania species	p. 281
The life cycle of Plasmodium falciparum	p. 281
Helminths are multicellular, macroscopic parasites	p. 282
Structure of the trematode Schistosoma mansoni	p. 283
Life cycle of Schistosoma mansoni	p. 284
Structure of the nematode Ascaris lumbricoides	p. 285
The life cycle of A. lumbricoides	p. 286
Immune responses to parasites	p. 286
Innate immunity to trypanosomes	p. 287
Adaptive immunity to trypanosomes	p. 287
Innate immunity to plasmodium	p. 288
Adaptive immunity to plasmodium	p. 289
Immunity to Leishmania – Th1 versus Th2	p. 290
Immunity to Giardia	p. 291
Immunity to schistosomes	p. 292
Innate immunity to schistosomes	p. 292
Adaptive immunity to schistosomes	p. 293
Granuloma formation in schistosomiasis	p. 294
Immunity to intestinal nematode worms	p. 294
Innate immunity to nematode worms in the gut	p. 294
Adaptive immunity to nematode worms in the gut	p. 295
Immune evasion strategies of parasites	p. 296
Trypanosome variant surface glycoproteins (VSGs)	p. 297
Plasmodium life cycle contributes to immune evasion	p. 298
Leishmania evade phagocytic killing	p. 298
Immune evasion strategies of helminths	p. 298
Summary	p. 300
Disorders of the Immune System	p. 302
Introduction to immune disorders	p. 302
Types of allergy	p. 302
Sensitization and the acute phase response	p. 304
Mast cell degranulation	p. 305
Late phase response	p. 306
Allergic asthma	p. 307
Mast cells and the early phase allergic asthma	p. 308
Epithelial cells can trigger allergic asthma	p. 308
T cells and the late phase of allergic asthma	p. 310
Allergic rhinitis	p. 310
Skin allergy and atopic dermatitis	p. 311
Food allergies	p. 311
T cell subsets in allergy	p. 312
Mechanisms of autoimmune disease	p. 313
Disregulation of tolerance and autoimmunity	p. 313
Inflammatory bowel disease	p. 316
Coeliac disease	p. 317
Systemic lupus erythematosus	p. 317
Other autoimmune diseases	p. 318
Immunodeficiencies	p. 320
Summary	p. 321
Mucosal Tumour Immunology	p. 322
Introduction	p. 322
Transformation into cancer cells	p. 322
Proto-oncogene activation	p. 323
Mutation in the p53 protein	p. 324
Mutant Ras proteins enhance proliferation	p. 324
Aneuploidy and colorectal cancer	p. 324
Tumourigenesis	p. 324
Angiogenesis	p. 326
Metastasis	p. 327
The immune system and cancer	p. 327
Immune surveillance	p. 328
Immunogenicity of tumour cells	p. 329
Recognition of transformed cells	p. 330
Tumour associated antigens	p. 331
Carcinoembryonic antigen in colorectal cancer	p. 331
Melanoma differentiation antigens	p. 332
Viral tumour associated antigens	p. 332
Effector molecules during tumour immune surveillance	p. 333
Dendritic cells modulate anti-tumour immune responses	p. 333
Tumour reactive T cells are activated in lymph nodes	p. 335
NK cell recognition – missing self	p. 335
NKG2D receptor on NK cells	p. 335
Macrophages and neutrophils phagocytose tumour cells but support tumour growth	p. 336
Immune cells can augment tumour growth	p. 337
Immune evasion strategies	p. 337
Darwinian selection and tumour cell escape	p. 338
Cytokine environment and tumour escape	p. 339
Tumours have disregulated MHC expression and antigen presentation	p. 339
Tumour escape through Fas/FasL	p. 340
Summary	p. 341
Vaccination	p. 342
Introduction	p. 342
The principles of vaccination	p. 342
Passive immunization	p. 344
Active immunization	p. 344
Processing of the vaccine for immune recognition	p. 344
Adaptive Immune response following vaccination	p. 347
Vaccine adjuvants	p. 347
Alum	p. 348
Freund’s complete adjuvant	p. 348
Mucosal adjuvants and vaccine delivery	p. 350
Prospects in adjuvant design	p. 350
Th1/Th2 polarization and vaccine development	p. 351
Live-attenuated vaccines	p. 351
Inactivated vaccines	p. 353
Polysaccharide vaccines	p. 354
Peptide vaccines	p. 354
DNA vaccination	p. 355
Immuno-stimulatory complexes (ISCOMs)	p. 355
Dendritic cell vaccines	p. 358
Mucosal administration of vaccines	p. 359
Nasally administered vaccine against genital infections	p. 360
New strategies for vaccine development	p. 360
Summary	p. 362
Glossary of Terms	p. 363
Index	p. 374
Table of Contents provided by Publisher. All Rights Reserved.