Reinhard Pabst and Hermann J. RothkotterCathryn Nagler-AndersonJudy H. ChoR. Balfour SartorWarren Strober and Ivan J. FussThomas T. MacDonald and Giovanni MonteleoneEdward E.S. Nieuwenhuis and Richard S. BlumbergFrancisco Leon and Lesley E. Smythies and Phillip D. Smith and Brian L. KelsallCharles O. Elson and Yingzi Cong and Casey T. WeaverPer Brandtzaeg and Hege S. Carlsen and Trond S. HalstensenClaudio Fiocchi and Kenji Ina and Silvio Danese and Andre Z.A. Leite and Jon D. VogelStephan C. Bischoff and Thomas GebhardtJonathan Braun and Stephan R. TarganRainer DuchmannMartin H. Holtmann and Markus F. Neurath

1 Structure and Function of the Gut Mucosal Immune System	p. 1
Introduction	p. 1
Intraepithelial Lymphocytes (IEL)	p. 1
Lamina Propria Lymphocytes (LPL)	p. 3
Lymphocyte-Filled Villi (LFV)	p. 4
Cryptopatches (CP)	p. 5
Isolated Lymphoid Follicles (DLF)	p. 5
Peyer's Patches (PP)	p. 6
Lymphoid Structures in the Large Intestine	p. 7
Mesenteric Lymph Nodes, Part of the Gut Immune System	p. 7
Gut Lymphatics	p. 8
Liver-Also a Part of the Gut Immune System?	p. 8
Dynamics in the Gut Immune System	p. 9
Conclusions	p. 9
Note Added in Proof	p. 9
2 Functional Aspects of the Mucosal Immune System	p. 15
Phenotypically and Functionally Unique Lymphocyte Populations in the Gut Associated Lymphoid Tissue	p. 15
Mechanisms Governing Non-Responsiveness to Food Proteins and Commensal Bacteria	p. 18
3 Recent Progress in Inflammatory Bowel Disease Genetics	p. 24
Introduction	p. 24
IBD Epidemiology	p. 24
The Human Genome Project and the Challenge of Complex Genetic Disorders	p. 25
Linkage Studies in IBD	p. 26
Association Studies in IBD	p. 27
Future Directions	p. 30
4 Microbial and Dietary Factors in the Pathogenesis of Chronic, Immune-Mediated Intestinal Inflammation	p. 35
Introduction	p. 35
Evidence of Bacterial Induction and Maintenance of Intestinal Inflammation	p. 38
Induction of Mucosal Immune Responses by Bacterial and Dietary Antigens and Adjuvants	p. 42
Conclusion	p. 48
5 Experimental Models of Mucosal Inflammation	p. 55
Introduction	p. 55
General Features of Models of Mucosal Inflammation	p. 56
Representative Models of Mucosal Inflammation	p. 68
Tabular Summary of Models of Mucosal Inflammation	p. 80
Conclusion	p. 80
6 Overview of Role of the Immune System in the Pathogenesis of Inflammatory Bowel Disease	p. 98
Abstract	p. 98
Introduction	p. 98
Crohn's Disease, but Not Ulcerative Colitis Bears the Stigmata of a Th1 Mediated Immune Response	p. 99
The Role of T Cells in Ulcerative Colitis	p. 100
The Role of Antibody in Ulcerative Colitis	p. 100
Nonspecific Effector Mechanisms Down-Stream of the Immune System Cause Tissue Injury in Crohn's Disease and Ulcerative Colitis	p. 102
The Immune System Fails to Negatively Regulate in CD and UC	p. 103
7 The Role of the Epithelial Barrier in Inflammatory Bowel Disease	p. 108
Introduction	p. 108
Bacteria and the Epithelium	p. 108
Bacteria and IBD	p. 109
The Epithelial Cell as Effector Cell in IBD	p. 110
Luminal Antigens, Fate and Processing	p. 112
IEC and Mucosal Barrier Function/Permeability	p. 113
Conclusion	p. 113
8 Involvement of Dendritic Cells in the Pathogenesis of Inflammatory Bowel Disease	p. 117
Introduction	p. 117
Current Views on Dendritic Cell Biology	p. 117
Intestinal Dendritic Cells	p. 119
Dendritic Cells in Inflammatory Bowel Disease	p. 122
Intestinal Macrophages	p. 126
Intestinal Macrophages in IBD	p. 126
Summary	p. 127
9 Alterations of T Lymphocytes in Inflammatory Bowel Diseases	p. 133
CD4[superscript +] T Cell Subsets in the Intestine	p. 134
Intestinal T Effector Cells	p. 136
Th2 Effectors in IBD	p. 136
Intestinal T Regulatory Cells	p. 138
CD4[superscript +]CD45RB[superscript Io] T Cells	p. 138
T-Regulatory-1 Cells (Tr1)	p. 139
T-Helper-3 Cells (Th3)	p. 139
[alpha subscript E Beta subscript 7 superscript +] T Cells	p. 140
What Drives Effector and Regulatory T Cells in IBD?	p. 141
Conclusion	p. 143
10 The B-Cell System in Inflammatory Bowel Disease	p. 149
Abstract	p. 149
Introduction	p. 150
B Cell-Mediated Mucosal Homeostasis in the Normal Gut	p. 150
Humoral Immunity and Immune Exclusion in IBD Lesions	p. 152
Local Production of Antibodies to the Indigenous Gut Flora in IBD	p. 153
Local Production of Anti-Epithelial IgG1 Autoantibodies in Ulcerative Colitis	p. 154
Local Production and Diagnostic Aid of Other (Auto)Antibodies in IBD	p. 156
Mechanisms for Induction of Local Proinflammatory B-Cell Responses	p. 157
IBD Apparently Reflects Break of Oral Tolerance against Indigenous Bacteria	p. 161
11 Alterations of Mesenchymal and Endothelial Cells in Inflammatory Bowel Diseases	p. 168
Abstract	p. 168
Introduction	p. 168
Mesenchymal Cells	p. 169
Smooth Muscle Cells	p. 169
Fibroblasts and Myofibroblasts	p. 169
Endothelial Cells	p. 170
Human Intestinal Microvascular Endothelial Cells	p. 171
Integration of Intestinal Immune-Nonimmune Cell Interactions by the CD40/CD40 Ligand System	p. 172
12 Role of Mast Cells and Eosinophils in Neuroimmune Interactions Regulating Mucosal Inflammation in Inflammatory Bowel Disease	p. 177
Introduction	p. 177
Intestinal Mast Cells and Eosinophils	p. 178
Role of Mast Cells and Eosinophils in Intestinal Inflammation	p. 182
Structure and Function of The Enteric Nervous System	p. 184
Mechansims of Mast Cell / Eosinophil-Neuroimmune-Crosstalk in the Gut	p. 186
Neurophysiological Effects of Mast Cell and Eosinophil Activation	p. 191
Alterations of Neuroimmune-Crosstalk in IBD	p. 194
Conclusions	p. 197
13 Multiparameter Analysis of Immunogenetic Mechanisms in Clinical Diagnosis and Management of Inflammatory Bowel Disease	p. 209
Abstract	p. 209
NOD2 and Innate Anti-Microbial Processes in IBD Diagnosis	p. 209
Anti-Microbial Antibodies and Adaptive Immune Components in IBD Diagnosis	p. 211
Autoantibodies in IBD Diagnosis	p. 213
Multiparameter Analysis of Immunogenetic Traits in IBD Diagnosis	p. 213
14 The Role of Probiotics and Antibiotics in Regulating Mucosal Inflammation	p. 219
Abstract	p. 219
Probiotics: Animal Studies and Clinical Trials	p. 219
Probiotics: Mechanisms	p. 220
Antibiotics: Animal Studies and Clinical Trials	p. 221
Antibiotics: Mechanisms	p. 221
General Problems	p. 222
Perspectives	p. 222
15 From Immunogenic Mechanisms to Novel Therapeutic Approaches in Inflammatory Bowel Disease	p. 227
Abstract	p. 227
Introduction	p. 227
Genetic Factors	p. 228
Physiological "Hyporeactivity" of the Intestinal Immune System	p. 229
Activation of the Mucosal Immune System in IBD	p. 229
Novel Therapeutic Approaches	p. 234
Concluding Remarks	p. 238
Index	p. 243