Immune Mediated Diseases (eBook)

Contents 5
PREFACE AND ACKNOWLEDGMENTS 10
List of Contributing Speakers 12
Immune-Mediated Diseases 21
1 Immune-Mediated Diseases: Where Do We Stand? 22
1. Immune-Mediated Diseases: Diversity 22
2. Immune-Mediated Diseases: Statistics 24
3. Immune-Mediated Diseases: Correlations 26
4. Concluding Remarks 29
References 29
Immunodeficiencies: News and Updates 32
2 The Four Most Common Pediatric Immunodeficiencies 33
1. Transient Hypogammaglobulinemia of Infancy 33
1.1. Definition and History 33
1.2. Etiology 34
1.3. Clinical Features 34
1.4. Laboratory Features 35
1.5. Management and Prognosis 35
2. IgG Subclass Immunodeficiency 35
2.1. Definition and History 35
2.2. Etiology 36
2.3. Clinical Features 36
2.4. Laboratory Features 37
2.5. Management and Prognosis 37
3. Impaired Polysaccharide Responsiveness 38
3.1. Definition and History 38
3.2. Etiology 38
3.3. Clinical Features 39
3.4. Laboratory Features 39
3.5. Treatment and Prognosis 39
4. Selective IgAD Deficiency 40
4.1. Definition and History 40
4.2. Etiology 40
4.3. Clinical Features 41
4.4. Laboratory Features 41
4.5. Treatment and Prognosis 41
5. Conclusions 42
References 42
3 Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Inheritance: Model for Autoaggression 45
1. Introduction 45
2. Clinical and Pathologic Manifestations of IPEX 46
2.1. Gastrointestinal Symptoms and Failure to Thrive 46
2.2. Autoimmune Endocrinopathy 47
2.3. Autoimmune Hematologic Disorders 47
2.4. Dermatologic Abnormalities 47
2.5. Infections 47
2.6. Other Clinical Manifestations 48
2.7. Laboratory Findings and Histopathology 48
3. Molecular Basis of IPEX 48
4. Function of FOXP3 49
5. Foxp3 and Treg Cells 50
6. Fox Mutation Analysis in Patients with the IPEX Phenotype 50
7. Diagnoses and Treatment of IPEX 51
8. Animal Models 51
9. Conclusions 52
References 52
4 DiGeorge Syndrome/Velocardiofacial Syndrome: The Chromosome 22q11.2 Deletion Syndrome 55
1. Nomenclature 55
2. Genetics 56
3. Management 58
4. Conclusions 62
References 62
5 Leukocyte Adhesion Deficiencies: Molecular Basis, Clinical Findings, and Therapeutic Options 68
1. Introduction 68
2. Leukocyte Adhesion Deficiency I 69
3. Leukocyte Adhesion Deficiency II 72
4. Leukocyte Adhesion Deficiency III 74
5. Conclusions 75
References 75
6 Nijmegen Breakage Syndrome 78
1. Introduction 78
2. Genetic Basis for NBS 79
3. Clinical Presentation and Therapy 80
4. Data from Russian Clinical Children’s Hospital 81
References 82
7 Neutrophil Activity in Chronic Granulomatous Disease 85
1. Introduction 85
2. Experimental Procedures 86
3. Results 87
3.1. Analysis of Oxidative Burst in GCD 87
3.2. Expression of Degranulation Markers in CGD 88
3.3. Intracellular and plasma a-defensins in CGD 88
4. Discussion 89
References 90
8 Mycobacterial Infections in Primary Immunodeficiency Patients 91
1. Introduction 91
2. Mycobacterium Infections and Immunodeficiencies 92
3. Results 93
4. Conclusions 95
References 96
Allergy and Autoimmunity: Prevention or Treatment? 98
9 SLE 1, 2, 3…Genetic Dissection of Lupus 99
1. Introduction 99
2. Genetic Dissection of Murine Lupus 100
3. Aberrant Adaptive Immunity in Lupus 101
4. Aberrant Adaptive Immunity in Lupus 102
5. Conclusions 106
References 106
10 Network of Myeloid and Plasmacytoid Dendritic Cells in Atopic Dermatitis 110
1. Introduction 110
2. Network of Myeloid DCs in AD 111
3. Balance of LCs and IDECs Predicts the Severity of AD 113
4. Deficiency of Plasmacytoid DCs in AD 114
5. Conclusions 115
Acknowledgments 115
References 115
11 Peptide-Based Therapy in Lupus: Promising Data 118
1. Introduction 118
2. Are Peptides Suitable Agents for Therapeutics in Autoimmune Diseases? 119
3. Potential of Peptide Therapeutics for Treating Lupus Patients 120
4. A New Peptide Analogue for Treating Lupus Patients? The Potential of Peptide P140 121
5. Final Remarks 122
Acknowledgements 123
References 123
12 Reduced Number and Function of CD4+CD25highFoxP3+ Regulatory T Cells in Patients with Systemic Lupus Erythematosus 126
1. Introduction 126
2. Experimental Design 127
3. Results 128
3.1. CD4+CD25+ and CD4+CD25highFoxP3+ T Cell Numbers are Reduced in Patients with SLE 128
3.2. Patients with SLE Display Impaired Function of CD4+CD25+ T Cells 129
4. Discussion 129
References 131
Tumor Immunity in New Dimensions 133
13 Role of Altered Expression of HLA Class I Molecules in Cancer Progression 134
1. Introduction 134
2. Altered Phenotypes of HLA Class I in Various Types of Cancer 136
3. Molecular Mechanisms of HLA Class I Alterations in Tumors 136
4. Association of HLA Class I Alterations with Tumor Escape and Cancer Progression 138
5. Implication of HLA Class I Defects for Cancer Immunotherapy 139
6. Conclusions 140
Acknowledgements 140
References 140
14 Intrathymic Selection: New Insight into Tumor Immunology 143
1. Background 143
2. Tumor-Specific and Tumor-Associated Antigens as the Consequences of Genetic and Epigenetic Alterations 145
3. Does Immunological Surveillance Make Tumor-Specific Antigens Undetectable? 146
4. Gaze into Cells: MHC-Binding Motifs 147
5. Aire and Thymic Selection 148
6. Transduction with Allorestricted TCR as a Mean to Overcome Central Tolerance 149
References 151
15 Crosstalk Between Apoptosis and Antioxidants in Melanoma Vasculogenic Mimicry 155
1. Introduction 155
2. Early CLS Formation Requires Activation of Apoptotic Pathways 156
2.1. Timeand Dose-Dependent Effects of Antioxidants on Melanoma Cells 158
2.2. Antioxidants Inhibit the Formation of CLS 159
3. CLS Formation Requires Activation of Apoptotic Pathways Mediated by Mitochondrial Cytochrome c Release and Caspase-3 Activation 160
4. Conclusions 161
Acknowledgments 162
References 162
16 Immunological Role of Dendritic Cells in Cervical Cancer 164
1. Human Papillomavirus and Cervical Cancer 164
2. Langerhans Cells in the Uterine Cervix 165
3. Langerhans Cells in Cervical Neoplasia 166
4. DC-Based Vaccines for Cervical Cancer 167
5. Conclusions 168
References 168
17 Sensitizing Tumor Cells to Immune-Mediated Cytotoxicity 172
1. Introduction 172
2. Direct Cell–Mediated Cytotoxicity 173
3. Immune-Mediated Tumor Destruction In vivo 175
4. Augmenting Immune-Mediated Cytotoxicity 176
5. Future Directions and Concluding Remarks 178
Acknowledgments 179
References 179
18 Inhibition of Dendritic Cell Generation and Function by Serum from Prostate Cancer Patients: Correlation with Serum-Free PSA 181
1. Introduction 181
2. Experimental Procedures 183
3. Results 184
4. Discussion 185
Acknowledgments 188
References 188
Immunomodulators 191
19 Alarmins Initiate Host Defense 192
1. Introduction: Properties of Alarmins 192
2. Alpha Defensins 193
3. Cathelicidin (LL37)/CRAMP 195
4. Eosinophil-Derived Neurotoxin 195
5. High-Mobility Group Box 1 196
6. Candidate Alarmins and Pseudo-Alarmins 197
Acknowledgements 198
References 198
20 Gangliosides as Immunomodulators 202
1. Gangliosides structure 202
2. Gangliosides Biosynthesis 203
3. Functions 204
4. Changing Ganglioside Profile in Transformed Cells 204
5. Immunomodulatory Activities of Gangliosides 205
5.1. T Cells 205
5.2. Antigen-Presenting Cells 206
6. Role of Ganglioside Structure in Immunomodulation 206
7. Concluding Remarks 207
References 207
21 Functional Changes of Macrophages Induced by Dimeric Glycosaminylmuramyl Pentapeptide 211
1. Introduction 211
2. Experimental Procedures 212
3. Results 213
4. Discussion 214
Acknowledgments 215
References 215
New Insights in Immune Regulation 217
22 Myeloid-Derived Suppressor Cells 218
1. Introduction 218
2. Myeloid Suppressor Cells 219
3. TGF- 221
4. L-Arginine Metabolism 221
5. Reactive Oxygen Species 222
6. Peroxynitrites 223
7. Improvement of Antitumor Immunity Through MDSC Elimination or Stimulation of Their Differentiation 223
References 225
23 The Lytic NK Cell Immunological Synapse and Sequential Steps in Its Formation 229
1. Introduction—Natural Killer Cells 229
2. NK Cell Function 230
3. NK Cell Cytoskeleton and the Immunological Synapse 231
4. Sequential Steps in Formation and Function of the Lytic NK Cell IS 232
5. Conclusions 233
Acknowledgments 234
References 234
24 Infective, Neoplastic, and Homeostatic Sequelae of the Loss of Perforin Function in Humans 238
1. Introduction 238
2. Molecular and Cellular Functions of Perforin: A Putative Domain Structure 239
3. Congenital perforin deficiency and other causes of FHL 240
4. Perforin Alleles Encoding Partial Loss of Function 240
5. Ala91Val, a Common Hypomorphic Perforin Allele 242
6. Conclusions 242
References 243
25 Natural Killer T (NKT) Cell Subsets in Chlamydial Infections 246
1. Introduction 246
2. NKT Cells 246
3. NKT Cells in Chlamydial Lung Infection 247
3. Conclusions 249
Acknowledgments 249
References 249
26 Memory T Cells in Allograft Rejection 250
1. Memory T Cells: Generation, Phenotype, and Functions 250
2. Alloreactive T Cell Memory 252
3. Memory T Cells and Costimulation 253
3.1. Classical Costimulatory Pathways 253
3.2. Alternative Costimulatory Pathways 254
4. Altering Memory T Cell Trafficking 254
5. Conclusions 255
References 256
27 Differences in Dendritic Cell Activation and Distribution After Intravenous, Intraperitoneal, and Subcutaneous Injection of Lymphoma Cells in Mice 260
1. Introduction 260
2. Experimental Procedures 261
3. Results 262
4. Discussion 264
Acknowledgements 266
References 266
28 Role of IL-1-Mediated Inflammation in Tumor Angiogenesis 268
1. Introduction 268
2. IL-1 and Inflammation 269
3. IL-1 and Tumor Angiogenesis 270
Acknowledgments 271
References 272
News in Immunodiagnostics and Immunomonitoring 274
29 New Approaches for Monitoring CTL Activity in Clinical Trials 275
1. Immunological Assays for Monitoring Cancer Vaccine Trials 275
2. Granzyme B ELISPOT Assay as an Alternative to 51Cr Release 276
3. Advantages of the ELISPOT Method 278
4. Application of the Gr B ELISPOT Assay for Monitoring Clinical Samples 279
4.1. CTL Reactivity to Cancer Vaccine Components 279
4.2. CTL Reactivity to Primary Tumors 280
4.3. Additional Applications of GrB ELISPOT 281
5. Development of a Perforin ELISPOT Assay 282
6. Conclusions 283
Acknowledgments 283
References 284
30 Serum Levels of Soluble HLA and IL-2R Molecules in Patients with Urogenital Chlamydia Infection 287
1. Introduction 287
2. Experimental Design 288
3. Results 289
4. Discussion 289
References 290
31 Evaluation of Suspected Immunodeficiency 292
1. Introduction 292
2. Screening Tests of Immune Function 293
3. Immune Cell Quantitation and Characterization 294
4. Testing of Immune Function 297
5. Mutation Analysis 299
6. Conclusions 299
Reference 300
32 Frequently Ill Children 302
1. Introduction 302
2. Experimental Procedures 303
3. Results 304
4. Discussion 306
References 307
33 Evaluation of Bactericidal Activity of Human Biological Fluids by Flow Cytofluorimetry 308
1. Introduction 308
2. Experimental Procedures 309
3. Results 309
3.1. Bactericidal Activity of Biological Fluids from Healthy Volunteers 309
3.2. Bactericidal Activity of Biological Fluids from Patients with Immunological Disorders 310
4. Discussion 310
References 311
Immunotherapy and Vaccines 312
34 Rational Development of Antigen-Specific Therapies for Type 1 Diabetes 313
1. The Importance to Consider Pre-existing Autoimmunity When Administering Self-Antigens 313
2. Immunity Versus Tolerance Viewed in an Operational Context 314
3. Antigenic “Drivers” Versus “Followers” in Autoimmunity—How to Make the Correct Antigenic Choice for Immunotherapy? 315
4. Human Studies of Antigen-Specific Interventions in T1D 316
5. Safety Issues 317
6. Concluding Remarks 318
References 318
35 Interleukin-7 Immunotherapy 320
1. Introduction 320
1.1. IL-7 in Immune Development 321
1.2. IL-7 as a Homeostatic Cytokine 322
1.3. Role of IL-7 in Modulation of Immune Responses 323
1.4. Patterns of Immune Reconstitution 323
2. Phase I Study of rhIL-7 in Humans 324
2.1. Subject Population and Study Design 325
2.2. Results 325
3. Conclusions 328
Acknowledgments 329
References 329
36 Transmembrane Interactions as Immunotherapeutic Targets: Lessons from Viral Pathogenesis 333
1. Introduction 333
2. SCHOOL Model of MIRR Signaling 335
3. Transmembrane Interactions as Immunotherapeutic Targets 336
3.1. Transmembrane Peptides and Immune Cell Activation 337
3.2. Transmembrane Interactions in HIV Pathogenesis 340
3.3. Transmembrane Interactions in CMV Pathogenesis 340
4. Lessons from Viral Pathogenesis 341
5. Conclusions 341
Acknowledgments 341
References 342
37 Tumor Cell Vaccines 343
1. Introduction 343
2. Anticancer Vaccine Approaches Derived from Autologous and Allogeneic Tumor Cells 344
3. Adjuvants 345
4. Modified Tumor Cells 345
5. Immune Response to Tumor Cell Vaccines 345
6. Allogeneic Vaccines 346
6.1. Allogeneic Tumor Cell Vaccines for Melanoma 346
6.2. Allogeneic Tumor Cell Vaccines for Pancreatic Cancer 347
6.3. Allogeneic Tumor Cell Vaccines for Prostate Cancer 347
7. Autologous Vaccines 347
7.1. Autologous Tumor Cell Vaccines for Melanoma 347
7.2. Autologous Tumor Cell Vaccines for Colon Cancer 348
7.3. Autologous Tumor Cell Vaccines for Renal Cell Carcinoma 348
7.4. Autologous Tumor Cell Vaccines for Lung Cancer 348
8. Assessing Effect of Cancer Vaccines: Immune Monitoring 349
9. Conclusion 349
References 351
38 T Cell Tolerance to Tumors and Cancer Immunotherapy 354
1. Introduction 354
2. Tumor Antigens 355
3. T Cell Tolerance and Antitumor Responses 356
4. Peripheral Tolerance to Self/Tumor Antigens 356
5. Overcoming Tolerance Leads to Tumor Immunity 357
6. Modulating Tolerance of Tumor-Specific T cells in a Murine Model of Prostate Cancer 359
7. Conclusions 360
Acknowledgments 361
References 361
39 Herpes Simplex Virus: Treatment with Antimicrobial Peptides 366
1. Herpes Simplex Virus Infection 366
2. Immune Response Against Herpes Virus Infection 367
3. Antimicrobial Peptides 369
4. Treatment of HSV Infections 370
References 371
40 Vaccine Containing Natural TLR Ligands Protects from Salmonella typhimurium Infection in Mice and Acute Respiratory Infections in Children 374
1. Introduction 374
2. Potentiators of Innate Immunity 375
3. VP-4 Induces Rapid but Short-Lasting Protection Against Salmonella typhimurium Infection 375
4. Repeated Mucosal Applications of VP-4 Protect Children from ARIs 376
5. Conclusions 377
References 377
41 Lymphocyte Subpopulations in Melanoma Patients Treated with Dendritic Cell Vaccines 378
1. Introduction 378
2. Experimental Design 378
3. Results 379
3.1. Phenotypic Analysis of Lymphocytes in Melanoma Patients from Groups 1 and 2 (Disease-Free Patients Prior to Therapy) 379
3.2. Phenotypic Analysis of Lymphocytes in Patients with Disseminated Melanoma (Groups 3 and 4) 381
4. Discussion 382
5. Conclusions 383
Acknowledgments 383
References 383
42 Cell Technologies in Immunotherapy of Cancer 384
1. Introduction 384
2. Results and Discussion 385
3. Conclusions 389
References 389
43 Therapeutic Potential of Cannabinoid-Based Drugs 391
1. Introduction 391
2. Endocannabinoid System 392
2.1. Cannabinoid-Based Drugs 392
2.2. Cannabinoid Receptors 393
3. Anti-inflammatory Effects of Cannabinoids 394
4. Completed Clinical Trials 395
4.1. Multiple Sclerosis (MS) 395
4.2. Traumatic Brain Injury 397
4.3. Rheumatoid Arthritis 398
4.4. Neuropathic Pain 398
5. Future Clinical Trials 400
5.1. Intestinal Disorders 400
5.2. Alzheimer’s Disease 400
5.3. Atherosclerosis 401
5.4. Osteoporosis 402
6. Conclusions 402
References 403
44 Micro-and Nanoparticle-Based Vaccines for Hepatitis B 410
1. Introduction 410
2. Techniques for the Preparation of Nano/Microparticles 411
3. Oral Vaccination 412
4. Intranasal Delivery 413
5. DNA-Based Vaccination 413
6. Perspectives 414
References 414
45 Mast Cells, T Cells, and Inhibition by Luteolin: Implications for the Pathogenesis and Treatment of Multiple Sclerosis 417
1. Introduction 417
2. Mast Cell Activation of T Cells 419
3. Mast Cell Mediators 420
4. Effect of Flavonoids 421
Acknowledgments and Disclosure 421
References 421
Index 425