Advances in Immunopharmacology (eBook)

Front Cover 1
Advances in Immunopharmacology 3 4
Copyright Page 5
Table of Contents 6
Part 1: Special Lectures 12
Chapter 1. From Natural Products Chemistryto Immunopharmacology 14
I. New analytical methods 14
II. From the Ascaris egg to immunodeterminant dideoxyhexoses 14
III. An excursion into the mysterious world of Mycobacteria 15
IV. Trehalose esters as immunomodulators 15
V. From Wax D to MDP 16
VI. Desmuramyl peptides 16
VII. Specific targeting of muramylpeptides 17
VIII. Muramylpeptides as sleep factors 17
IX. "New activities of muramyl peptides" 17
X. A synthetic Freund's adjuvant 18
XI. The future of muramylpeptides 18
REFERENCES 19
Chapter 2. The Story of Bacterial Endotoxin 24
SUMMARY 24
I. HISTORY 24
II. WHAT IS ENDOTOXIN 25
III. THE DETOUR : ENTEROBACTERIAL S . R MUTATION 28
IV. CHEMISTRY OF LIPID A 31
V. ABOUT ENDOTOXIN STANDARD, TEST, AND DEFINITION 35
VI. CHEMICAL AND BIO-SYNTHESIS OF LIPID A 37
REFERENCES 42
Chapter 3. Experimental and Clinical Studies on the Antitumor and Antimicrobial Activities of Nocardial Cell Wall Skeleton and Muramyldipeptide Derivatives 46
ABSTRACT 46
KEYWORDS 46
INTRODUCTION 46
I. CANCER IMMUNOTHERAPY WITH BACTERIAL FRACTIONS AND SYNTHETIC ADJUVANTS 47
II. STIMULATION WITH IMMUNOADJUVANTS OF HOST RESISTANCE AGAINST BACTERIAL AND VIRAL INFECTIONS 50
REFERENCES 53
Part 2: Immunotherapy of Human Disease 56
Chapter 4. Current Status of the Immunotherapyand Biological Therapy of Cancer 58
REFERENCES 65
Chapter 5. Immunotherapy of Acquired Immune Deficiency Syndrome (AIDS), AIDS-related Complex and Subjects at Risk 66
INTRODUCTION 66
1. CELLULAR ENGINEERING 67
2. MOLECULAR ENGINEERING 68
3. PHARMACOLOGIC IMMUNOMODULATORS 71
4. MISCELLANEOUS 73
REFERENCES 76
Chapter 6. An Update on Interferon in Infectious Diseases 80
INTRODUCTION 80
REFERENCES 84
Chapter 7. Immunotherapy of Connective Tissue Disease 86
ABSTRACT 86
KEYWORDS 86
INTRODUCTION 86
CHRONOPHARMACOLOGY 87
IMMUNOSUPPRESSANTS 87
IMMUNOMODULATORS 87
REFERENCES 91
Chapter 8. Hopes for Immunorestorative Therapyin Autoimmune Diseases 94
ABSTRACT 94
KEYWORDS 94
INTRODUCTION 94
CONCLUSION 99
ACKNOWLEDGEMENT 99
REFERENCES 99
Part 3: Mechanisms of Cell Activation 102
Chapter 9. The Biochemical Mechanism of Cellular Activation 104
ABSTRACT 104
KEYWARDS 104
INTRODUCTION 104
DlSCUSSION 108
REFERENCES 109
Chapter 10. Membrane Transport in the Messenger Function of Calcium (Ca) 112
ABSTRACT 112
KEYWORDS 112
REFERENCES 117
Chapter 11. Stimulus Activation Couplingin Neutrophils 120
ABSTRACT 120
INTRODUCTION 120
MATERIALS AND METHODS 121
RESULTS AND DISCUSSION 121
ACKNOWLEDGEMENT 124
REFERENCES 124
Chapter 12. Mechanisms of Arachidonic Acid Turnover Implicated in Cell Activation 126
KEYWORDS 126
INTRODUCTION 126
ACKNOWLEDGEMENT 136
REFERENCES 136
Chapter 13. Release of Prostaglandins and Modulation of Leukocyte Functions 138
ABSTRACT 138
KEYWORDS 138
INTRODUCTION 138
PROSTAGLANDIN SYNTHESIS BY MACROPHAGES 139
INDUCTION OF PROSTAGLANDIN SYNTHESIS BY COMPLEMENT 140
MODULATION OF PROSTAGLANDIN SYNTHESIS BY LYMPHOKINES 142
ACKNOWLEDGEMENT 146
REFERENCES 146
Part 4: Immunological Mediators as Agentsor Targets of Manipulation I 148
Chapter 14. Human Tumor Necrosis Factor (LuKII):Recent Developments 150
ABSTRACT 150
INTRODUCTION 150
RESULTS 151
DISCUSSION 157
ACKNOWLEDGMENTS 158
REFERENCES 158
Chapter 15. Factors from T Suppressor Cells: Current Status and Perspectives 160
INTRODUCTION 160
REFERENCES 162
Chapter 16. T Cell Factors Involved in the Regulationof the IgE Antibody Response 164
ABSTRACT 164
INTRODUCTION 164
ACKNOWLEDGEMENT 171
REFERENCES 171
Chapter 17. T Cell-derived Immunoglobulin-Binding Factors (IBF): Molecular Heterogeneityand Inhibition of Ig Synthesisby . Cell Hybrldomas 172
INTRODUCTION 172
MATERIALS AND METHODS 173
RESULTS 174
CONCLUDING REMARKS 178
REFERENCES 178
Part 5: Pharmacology of Cellular Activation 180
Chapter 18. The Initial Events in Leukocytic Stimulation 182
ABSTRACT 182
NTRODUCTION 182
REFERENCES 186
Chapter 19. Role of Eicosanoids in Lymphocyte Activation: A Review 188
Introduction 188
References 197
Chapter 20. Mechanisms and Pharmacology of NK Cell Activity 200
Regulation of Cytotoxic Activity of NK Cells 200
Mechanism of Cytotoxicity by NK Cells 201
REFERENCES 203
Chapter 21. Mechanisms of Neutrophil Activation: Phosphoinositides, Protein Kinase Cand Calcium Movements 204
ABSTRACT 204
KEYWORDS 204
Neutrophil Function 204
Stimulus - response coupling 205
Calcium movements during neutrophil activation 206
Protein kinase C and cell activation 207
Synergism between calcium and protein kinase C in the activation sequence 207
Phosphoinositide turnover and signalling 208
REFERENCES 210
Chapter 22. Biochemical Events Involved in IgE- Mediated Mast Cell Activation for Mediator Release 212
ABSTRACT 212
KEYWORDS 212
INTRODUCTION 212
ACKNOWLEDGEMENT 219
REFERENCES 219
Chapter 23. Regulation of the 5-Lipoxygenase Pathway of Arachidonic Acid Metabolism by N-3 Fatty Acids 222
ABSTRACT 222
KEYWORDS 222
INTRODUCTION 222
METABOLIC CASCADE FOR N-6 AND N-3 FATTY ACIDS VIA THE 5-LIPOXYGENASE PATHWAY 223
N-3 FATTY ACIDS AND THE HUMAN 5-LIP0)0rGENASE PATHWAY 223
N.3 FATTY ACIDS AND AN ALTERED INFLAMMATORY RESPONSE 225
REFERENCES 225
Part 6: Immunological Mediators as Agentsor Targets of Manipulation II 228
Chapter 24. Interleukin 1 Mediated in Vitro Antitumor Activities 230
ABSTRACT 230
KEYWORDS 230
INTRODUCTION 230
CONCLUSIONS 232
ACKNOWLEDGEMENT 232
REFERENCES 233
Chapter 25. The Biological Activities of Human Interleukin-1: Purified and Recombinant Materials 234
ABSTRACT 234
INIRODUCTION 234
MULTIPLE IL-1 FORMS 235
CLINCAL RELEVANCE OF THE HUMAN IL-1 FAMILY 238
POSSIBLE ROLE FOR IL-1 AS AN IMMUNOMODULATOR 239
SUMMARY 239
ACKNOWLEDGEMENTS 239
REFERENCES 240
Chapter 26. New Strategies of Immunotherapy1 242
ABSTRACT 242
KEYWORDS 242
INTRODUCTION 242
Part 7: Down Modulation of Immunityand Toxicology 248
Chapter 27. Immunological Properties of Ciclosporin (Sandimmune®) 250
INTRODUCTION 250
Transplantation 254
Autoimmune diseases 255
Mechanism of action 257
Conclusions 260
Chapter 28. Cellular Requirements and Mechanisms of Action of Antigen-specific Suppressor. Cell Factors 262
ABSTRACT 262
KEYWORDS 262
INTRODUCTION 262
COMMENTARY 266
ACKNOWLEDGMENT 267
REFERENCES 267
Chapter 29. Immunomodulation by Anticancer Compounds 268
Anthracyclines 269
Vinca Alkaloids 271
Cyclophosphamide 272
Concluding Remarks 273
References 273
Chapter 30. Modulation of Immunity by Xenobiotics 278
ABSTRACT 278
KEYWORDS 278
INTRODUCTION 279
APPROACHES FOR ASSESSING IMMUNOMODULATION INDUCED BY XENOBIOTICS 281
CHARACTERIZING IMMUNOMODULATION INDUCED BY POLYCYCLIC AROMATIC HYDROCARBON CARCINOGENS 281
REFERENCES 285
Chapter 31. Perspectives in the Management of Allergie and Pseudo-A Uergic Reactions 288
1. Interference with the sensitization process 288
2. Interference with the development of effector cells (basophiIs/mast cells) 290
3. Interference with the function of effector cells (e.g. basophils, mast cells, secondary inflammatory cells) 291
4. Antagonists of the effects of pharmacological mediators 291
REFERENCES 292
Part 8: Monoclonal Antibodies as Therapeutic Agents and in Immunodiagnosis 294
Chapter 32. Tumour Inhibitory Properties of Monoclonal Antibody 791T/36- Drug Conjugates 296
ABSTRACT 296
KEYWORDS 296
INTRODUCTION 296
TUMOUR LOCALIZATION WITH MONOCLONAL ANTIBODY 791T/36 297
MONOCLONAL ANTIBODY 791T/36-DRUG CONJUGATION 297
THERAPEUTIC ACTIVITY OF DRUG-ANTIBODY CONJUGATES 301
CONCLUSIONS 302
ACKNOWLEDGEMENTS 302
REFERENCES 303
Chapter 33. Treatment of Malignant Melanoma witha Mouse Monoclonal IgG3 Antibody Detecting the Ganglioside GD3 304
ABSTRACT 304
KEYWORDS 304
INTRODUCTION 304
RESULTS 304
TUMOR RESPONSE OF PATIENTS TREATED WITH R24 306
SUMMARY AND CONCLUSIONS 306
ACKNOWLEDGEMENT 307
REFERENCES 307
Chapter 34. Immunotoxins 308
INTRODUCTION 308
BONE MARROW TRANSPLANTATION 308
IN VIVO USE OF IMMUNOTOXINS 309
POTENTIATION OF TOXICITY OF A-CHAIN IMMUNOTOXINS 309
CONCLUDING DISCUSSION 310
REFERENCES 311
Chapter 35. Monoclonal Antibodies as Diagnosticand Therapeutic Cardiovascular Agents 314
Keywords 314
Introduction 314
Species Specificity of a Monoclonal Antifibrin Antibody 315
In Vivo Localization of Human Fibrin with Monoclonal Antífibrin-64C5 316
Therapeutic Potential of Fibrín-flpeeifíe Antibodies as Agents for Thrombolysis 316
Ckmclusion 316
References 317
Chapter 36. Novel Antibodies by DNA Transfection 320
ABSTRACT 320
KEYWORDS 320
INTRODUCTION 320
EXPRESSION SYSTEMS FOR IMMUNOGLOBULIN GENES 321
MAKING CHIMAERIC ANTIBODIES WITH HUMAN EFFECTOR FUNCTIONS 322
MAKING RECOMBINANT ANTIBODIES WITH NOVEL EFFECTOR FUNCTIONS 323
Fab-TAGGING FOR ENZYME PURIFICATION 323
SUMMARY AND PROSPECT 324
REFERENCES 324
Part 9: Genetically Engineered and Synthetic Vaccines 326
Chapter 37. Prediction of Biologically Active 
328 
ABSTRACT 328
KEYWORDS 328
INTRODUCTION 328
I. Present Vaccines 328
II. Synthetic Vaccines 329
III. Prediction oL BiQiogically Active Epitopes 333
ACKNOWLEDGEMENT 338
REFERENCES 338
Chapter 38. Use of Muramyl Peptides in Syntheticand Semisynthetic Vaccines 340
INTRODUCTION 340
CONCLUSIONS 344
REFERENCES 345
Chapter 39. Design of Hepatitis B Vaccines 348
ABSTRACT 348
KEYWORDS 348
INTRODUCTION 348
"FIRST GENERATION" HEPATITIS . VACCINES 349
"SECOND GENERATION" HEPATITIS . VACCINES 349
DESIGN OF NOVEL HEPATITIS . VACCINES 350
REFERENCES 355
Chapter 40. Synthetic Peptides as the Basis for Future Vaccines. Application in theInfluenza and Cholera Toxin Systems 358
INTRODUCTION 358
SYNTHETIC VACCINE AGAINST INFLUENZA VIRUS 359
SYNTHETIC ANTI-INFLUENZA VACCINE WITH BUILT-IN ADJUVANTICITY 362
CHOLERA TOXIN (CT) 363
NEUTRALIZATION OF HEAT-LABILE TOXIN OF E. COLI 365
CONCLUDING REMARKS 366
REFERENCES 366
Chapter 41. Sporozoite Malaria Vaccines 368
ABSTRACT 368
KEYWORDS 368
REFERENCES 371
Part 10: Workshop Sessions 374
Chapter 42. Bacteria, Bacterial Fractions and Products as Immunomodulators I 376
Glucans as Immunomodulators 380
REFERENCES 385
Chapter 43. Mediators and Mechanisms I 388
Chapter 44. Thymic Hormones 390
Chapter 45. Synthetic Immunomodifiers 392
Chapter 46. Interactions between the Neuroendocrineand Immune Systems 400
1. Hormones and immunological activities. 401
2. Neurotrans mitters and peptides and immunological activities 402
3. Benzodiazepines, immuner eactivity and macrophage binding 403
Concluding Remarks 404
Chapter 47. Interferons and Inducers 406
Chapter 48. Glucans as Immunomodifier II 408
ABSTRACT 409
KEY WORDS 409
Chapter 49. Synthetic Immunomodifiers II 414
Chapter 50. Mediators and Mechanisms 418
Chapter 51. MDP and Derivatives I 420
Chapter 52. Thymic Hormones II 426
Chapter 53. Bacteria, Bacterial Fractions and 
430 
PRECLINICAL INVEST IGATIONS WITH OK - 432 431
CLINICAL STUDIES 432
Chapter 54. other Immunomodifiers from NaturalSources 434
Chapter 55. Immunodepressive Agents 436
Chapter 56. Bacteria, Bacterial Fractions and Products as Immunomodulators III 440
Chapter 57. Immunotoxicology 442
Chapter 58. Cyclization Products of Phenylthiourea Compounds in Adulterated Rapeseed Oilas possible Aetiological Factor in Spanish Toxic Oil Syndrome 450
INTRODUCTION 450
A NEW APPROACH 450
CONCLUSION 452
REFERENCES 453
Chapter 59. TCDF Induced Alterations of IL-1 Responsiveness and Production in Adultor Perinatal Treated Mice 454
Chapter 60. Thymocytes as Target of Dialkyltin Toxicity 456
INTRODUCTION 456
RESULTS AND DISCUSSION 456
REFERENCES 458
Chapter 61. The Pophteal Lymph Node Assay:A Test System for Chemically InducedAutoimmune and Allergic Reactions 460
INTRODUCTION 460
MATERIALS AND METHOD 460
RESULTS AND DISCUSSION 460
REFERENCES 462
Chapter 62. Differential Sensitivity to 3-Methylcholanthrene (3MC) InducedImmunosuppression in Young and Old Mice 464
Chapter 63. Anti-Allergie Agents „ Summary 466
Chapter 64. Pharmacology of Macrophages and Related Cells 470
SUMMARY 470
Chapter 65. Synthetic Immunostimulants III 472
Chapter 66. Immunopharmacology of Inflammation 476
ABSTRACT 477
KEYWORDS 477
INTRODUCTION 477
Chapter 67. Novel Vaccines 480
Chapter 68. Monoclonal Antibodies as Pharmacological Agents 486
Chapter 69. Novel Approaches inImmune Manipulation 488
REFERENCES 489
Chapter 70. MDP and Derivatives II 490
Chapter 71. Thymic Hormones, Interleukins, Endotoxin and Thymomimetic Drugs in. Lymphocyte Ontogeny 498
REFERENCES 508
Author Index 510