Immunology of the Liver (eBook)

Front Cover 1
Immunology of the Liver 4
Copyright Page 5
Table of Contents 8
EDITORS' FOREWORD 6
PARTICIPANTS 11
OPENING ADDRESS 14
PART I: CLINICAL, MORPHOLOGICAL AND VIROLOGICAL ASPECTS 16
CHAPTER 1. CLINICAL SPECTRUM OF AUTO-IMMUNE LIVER DISEASE 18
HEPATIC DISEASES FULFILLING CRITERIA OF PRIMARY AUTO-IMMUNE DISORDERS 18
ACTIVE CHRONIC HEPATITIS 19
PRIMARY BILIARY CIRRHOSIS 21
CRAIG-SCHIFF-BOONE SYNDROME 21
OCCURRENCE OF LIVER DISEASE IN THE "COLLAGEN DISORDERS" 22
FELTY'S SYNDROME 22
PROBLEMS FOR THE FUTURE 25
REFERENCES 25
DISCUSSION 26
CHAPTER 2. THE PATHOLOGY OF CHRONIC HEPATITIS 28
CHRONIC PERSISTENT HEPATITIS 28
CHRONIC AGGRESSIVE HEPATITIS 28
PRIMARY BILIARY CIRRHOSIS 29
INTERRELATIONS OF ACUTE AND CHRONIC HEPATITIS 29
REFERENCES 31
DISCUSSION 31
CHAPTER 3. MORPHOLOGICAL AND IMMUNOLOGICAL STUDIES ON CHRONIC AGGRESSIVE HEPATITIS AND PRIMARY BILIARY CIRRHOSIS 34
INTRODUCTION 34
CLASSIFICATION OF CHRONIC HEPATITIS 34
ANALYSIS OF CHRONIC AGGRESSIVE HEPATITIS WITH SPECIAL REFERENCE TO PIECEMEAL NECROSIS 35
PRIMARY BILIARY CIRRHOSIS 40
CONCLUSIONS 41
REFERENCES 42
DISCUSSION 42
CHAPTER 4. THE AUSTRALIA ANTIGEN IN AUTO-IMMUNE LIVER DISEASE 45
INCIDENCE OF POSITIVE RESULTS 45
RESULTS IN ACTIVE CHRONIC HEPATITIS 46
TRANSMISSION OF Au ANTIGEN FROM MOTHER TO CHILD 47
FACTORS DETERMINING FREQUENCY OF Au ANTIGEN IN ACTIVE CHRONIC HEPATITIS 49
DIFFERENCES BETWEEN Au ANTIGEN POSITIVE AND NEGATIVE ACTIVE CHRONIC HEPATITIS 51
AETIOLOGY OF Au ANTIGEN NEGATIVE ACTIVE CHRONIC HEPATITIS 52
CONCLUSIONS 53
REFERENCES 54
DISCUSSION 54
CHAPTER 5. AUSTRALIA ANTIGEN IN THE CHILEAN POPULATION 56
INCIDENCE OF AUSTRALIA ANTIGEN IN DIFFERENT POPULATION GROUPS 56
FAMILY STUDIES 56
INCIDENCE OF AUSTRALIA ANTIGEN IN ACUTE AND CHRONIC LIVER DISEASES 57
ANTIBODY TO AUSTRALIA ANTIGEN IN CHILE 59
CONCLUSIONS 61
REFERENCES 61
DISCUSSION 61
CHAPTER 6. ELECTRON MICROSCOPIC OBSERVATIONS ON SH ANTIGEN USING POSITIVE STAINING 64
POSITIVE STAINING TECHNIQUE 64
DEMONSTRATION OF THREE COMPONENTS IN LARGER PARTICLES 66
CONCLUSIONS 66
REFERENCES 66
CHAPTER 7. ROUND TABLE DISCUSSION ON CLINICAL, MORPHOLOGICAL AND VIROLOGICAL ASPECTS 67
PART II: THE OCCURRENCE AND ROLE OF ANTIBODIES 70
CHAPTER 8. OCCURRENCE AND DISTRIBUTION OF TISSUE ANTIBODIES IN LIVER DISEASES 72
ACUTE VIRAL HEPATITIS 72
USE IN DIFFERENTIAL DIAGNOSIS 73
PATTERN OF ANTIBODIES IN CHRONIC LIVER DISEASE 74
MITOCHONDRIAL ANTIBODIES WITHOUT OVERT LIVER DISEASE 76
UNIFIED CONCEPT OF AUTO-IMMUNE LIVER DISEASE 82
REFERENCES 82
DISCUSSION 83
CHAPTER 9. ANTIBODIES RELATED TO MITOCHONDRIA: MULTIPLE SPECIFICITIES AND CLINICAL ASSOCIATIONS 86
LOCALIZATION OF MITOCHONDRIAL ANTIGEN 86
IMMUNOFLUORESCENT STUDIES ON VARIOUS TISSUES 87
MITOCHONDRIA ASSOCIATED ANTIBODIES IN SYPHILIS AND FALSE POSITIVE REACTORS 89
THE RELATION BETWEEN "M" AND CARDIOLIPIN ANTIBODIES 92
A FURTHER MITOCHONDRIAL ANTIBODY 93
CONCLUSIONS 95
REFERENCES 96
DISCUSSION 96
CHAPTER 10. ANTIBODIES TO BILE CANALICULI IN PATIENTS WITH CHRONIC ACTIVE LIVER DISEASE 99
DEFINITION AND THE SERIES EXAMINED 99
DEMONSTRATION OF BILE CANALICULAR ANTIBODY 100
INCIDENCE OF THE BILE CANALICULAR ANTIBODY 102
RELATION TO SERUM ANTIBODIES, BIOCHEMICAL AND CLINICAL CHANGES 103
EXAMINATION FOR BILE CANALICULAR ANTIBODY WITH HUMAN LIVER 107
CONCLUSION 107
DISCUSSION 108
CHAPTER 11. SERUM TOTAL HAEMOLYTIC COMPLEMENT IN LIVER DISEASE 110
THE COMPLEMENT SYSTEM AND PREVIOUS STUDIES IN LIVER DISEASE 110
TOTAL HAEMOLYTIC COMPLEMENT LEVELS IN PRESENT SERIES 110
POSSIBLE MECHANISMS INVOLVED 113
INCREASED UTILIZATION IN AUTO-IMMUNE LIVER DISEASE 114
CONCLUSION AND FINDINGS AFTER LIVER TRANSPLANTATION 114
REFERENCES 116
DISCUSSION 117
CHAPTER 12. PROPERTIES OF ANTIBODIES REACTING WITH HOMOLOGOUS AND HETEROLOGOUS LIVER MITOCHONDRIAL FRACTIONS 120
METHODS AND TECHNIQUES 120
RESULTS 121
DISCUSSION 130
REFERENCES 132
CHAPTER 13. ROUNDTABLE DISCUSSION ON THE OCCURRENCE AND ROLE OF ANTIBODIES 134
PART III: CELL MEDIATED RESPONSES AND MANIFESTATIONS OF IMMUNOLOGICAL DAMAGE 140
CHAPTER 14. THEORETICAL BASIS OF THE LEUCOCYTE MIGRATION TEST 142
DETAILS OF TECHNIQUE AND SIGNIFICANCE OF INHIBITION 142
MECHANISM OF MIGRATION AND INHIBITION 145
STUDIES WITH DIFFERENT CELL PREPARATIONS 145
IMPORTANCE OF AGGLUTINATION IN MECHANISM OF INHIBITION 147
OCCURRENCE OF STIMULATION OF MIGRATION UNDER CERTAIN CONDITIONS 147
INHIBITION OF MIGRATION AND PHAGOCYTIC ACTIVITY 149
SUMMARY 149
REFERENCES 149
DISCUSSION 150
CHAPTER 15. LEUCOCYTE MIGRATION IN ACTIVE CHRONIC HEPATITIS AND PRIMARY BILIARY CIRRHOSIS 152
LEUCOCYTE MIGRATION TECHNIQUE 152
EFFECT OF TEMPERATURE AND ENZYME INHIBITION ON MIGRATION 152
PREPARATION OF FOETAL LIVER ANTIGEN AND ITS EFFECT ON NORMAL LEUCOCYTES 154
RELATIONSHIP BETWEEN STIMULATION AND INHIBITION OF MIGRATION 154
RESULTS IN LIVER DISEASE 156
RELATION OF MIGRATION INDEX TO TREATMENT AND LIVER FUNCTION 158
CONCLUSIONS AND MODEL OF AUTO-IMMUNE LIVER DISEASE 160
REFERENCES 161
DISCUSSION 161
CHAPTER 16. THE ANERGIC STATE AND OTHER IMMUNOLOGICAL CHANGES IN PRIMARY BILIARY CIRRHOSIS 164
SKIN TESTING WITH TUBERCULIN OR DNCB 165
LYMPHOCYTE TRANSFORMATION TO PHYTOHAEMAGGLUTININ 166
RELATION OF ANERGY TO CLINICAL AND PATHOLOGICAL GRADE 167
RELATION BETWEEN LYMPHOCYTE TRANSFORMATION, TUBERCULIN AND DNCB TESTING 168
STUDIES WITH HAEMOCYANIN 168
CONCLUSIONS 169
REFERENCES 169
DISCUSSION 169
CHAPTER 17. INDUCTION AND TRANSFER OF AUTO-IMMUNE PERIDUCTULAR FIBROSIS IN INBRED RAT STRAINS - WITH EVIDENCE FOR PREDOMINANTLY CELL-MEDIATED PATHOGENESIS 172
DEVELOPMENT OF ANIMAL MODEL 172
HISTOLOGICAL APPEARANCES OF LIVER LESIONS 174
FINDINGS IN ANIMALS IMMUNIZED BY TRANSFER OF SPLEEN CELLS 177
QUANTITATION OF HISTOLOGICAL CHANGES 177
CHANGES IN SKIN REACTIVITY 179
RELATIVE ROLES OF CELLULAR VERSUS ANTIBODY AUTO-IMMUNITY 182
CYTOTOXICITY OF LYMPHOCYTES 182
REFERENCES 183
DISCUSSION 183
CHAPTER 18. CHARACTERIZATION AND ISOLATION OF LIVER SPECIFIC PROTEINS IN DIFFERENT SPECIES: THEIR IMPORTANCE FOR EXPERIMENTAL MODELS AND IN DIAGNOSIS OF CHRONIC HEPATITIS 186
OCCURRENCE OF LIVER SPECIFIC AUTO-ANTIBODY 186
INDUCTION OF TOLERANCE USING HUMAN LIVER PROTEIN 188
PRODUCTION OF ACTIVE CHRONIC HEPATITIS BY IMMUNIZATION PROCEDURES 192
DEMONSTRATION OF SPECIFICALLY SENSITIZED CELLS IN HUMAN ACTIVE CHRONIC HEPATITIS 193
STUDIES WITH PERFUSED RAT LIVER 196
CONCLUSION 201
DISCUSSION 202
CHAPTER 19. IMMUNOLOGIC OBSERVATIONS AND ELECTRON MICROSCOPY OF HALOTHANE -INDUCED HEPATIC INJURY 203
CERTAIN HISTOLOGICAL FEATURES 203
TIMING OF ONSET 203
SIGNIFICANCE OF POST-OPERATIVE FEVER 203
OCCURRENCE OF MITOCHONDRIAL ANTIBODIES 204
ELECTRON MICROSCOPY CHANGES 204
LYMPHOCYTE TRANSFORMATION 205
ROLE OF SENSITIZATION 206
ACKNOWLEDGEMENT 207
REFERENCES 207
DISCUSSION 207
CHAPTER 20. STUDIES ON MULTI-SYSTEM INVOLVEMENT IN ACTIVE CHRONIC HEPATITIS AND PRIMARY BILIARY CIRRHOSIS 211
DEFINITION OF SJÖGREN'S SYNDROME 211
SJÖGREN'S SYNDROME IN AUTO-IMMUNE LIVER DISEASE 212
RENAL TUBULAR ACIDOSIS 214
OTHER SYSTEMIC MANIFESTATIONS 216
REFERENCES 219
DISCUSSION 219
CHAPTER 21. SOME ASPECTS OF HUMORAL AND DELAYED HYPERSENSITIVITY IN CHRONIC HEPATITIS 221
LYMPHOCYTE TRANSFORMATION IN LIVER DISEASE 221
PATIENTS STUDIED AND TECHNIQUES 222
RESULTS 222
CONCLUSIONS 226
REFERENCES 226
CHAPTER 22. ROUND TABLE DISCUSSION ON CELL MEDIATED RESPONSES AND MANIFESTATIONS OF IMMUNOLOGICAL DAMAGE 227
PART IV: RESULTS OF IMMUNOSUPPRESSIVE THERAPY 232
CHAPTER 23. PROBLEMS OF MULTI-CENTRE TRIALS, ILLUSTRATED BY THE COPENHAGEN TRIAL OF STEROID THERAPY IN CIRRHOSIS 234
THE RESULTS 234
REGISTRATION AND PROCESSING SYSTEM 238
CONCLUSIONS 239
REFERENCES 243
DISCUSSION 243
CHAPTER 24. PREDNISOLONE THERAPY IN ACTIVE CHRONIC HEPATITIS 244
PATIENTS STUDIED AND BASE-LINE BIOCHEMICAL DATA 244
CLINICAL COURSE AND MORTALITY 248
CHANGES IN BIOCHEMICAL INDICES 249
REFERENCES 249
DISCUSSION 250
CHAPTER 25. A LONG-TERM STUDY OF IMMUNOSUPPRESSIVE THERAPY IN ACTIVE CHRONIC HEPATITIS 251
SELECTION OF PATIENTS 251
RESULTS TO-DATE 253
OVERALL BENEFIT AND TOXICITY 253
REFERENCES 253
DISCUSSION 259
CHAPTER 26. TREATMENT OF CHRONIC HEPATITIS WITH AZATHIOPRINE AND PREDNISONE COMBINED 260
SELECTION OF PATIENTS 260
RESULTS OF THERAPY 261
DETAILS OF THERAPEUTIC SCHEDULE 261
DISCONTINUATION OF THERAPY 264
REFERENCE 266
CHAPTER 27. A CONTROLLED TRIAL OF PREDNISONE AND AZATHIOPRINE IN ACTIVE CHRONIC HEPATITIS 267
DESCRIPTION OF TRIAL AND SELECTION OF PATIENTS 267
COMPARABILITY OF CONTROL AND TREATED GROUPS 267
CRITERIA FOR IMPROVEMENT 269
RESPONSE TO TREATMENT 269
CONCLUSIONS 272
ADDENDUM 272
DISCUSSION 273
CHAPTER 28. EXPERIENCE WITH AZATHIOPRINE IN PRIMARY BILIARY CIRRHOSIS 275
SELECTION OF PATIENTS 275
DURATION OF TRIAL 275
OVERALL RESULTS 276
CONCLUSIONS 277
DISCUSSION 278
CHAPTER 29. ROUND TABLE DISCUSSION ON RESULTS OF IMMUNO-SUPPRESSIVE THERAPY 280
PART V: SOME ASPECTS OF THE IMMUNOLOGY OF LIVER TRANSPLANTATION 286
CHAPTER 30. RESULTS WITH RELATION TO TISSUE TYPING AND RECURRENCE OF PRIMARY HEPATOMA 288
IMMEDIATE RESULTS 288
DETAILS OF TWO LONG TERM SURVIVORS 289
THE OVERALL RESULTS 290
OCCURRENCE OF JAUNDICE 291
RELATION BETWEEN REJECTION AND TISSUE TYPING 292
RECURRENCE OF HEPATOMA AFTER TRANSPLANTATION 294
SUMMARY 294
ACKNOWLEDGEMENT 295
REFERENCES 295
DISCUSSION 295
CHAPTER 31. THE LEUCOCYTE MIGRATION TEST IN ASSESSMENT OF REJECTION 297
EARLY REJECTION EPISODES 297
LATER CHANGES 300
CONFLICTING FINDINGS IN ONE PATIENT 303
CONCLUSIONS 303
REFERENCES 303
DISCUSSION 304
CHAPTER 32. ASSAY OF SERUM IMMUNOSUPPRESSIVE ACTIVITY AFTER LIVER TRANSPLANTATION 306
THE TEST SYSTEM 306
SERUM LEVELS AFTER TRANSPLANTATION 308
SERUM ASSAY RELATED TO TYPE OF DISTURBED LIVER FUNCTION 311
CONCLUSIONS 313
REFERENCES 313
DISCUSSION 313
CHAPTER 33. IMMUNOLOGICAL ASPECTS OF ORGAN GRAFTING IN THE PIG 315
PROLONGED SURVIVAL OF LIVER ALLOGRAFTS IN THE PIG 315
PROTECTIVE EFFECT OF A LIVER GRAFT 316
STUDIES WITH ANTIGEN EXTRACTS 317
APPLICATION OF FINDINGS TO OTHER SPECIES 318
DISCUSSION 319
INDEX 324