Mims' Pathogenesis of Infectious Disease (eBook)

Front Cover 1
Mims’ Pathogenesis of Infectious Disease 4
Copyright Page 5
Contents 6
Preface 8
1 General Principles 10
Bibliography 16
2 Attachment to and Entry of Microorganisms into the Body 18
Introduction 18
Adhesion/Entry: Some General Considerations 23
The Skin 24
Small Bites 25
Large Bites 25
Respiratory Tract 26
Gastrointestinal Tract 29
Mechanisms of Attachment to and Invasion of the Gastrointestinal Tract 33
General Considerations 33
Enteropathogenic E. coli (EPEC) 34
Enterohaemorrhagic E. coli (EHEC) 35
Shigella 35
Salmonella 36
Histotoxic Salmonella 36
Nonhistotoxic Salmonella 37
Yersinia 37
Campylobacter jejuni 37
Giardia lamblia 38
Entamoeba histolytica 38
Oropharynx 38
Urinogenital Tract 40
Conjunctiva 42
The Normal Microbiota 43
Importance of the Normal Microbiota to the Host 44
Opportunistic Infection 46
Exit of Microorganisms from the Body 48
Respiratory Tract 49
Saliva 50
Skin 51
Intestinal Tract 51
Urinogenital Tract 53
Blood 56
Miscellaneous 56
No Shedding 56
Bibliography 57
3 Early Stages of Infection After Pathogen Entry 60
Growth in Epithelial Cells 60
Intracellular Microorganisms and Spread Through the Body 63
Subepithelial Invasion 65
The Inflammatory Response 66
Tissue Fluids 70
Lymphatics and Lymph Nodes 70
Phagocytic Cells 71
Nutritional Requirements of Invading Microbes 72
Bibliography 73
4 Encounter of Microbes with Phagocytic Cells 76
Cell Biology of Phagocytosis 78
Phagocytosis in Polymorphonuclear Leucocytes 79
Phagocytosis in Macrophages 84
Microbial Strategy in Relation to Phagocytes 86
Inhibition of Chemotaxis or the Mobilisation of Phagocytic Cells 87
Inhibition of Adsorption of Microorganism to Surface of Phagocytic Cell 90
Inhibition of Phagocytosis – Opsonins 90
Inhibition of Fusion of Lysosome with Phagocytic Vacuole 93
Escape from the Phagosome 93
Resistance to Killing and Digestion in the Phagolysosome 94
Growth in the Phagocytic Cell 95
Killing the Phagocyte 97
Entry into the Host Cell Other Than by Phagocytosis 98
Consequences of Defects in the Phagocytic Cell 99
Summary 101
Bibliography 101
5 The Spread of Microbes Through the Body 104
Direct Spread 105
Microbial Factors Promoting Spread 106
Spread Via Lymphatics 106
Spread Via the Blood 108
Blood–Tissue Junctions 108
Form in Which Microorganism Is Carried in the Blood 113
Free in the Plasma 113
Leucocyte (White Cell) Associated 113
Red Cell Associated 114
Platelet Associated 115
Reticuloendothelial System 115
Haematogenous Spread and the Nature of the Vascular Bed 117
Central Nervous System 119
Skeletal and Cardiac Muscle 119
The Skin 119
The Foetus 122
Miscellaneous Sites 124
Spread Via Other Pathways 124
Cerebrospinal Fluid 124
Pleural and Peritoneal Cavities 125
Nerves 125
Bibliography 126
6 The Immune Response to Infection 128
Antibody Response 135
Types of Immunoglobulin 135
Protective Action of Antibodies 140
T-Cell-Mediated Immune Response 142
NK Cells 144
Macrophages, Neutrophils and Mast Cells 145
Complement and Related Defence Molecules 148
Conclusions Concerning the Immune Response to Microorganisms 152
Bibliography 153
7 Microbial Strategies in Relation to the Immune Response 154
Induction of Immunological Tolerance 155
Prenatal Infection 155
Desensitisation of Immune Cells by Circulating Antigens 156
Molecular Mimicry 157
Conclusion About Inducing Tolerance 158
Immunosuppression 159
General Immunosuppression 159
Antigen-Specific Suppression and Regulatory T Cells 161
Absence of a Suitable Target for the Immune Response 163
Microbial Presence in Bodily Sites Inaccessible to the Immune Response 164
Induction of Inappropriate Antibody and T-Cell Responses 165
Antibodies Mopped up by Soluble Microbial Antigens 167
Local Interference with Immune Forces 168
Reduced Interferon Induction or Responsiveness 171
Antigenic Variation 172
Antigenic Variation Within the Infected Individual 172
Antigenic Variation at the Population Level 174
Bibliography 178
8 Mechanisms of Cell and Tissue Damage 180
Infection with No Cell or Tissue Damage 185
Direct Damage by Microorganisms 186
Microbial Toxins 188
Protein Toxins 189
Toxins Which Act Extracellularly 189
Toxins Which Damage Membranes 190
Proteases 190
Phospholipases 190
Clostridium perfringens a-Toxin 190
Pore-Forming Toxins 191
Cholesterol-Binding Cytolysins 191
Pneumolysin 191
RTX Toxins 193
Staphylococcal a-Toxin 194
Detergent-Like Toxins 194
Binary Toxins 194
Toxins with Intracellular Targets 195
Self-Translocation 195
Direct Injection 195
Receptor-Mediated Endocytosis 195
Translocation of Toxiphore into the Cytoplasm 196
Direct Escape from Endosome 196
Route to Endoplasmic Reticulum 196
Intracellular Targets 199
Superantigens: Toxins with Multiple Biological Activities 199
Significance of Toxins in Disease 204
Cholesterol-Binding Cytolysins 204
Corynebacterium diphtheriae 204
ShT and ShLT 204
Vibrio cholerae and CT 206
Bordetella pertussis Toxin (Pertussigen) 209
Clostridial Neurotoxins 210
Anthrax Toxin 211
Clostridium difficile 211
Fungal Exotoxins 212
Cell-Associated Toxins 212
Endotoxins 213
Location in Cell Envelope 213
Structure 213
Immunochemistry and Seroclassification 215
Biological Properties 215
General Observations on Toxins 217
Indirect Damage via Inflammation 218
Indirect Damage via the Immune Response (Immunopathology) 219
Type 1: Anaphylactic Reactions 221
Type 2: Cytolytic or Cytotoxic Reactions 222
Type 3: Immune Complex Reactions 222
Glomerulonephritis and Vasculitis 223
Allergic Alveolitis 227
Other Immune Complex Effects 227
Type 4: Cell-Mediated Reactions 227
Other Indirect Mechanisms of Damage 229
Stress, Haemorrhage, Placental Infection and Tumours 229
Co-infections 231
Diarrhoea 232
Bibliography 239
9 Recovery from Infection 242
Immunological Factors in Recovery 242
Antibody 243
Cell-Mediated Immunity 247
Inflammation 251
Complement 252
Interferons 254
Multimechanistic Recovery: An Example 256
Temperature 258
Tissue Repair 259
In the skin 260
In the Respiratory Tract 260
In the Liver 261
In the Foetus 261
Resistance to Re-Infection 262
Bibliography 264
10 Failure to Eliminate Microbe 266
Latency 268
Viable But Noncultivable Forms 273
Persistent Infection with Shedding 273
Epidemiological Significance of Persistent Infection with Shedding 276
Persistent Infection Without Shedding 277
Significance for the Individual of Persistent Infections 279
Conclusions 280
Bibliography 280
11 Host and Microbial Factors Influencing Susceptibility 282
Genetic Factors in the Microorganism 283
Genetic Factors in the Host 288
Age of Host 290
Sex of Host 292
Malnutrition of the Host 293
Stress and Hormonal Factors 295
Other Factors 298
Bibliography 298
12 Vaccines and How They Work 300
Introduction 300
What Is a Vaccine? 301
What Do We Ask of an Ideal Vaccine? 301
General Principles 302
The Vaccine Should Induce the Right Type of Immune Response 302
The Vaccine Should Induce an Immune Response in the Right Place 302
The Vaccine Should Induce an Immune Response to the Right Antigens 302
Resistance to Some Infectious Diseases Does Not Depend on Immunity to the Infectious Agent 302
There Are Important Differences in Principle Between Killed and Live Vaccines 303
Factors Determining the Duration of Resistance 303
The Concept of Attenuation 303
The Concept of Monotypic Microbes 306
Adjuvants 306
The Age at Which Vaccines Should Be Given 307
Complications and Side Effects of Vaccines 308
The Development of New Vaccines 308
Attenuated Viruses and Bacteria as Carriers 310
Reverse Vaccinology 310
Bibliography 311
Appendix 314
Conclusions 322
Glossary 326
Index 332