Sex Hormones and Immunity to Infection (eBook)

157857_1_En_FM1_OnlinePDF 1
157857_1_En_1_Chapter_OnlinePDF 9
Chapter Chapter 1: Sex Differences in Susceptibility to Infection: An Evolutionary Perspective 9
Introduction 9
Levels of Analysis: Proximate and Ultimate Explanations in Biology 11
Sexual Selection and Sex Differences in Infection 12
The Role of Life History Theory 14
Empirical Approaches 14
Theoretical Approaches 16
Future Directions 23
References 24
157857_1_En_2_Chapter_OnlinePDF 26
Chapter Chapter 2: Effects of Sex Steroids on Innate and Adaptive Immunity 26
Sources of Sex Steroids: Physiological and Exogenous 26
Sex Steroid Regulation of Innate Immune Cells 28
Neutrophils 28
Macrophages 29
Dendritic Cells 30
Natural Killer Cells 31
Sex Steroid Regulation of Proinflammatory Cytokines and Chemokines 32
TLR Signaling 32
Proinflammatory Cytokines 34
TNF-a and IL-1a/beta 34
IL-12 35
IL-18 36
IL-27 36
IFN-gamma 37
Proinflammatory Chemokines 38
NOS2-Derived Nitric Oxide 39
NFkappaB 39
Sex Steroid Regulation of T Cell Responses 40
Th1 Cells and T-Bet 41
Th2 Cells and IL-4 41
Th17 Cells and IL-17 42
Regulatory T Cells 43
Conclusions 44
References 45
157857_1_En_3_Chapter_OnlinePDF 59
Chapter Chapter 3: Sex Steroid Receptors in Immune Cells 59
Introduction 59
Estrogen Receptors 60
Estrogen Receptor Expression and Ligands 60
ER Expression in Immune Cells 60
Endogenous, Pharmacological or Environmental ER Ligands 61
Choosing Appropriate Model Systems for ER Studies 62
Mechanisms of Estrogen Receptor Signaling 63
ER Structure and Functional Domains 63
ERs Function as Nuclear Transcription Factors 64
ERs are Signal Transduction Molecules 67
ER Signaling Regulates Pathways Important for Immune Responses 68
NF-kappaB 68
STAT Proteins 69
TGF-beta 69
Survival and Proliferation Pathways 70
ER Signaling and ER Ligands in Immune Cell Development 70
Hematopoietic Progenitors 70
Dendritic Cells 71
Lymphocytes 72
Androgen Receptors 72
Androgen Receptor Expression and Ligands 72
AR Expression in Immune Cells 72
AR Ligands 73
Mechanisms of Androgen Receptor Signaling 74
AR Structure and Functional Domains 74
Nuclear AR Signaling Pathways 75
Functions of AR in Nongenomic Signal Transducing Pathways 75
AR Cross-Talk with Other Cellular Signaling Pathways 76
Effects of Androgens and ARs on Immune Function 77
Androgens and AR in Immune Cell Development 78
Progesterone Receptors 79
Progesterone Receptor Expression and Receptor Ligands 79
PR Expression in Immune Cells 79
PR Ligands 79
Mechanism of Progesterone Receptor Signaling 80
PR Structure and Functional Domains 80
PRs Function as Nuclear Transcription Factors 80
PR Ligand-Independent Signaling 81
PR as Signal Transducing Molecules 81
PR Signaling and PR Ligands in Immune Cell Development 82
Conclusions 83
References 83
157857_1_En_4_Chapter_OnlinePDF 98
Chapter Chapter 4: Sex Differences in Susceptibility to Viral Infection 98
Basic Virology 98
What are Viruses? 98
DNA and RNA Viruses 99
Replication and Utilization of Host Cell Machinery for Survival 100
Virus Receptors 100
Host Immune Responses Against Viruses 101
Detection of Viruses by Host Cells 101
Type 1 Interferons 102
Adaptive Immune Responses to Viruses 103
Sex Differences in Response to Viral Infection 103
Sexually Transmitted Viruses 106
Picornaviruses 107
Hantaviruses 110
Encephalitis-Causing Viruses 113
Paramyxoviruses 113
Genetic Factors 114
Sex Chromosomes 114
Disease Susceptibility Genes 115
Virus Genes 116
Conclusions 116
References 118
157857_1_En_5_Chapter_OnlinePDF 128
Chapter Chapter 5: Sex Differences in Innate Immune Responses to Bacterial Pathogens 128
Introduction 128
Sex-Based Differences in Susceptibility to Bacterial Infection and Sepsis 129
Males Exhibit Greater Incidence and Severity of Bacteremia, Endotoxemia, and Higher Tissue Bacterial Burdens Following Infecti 129
Sex-Based Differences in the Production of Inflammatory Cytokines and Development of Bacterial Septic Shock 131
Sex-Based Differences in the Expression and Functionality of Receptors for Conserved Bacterial Motifs 132
Sex Steroid Hormones Affect Susceptibility to Bacterial Infection Through Effects on Innate Immune Cells 135
Susceptibility to Bacterial Infection and Sepsis Differ With Age and Reproductive Status 135
Effects of Sex Steroid Hormones on Susceptibility to Bacterial Infection 137
Effects of Sex Steroid Hormones on Immune Cell Function 139
Effects of Sex Hormones on the Induction of Pattern Recognition Receptors and Signal Transduction Pathways 143
Summary and Conclusions 145
References 146
157857_1_En_6_Chapter_OnlinePDF 152
Chapter Chapter 6: Sex Hormones and Regulation of Host Responses Against Parasites 152
Parasites: Their Global Importance 152
Sex Differences in Susceptibility to Parasites 154
Male-biased Infections 154
Female-biased Infections 154
Sex Differences in Immune Responses to Parasites 158
Neutrophils 159
Mast Cells and Eosinophils 160
Macrophages 160
Dendritic Cells 161
NK Cells 161
B Cells 162
T Cells 162
Role of Sex Steroids in Response to Specific Parasites 162
Sexual Dimorphism in the Response to Leishmania infection: A Not So Simple Paradigm 164
Plasmodium Infections and Th1/Th2 Immunity: Are Females Better Balanced? 166
Toxoplasma gondii Infections and Th1/Th2 Immunity: The Males Have It 168
Trypanosomes 171
American Trypanosomiasis 171
African Trypanosomiasis 172
Other Protozoans - a Mixed Bag 173
Giardiasis and Amebiasis 173
Babesiosis 174
Trichomoniasis 175
Sexual Dimorphism in Response to Helminth Parasites: Female Th2 Dominance 176
Implications for Human Disease/Consideration for Drug and Vaccine Development 178
Future Direction for the Field 179
References 179
157857_1_En_7_Chapter_OnlinePDF 192
Chapter Chapter 7: Sex Differences in Parasitic Infections: Beyond the Dogma of Female-Biased Resistance 192
Introduction 192
Sex Differences in Immune Responses to Parasites 193
Examples of Female-Biased Susceptibility to Parasites 194
Protozoan Parasites 194
Helminth Parasites 195
Cestode parasites 195
Nematode parasites 197
Evidence that Hormones Contribute to Female-Biased Susceptibility 198
Host Hormones Directly Affect Parasite Growth and Reproduction 198
Parasite-Derived Hormonal Mechanisms Affect Parasite Physiology 200
Synthesis of hormones by parasites 195
Synthesis of hormone receptors by parasites 195
Conclusions and Future Directions 202
References 203
157857_1_En_8_Chapter_OnlinePDF 210
Chapter Chapter 8: Progesterone, Pregnancy, and Innate Immunity 210
Pregnancy and the Immune System 210
Pregnancy and NK Cells 211
Pregnancy and Cytokine Responses 212
The Effect of Progesterone on the Maternal Immune System 214
Progesterone Receptors (PRs) 215
Progesterone-Regulated Genes 217
Progesterone and Immunity During Pregnancy 218
Progesterone and DCs During Pregnancy 218
Progesterone and NK Cells During Pregnancy 218
Progesterone and Cytokine Production During Pregnancy 220
Conclusion and Future Directions 222
References 223
157857_1_En_9_Chapter_OnlinePDF 232
Chapter Chapter 9: Pregnancy and Susceptibility to Parasites 232
Introduction 232
Immunological Interactions Within the Placenta During Normal Pregnancy 233
Placentation 233
Implications of Placentation Being an Immunological Process 237
Impact of Pregnancy on the Systemic Immune System 237
Interaction of Parasitic Infections and Pregnancy 237
Congenital Transmission and Disruption of Pregnancy by Parasites 238
Parasite-Mediated Pathology 238
Immunological Interference 239
Protozoan Infections and Pregnancy 239
T. gondii 239
Trypanosoma cruzi 244
Leishmania spp. 245
Plasmodium spp. 246
Metazoan Infections 248
Schistosomes 248
Filariasis 249
Intestinal Helminths 249
Conclusions and Future Directions 250
References 251
157857_1_En_10_Chapter_OnlinePDF 262
Chapter Chapter 10: Sex Steroids and Risk of Female Genital Tract Infection 262
The Role of Sex Steroids on Female Lower Genital Tract Immunity 262
Association of Genital Tract Infections with Menstrual Cycle, Pregnancy, or COC Use in Women 267
Bacterial Genital Tract Infections 267
Viral Genital Tract Infections 270
Fungal Genital Tract Infections 275
Parasitic Genital Tract Infections 276
Summary and Outstanding Research Questions 276
References 277
157857_1_En_11_Chapter_OnlinePDF 285
Chapter Chapter 11: Sex, Pregnancy and Measles 285
Introduction 285
Measles and Measles Vaccines 286
Measles 286
Vaccinations for Measles 287
Immunity to Measles Virus Infection 288
Protective Immunity 288
Immune Suppression Following Measles Virus Infection 288
Sex Differences in Measles-Induced Mortality 289
Sex Differences in Immune Responses to Wild-Type Measles Virus 291
Sex Differences in Immune Responses to Standard-Titer Measles Vaccine 293
Sex Differences in Mortality Following High-Titer Measles Vaccine 294
Impact of Maternal Infection During Pregnancy on Measles Immunity 297
Maternal Infections and the Transfer of Antimeasles Antibodies 297
Maternal Infections and Cellular Immune Responses in the Infant 298
Maternal Schistosomiasis and Offspring Immune Responses 298
Conclusions 300
References 300
157857_1_En_12_Chapter_OnlinePDF 307
Chapter Chapter 12: Epilogue: Challenges for the Future 307
Natural Selection, Sexual Selection and the Evolution of Sexual Dimorphism 307
Male-Associated Immuno-incompetence: Limitations of Bateman´s Principle and the Immunocompetence Handicap Hypothesis 308
Beyond the Dogma of Female-Biased Resistance 309
Limitations of Current Knowledge About Immune-Endocrine Interactions 310
Sex-Determining Chromosomes in Mammals and Their Influence on Immunity 311
Sex Differences in Vaccinology and Therapeutics 312
References 314
157857_1_En_BM2_Chapter_OnlinePDF 316
: Index 316