1 Viruses and Immune Responses: A Dynamical View ............... 1
1.1 Viruses .................................................. 3
1.2 Basic Immunological Background ........................... 5
1.3 Experimental Mouse Models of CTL Dynamics ............... 13
1.4 Human Pathogenic Infectious ............................. 15
1.5 Virus Dynamics and Mathematical Modeling ................ 18
1.6 Immune Response Dynamics: Structure of the Book ......... 23
2 Models of CTL Responses and Correlates of Virus Control ..... 25
2.1 Virus Dynamics .......................................... 26
2.2 Simplest Model for CTL Dynamics ......................... 28
2.3 Saturated CTL Expansion ................................. 31
2.4 Precursor Versus Effector CTL ........................... 32
2.5 Programmed CTL Proliferation ............................ 34
2.6 Summary ................................................. 40
3 CTL Memory .................................................. 41
3.1 The Generation of CTL Memory: Biological Background ..... 43
3.2 Mathematical Models of CTL Memory ....................... 43
3.3 Resolution of Primary Infection: Mathematical
Predictions ............................................. 45
3.4 Resolution of Primary Infection: Experimental Studies ... 47
3.5 Protection Against Rechallenge: Mathematical
Predictions ............................................. 49
3.6 Protection Against Rechallenge: Experimental Studies .... 51
3.7 Summary ................................................. 53
4 CD4 T Cell Help ............................................. 55
4.1 Comparison of the Two Helper Pathways ................... 63
4.2 How Does Help Work? ..................................... 63
4.3 Infection Dynamics in Helper Deficient Hosts ............ 66
4.4 Summary ................................................. 70
5 Immunodominance ............................................. 71
5.1 A Mathematical Model for Multiple CTL Clones ............ 72
5.2 Theory and Data ......................................... 75
5.3 An Unusual Pattern of Immunodominance ................... 77
5.4 Summary ................................................. 84
6 Multiple Infections and CTL Dynamics ........................ 85
6.1 Mathematical Model ...................................... 86
6.2 Virus Control and Antigenic Heterogeneity ............... 87
6.3 Two Heterologous Infections ............................. 88
6.4 Multiple Heterologous Infections ........................ 90
6.5 Experimental Studies .................................... 93
6.6 Coinfection: Viruses and Bacteria ....................... 94
6.7 Vaccination ............................................. 95
6.8 The Immune Phenome and Aging ............................ 96
6.9 Summary ................................................. 97
7 Control versus CTL-Induced Pathology ........................ 99
7.1 Basic Mathematical lnsights ............................ 100
7.2 CTL-Induced Pathology in LCMV Infection ................ 103
7.3 CTL-Induced Pathology and HIV Infection ................ 108
7.4 Summary ................................................ 111
8 Lytic versus Nonlytic Activity ............................. 113
8.1 Modeling Lytic and Nonlytic CTL Responses .............. 115
8.2 Effect of Lytic and Nonlytic Immunity on Virus
Control ................................................ 116
8.3 Noncytopathic Viruses .................................. 118
8.4 More Cytopathic Viruses ................................ 121
8.5 Summary ................................................ 123
9 Dynamical Interactions between CTL and Antibody
Responses .................................................. 125
9.1 Modeling Competition between CTL and Antibody
Responses .............................................. 126
9.2 Competition during Acute Infection ..................... 128
9.3 Effect of Viral Evolution during Chronic Infection ..... 129
9.4 Application: Experimental Data on HCV Infection ........ 133
9.5 Summary ................................................ 136
10 Effector Molecules and CTL Homeostasis ..................... 137
10.1 CTL Homeostasis and Predator Prey Dynamics ............ 138
10.2 Effector Molecules and Immunodominance ................ 140
10.3 The Role of Antigen for CTL Proliferation ............. 142
10.4 Programmed CTL Proliferation and the Role of CTL
Effectors ............................................. 143
10.5 Effector Molecules and CTL Homeostasis in VSV
Infection ............................................. 144
10.6 Summary ............................................... 145
11 Virus-Induced Subversion of CTL Responses .................. 147
11.1 A Basic Model for Virus-Induced Impairment of Help .... 149
11.2 What Determines the Outcome of Infection? ............. 151
11.3 Robustness of Predictions ............................. 153
11.4 Experimental Verification: CTL Exhaustion in LCMV
Infection ............................................. 156
11.5 Helper-Dependent versus Independent CTL Responses ..... 158
11.6 Immune Impairment and the Level of Immune Responses ... 163
11.7 Summary ............................................... 165
12 Boosting Immunity against Immunosuppressive Infections ..... 167
12.1 Basic Properties of Immune Impairment ................. 168
12.2 T Cell Dynamics during Therapy ........................ 170
12.3 Application: Early Treatment of SIV / HIV ............. 174
12.4 Application: Treatment of HCV Infection ............... 178
12.5 Treatment Interruptions ............................... 179
12.6 Summary ............................................... 181
13 Evolutionary Aspects of Immunity ........................... 183
13.1 A Single Population of Pathogens ...................... 184
13.2 Two Competing Pathogen Populations .................... 186
13.3 Pathogen Competition and the Evolution of Memory
Duration .............................................. 188
13.4 Application to Immunological Observations ............. 191
13.5 Summary ............................................... 192
References .................................................... 195
Index ......................................................... 217
| 
