Killer Cell Dynamics: Mathematical and Computational Approaches to Immunology

Cover......Page 1
Editors......Page 2
Title: Killer Cell Dynmaics: Mathematical and Computational Approaches to Immunology......Page 4
ISBN-13: 978-0-387-30893-7......Page 5
Dedication......Page 6
Preface......Page 7
Contents......Page 10
1  V iruses and Immune Responses: A Dynamica View......Page 13
1.1 Viruses......Page 15
1.2 Basic Immunological Background......Page 17
1.3 Experimental Mouse Models of CTL Dynamics......Page 25
1.4 Human Pathogenic Infections......Page 27
1.5 Virus Dynamics and Mathematical Modeling......Page 30
1.6 Immune Response Dynamics: Structure of the Book......Page 35
2  Models of CTL Responses and Correlates of Virus Control......Page 37
2.1 Virus Dynamics......Page 38
2.2 Simplest Model for CTL Dynamics......Page 40
2.3 Saturated CTL Expansion......Page 43
2.4 Precursor Versus Effector CTL......Page 44
2.5 Programmed CTL Proliferation......Page 46
2.6 Summary......Page 52
3  CTL Memory......Page 53
3.2 Mathematical Models of CTL Memory......Page 55
3.3 Resolution of Primary Infection: Mathematical Predictions......Page 57
3.4 Resolution of Primary Infection: Experimental Studies......Page 59
3.5 Protection Against Rechallenge: Mathematical Predictions......Page 61
3.5.1 Protection After Virus Elimination......Page 62
3.6 Protection Against Rechallenge: Experimental Studies......Page 63
3.7 Summary......Page 65
4  CD4 T Cell Help......Page 66
The CD4-APC-CTL Pathway......Page 68
The Classical Pathway......Page 72
4.2 How Does Help Work?......Page 74
4.3 Infection Dynamics in Helper Deficient Hosts......Page 77
4.4 Summary......Page 81
5  Immunodominance......Page 82
5.1 A Mathematical Model for Multiple CTL Clones......Page 83
5.2 Theory and Data......Page 86
5.3 An Unusual Pattern of Immunodominance......Page 88
5.4 Summary......Page 95
6  Multiple Infections and CTL Dynamics......Page 96
6.1 Mathematical Model......Page 97
6.2 Virus Control and Antigenic Heterogeneity......Page 98
6.3 Two Heterologous Infections......Page 99
6.4 Multiple Heterologous Infections......Page 101
6.5 Experimental Studies......Page 104
6.6 Coinfection: Viruses and Bacteria......Page 105
6.7 Vaccination......Page 106
6.8 The Immune Phenome and Aging......Page 107
6.9 Summary......Page 108
7  Control versus CTL-Induced Pathology......Page 109
7.1 Basic Mathematical Insight......Page 110
7.2 CTL-Induced Pathology in LCMV Infection......Page 113
7.3 CTL-Induced Pathology and HIV Infection......Page 118
7.4 Summary......Page 121
8  Lytic versus Nonlytic Activity......Page 122
8.1 Modeling Lytic and Nonlytic CTL Responses......Page 124
8.2 Effect of Lytic and Nonlytic Immunity on Virus Control......Page 125
8.3 Noncytopathic Viruses......Page 127
8.4 More Cytopathic Viruses......Page 130
8.5 Summary......Page 132
9  Dynamical Interactions between CTL andAntibody Responses......Page 134
9.1 Modeling Competition between CTL and Antibody Responses......Page 135
9.2 Competition during Acute Infection......Page 137
9.3 Effect of Viral Evolution during Chronic Infection......Page 138
9.4 Application: Experimental Data on HCV Infection......Page 142
9.5 Summary......Page 145
10  Effector Molecules and CTL Homeostasis......Page 146
10.1 CTL Homeostasis and Predator–Prey Dynamics......Page 147
10.2 Effector Molecules and Immunodominance......Page 149
10.3 The Role of Antigen for CTL Proliferation......Page 151
10.4 Programmed CTL Proliferation and the Role of CTL Effectors......Page 152
10.5 Effector Molecules and CTL Homeostasis in VSV Infection......Page 153
10.6 Summary......Page 154
11  Virus-Induced Subversion of CTL Responses......Page 155
11.1 A Basic Model for Virus-Induced Impairment of Help......Page 157
11.2 What Determines the Outcome of Infection?......Page 159
11.3 Robustness of Predictions......Page 161
11.4 Experimental Verification: CTL Exhaustion in LCMV Infection......Page 164
11.5 Helper-Dependent versus Independent CTL Responses......Page 166
11.6 Immune Impairment and the Level of Immune Responses......Page 171
11.7 Summary......Page 173
12  Boosting Immunity against Immunosuppressive Infections......Page 175
12.1 Basic Properties of Immune Impairment......Page 176
12.2 T Cell Dynamics during Therapy......Page 178
12.3 Application: Early Treatment of SIV/HIV......Page 182
12.4 Application: Treatment of HCV Infection......Page 186
12.5 Treatment Interruptions......Page 187
12.6 Summary......Page 189
13  Evolutionary Aspects of Immunity......Page 190
13.1 A Single Population of Pathogens......Page 191
13.2 Two Competing Pathogen Populations......Page 193
13.3 Pathogen Competition and the Evolution of Memory Duration......Page 195
13.4 Application to Immunological Observations......Page 198
13.5 Summary......Page 199
References......Page 201
Index......Page 223