Subject Index Adaptive immunity dependence on innate immunity 9, 10 evolution 10 Aging anti-inflammatory agents in counteraction 202 beneficial polymorphisms 199 201 definition 18, 189 innate immunity effects eosinophils 198, 199 immunosenescence 190 mast cells 198 monocyte/macrophages 192, 194 196 natural killer cells 192, 196, 197 natural killer T cells 192, 197, 198 neutrophils 191 194 sex hormone effects 201 theory of aging 189, 190 Airway epithelium antimicrobial and immunomodulatory peptides/proteins 152 156 dual oxidase function 181 183 immunity components 147, 148 innate immunity impairment cystic fibrosis 157 159 primary ciliary dyskinesia 159, 160 oxidative killing and pathogen clearance 156, 157 pathogen detection and signaling pattern recognition receptors 149 151 virus detection 151, 152 Alarmins, danger signals 113, 114 Amoeba, origins of immune system components 7 Antimicrobal peptides (AMPs), see also specific peptides airway epithelium 152 156 arthropods 35, 36, 38 chemokine activity 66, 67, 103, 110 113 expression induction 64, 65 mammals 36, 62 64 pathology 67, 68 prospects for study 70, 71 proteolytic generation 65, 66 structure and mode of action 62 therapeutic prospects 69, 70 Astrocyte, innate immunity role 17 Caloric restriction (CR), anti-aging effects 202 Cathelicidins airway epithelium 154, 155 structure 63, 64 types 64 CD14, Toll-like receptor coreceptor 47, 48 Chemokines antibacterial peptides and proteins CC chemokines 106, 107 ELR-negative CXC chemokines 108, 109 ELR-positive CXC chemokines 107, 108 structural requirements 105, 106 antimicrobial peptides and chemokine activity 66, 67, 103, 110 113 classification 101, 102, 104, 105 kinocidins 114 leukocyte activation 124 mucosal immunity 112, 113 receptors 105 structure 102, 104 Chronic granulomatous disease (CGD), Nox2 deficiency 165, 167 Clonal selection theory 4 Complement anaphylotoxin C3a chemokine activity 113 207
Complement (continued) C3 cleavage and antimicrobial peptide production 66 cascade alternative pathway 85 classical pathway 83, 84 lectin pathway 84, 85 overview 82, 83 regulation 87 89 terminal pathway 85 overview of components and functions 78 81, 83 pathology activating stimulus persistence 91 93 dysregulation 90 insufficiency 89, 90 microbe exploitation 93 microbe-driven counterattacks 92, 93 tumors and functional failure 93 receptors C1q receptors 87 C5 87 CR1 86 CR2 86 CR3 53, 86, 87 phagocytosis role 128, 129 therapeutic targeting activation inhibition 94 monoclonal antibodies 94, 96 principles 95 regulator proteins 94 tumor attack stimulation 96 vaccination improvement and cancer therapy support 96, 97 Coral, origins of immune system components 8 Crohn s disease, peptide defects 68 Crystal cell, insect innate immunity 23, 37 C-type lectin receptors (CLRs) arthropods 32 cell distribution 15 dectin-1 53 functional overview 15, 16 mannose receptor 51, 52 structure 50, 51 Cystic fibrosis (CF), innate immunity impairment 157 159 Danger hypothesis 113 DC-SIGN, functional overview 52, 53 Dectin-1, functional overview 53 Defensins airway epithelium 154 chemokine activity 110 knockout mice 67, 68 mucosal immunity 112, 113 structure 62 types 36, 61, 62 Dendritic cell (DC) C-type lectin receptors 15 innate immunity role 16, 25 Nox2 function 180 Drosophila peptides 35, 36 cellular encapsulation 33 cytokines in innate immunity 26 gut immunity and symbiont survival 39, 40 hematopoiesis 22 immune response overview 13 innate immunity cells comparison with mammalian cells 36 38 crystal cells 23 granulocytes 23 lamellocytes 23 plasmatocytes 22, 23 pattern recognition receptors 28 31 phagocytosis 33 35 Dual oxidases, see Nox/Duox proteins Duox, see Nox/Duox proteins Encapsulation, mechanisms 33 Eosinophil aging effects 198, 199 functional overview 25 Nox2 function 179 Epidermal growth factor receptor (EGFR), activation and peptide induction 65 Fc receptors, phagocytosis role 128 Granulocyte, insect innate immunity 23, 27 Granulocyte-macrophage colony-stimulating factor (GM-CSF), innate immunity role 26 Granulysin, chemokine activity 111, 112 Heparin-binding protein (HBP), chemokine activity 110, 111 HMGB1, danger signals 113, 114 Human cationic antimicrobial protein-18 (hcap-18) airway epithelium 155 chemokine activity 111 208 Subject Index
Hydra, origins of immune system components 8 Hydrogen peroxide, generation and toxicity 172 Immunosenescence, see Aging Integrins, leukocyte rolling mediation 124 Interleukin-4 (IL-4), innate immunity role 26 Interleukin-5 (IL-5), innate immunity role 26 Interleukin-12 (IL-12), innate immunity role 26 Interleukin-13 (IL-13), innate immunity role 26 Kinocidin, definition 114 Kostmann s disease, peptide defects 68 Lactoferrin, airway epithelium 153, 154 Lactoperoxidase (LPO) airway epithelium and pathogen killing 157, 158 oxygen metabolites 174 Lamellocyte, insect innate immunity 23, 37 Lectin receptors, see C-type lectin receptors Lipopolysaccharide (LPS) pathogen-associated molecular patterns 28 scavenger receptor binding 50 LL-37 (antimicrobial peptide) airway epithelium 155 chemokine activity 111 Lysozyme airway epithelium 153 insect gut expression 38 41 Macrophage, see Monocyte/macrophages Mannose receptor (MR), functional overview 51, 52 Mast cell aging effects 198 innate immunity role 17 M cell, innate immunity in gut 41 Melanoma differentiation-associated gene-5 (MDA5), airway epithelium 151, 152 Monocyte/macrophages (MMs) adaptive immunity role 133 aging effects 192, 194 196 cytokine production 131, 132 differentiation 121, 122 functional overview 24, 119, 120 inflammation resolution apoptotic neutrophil phagocytosis 136 138 general mechanisms 133 135 inflammation role 120 migration in non-inflammatory conditions 127, 128 Nox2 function 179, phagocytosis, see Phagocytosis Myeloperoxidase (MPO), oxygen metabolites 172, 173 NADPH oxidase, see Nox/Duox proteins Natural killer (NK) cell aging effects 192, 196, 197 functional overview 25 Natural killer T cell, aging effects 192, 197, 198 Network theory 5 Neutrophil activation signaling 17 adhesion and migration basement membrane migration 127 chemokine activation 124 crawling 126 inside-out signaling 125 outside-in signaling 125 paracellular migration 126, 127 rolling mediation integrins 124 selectins 123, 124 traffic and margination 123 transcellular migration 127 transendothelial migration 122, 123, 125, 126 aging effects 191 194 coronins 16, 17 differentiation 121, 122 functional overview 24 granule proteins and chemokine activity 110 inflammation role 119 myeloperoxidase 172, 173 Nox2 function 174 176 Nox/Duox proteins in phagosome 176 178 phagocytosis, see Phagocytosis Neutrophil extracellular trap (NET), structure and function 178 Neutrophil gelatinase-associated lipocalin (NGAL) 155 NOD-like receptors (NLRs) airway epithelium 150, 151 functional overview 54, 55 phagocytosis role 129 Subject Index 209
Nox/Duox proteins activated complexes 167, 168 dual oxidase function airways 181 183 gastrointestinal tract 184 oral cavity 181 overview 180, 181 neutrophil phagosome function 176 178 Nox2 deficiency in chronic granulomatous disease 165, 167 dendritic cell function 179 eosinophil function 179 monocyte/macrophage function 179 neutrophil function 174 176 overview 164, 165 oxidative killing and pathogen clearance in airway epithelium 156, 157 oxygen metabolites 170 174 priming and activation 175, 176 structure 165 168 termination 175 types and features Duox1 170 Duox2 170 Nox1 168, 169, 184, 185 Nox2 168 Nox3 169 Nox4169, 185 Nox5 169 OmpA, innate immunity receptors 50 Opsonization advantages 31 arthropods 31, 32 Pathogen-associated molecular patterns (PAMPs) arthropods 27, 28 bacterial products 28 Pattern recognition receptors (PRRs), see also specific receptors arthropods 28 31 classification 45, 46 ligands 56 Peptidoglycan recognition proteins (PGRPs), Drosophila function 28, 29 Peptidoglycans, pathogen-associated molecular patterns 28 Phagocytosis adaptive immunity role 133 arthropods 33 35 cytokine production 131, 132 history of study 1 4 inflammation resolution apoptosis 135, 136 general mechanisms 133 135 macrophage phagocytosis of apoptotic neutrophils 136 138 pathogen activation and destruction 130, 131 phagocyte receptors complement receptors 128, 129 Fc receptors 128 lectins 129 NOD-like receptors 120 scavenger receptors 129, 130 signaling pathways 130 Toll-like receptors 120 Phosphatidylinositol 3-kinase, phagocytosis signaling 130 Phospholipase C (PLC), phagocytosis signaling 130 Plasmatocyte, insect innate immunity 22, 23, 26, 37 Polymorphonuclear neutrophil, see Neutrophil Primary ciliary dyskinesia (PCD), innate immunity impairment 159, 160 Protein kinase C (PKC), phagocytosis signaling 130 Protozoans, origins of immune system components 6 Reactive oxygen species (ROS) airway epithelium 156, 157 NADPH oxidase, see Nox/Duox proteins signaling 178 theory of aging 189 191 Retinoic acid-induced gene-i (RIG-I), airway epithelium 151, 152 Retrocyclin, therapeutic prospects 69, 70 Rho, phagocytosis signaling 130 Scavenger receptors classes and functions 48 50 microbial ligands 50 phagocytosis role 120 structure 49 Selectins, leukocyte rolling mediation 123, 124 Sex hormones, innate immunity effects 201 Siglecs, functional overview 54 210 Subject Index
SLPI, airway epithelium role 155 Sponges, origins of immune system components 7, 8 Surfactant proteins antimicrobial activity 155 cystic fibrosis effects 159 Toll-like receptors (TLRs) adaptor proteins 46 airway epithelium 149 151 ancestry 7, 8 CD14 coreceptor 47, 48 functional overview 14, 15 innate sensing overview 8, 9 phagocytosis role 129 therapeutic targeting 15 TLR9 and DNA recognition 16 types 46, 47, 149, 150 Vaginosis, peptide defects 68 Subject Index 211