Alt Advances in Immunology

1. Auflage 2015
ISBN: 978-0-12-802432-4
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 126, 244 Seiten

Reihe: Advances in Immunology

Advances in Immunology, a long-established and highly respected publication, presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for the future. - Contributions from leading authorities - Informs and updates on all the latest developments in the field

Autoren/Hrsg.

Alt, Frederick W.

Inhaltsverzeichnis

1;Front Cover;1
2;Advances in Immunology;4
3;Copyright;5
4;Contents;6
5;Contributors;8
6;Chapter 1: NOD.H-2h4 Mice: An Important and Underutilized Animal Model of Autoimmune Thyroiditis and Sjogren´s Syndrome;10
6.1;1. Introduction;11
6.2;2. Spontaneous Autoimmune Thyroiditis;13
6.2.1;2.1. SAT in WT NOD.H-2h4 mice/importance of iodine;13
6.2.2;2.2. B cells and autoantibodies in SAT;17
6.2.3;2.3. T cells as effector cells in SAT;19
6.2.4;2.4. Regulatory T cells in SAT;20
6.2.5;2.5. IFN-. is required for development of SAT;23
6.2.6;2.6. CD40 and CD40/CD154 interactions in SAT;24
6.3;3. TEC Hyperplasia/Proliferation;25
6.3.1;3.1. TEC H/P develops only if IFN-. is absent;25
6.3.2;3.2. TEC H/P histology, incidence, and kinetics of development;26
6.3.3;3.3. Mice with severe TEC H/P have reduced thyroid function and thyroid fibrosis;28
6.3.4;3.4. TEC H/P is a T cell-dependent autoimmune disease;29
6.3.4.1;3.4.1. CD4+ versus CD8+ T cells;30
6.3.4.2;3.4.2. B cells in TEC H/P;31
6.3.5;3.5. TGF-ß and TNF-a are effector cytokines for TEC H/P;32
6.3.6;3.6. Use of the adoptive transfer model to examine kinetics of TEC H/P development and assess therapeutic protocols;34
6.3.7;3.7. Agonistic anti-CD40 induces proliferation of thyrocytes in IFN-.-/- NOD.H-2h4 mice promotes development of severe TE...;35
6.3.8;3.8. Some IFN-.-/- NOD.H-2h4 mutants develop early and severe TEC H/P;38
6.3.8.1;3.8.1. CD28-/- mice;38
6.3.8.2;3.8.2. PD-1-/-IFN-.-/- NOD.H-2h4 mice;41
6.4;4. NOD.H-2h4 Mice Can Be Used as a Model of Experimentally Induced Autoimmune Thyroiditis;42
6.5;5. SS in NOD.H-2h4 Mice and NOD.H-2h4 Mutants;43
6.6;6. Concluding Remarks;45
6.7;Acknowledgments;46
6.8;References;47
7;Chapter 2: Approaches for Analyzing the Roles of Mast Cells and Their Proteases In Vivo;54
7.1;1. Mast Cell Biology;55
7.1.1;1.1. Origin and tissue distribution of mast cells;55
7.1.2;1.2. The spectrum of mast cell-derived mediators;56
7.1.3;1.3. Phenotypic heterogeneity and functional plasticity;57
7.1.4;1.4. Mast cell-associated proteases and their cellular distribution;59
7.2;2. Nongenetic Approaches for Analyzing the Functions of Mast Cells and Mast Cell-Associated Proteases In Vivo;63
7.2.1;2.1. Pharmacological approaches;63
7.2.1.1;2.1.1. Mast cell stabilizers;63
7.2.1.2;2.1.2. Mast cell activators;64
7.2.1.3;2.1.3. Purified or recombinant mast cell proteases;64
7.2.1.4;2.1.4. Tryptase and chymase inhibitors;65
7.2.1.5;2.1.5. Tyrosine kinase inhibitors;66
7.2.2;2.2. Antibody-based approaches;67
7.3;3. Genetic Approaches for Analyzing the Functions of Mast Cells In Vivo;67
7.3.1;3.1. Mice with mutations affecting c-kit structure or expression and ``MC knockin mice´´;68
7.3.2;3.2. MC-deficient mice with normal c-kit;71
7.3.2.1;3.2.1. Mcpt5-Cre;R-DTA mice;77
7.3.2.2;3.2.2. Cpa3Cre/+-``Cre-Master´´ mice;77
7.3.2.3;3.2.3. Cpa3-Cre;Mcl-1fl/fl-``Hello Kitty´´ mice;78
7.3.3;3.3. Inducible models of mast cell deficiency;79
7.3.3.1;3.3.1. Mcpt5-Cre;iDTR mice;79
7.3.3.2;3.3.2. ``Mas-TRECK´´ mice;80
7.3.3.3;3.3.3. Cpa3-Cre;iDTR mice;81
7.3.3.4;3.3.4. KitCreERT2 and KitCreERT2/+R26-GFPStopFDTA mice;81
7.3.4;3.4. Specific deletion of mast cell-associated products by Cre-lox approaches;82
7.4;4. Genetic Approaches for Analyzing the Functions of Mast Cell-Associated Proteases In Vivo;84
7.5;5. Using Mast Cell-Deficient or Mast Cell-Associated Protease-Deficient Mice to Analyze Functions of Mast Cells or Their ...;88
7.5.1;5.1. Settings in which similar results have been obtained using multiple models of mast cell deficiency and/or deficienci...;88
7.5.1.1;5.1.1. IgE-dependent local and systemic anaphylaxis reactions;88
7.5.1.2;5.1.2. Intestinal nematode infections;89
7.5.1.3;5.1.3. Resistance to animal venoms;90
7.5.1.4;5.1.4. Effects on inflammation during innate and adaptive immune responses;92
7.5.1.5;5.1.5. Mouse models of bacterial infection;93
7.5.1.6;5.1.6. Tissue remodeling and pathology in disease settings;98
7.5.2;5.2. Settings in which divergent results have been obtained using multiple models of MC deficiency or deficiencies in MC-...;98
7.5.2.1;5.2.1. Wound healing and tissue remodeling;98
7.5.2.2;5.2.2. Mouse models of autoimmune arthritis;100
7.5.2.3;5.2.3. Experimental autoimmune encephalomyelitis;102
7.5.2.4;5.2.4. Mouse models of asthma;103
7.5.2.5;5.2.5. Cutaneous contact hypersensitivity;105
7.5.2.6;5.2.6. Experimental glomerulonephritis;108
7.5.3;5.3. Potential effects of strain background, the host microbiome, and/or differences in animal husbandry;109
7.5.4;5.4. Importance of experimental design in studying the roles of mast cells and mast cell-associated proteases in vivo;110
7.6;6. General Recommendations Regarding the Use of Mast Cell-Deficient or Mast Cell-Associated Protease-Deficient Mice to An...;112
7.7;7. Perspective;113
7.8;Acknowledgments;117
7.9;References;117
8;Chapter 3: Epithelial Cell Contributions to Intestinal Immunity;138
8.1;1. Introduction;139
8.1.1;1.1. Overview of epithelial-microbial interactions in the mammalian intestine;139
8.1.2;1.2. The intestinal microbiota;140
8.1.3;1.3. Germ-free mice as experimental tools;141
8.2;2. Cellular Makeup of the Intestinal Epithelial Barrier;142
8.2.1;2.1. Enterocytes;142
8.2.2;2.2. Goblet cells;143
8.2.3;2.3. Paneth cells;143
8.2.4;2.4. Enteroendocrine cells;143
8.2.5;2.5. M cells;144
8.3;3. Epithelial Cell Sensing of Intestinal Microbes;144
8.3.1;3.1. Epithelial detection of microbes by pattern recognition receptors;144
8.3.2;3.2. Tissue-specific modulation of epithelial cell-specific innate immune responses;147
8.4;4. Mucus Production by the Intestinal Epithelium;148
8.4.1;4.1. Secretion and assembly of the mucus layer;148
8.4.2;4.2. Regulation of mucus production;148
8.5;5. Epithelial Antimicrobial Proteins;150
8.5.1;5.1. Epithelial antimicrobial protein families;151
8.5.1.1;5.1.1. Defensins;151
8.5.1.2;5.1.2. Lectins;152
8.5.1.3;5.1.3. Cathelicidins;153
8.5.1.4;5.1.4. Lysozyme and phospholipase A2;154
8.5.1.5;5.1.5. Lipocalin;154
8.5.1.6;5.1.6. RNases;154
8.5.2;5.2. Regulation of epithelial antimicrobial proteins;154
8.5.2.1;5.2.1. Transcriptional regulation of epithelial antimicrobial protein expression;155
8.5.2.2;5.2.2. Developmental regulation of antimicrobial protein expression;158
8.5.2.3;5.2.3. Posttranslational regulation of antimicrobial protein function;158
8.5.2.4;5.2.4. Regulation of antimicrobial protein secretion;159
8.5.3;5.3. In vivo functions of epithelial antimicrobial proteins;159
8.5.3.1;5.3.1. Protection against pathogens;160
8.5.3.2;5.3.2. Shaping microbiota composition;161
8.5.3.3;5.3.3. Limiting bacterial-epithelial cell contact;161
8.6;6. Intestinal Epithelial Cell Autophagy;162
8.6.1;6.1. Autophagy as a barrier to bacterial dissemination;162
8.6.2;6.2. Autophagy-dependent regulation of protein secretion;163
8.7;7. Epithelial Regulation of Adaptive Immunity;163
8.7.1;7.1. Transcytosis of immunoglobulin A;164
8.7.2;7.2. Cytokine secretion;165
8.7.3;7.3. Antigen delivery to subepithelial immune cells;165
8.8;8. Bacterial Stimulation of Epithelial Cell Repair;166
8.8.1;8.1. MyD88-dependent epithelial repair;167
8.8.2;8.2. Activation of epithelial repair by reactive oxygen species;168
8.9;9. Epithelial Dysfunction in Inflammatory Disease;168
8.10;10. Future Perspectives;170
8.11;Acknowledgments;171
8.12;References;171
9;Chapter 4: Innate Memory T cells;182
9.1;1. Introduction;183
9.2;2. Innate Memory T Cells Produced Through Response to Lymphopenia;185
9.2.1;2.1. Identification of lymphopenia-induced memory T cells;185
9.2.2;2.2. The role of TCR specificity on lymphopenia-induced innate memory T cell generation;188
9.2.3;2.3. The role of IL-7 in lymphopenia-induced innate memory T cell generation;191
9.2.4;2.4. Relationship between naïve T cell proliferation and generation of innate memory cells;193
9.3;3. Innate Memory CD8+ T Cells Induced by IL-4;194
9.3.1;3.1. A subset of NKT cells produces IL-4 to induce innate memory CD8+ T cell differentiation;196
9.3.2;3.2. Factors that regulate the generation of PLZF+ NKT cells and IL-4-induced memory CD8+ T cells;199
9.3.3;3.3. Distinctions between IL-4- and lymphopenia-induced memory CD8+ T cells;203
9.4;4. Innate Memory T Cells in Normal Homeostasis: ``Virtual Memory´´ T Cells;204
9.5;5. The Role of Innate Memory T Cells in Immunity;207
9.5.1;5.1. Functional properties of lymphopenia-induced memory cells;207
9.5.2;5.2. Functional properties of IL-4-induced memory CD8+ T cells;209
9.5.3;5.3. Functional properties of virtual memory CD8+ T cells;210
9.6;6. Innate Memory Cells in Humans?;211
9.7;References;213
10;Index;224
11;Contents of Recent Volumes;230
12;Color Plate;246

Leseproben

Chapter 2 Approaches for Analyzing the Roles of Mast Cells and Their Proteases In Vivo
Stephen J. Galli*,†,1; Mindy Tsai*; Thomas Marichal*,‡; Elena Tchougounova§; Laurent L. Reber*; Gunnar Pejler¶,#    * Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
† Microbiology & Immunology, Stanford University School of Medicine, Stanford, California, USA
‡ GIGA-Research and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium
§ Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
¶ Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
# Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
1 Corresponding author: email address: [e-mail] Abstract
The roles of mast cells in health and disease remain incompletely understood. While the evidence that mast cells are critical effector cells in IgE-dependent anaphylaxis and other acute IgE-mediated allergic reactions seems unassailable, studies employing various mice deficient in mast cells or mast cell-associated proteases have yielded divergent conclusions about the roles of mast cells or their proteases in certain other immunological responses. Such “controversial” results call into question the relative utility of various older versus newer approaches to ascertain the roles of mast cells and mast cell proteases in vivo. This review discusses how both older and more recent mouse models have been used to investigate the functions of mast cells and their proteases in health and disease. We particularly focus on settings in which divergent conclusions about the importance of mast cells and their proteases have been supported by studies that employed different models of mast cell or mast cell protease deficiency. We think that two major conclusions can be drawn from such findings: (1) no matter which models of mast cell or mast cell protease deficiency one employs, the conclusions drawn from the experiments always should take into account the potential limitations of the models (particularly abnormalities affecting cell types other than mast cells) and (2) even when analyzing a biological response using a single model of mast cell or mast cell protease deficiency, details of experimental design are critical in efforts to define those conditions under which important contributions of mast cells or their proteases can be identified. Keywords Basophils c-kit Cre recombinase Mouse model Stem cell factor 1 Mast Cell Biology
1.1 Origin and tissue distribution of mast cells
Mast cells (MCs) are long-lived granulated cells derived from hematopoietic precursors; such MC progenitors ordinarily are found only in small numbers in the blood and complete their differentiation and maturation in the microenvironments of almost all vascularized tissues (Douaiher et al., 2014; Galli, Grimbaldeston, & Tsai, 2008; Gurish & Austen, 2012; Moon et al., 2010). Like cells in the monocyte lineage, mature MCs located in the tissues can proliferate after appropriate stimulation (Galli, Borregaard, & Wynn, 2011). In addition, increased recruitment, survival, and maturation of MC progenitors may also contribute to the local expansion of MC populations (Galli et al., 2008; Gurish & Austen, 2012). Stem cell factor (SCF), the ligand for Kit, is produced by structural cells in the tissues (and also by MCs) and plays a crucial role in MC development, survival, migration, and function (Douaiher et al., 2014; Galli, Zsebo, & Geissler, 1994; Gurish & Austen, 2012; Moon et al., 2010). Other growth factors (Galli et al., 2008; Gurish & Austen, 2012) that have been shown to influence MC growth and survival include interleukin (IL)-3, IL-4, IL-9, IL-10, IL-33, and TGF-ß. MCs are distributed throughout nearly all tissues, and often in close proximity to potential targets of their mediators such as epithelia and glands, smooth muscle and cardiac muscle cells, fibroblasts, blood and lymphatic vessels, and nerves. Mature MCs are particularly abundant in tissues and organs exposed to the external environment, such as the skin, the lung, and the gut (Galli et al., 2008). 1.2 The spectrum of mast cell-derived mediators
MCs can store and release upon degranulation and/or secrete de novo a wide spectrum of biologically active mediators, many of which also can be produced by other cell types. During IgE-associated biologic responses, the antigen-dependent cross-linking of antigen-specific IgE bound to Fc?RI on the plasma membrane of MCs induces the aggregation of Fc?RI, thereby activating downstream signaling events that lead to the secretion of biologically active products implicated in allergic reactions (Blank & Rivera, 2004; Boyce, 2007; Galli & Tsai, 2012; Metcalfe, Peavy, & Gilfillan, 2009; Rivera, Fierro, Olivera, & Suzuki, 2008). Following antigen binding, MCs very rapidly release into the extracellular space mediators pre-stored in their cytoplasmic granules, for example, vasoactive amines (histamine and serotonin), neutral proteases (tryptases, chymases, and carboxypeptidase A3 [CPA3]), proteoglycans (e.g., heparin), and some cytokines and growth factors by a process called degranulation. A second class of secreted products is generated by de novo synthesis of proinflammatory lipid mediators, such as prostaglandins and leukotrienes. Finally, MCs are also able to synthesize and secrete a large number of growth factors, cytokines, and chemokines, e.g., IL-1, IL-6, IL-10, and TNF-a, VEGF, angiopoietin-1, TGF-ß, and many others, with the types and amounts of such products that are released being influenced by factors such as the type and species of origin of the MCs, the nature of the stimulus inducing MC activation (Galli, Kalesnikoff, et al., 2005; Galli, Nakae and Tsai, 2005; Moon et al., 2010), and, in the case of IgE-dependent MC activation, whether the activation is by low- or high-affinity stimuli (Suzuki et al., 2014). Notably, MCs can be activated to secrete biologically active products not only by IgE and specific antigen, but by a long list of other stimuli including physical agents, products of diverse pathogens (Abraham & St John, 2010), many innate danger signals (Supajatura et al., 2002), certain endogenous peptides and structurally similar peptides found in invertebrate and vertebrate venoms (Akahoshi et al., 2011; Metz et al., 2006; Schneider, Schlenner, Feyerabend, Wunderlin, & Rodewald, 2007), and products of innate and adaptive immune responses including products of complement activation (Schäfer et al., 2012), certain chemokines and cytokines (including IL-33; Enoksson et al., 2011; Lunderius-Andersson, Enoksson, & Nilsson, 2012), and immune complexes of IgG. The ability of MCs to secrete biologically active mediators can be modulated by many factors, including interactions with other granulocytes (Fantozzi et al., 1985), regulatory T cells (Gri et al., 2008), or lymphocytes (Gaudenzio et al., 2009), and certain cytokines, including the main MC development and survival growth factor, the Kit ligand, SCF (Galli, Kalesnikoff, et al., 2005; Galli, Nakae, et al., 2005; Galli, Zsebo, et al., 1994; Hill et al., 1996; Ito et al., 2012), as well as IL-33 (Komai-Koma et al., 2012) and interferon-? (Okayama, Kirshenbaum, & Metcalfe, 2000). Many mediators which can be produced by MCs have been shown to have various positive or negative effects on the function of diverse immune or structural cells, findings which indicate that MCs at least have the potential to influence inflammation, hemostasis, tissue remodeling, cancer, metabolism, reproduction, behavior, sleep, homeostasis, and many other biological responses (Galli et al., 2008; Gilfillan & Beaven, 2011; Kennelly, Conneely, Bouchier-Hayes, & Winter, 2011; Ribatti & Crivellato, 2011). 1.3 Phenotypic heterogeneity and functional plasticity
Many phenotypic and functional characteristics of MCs, such as proliferation, survival, and ability to store and/or secrete various products, as well as the magnitude and nature of their secretory responses to particular activation signals, can be modulated or “tuned” by many environmental and genetic factors (Galli, Kalesnikoff, et al., 2005; Galli, Nakae, et al., 2005). The properties of individual MCs thus may differ depending on the genetic background of the host and/or the local or systemic levels of factors that affect various aspects of MC biology. This “plasticity” of multiple aspects of MC phenotype can result in the development of phenotypically distinct populations of MCs in various anatomic sites and in different animal species. Such altered expression of...