Advances in Immunology

 
 
Academic Press
  • 1. Auflage
  • |
  • erschienen am 26. Februar 2015
  • |
  • 244 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
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978-0-12-802432-4 (ISBN)
 
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.

Key features:

* Contributions from leading authorities * Informs and updates on all the latest developments in the field

0065-2776
  • Englisch
  • Saint Louis
  • |
  • USA
Elsevier Science
  • 5,48 MB
978-0-12-802432-4 (9780128024324)
0128024321 (0128024321)
weitere Ausgaben werden ermittelt
1 - Front Cover [Seite 1]
2 - Advances in Immunology [Seite 4]
3 - Copyright [Seite 5]
4 - Contents [Seite 6]
5 - Contributors [Seite 8]
6 - Chapter 1: NOD.H-2h4 Mice: An Important and Underutilized Animal Model of Autoimmune Thyroiditis and Sjogren´s Syndrome [Seite 10]
6.1 - 1. Introduction [Seite 11]
6.2 - 2. Spontaneous Autoimmune Thyroiditis [Seite 13]
6.2.1 - 2.1. SAT in WT NOD.H-2h4 mice/importance of iodine [Seite 13]
6.2.2 - 2.2. B cells and autoantibodies in SAT [Seite 17]
6.2.3 - 2.3. T cells as effector cells in SAT [Seite 19]
6.2.4 - 2.4. Regulatory T cells in SAT [Seite 20]
6.2.5 - 2.5. IFN-. is required for development of SAT [Seite 23]
6.2.6 - 2.6. CD40 and CD40/CD154 interactions in SAT [Seite 24]
6.3 - 3. TEC Hyperplasia/Proliferation [Seite 25]
6.3.1 - 3.1. TEC H/P develops only if IFN-. is absent [Seite 25]
6.3.2 - 3.2. TEC H/P histology, incidence, and kinetics of development [Seite 26]
6.3.3 - 3.3. Mice with severe TEC H/P have reduced thyroid function and thyroid fibrosis [Seite 28]
6.3.4 - 3.4. TEC H/P is a T cell-dependent autoimmune disease [Seite 29]
6.3.4.1 - 3.4.1. CD4+ versus CD8+ T cells [Seite 30]
6.3.4.2 - 3.4.2. B cells in TEC H/P [Seite 31]
6.3.5 - 3.5. TGF-ß and TNF-a are effector cytokines for TEC H/P [Seite 32]
6.3.6 - 3.6. Use of the adoptive transfer model to examine kinetics of TEC H/P development and assess therapeutic protocols [Seite 34]
6.3.7 - 3.7. Agonistic anti-CD40 induces proliferation of thyrocytes in IFN-.-/- NOD.H-2h4 mice promotes development of severe TE... [Seite 35]
6.3.8 - 3.8. Some IFN-.-/- NOD.H-2h4 mutants develop early and severe TEC H/P [Seite 38]
6.3.8.1 - 3.8.1. CD28-/- mice [Seite 38]
6.3.8.2 - 3.8.2. PD-1-/-IFN-.-/- NOD.H-2h4 mice [Seite 41]
6.4 - 4. NOD.H-2h4 Mice Can Be Used as a Model of Experimentally Induced Autoimmune Thyroiditis [Seite 42]
6.5 - 5. SS in NOD.H-2h4 Mice and NOD.H-2h4 Mutants [Seite 43]
6.6 - 6. Concluding Remarks [Seite 45]
6.7 - Acknowledgments [Seite 46]
6.8 - References [Seite 47]
7 - Chapter 2: Approaches for Analyzing the Roles of Mast Cells and Their Proteases In Vivo [Seite 54]
7.1 - 1. Mast Cell Biology [Seite 55]
7.1.1 - 1.1. Origin and tissue distribution of mast cells [Seite 55]
7.1.2 - 1.2. The spectrum of mast cell-derived mediators [Seite 56]
7.1.3 - 1.3. Phenotypic heterogeneity and functional plasticity [Seite 57]
7.1.4 - 1.4. Mast cell-associated proteases and their cellular distribution [Seite 59]
7.2 - 2. Nongenetic Approaches for Analyzing the Functions of Mast Cells and Mast Cell-Associated Proteases In Vivo [Seite 63]
7.2.1 - 2.1. Pharmacological approaches [Seite 63]
7.2.1.1 - 2.1.1. Mast cell stabilizers [Seite 63]
7.2.1.2 - 2.1.2. Mast cell activators [Seite 64]
7.2.1.3 - 2.1.3. Purified or recombinant mast cell proteases [Seite 64]
7.2.1.4 - 2.1.4. Tryptase and chymase inhibitors [Seite 65]
7.2.1.5 - 2.1.5. Tyrosine kinase inhibitors [Seite 66]
7.2.2 - 2.2. Antibody-based approaches [Seite 67]
7.3 - 3. Genetic Approaches for Analyzing the Functions of Mast Cells In Vivo [Seite 67]
7.3.1 - 3.1. Mice with mutations affecting c-kit structure or expression and ``MC knockin mice´´ [Seite 68]
7.3.2 - 3.2. MC-deficient mice with normal c-kit [Seite 71]
7.3.2.1 - 3.2.1. Mcpt5-Cre [Seite 77]
7.3.2.2 - 3.2.2. Cpa3Cre/+-``Cre-Master´´ mice [Seite 77]
7.3.2.3 - 3.2.3. Cpa3-Cre [Seite 78]
7.3.3 - 3.3. Inducible models of mast cell deficiency [Seite 79]
7.3.3.1 - 3.3.1. Mcpt5-Cre [Seite 79]
7.3.3.2 - 3.3.2. ``Mas-TRECK´´ mice [Seite 80]
7.3.3.3 - 3.3.3. Cpa3-Cre [Seite 81]
7.3.3.4 - 3.3.4. KitCreERT2 and KitCreERT2/+R26-GFPStopFDTA mice [Seite 81]
7.3.4 - 3.4. Specific deletion of mast cell-associated products by Cre-lox approaches [Seite 82]
7.4 - 4. Genetic Approaches for Analyzing the Functions of Mast Cell-Associated Proteases In Vivo [Seite 84]
7.5 - 5. Using Mast Cell-Deficient or Mast Cell-Associated Protease-Deficient Mice to Analyze Functions of Mast Cells or Their ... [Seite 88]
7.5.1 - 5.1. Settings in which similar results have been obtained using multiple models of mast cell deficiency and/or deficienci... [Seite 88]
7.5.1.1 - 5.1.1. IgE-dependent local and systemic anaphylaxis reactions [Seite 88]
7.5.1.2 - 5.1.2. Intestinal nematode infections [Seite 89]
7.5.1.3 - 5.1.3. Resistance to animal venoms [Seite 90]
7.5.1.4 - 5.1.4. Effects on inflammation during innate and adaptive immune responses [Seite 92]
7.5.1.5 - 5.1.5. Mouse models of bacterial infection [Seite 93]
7.5.1.6 - 5.1.6. Tissue remodeling and pathology in disease settings [Seite 98]
7.5.2 - 5.2. Settings in which divergent results have been obtained using multiple models of MC deficiency or deficiencies in MC-... [Seite 98]
7.5.2.1 - 5.2.1. Wound healing and tissue remodeling [Seite 98]
7.5.2.2 - 5.2.2. Mouse models of autoimmune arthritis [Seite 100]
7.5.2.3 - 5.2.3. Experimental autoimmune encephalomyelitis [Seite 102]
7.5.2.4 - 5.2.4. Mouse models of asthma [Seite 103]
7.5.2.5 - 5.2.5. Cutaneous contact hypersensitivity [Seite 105]
7.5.2.6 - 5.2.6. Experimental glomerulonephritis [Seite 108]
7.5.3 - 5.3. Potential effects of strain background, the host microbiome, and/or differences in animal husbandry [Seite 109]
7.5.4 - 5.4. Importance of experimental design in studying the roles of mast cells and mast cell-associated proteases in vivo [Seite 110]
7.6 - 6. General Recommendations Regarding the Use of Mast Cell-Deficient or Mast Cell-Associated Protease-Deficient Mice to An... [Seite 112]
7.7 - 7. Perspective [Seite 113]
7.8 - Acknowledgments [Seite 117]
7.9 - References [Seite 117]
8 - Chapter 3: Epithelial Cell Contributions to Intestinal Immunity [Seite 138]
8.1 - 1. Introduction [Seite 139]
8.1.1 - 1.1. Overview of epithelial-microbial interactions in the mammalian intestine [Seite 139]
8.1.2 - 1.2. The intestinal microbiota [Seite 140]
8.1.3 - 1.3. Germ-free mice as experimental tools [Seite 141]
8.2 - 2. Cellular Makeup of the Intestinal Epithelial Barrier [Seite 142]
8.2.1 - 2.1. Enterocytes [Seite 142]
8.2.2 - 2.2. Goblet cells [Seite 143]
8.2.3 - 2.3. Paneth cells [Seite 143]
8.2.4 - 2.4. Enteroendocrine cells [Seite 143]
8.2.5 - 2.5. M cells [Seite 144]
8.3 - 3. Epithelial Cell Sensing of Intestinal Microbes [Seite 144]
8.3.1 - 3.1. Epithelial detection of microbes by pattern recognition receptors [Seite 144]
8.3.2 - 3.2. Tissue-specific modulation of epithelial cell-specific innate immune responses [Seite 147]
8.4 - 4. Mucus Production by the Intestinal Epithelium [Seite 148]
8.4.1 - 4.1. Secretion and assembly of the mucus layer [Seite 148]
8.4.2 - 4.2. Regulation of mucus production [Seite 148]
8.5 - 5. Epithelial Antimicrobial Proteins [Seite 150]
8.5.1 - 5.1. Epithelial antimicrobial protein families [Seite 151]
8.5.1.1 - 5.1.1. Defensins [Seite 151]
8.5.1.2 - 5.1.2. Lectins [Seite 152]
8.5.1.3 - 5.1.3. Cathelicidins [Seite 153]
8.5.1.4 - 5.1.4. Lysozyme and phospholipase A2 [Seite 154]
8.5.1.5 - 5.1.5. Lipocalin [Seite 154]
8.5.1.6 - 5.1.6. RNases [Seite 154]
8.5.2 - 5.2. Regulation of epithelial antimicrobial proteins [Seite 154]
8.5.2.1 - 5.2.1. Transcriptional regulation of epithelial antimicrobial protein expression [Seite 155]
8.5.2.2 - 5.2.2. Developmental regulation of antimicrobial protein expression [Seite 158]
8.5.2.3 - 5.2.3. Posttranslational regulation of antimicrobial protein function [Seite 158]
8.5.2.4 - 5.2.4. Regulation of antimicrobial protein secretion [Seite 159]
8.5.3 - 5.3. In vivo functions of epithelial antimicrobial proteins [Seite 159]
8.5.3.1 - 5.3.1. Protection against pathogens [Seite 160]
8.5.3.2 - 5.3.2. Shaping microbiota composition [Seite 161]
8.5.3.3 - 5.3.3. Limiting bacterial-epithelial cell contact [Seite 161]
8.6 - 6. Intestinal Epithelial Cell Autophagy [Seite 162]
8.6.1 - 6.1. Autophagy as a barrier to bacterial dissemination [Seite 162]
8.6.2 - 6.2. Autophagy-dependent regulation of protein secretion [Seite 163]
8.7 - 7. Epithelial Regulation of Adaptive Immunity [Seite 163]
8.7.1 - 7.1. Transcytosis of immunoglobulin A [Seite 164]
8.7.2 - 7.2. Cytokine secretion [Seite 165]
8.7.3 - 7.3. Antigen delivery to subepithelial immune cells [Seite 165]
8.8 - 8. Bacterial Stimulation of Epithelial Cell Repair [Seite 166]
8.8.1 - 8.1. MyD88-dependent epithelial repair [Seite 167]
8.8.2 - 8.2. Activation of epithelial repair by reactive oxygen species [Seite 168]
8.9 - 9. Epithelial Dysfunction in Inflammatory Disease [Seite 168]
8.10 - 10. Future Perspectives [Seite 170]
8.11 - Acknowledgments [Seite 171]
8.12 - References [Seite 171]
9 - Chapter 4: Innate Memory T cells [Seite 182]
9.1 - 1. Introduction [Seite 183]
9.2 - 2. Innate Memory T Cells Produced Through Response to Lymphopenia [Seite 185]
9.2.1 - 2.1. Identification of lymphopenia-induced memory T cells [Seite 185]
9.2.2 - 2.2. The role of TCR specificity on lymphopenia-induced innate memory T cell generation [Seite 188]
9.2.3 - 2.3. The role of IL-7 in lymphopenia-induced innate memory T cell generation [Seite 191]
9.2.4 - 2.4. Relationship between naïve T cell proliferation and generation of innate memory cells [Seite 193]
9.3 - 3. Innate Memory CD8+ T Cells Induced by IL-4 [Seite 194]
9.3.1 - 3.1. A subset of NKT cells produces IL-4 to induce innate memory CD8+ T cell differentiation [Seite 196]
9.3.2 - 3.2. Factors that regulate the generation of PLZF+ NKT cells and IL-4-induced memory CD8+ T cells [Seite 199]
9.3.3 - 3.3. Distinctions between IL-4- and lymphopenia-induced memory CD8+ T cells [Seite 203]
9.4 - 4. Innate Memory T Cells in Normal Homeostasis: ``Virtual Memory´´ T Cells [Seite 204]
9.5 - 5. The Role of Innate Memory T Cells in Immunity [Seite 207]
9.5.1 - 5.1. Functional properties of lymphopenia-induced memory cells [Seite 207]
9.5.2 - 5.2. Functional properties of IL-4-induced memory CD8+ T cells [Seite 209]
9.5.3 - 5.3. Functional properties of virtual memory CD8+ T cells [Seite 210]
9.6 - 6. Innate Memory Cells in Humans? [Seite 211]
9.7 - References [Seite 213]
10 - Index [Seite 224]
11 - Contents of Recent Volumes [Seite 230]
12 - Color Plate [Seite 246]
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: sgalli@stanford.edu

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...

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