Antigen Presenting Cells,9783527311088

Antigen Presenting Cells

by ;
ISBN13: 9783527311088
ISBN10: 3527311084
Format: Hardcover
Pub. Date: 2005-12-01
Publisher(s): Blackwell Pub
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Summary

This novel, multidisciplinary handbook highlights recent evidence that antigen presenting cells (APCs) are not only key players in the initiation or prevention of an antigen-specific T lymphocyte-mediated adaptive immune response, but also critical regulators and integrators in the interplay between our innate and adaptive immune system. Structured in a clear way to allow access to a very broad readership, the book is written from the viewpoint of a biochemist, immunologist, and scientist with experience in drug development. It covers all cell types involved in antigen presentation, providing the latest immunological facts with a focus on drug development. Backed by a glossary explaining all important technical terms, this short but comprehensive reference covers basic introductory aspects right up to details for advanced specialists.

Author Biography

Born in 1962, <b>Harald Kropshofer</b> gained his PhD in 1993 from the University of T&amp;uuml;bingen. He subsequently did his post-doc at the German Cancer Research Center, Heidelberg, before becoming senior scientist and group leader there in 1997. In 2000 he gained his lecturing qualification at the University of Heidelberg and in the same year joined the Basel Institute for Immunology as the Group leader in Antigen Presentation. He has been working at F. Hoffmann-La Roche, Basel, since 2002, where he is currently Head of Applied Immunology.<br> Dr. Kropshofer is a recipient of, among others, the Otto-Westphal Award from the German Society for Immunology, the Robert-Koch Award for Postdoctoral Scientists, and the Georges-Koehler Award from the German Society for Immunology. He has filed three patents, and has around fifty publications to his name.<br> <br> Born in 1967, <b>Anne Barbara Vogt</b> gained her doctorate in 1995 from the University of T&amp;uuml;bingen, before doing her post-doc at the German Cancer Research Center, Heidelberg. From 2000 to 2001, she was Group leader at the Basel Institute for Immunology, joining F. Hoffmann-La Roche in 2002, where she is currently Group leader at the Roche Center for Medical Genomics. Dr. Vogt is the recipient of several fellowships and of the Langener Wissenschaftspreis from the Paul-Ehrlich Institute and the Georges-Koehler Award, given by the German Society for Immunology. She has filed three patents, and has some 40 publications to her name.

Table of Contents

Preface xv
List of Contributors
xix
List of Abbreviations
xxiii
Color Plates xxvii
Part I Antigen Presentation in the Immune System
1(24)
Some Old and Some New Findings on Antigen Processing and Presentation
3(22)
Emil R. Unanue
Introduction
3(1)
HEL Processing
4(5)
Selection of Peptide Segments of HEL
9(2)
HEL: Conformational Isomers
11(5)
Biology of Type B T Cells
15(1)
Negative Selection and Peripheral Activation to HEL Peptides
16(1)
Response to HEL Immunization in the Draining Lymph Node
17(8)
Part II Molecular Mechanisms of Antigen Processing
25(132)
Antigen Entry Routes -- Where Foreign Invaders Meet Antigen Presenting Cells
27(24)
Percy A. Knolle
Introduction
27(1)
Antigen Entry via the Gastrointestinal Tract
28(7)
Peyer's Patches
29(1)
Mesenteric Lymph Node
30(1)
Dendritic Cells of the Lamina Propria
31(2)
Pathogens Target Intestinal Antigen Presenting Cells
33(2)
Antigen Entry via the Skin
35(3)
Systemic Dissemination of Antigens/Infectious Microorganisms
38(1)
Antigen Presenting Cells in the Liver
39(5)
Dendritic Cells
39(2)
Kupffer Cells
41(1)
Liver Sinusoidal Endothelial Cells
42(2)
Conclusion
44(7)
Antigen Processing in the Context of MHC Class I Molecules
51(38)
Frank Momburg
Tracing the Needle in the Haystack: The Efficiency of Antigen Processing and Presentation by MHC Class I Molecules
51(2)
The ``Classical'' Route: Loading of MHC Class I Molecules With Peptides Generated in the Cytoplasm
53(7)
Cytosolic Peptide Processing by Proteasomes and other Proteases
53(3)
Structure and Function of the Proteasomal Core and Interferon-induced Subunits
56(1)
Targeting Proteins for ATP-dependent Degradation by 26S Proteasomes
56(1)
Cleavage Properties of (Immuno)Proteasomes
57(2)
Peptide Processing by Nonproteasomal Cytosolic Peptidases
59(1)
Crossing the Border -- Peptide Translocation into the ER by TAP
60(3)
Structure and Function of TAP
60(2)
Substrate Specificity of TAP
62(1)
TAP-independent Peptide Entry into the ER
63(1)
Fitting in the Best: TAP-associated Peptide Loading Complex Optimizes MHC-I Peptide Binding
63(7)
Structure of MHC-I Molecules
64(1)
Early Steps in the Maturation of MHC-I Molecules
64(2)
Structure and Molecular Interactions of Tapasin
66(1)
Optimization of Peptide Loading in the TAP-associated Loading Complex
67(3)
On the Way Out: MHC-I Antigen Processing along the Secretory Route
70(3)
Closing the Circle -- Cross-presentation of Endocytosed Antigens by MHC-I Molecules
73(16)
Phagosome-to-cytosol Pathway of MHC-I Peptide Loading
73(3)
Endolysosomal Pathway of MHC-I Peptide Loading
76(13)
Antigen Processing for MHC Class II
89(40)
Anne B. Vogt
Corinne Ploix
Harald Kropshofer
Introduction
89(1)
Types of Antigen Presenting Cells
90(3)
Macrophages, B Lymphocytes and DCs
90(1)
Tissue-resident APCs
91(1)
Maturation State of APCs
92(1)
Immature APCs
92(1)
Mature APCs
92(1)
Antigen Uptake by APCs
93(4)
Macropinocytosis
93(1)
Phagocytosis
94(1)
Receptors for Endocytosis
95(2)
Generation of Antigenic Peptides
97(5)
Reduction of Disulfide Bonds: GILT
97(1)
Regulation of the Proteolytic Milieu
98(1)
Protease/MHC Interplay in Antigen Processing
99(3)
Assembly of MHC II Molecules
102(7)
Structural Requirements of MHC II
102(1)
Biosynthesis of MHC II
103(1)
Chaperones for Peptide Loading
104(1)
HLA-DM/H2-DM
104(3)
HLA-DO/H2-DO
107(2)
Export of MHC II and Organization on the Cell Surface
109(5)
Membrane Microdomains
109(3)
Tubular Transport
112(2)
Viral and Bacterial Interference
114(2)
Concluding Remarks
116(13)
Antigen Processing and Presentation by CD1 Family Proteins
129(28)
Steven A. Porcelli
D. Branch Moody
Introduction
129(1)
CD1 Genes and Classification of CD1 Proteins
129(1)
Structure and Biosynthesis of CD1 Proteins
130(6)
Three-dimensional (3D) Structures of CD1 Proteins
132(1)
Molecular Features of CD1--Lipid Complexes
133(2)
CD1 Pockets and Portals
135(1)
Foreign Lipid Antigens Presented by Group 1 CD1
136(1)
Self Lipid Antigens Presented by CD1
137(1)
Group 2 CD1-restricted T Cells
138(2)
Antigens Recognized by Group 2 CD1-restricted T Cells
139(1)
Tissue Distribution of CD1 Proteins
140(1)
Subcellular Distribution and Intracellular Trafficking of CD1
140(6)
Trafficking and Localization of CD1a
141(1)
Trafficking and Localization of CD1b
141(2)
Trafficking and Localization of CD1c
143(1)
Trafficking and Localization of CD1d
144(1)
Trafficking and Localization of CD1e
145(1)
Antigen Uptake, Processing and Loading in the CD1 Pathway
146(4)
Cellular Uptake of CD1-presented Antigens
146(1)
Endosomal Processing of CD1-presented Antigens
147(1)
Accessory Molecules for Endosomal Lipid Loading of CD1
148(1)
Non-endosomal Loading of Lipids onto CD1 Molecules
149(1)
Conclusions
150(7)
Part III Antigen Presenting Cells' Ligands Recognized by T- and Toll-like Receptors
157(88)
Naturally Processed Self-peptides of MHC Molecules
159(40)
Harald Kropshofer
Sebastian Spindeldreher
Introduction
159(1)
Milestone Events
160(12)
Nomenclature
160(1)
Autologous Peptides
160(1)
Endogenous Peptides
161(1)
Natural Peptides Ex Vivo and In Vitro
161(1)
Extra Electron Density Associated to MHC Molecules
162(1)
Acidic Peptide Elution Approach
163(2)
First Natural Foreign Peptides on MHC Class II
165(1)
First Natural Viral Epitopes on MHC Class I
165(1)
Self-peptide Sequencing on MHC Class I: the First Anchor Motifs
166(1)
First Murine MHC Class II-associated Self-peptides: Nested Sets
167(2)
First Human MHC Class II-bound Self-peptides: Hydrophobic Motifs
169(3)
Progress in Sequence Analysis of Natural Peptides
172(5)
Edman Microsequencing
172(1)
Electrospray Ionization Tandem Mass Spectrometry
173(2)
Automated Tandem Mass Spectrometry
175(1)
MAPPs: MHC-associated Peptide Proteomics
176(1)
Natural Class II MHC-associated Peptides from Different Tissues and Cell-types
177(6)
Peripheral Blood Mononuclear Cells
177(1)
Myeloid Dendritic Cells
178(1)
Medullary Thymic Epithelial Cells
179(2)
Splenic APCs
181(1)
Tumor Cells
181(1)
Autoimmunity-related Epithelial Cells
182(1)
The CLIP Story
183(6)
CLIP in APCs Lacking HLA-DM
184(1)
Flanking Residues and Self-release of CLIP
184(1)
CLIP in Tetraspan Microdomains
185(3)
CLIP as an Antagonist of TH1 Cells
188(1)
Outlook: Natural Peptides as Diagnostic or Therapeutic Tools
189(10)
Target Cell Contributions to Cytotoxic T Cell Sensitivity
199(22)
Tatiana Lebdeva
Michael L. Dustin
Yuri Sykulev
Introduction
199(1)
Intercellular Adhesion Molecule 1 (ICAM-1)
200(8)
Adhesion Molecules on the Surface of APC and Target Cells
200(1)
ICAM-1 Structure and Topology on the Cell Surface
200(1)
ICAM-1 as Co-stimulatory Ligand and Receptor
201(2)
ICAM-1-mediated Signaling
203(3)
Role of ICAM-1 in Endothelial Response to Leukocytes
206(1)
ICAM-1 Association with Lipid Rafts
206(2)
Major Histocompatability Complex (MHC)
208(7)
MHC Molecules
208(1)
Molecular Associations of MHC-I Molecules
208(3)
Association of MHC-I and ICAM-1
211(1)
Could APC and Target Cells Play an Active Role in Ag Presentation?
212(1)
Identical pMHCs are Clustered in the Same Microdomain
212(1)
Identical pMHC can be Recruited to the Same Microdomain During Target Cell-T Cell Interaction
213(1)
Co-clustering of MHC and Accessory Molecules
213(1)
Role of Cytoskeleton
214(1)
Conclusion
215(6)
Stimulation of Antigen Presenting Cells: from Classical Adjuvants to Toll-like Receptor (TLR) Ligands
221(24)
Martin F. Bachmann
Annette Oxenius
Synopsis
221(1)
Pathogen-associated Features that Drive Efficient Immune Responses
221(1)
Composition and Function of Adjuvants
222(2)
TLR Protein Family in Mammals
224(6)
TLR4
226(1)
TLR2
227(1)
TLR5
227(1)
TLR11
228(1)
TLR12 and TLR13
228(1)
Nucleic Acids as PAMPs
228(1)
TLR3
228(1)
TLR7 and TLR8
229(1)
TLR9
229(1)
Compartmentalization of Sensing Renders the Nucleic Acid PAMPs
229(1)
TLR Signaling
230(3)
Signal Transduction Across the Membrane
231(1)
MyD88-dependent Pathways
231(1)
MyD88-independent Pathways
232(1)
TLR-independent Recognition of PAMPs: Nods, PKR and Dectin-1
233(2)
Nods
233(1)
PKR (IFN-inducible dsRNA-dependent Protein Kinase)
234(1)
Dectin-1
234(1)
Therapeutic Potential of TLRs and their Ligands
235(2)
Conclusion
237(8)
Part IV The Repertoire of Antigen Presenting Cells
245(294)
Evolution and Diversity of Macrophages
247(84)
Nicholas S. Stoy
Evolution of Macrophages: Immunity without Antigen Presentation
247(10)
Introduction
247(1)
Drosophila: a Window into Innate Immunity
247(8)
Evolution of Adaptive Immunity: Macrophages in a New Context
255(2)
Diversity of Macrophages in Mammalian Tissues
257(74)
Classifying Heterogeneity
257(1)
Phenotypic Manipulations and Transdifferentiations: Routes to and from Macrophages
258(4)
Function-related `Markers' in Macrophages and DCs
262(4)
Macrophage Phenotypic Diversity in Response to Microbial Challenge
266(17)
Interactions between Tissue Microenvironments and Macrophages Generate Diversity
283(9)
Sequential and Regulatory Changes in Macrophage Phenotypes: Limiting Pro- and Antiinflammatory Responses
292(1)
Pre-TLR and TLR Regulation of Immune Responses
293(1)
Signal Transduction in the Regulation of Immune Responses
294(5)
Regulation of Immune Responses by Cytokines and other Bioactive Molecules
299(1)
Regulation of Immune Responses by Decoys
300(1)
Regulation of Immune Responses by the Adaptive Immune System
300(1)
Regulation of Immune Responses by Apoptosis
301(1)
Interaction of Regulatory Mechanisms during Immune Responses
301(1)
Macrophage Diversity: an Overview
302(29)
Macrophages--Balancing Tolerance and Immunity
331(84)
Nicholas S. Stoy
Balancing Tolerance and Immunity
331(25)
Introduction
331(1)
Macrophage Phenotypes: Effects on Immunity and Tolerance
332(2)
Concept of Innate (Peripheral) Tolerance
334(1)
Concept of Adaptive Tolerance
335(7)
Innate Tolerance: Receptors, Responses and Mechanisms
342(7)
Incorporating NK and NT Cells into the Innate Tolerance/Innate Immunity Paradigm
349(5)
Definitions and Terminology
354(2)
Ramifications of the Paradigm: Asthma
356(6)
Ramifications of the Paradigm: Autoimmunity
362(16)
Summary and Conclusions: Towards Immune System Modeling and Therapeutics
378(37)
Polymorphonuclear Neutrophils as Antigen-presenting Cells
415(26)
Amit R. Ashtekar
Bhaskar Saha
Introduction
415(2)
PMN as Antigen-presenting Cells
417(17)
Basic Criteria of an APC for T Cells
417(1)
Acquisition of Antigens
418(2)
Antigen Processing
420(4)
Expression of MHC Class I/II and Co-stimulatory Molecules
424(3)
Delivery of Second Signal
427(3)
Alteration in Cytokine Milieu
430(4)
Evolution of Newer Thoughts as PMN March to a Newer Horizon
434(7)
Microglia - The Professional Antigen-presenting Cells of the CNS?
441(20)
Monica J. Carson
Introduction: Microglia and CNS Immune Privilege
441(3)
What are Microglia?
441(1)
Is Immune Privilege Equivalent to Immune Isolation?
442(2)
Do Microglia Differ from Other Macrophage Populations?
444(4)
Microglia are Likely of Mesodermal Origin
444(1)
Parenchymal Microglia are not the only Myeloid Cells in the CNS
444(1)
In Contrast to other Macrophages, Parenchymal Microglia are not Readily Replaced by Bone Marrow Stem Cells
444(2)
Microglia Display Stable Differences in Gene Expression that Distinguish them from Other Macrophage Populations
446(1)
Morphology is not a Reliable Parameter to Differentiate Microglia from Other Macrophage Populations
447(1)
To What Extent is Microglial Phenotype Determined by the CNS Microenvironment?
448(1)
Microglia versus Macrophages/Dendritic Cells as Professional Antigen-presenting Cells
449(5)
In vitro and Ex Vivo Assays of Antigen-presentation
449(1)
Culture Conditions can have Profound Effects on Microglia Effector Functions as Assayed In Vitro
450(1)
In Vivo Assays of Antigen-presentation
451(1)
Antigen-presentation by Microglia is Necessary to Evoke or Sustain Neuroprotective T Cell Effector Function
451(2)
Why were Microglia Unable to Initiate Protective T Cell Responses?
453(1)
TREM-2 Positive Microglia may Represent Subsets Predisposed to Differentiate into Effective Antigen-presenting Cells
454(2)
Are Microglia the ``Professional Antigen-presenting Cell of the CNS?''
456(5)
Contribution of B Cells to Autoimmune Pathogenesis
461(42)
Thomas Dorner
Peter E. Lipsky
Introduction
461(2)
Autoimmunity and Immune Deficiency
463(9)
Basic Mechanisms Providing Diversity to the B Cell Receptor
463(2)
Ig V Gene Usage by B Cells of Healthy Individuals
465(1)
Potential Abnormalities in Molecular Mechanisms Underlying IgV Gene Usage in Systemic Autoimmune Diseases
465(1)
Lack of Molecular Differences in V(D)J Recombination in Patients with Systemic Autoimmune Diseases
466(1)
Receptor Editing/Revision and Autoimmunity
467(2)
Selective Influences Shaping the Ig V Gene Repertoire in Autoimmune Diseases
469(1)
IgV Gene Usage by Autoantibodies
469(1)
Role of Somatic Hypermutation in Generating Autoantibodies
470(2)
Disturbed Homeostasis of Peripheral B Cells in Autoimmune Diseases
472(1)
Signal Transduction Pathways in B Cells
473(9)
B Cell Function Results from Balanced Agonistic and Antagonistic Signals
474(1)
Altered B Cell Longevity can Lead to Autoimmunity
474(2)
Altered B Cell Activation can Lead to Autoimmunity
476(1)
Inhibitory Receptors of B Cells
477(3)
Inhibitory Receptor Pathways and Autoimmunity
480(2)
B Cell Abnormalities Leading to Rheumatoid Arthritis
482(5)
Activated B Cells may Bridge the Innate and Adaptive Immune System
483(1)
``Humoral Imprinting'' in Rheumatoid Arthritis
484(1)
Indications of Enhanced B Cell Activity in RA
485(1)
T Cell Independent B Cell Activation
486(1)
Depleting anti-B Cell Therapy as a Novel Therapeutic Strategy
487(16)
Dendritic Cells (DCs) in Immunity and Maintenance of Tolerance
503(20)
Magali de Heusch
Guillaume Oldenhove
Muriel Moser
Introduction
503(1)
Dendritic Family
503(1)
DCs at Various Stages of Maturation
504(1)
Immature DCs
505(1)
Homing of DCs into Secondary Lymphoid Organs
505(2)
DCs as Adjuvants
507(1)
DC Subsets
508(1)
Classical DCs
508(1)
Plasmacytoid DCs
508(1)
DCs in T Cell Polarization
509(1)
Tolerogenic DC
510(2)
Mechanisms of Tolerance
512(2)
Lack of Co-stimulation
512(1)
Peripheral Deletion of Autoreactive T Cells
512(1)
Dynamics of Cellular Contacts
512(1)
Induction of Regulatory T Cells
513(1)
CD28-B7 Bidirectional Signaling
514(1)
Crosspriming
515(1)
Cross-presentation and Cross-tolerization
515(1)
DC as Regulators of T Cell Recirculation
516(1)
DC-based Immunotherapy of Cancer
517(1)
Conclusion
517(6)
Thymic Dendritic Cells
523(16)
Kenneth Shortman
Li Wu
Thymic Dendritic Cells
523(1)
Localisation and Isolation of Thymic DC
523(1)
Pickup of Antigens by Thymic DC
524(1)
Subtypes of Thymic DC
525(1)
Major Thymic cDC Population
525(1)
Minor Thymic cDC Population
526(1)
Thymic pDC
527(1)
Maturation State and Antigen Processing Capacity of Thymic DC
527(1)
Cytokine Production by Thymic DC
528(1)
DC of the Human Thymus
529(1)
Turnover Rate and Lifespan of the Thymic DC
530(1)
Endogenous versus Exogenous Sources of Thymic DC
530(1)
Lineage Relationship and Differentiation Pathways of Thymic cDC
531(1)
Lineage Relationships and Developmental Pathways of Thymic pDC
532(1)
Thymic cDC do not Mediate Positive Selection
533(1)
Thymic cDC and Negative Selection
533(2)
Role of pDC in the Thymus
535(4)
Part V Antigen Presenting Cell-based Drug Development
539(46)
Antigen Presenting Cells as Drug Targets
541(44)
Siquan Sun
Robin Thurmond
Lars Karlsson
Introduction
541(1)
Roles of DC in disease
542(2)
Transplantation
542(1)
Autoimmune Diseases
542(1)
Allergy/Asthma
543(1)
Cancer
543(1)
Marketed Drugs Affecting APC function
544(3)
New Potential APC Drug Targets
547(14)
APC Activation
547(3)
Antigen Presentation
550(3)
Co-stimulation
553(2)
Cell Adhesion
555(2)
APC Chemotaxis
557(1)
APC Survival
558(1)
Intracellular Signaling
559(1)
APC Depletion
560(1)
APC per se as Drugs -- DC-based Immunotherapy Therapy
561(3)
DC-based Cancer Vaccines
561(1)
Targeting and Activating DC In Vivo
562(1)
DC-based Immunotherapy for Transplantation and Autoimmune Diseases
563(1)
Conclusion
564(21)
Glossary 585(14)
Index 599

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