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Antibody Fc
Linking Adaptive and Innate Immunity
- 1st Edition - August 6, 2013
- Editors: Margaret Ackerman, Falk Nimmerjahn
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 3 9 4 8 0 2 - 1
- eBook ISBN:9 7 8 - 0 - 1 2 - 3 9 4 8 1 8 - 2
Antibody Fc is the first single text to synthesize the literature on the mechanisms underlying the dramatic variability of antibodies to influence the immune response. The book… Read more
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Request a sales quoteAntibody Fc is the first single text to synthesize the literature on the mechanisms underlying the dramatic variability of antibodies to influence the immune response. The book demonstrates the importance of the Fc domain, including protective mechanisms, effector cell types, genetic data, and variability in Fc domain function. This volume is a critical single-source reference for researchers in vaccine discovery, immunologists, microbiologists, oncologists and protein engineers as well as graduate students in immunology and vaccinology.
Antibodies represent the correlate of protection for numerous vaccines and are the most rapidly growing class of drugs, with applications ranging from cancer and infectious disease to autoimmunity. Researchers have long understood the variable domain of antibodies, which are responsible for antigen recognition, and can provide protection by blocking the function of their target antigen. However, recent developments in our understanding of the protection mediated by antibodies have highlighted the critical nature of the antibody constant, or Fc domain, in the biological activity of antibodies. The Fc domain allows antibodies to link the adaptive and innate immune systems, providing specificity to a wide range of innate effector cells. In addition, they provide a feedback loop to regulate the character of the immune response via interactions with B cells and antigen-presenting cells.
- Clarifies the different mechanisms of IgG activity at the level of the different model systems used, including human genetic, mouse, and in vitro
- Covers the role of antibodies in cancer, infectious disease, and autoimmunity and in the setting of monoclonal antibody therapy as well as naturally raised antibodies
- Color illustrations enhance explanations of the immune system
vaccinologists, immunologists, microbiologists, oncologists, protein engineers, in academic and industrial research institutions; graduate students in immunology and vaccinology.
List of Contributors
1: Effector Mechanisms
Chapter 1. Antibody-Dependent Cellular Cytotoxicity (ADCC)
Brief History of ADCC
Effector Cells
Receptors Involved
Mechanisms of ADCC
ADCC in Monoclonal Antibody Therapy of Cancer
ADCC in Infectious Disease: A Correlate of Protection?
Rational Modification of ADCC Activity
Enhancing the Link between ADCC and Adaptive Immunity
Perspectives: Future Directions
Acknowledgments
References
Chapter 2. Antibody-Dependent Cellular Phagocytosis and Its Impact on Pathogen Control
Introduction
Phagocytic Cells and Their Fcγ Receptors
Fcγ Receptor-Mediated Phagocytosis by Phagocytes
Role of FcγR-Mediated Phagocytosis for Pathogen Uptake, Cellular Localization, and Pathogen Control
Concluding Remarks
References
Chapter 3. Interactions Between the Complement System and Fcγ Receptors
Preliminary Comments
Complement Fragment C3b Mediates Binding of IgG Immune Complexes to Primate Erythrocytes: Immune Adherence
Complement Fragment C3d Mediates Binding of Substrates to CR2 on B Cells: Antigen Trafficking and its Significance in HIV Disease
Cooperation/Synergy between Fcγ Receptors and Complement Receptors on Effector Cells
Cross-Talk between the C5a Receptor and FcγR on Effector Cells
Concluding Remarks
Abbreviations
References
2: Effector Cells
Chapter 4. Natural Killer Cells
Inhibitory Receptor Modules Inform a Useful and Self-Tolerant NK Cell Repertoire
Activating Immunoreceptors Mediate NK Cell Recognition of Tumors and Infected Cells
Adaptive Features of NK Cells
References
Chapter 5. Phagocytes and Immunoglobulins
Antibodies in the Context of Innate and Acquired Immune Recognition
General Characteristics of Mononuclear Phagocytes: Macrophages, Monocytes, and Dendritic Cells
General Characteristics of Granulocytes
Opsonic and Non-Opsonic Recognition in Phagocytes
Non-Opsonic Recognition: Pattern Recognition Receptors
Phagocyte Activation in Response to Non-Opsonic Recognition
Opsonic Recognition: FcRs and Complement Receptors
Phagocyte Cooperation During Inflammation
Phagocytosis
Antigen Presentation by DCs, Role of FcγRs
Collaboration Between FcR and Non-Opsonic Receptors
Concluding Remarks
References
Chapter 6. B Cells: Development, Differentiation, and Regulation by Fcγ Receptor IIB in the Humoral Immune Response
B Cell Development and Selection in the Bone Marrow
B Cell Selection, Activation, and Tolerance in the Peripheral Immune System
Generation of Plasma Cells and Memory B Cells in the Germinal Center
FcγRIIB Regulates B-Cell Activation and Apoptosis
FcγRIIB Inhibits Autoantibody Production
FcγRIIB as a Regulator of Long-Term Survival of Plasma Cells in the Bone Marrow
References
3: FcR
Chapter 7. Structural Recognition of Immunoglobulins by Fcγ Receptors
Introduction
Structures of Fcγ Receptors
Structure of the IgG Fc Domain
Structure of FcγRIII–Fc Complex
FcγRIII–Fc Binding Interface
FcγR Specificities for IgG Subclasses
Fc Receptor Isoform Affinities to IgG
Influence of FcR Polymorphism on IgG Recognition
Role of Fc Glycosylation in the Recognition of Antibodies by Fcγ Receptors
Recognition of Fc Receptors by Pentraxins
Conclusions
References
Chapter 8. FcγRs Across Species
Introduction
Human FcγRs
Mouse FcγRs
Human Versus Mouse FcγRs
Macaque FcγRs
Human Versus Macaque FcγRs
Conclusions
Acknowledgments
References
4: Variability of the Fc Domain
Chapter 9. Human IgG Subclasses
Introduction: Immunoglobulins and Humoral Immunity
Genetics
Structure–
Binding to Effector Molecules
IgG Antibody Responses
Therapeutic Considerations
Acknowledgment
References
Chapter 10. Antibody Glycosylation
Human Antibody: An Overview of Structure and Function
Human IgG Fc Structure and Function
Human IgG Fc Glycosylation
Role of IgG Fc Glycosylation in Fc Structure
Activities of IgG Glycoforms
Glycan Engineering of Antibodies
Endoglycosidases in Immune Evasion and Therapeutics
Variations of Antibody Glycosylation in Disease
Conclusion and Perspectives
References
5: Genetic Associations
Chapter 11. Activating and Inhibitory FcγRs in Autoimmune Disorders
Introduction
A Question of Balance: Co-expression of Activating and Inhibitory Fc Receptors
Establishing the Threshold for Cell Activation: Activating and Inhibitory Fc Receptor Signaling
Signaling Pathways of Activating Fc Receptors
Inhibitory Signaling Pathways
Disturbing the Threshold: Horror Autotoxicus
Changing the Expression Level of the Inhibitory Receptor on B Cells
FcγRIIB as a Regulator of Dendritic Cell Activity
The Role of FcγRIIB in the Efferent Response: Controlling Innate Immune Effector Cell Activation
The Activating Fc Receptors in the Efferent Response
Exogenous Factors Modulating the Balance: Cytokines and Sugar
Regaining the Balance: Therapeutic Interventions that Modulate FcR Expression
Conclusions
Acknowledgments
References
Chapter 12. Fcγ Receptor Polymorphisms and Susceptibility to Infection
Introduction
The Fcγ Receptor Family Genes
FcγR Distribution and Function
Genetic Variation in Human FcγRs
FcγRs and Infection: Evidence Base
FcγRs and Defense Against Infection
Conclusions
Acknowledgments and Funding
References
Chapter 13. Role of IgG Fc Receptors in Monoclonal Antibody Therapy of Cancer
Mechanisms of Action of Monoclonal Antibodies in Oncology
Development of Therapeutic Monoclonal Antibodies for the Treatment of Cancer
Fc-Mediated Effector Functions, Preclinical Data
Role for FcγR-Mediated Effector Functions, Clinical Data
Polymorphisms in FcγRs
Impact of FcγR Polymorphisms on mAb Treatment, Preclinical in Vitro Data
Impact of FcγR Polymorphisms in mAb Treatment, Clinical Data
Opportunities to Enhance FcγR-Mediated Effector Functions
Future Perspectives
References
6: Evolving Areas
Chapter 14. No Mechanism is an Island: Interactions Among Monoclonal Antibody Mechanisms of Action
Introduction
In Vitro Analysis
Animal Models
Clinical Trials
Individual Mechanisms of Action
Interacting Mechanisms
Conclusion
References
Chapter 15. Fc Receptor-Dependent Immunity
Fc Receptors and Signaling Mechanisms in Immune Effector Cells
Contribution of FcR-Mediated Immune Effector Functions of Antibodies to Protective Acquired Immunity
The Immune Effector Mechanisms of FcR-Dependent Functional Processes and their Applications in Immunotherapy and Immunomodulation
Acknowledgments
References
Chapter 16. Fcγ Receptors as Therapeutic Targets
Introduction
The A/I Ratio
Fc Glycan Control of FcγR Interactions
Activating and Inhibitory FcγR Expression
Anti-Inflammatory IgG Modulates FcγR Expression
FcγR Regulation During Autoimmune Disease
FcγR Regulation During Infection
FcγR Regulation During Cancer
Engineering IgG Immune Responses
Targeting Fcs to FcγRs
Engineering the Fc Peptide Backbone
Outlook and Perspectives
References
Chapter 17. Fc Protein Engineering
Introduction
The IgG Subclasses
IgG-Fc Binding Ligand: An Overview
Evaluation of IgG-Fc Engineered Proteins
IgG1 and IgG3 Binding and Activation of FcγR
IgG2 Binding and Activation of FcγR
IgG4 Binding and Activation of FcγR
The Neonatal Receptor FcγRn: Transcytosis and Catabolism
Classical Pathway of Complement Activation
Immunogenicity and Adverse Events
Human IgG-Fc Binding Ligands in Nature
Concluding Remarks
References
Chapter 18. Bacterial Modulation of Fc Effector Functions
Introduction
Immunoglobulin-Binding Proteins
Immunoglobulin Proteases
Immunoglobulin Glycan Hydrolases
Concluding Remarks
Acknowledgments
References
Chapter 19. Pathogenic Exploitation of Fc Activity
Introduction
ADE in Viruses
ADE in Protozoan Parasites of Macrophages: Leishmania
ADE in Other Intracellular Parasites and Bacteria
Concluding Thoughts
References
Chapter 20. Mechanisms of Immunoglobulin-Mediated Mucus Entrapment of Pathogens at Various Mucosal Surfaces
Introduction
Structure of Mucus
Mechanisms of Immunity at Mucosal Surfaces
Summary
Acknowledgments
References
Index
- No. of pages: 358
- Language: English
- Edition: 1
- Published: August 6, 2013
- Imprint: Academic Press
- Hardback ISBN: 9780123948021
- eBook ISBN: 9780123948182
MA
Margaret Ackerman
Margaret E. Ackerman studied molecular engineering at the Massachusetts Institute of Technology under K. Dane Wittrup, followed by postdoctoral studies at the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University under Galit Alter. She was appointed an Assistant Professor of Engineering at Dartmouth College’s Thayer School of Engineering in 2011, and an Assistant Professor in the Department of Microbiology and Immunology at Dartmouth’s Geisel School of Medicine in 2012. Her research group applies protein engineering, molecular biology, and mathematical modelling tools to design enhanced antibody therapeutics and and vaccines.
Affiliations and expertise
Thayer School of Engineering, Dartmouth College
Department of Microbiology and Immunology, Geisel School of MedicineFN
Falk Nimmerjahn
Falk Nimmerjahn studied Biology at the Universities of Bayreuth, Erlangen-Nuernberg and Munich in Germany. After his postdoctoral studies in the laboratory of Jeffrey Ravetch at the Rockefeller University in New York from 2004-2007, he was appointed as an Associate Professor at the University Hospital of Erlangen in 2007. Since 2010 he has been a full Professor of genetics and chairman of the Institute of Genetics at the University of Erlangen-Nuernberg in the Department of Biology. His research focuses on understanding the molecular and cellular mechanisms of mouse and human IgG activity. He authored more than 80 peer reviewed papers and several chapters in text books. For his work on immunoglobulin activity he was awarded several prizes, among them the Paul-Ehrlich and Ludwig Darmstädter Award for young scientists.
Affiliations and expertise
Institute of Genetics, Department of Biology, University of Erlangen-NürnbergRead Antibody Fc on ScienceDirect