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Advances in Immunology

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Contents

Contributors

Chapter One: Macrophages and Mitochondria: A Critical Interplay Between Metabolism, Signaling, and the Functional Activity

1. Introduction

2. Mitochondrial Metabolism Governs Macrophage Activation State

2.1. Metabolic Reprogramming in Proinflammatory Macrophages

2.2. Metabolic Profile in IL-4-Activated Macrophages

3. Mitochondrial ROS in Innate Immune Responses

3.1. mROS Are Crucial Components of Inflammatory Signaling Pathways

3.2. TLR Signaling Upregulates mROS Production

4. Mitochondrial-Mediated Antiviral Immunity

4.1. RIG-I-Like Receptors

4.2. Mitochondrial Antiviral Signaling

4.3. Proteins That Regulate MAVS Signaling

4.4. Mitochondrial Dynamics Regulate Antiviral Immunity

4.5. ROS Regulation of Antiviral Signaling

5. Inflammasome Activation and Mitochondria

5.1. The Mitochondrion Is a Scaffold for Inflammasome Activation

5.2. Mitochondrial Signals in Inflammasome Activation

5.3. Mitophagy Restrains Inflammasome Activation

6. Concluding Remarks

Acknowledgments

References

Chapter Two: Molecular Mechanisms of Somatic Hypermutation and Class Switch Recombination

1. Antibody Diversification During the Humoral Response

2. Molecular Mechanisms of SHM and CSR

2.1. Overview

2.2. Relevance for Humoral Immunity

3. DNA Deamination at the Igs

3.1. Activation-Induced Deaminase

3.2. Molecular Regulation of AID Activity

3.2.1. Biochemical Activity of AID

3.2.2. Limiting the Levels of AID in the Nucleus

3.3. Targeting AID to the Ig Loci

3.3.1. AID Piggybacks on Transcription to Access the DNA

3.3.2. The Ig Loci Contribute to AID Activity

3.3.3. Recruiting AID Activity to the Ig Locus Is a Team Effort

3.3.4. Contribution of RNA Processing to AID Targeting

3.4. Phosphorylation Focuses AID Activity to the Ig Locus

4. AID Initiates a DNA Repair Cascade

4.1. Detecting Uracil

4.2. The UNG and Base Excision Repair Arm

4.3. The MutSα-Initiated Arm

4.4. Interactions Between BER and MMR During Antibody Diversification

4.5. DNA Nicks and Breaks

4.6. Repairing the Breaks

5. Postdeamination Roles of AID?

6. Perspectives

Acknowledgments

References

Chapter Three: Emerging Major Histocompatibility Complex Class I-Related Functions of NLRC5

1. Background

2. Lessons From CIITA

2.1. CIITA: The Master Transcriptional Regulator of MHC Class II Genes

2.2. Transcriptional Regulation of CIITA

2.3. Transcriptional Regulation by CIITA

2.4. Transcriptional Targets of CIITA

3. NLRC5 and Its Role in Regulating MHC Class I Levels

3.1. Complex Transcriptional Regulation of MHC Class I Genes

3.2. NLRC5: A Transcriptional Regulator of MHC Class I Genes

3.3. NLRC5 vs CIITA: Similarities and Differences

3.4. CIITA: A Paradigm for NLRC5 Transcriptional Activity

3.5. Transcriptional Targets of NLRC5

3.6. NLRC5 Tunes MHC Class I Gene Transcription in Specific Tissues andConditions

4. NLRC5 and Its Emerging Roles in Health and Disease

4.1. Role of NLRC5 in CD8+ T Cell Selection and Maintenance

4.2. Role of NLRC5 in APCs

4.3. Further Considerations on the Role of NLRC5 in DCs

4.4. Role of NLRC5 in Infections

4.5. NLRC5 and Cancer

4.6. Further Considerations on the Role of NLRC5 in Cancer

5. Concluding Remarks

Acknowledgments

References

Chapter Four: Nucleic Acid Immunity

1. Introduction

2. Principles of Nucleic Acid Immunity in Different Species

3. Historic Overview of Different Fields Merging Into Nucleic Acid Immunity

4. Functional Components of Nucleic Acid Immunity

5. Innate and Adaptive Components in Nucleic Acid Immunity

6. Innate and Adaptive Nucleic Acid Immunity in Prokaryotes

7. Receptors and Nucleases Not Involving Classical Immune Functions

7.1. ADAR1

7.2. SAMHD1

7.3. PKR

7.4. IFIT1 and IFIT5

7.5. OAS

7.6. RNaseH

7.7. DNases

7.7.1. DNase I

7.7.2. DNase II

7.7.3. DNase III/Trex1

8. RNA Interference

9. Immune-Sensing Receptors

9.1. TLR3

9.2. TLR7 and TLR8

9.3. TLR9

9.4. RIG-I

9.5. MDA5 and LGP2

9.6. AIM2

9.7. cGAS/Sting

10. Conclusions

Acknowledgments

References

Chapter Five: About Training and Memory: NK-Cell Adaptation to Viral Infections

1. Introduction

1.1. NK-Cell Recognition Repertoire

1.2. Role of NK Cells in the Defense Against Viral Infections

2. NK-Cell Adaptations to Viral Infections

2.1. Skewing and Adaptation of NK-Cell Subsets After MCMV Infection

2.2. Skewing and Adaptation of NK-Cell Subsets After HCMV Infection

3. Functional Imprinting of Adaptive NK Cells

3.1. Functional Properties of MCMV-Induced Memory Ly49H+ NK Cells

3.2. Functional Properties of HCMV-Induced Adaptive NKG2C+ NK Cells

4. Epigenetic Remodeling as Hallmark of Immune Training and Memory

4.1. Epigenetic Imprinting of Human Adaptive NK Cells

4.2. Possible Role of Epigenetic Remodeling for NK-Cell Memory in MCMV

5. Training and Cross-Reactive Memory: Consequences for Heterologous Immunity

5.1. NK-Cell Training and Responses to Heterologous Pathogens

5.2. NK-Cell Cross-Reactive Memory and Heterologous Immunity

6. Outlook and Outstanding Questions

Acknowledgments

References

Index

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