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An Interplay of Cellular and Molecular Components of Immunology

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Our immune system defends us against infection by employing multiple lines of defense. The relevance of the immune response in human health, disease prevention, and vaccinations becomes evident when the immune system is compromised as in the case of pathogenic infections or autoimmune diseases. The reader will gain a fundamental understanding of the essential principles of immunology, such as how our immune system recognizes/fights infectious agents, how our body differentiates between foreign and self-cells/molecules, and how the memory from previous infections aids in a faster and more effective immune response. The book is divided into 17 chapters, providing an overview of the immune system and its components, including its organs and cells. Chapters on the major histocompatibility complex, the complement system, hypersensitivity and tolerance, antibody diversity through DNA rearrangements, and autoimmune diseases are included in the book which further broadens the understanding of this very complex system of our body. Chapters on transplantation immunology and vaccines provide a perspective on the application of these immunological concepts and will be of great interest to readers.

Key features of the book:

    • Simple, direct, and lucid language

    • Comprehensive coverage of concepts for better understanding

    • Well-labeled illustrations, flowcharts, and tables for enhanced learning

    • Every chapter is followed up with a detailed summary and questionnaire

    • A detailed glossary for users to know the right words

    • Chapters contributed/reviewed by experienced experts in this field

    The book provides broad, accessible, and up-to-date information about immunological perspectives to biotechnologists, biomedical scientists, biochemists, molecular biologists, and students from various streams of life sciences, including zoology, biotechnology, and microbiology, as well as instant access to a wealth of information.

    Author(s): Indrakant Kumar Singh, Poonam Sharma
    Publisher: CRC Press
    Year: 2022

    Language: English
    Pages: 375
    City: Boca Raton

    Cover
    Half Title
    Title Page
    Copyright Page
    Contents
    Preface
    Contributors
    Glossary
    Editors
    Abbreviations
    Chapter 1 Overview of Immune System
    1.1 Introduction and Background
    1.2 Human Pathogens: Plethora of Antigens
    1.3 Hematopoiesis
    1.4 Cells of the Immune System
    1.4.1 Lymphoid Lineage Cells
    1.4.2 Myeloid Lineage
    1.4.3 Antigen Presenting Cells (APCs)
    1.5 Lymphoid Organs
    1.5.1 Primary Lymphoid Organs
    1.5.1.1 Bone Marrow
    1.5.1.2 Thymus
    1.5.2 Secondary Lymphoid Organs
    1.5.2.1 Lymph Node
    1.5.2.2 Spleen
    1.5.2.3 MALT
    1.6 Types of Immune Responses
    1.6.1 Primary and Secondary Immune Response
    1.6.2 Active and Passive Immunity
    1.6.3 Innate and Adaptive Immunity
    1.6.3.1 Components of Innate Immunity
    1.6.3.2 Receptors of Innate Immunity
    1.6.3.3 Components of Adaptive Immunity
    1.6.3.4 Receptors of Adaptive Immunity
    1.6.3.5 Clonal Expansion
    1.6.4 Humoral and Cell-Mediated Immunity
    1.7 Immune Dysfunctions
    1.7.1 Immunodeficiency
    1.7.2 Autoimmune Disorders
    1.7.3 Allergies and Hypersensitivity
    1.7.4 Graft Rejection and Graft-versus-Host Disease
    1.8 Vaccines and Future Challenges
    1.9 Summary
    Questions
    Bibliography
    Chapter 2 Innate Immunity
    2.1 Introduction
    2.2 Understanding the Concept of Innate Immune Response
    2.2.1 Physical Barriers
    2.2.2 Chemical Barriers
    2.2.2.1 Antimicrobial Proteins
    2.2.2.2 Antimicrobial Peptides
    2.3 Cellular Innate Immune Response
    2.4 Cells Involved in Innate Immunity
    2.4.1 Lymphoid Cell-Natural Killer Cell
    2.4.2 Non-Lymphoid Cells
    2.4.2.1 Macrophages
    2.4.2.2 Mast Cells
    2.4.2.3 Dendritic Cells
    2.4.2.4 Eosinophils
    2.4.2.5 Neutrophils
    2.4.2.6 Basophils
    2.5 Inflammatory Response
    2.5.1 Inflammation and Innate Immunity
    2.5.2 Acute Phase Response and Innate Immunity
    2.6 Phagocytosis: A Major Process Involved in Innate Immunity
    2.6.1 Recognition of Microorganisms by Phagocytic Cells
    2.6.2 Mechanisms to Kill Phagocytosed Microbes
    2.7 Pattern Recognition Receptors (PRRs)
    2.7.1 Toll-Like Receptors (TLRs)
    2.7.2 C-type Lectin Receptor (CLRs)
    2.7.3 The Retinoic Acid-Inducible Gene-I-Like Receptors (RLRs)
    2.7.4 NOD like Receptors (NLRs)
    2.7.5 AIM2-Like Receptors (ALRs)
    2.7.6 Relationship between CLR, RLR and NLR Signaling Pathways
    2.8 Antimicrobial Peptides/Proteins Induced by PRRs
    2.8.1 Type I Interferons
    2.8.2 Cytokines
    2.8.3 Chemokines
    2.9 Enzymes Activated by PRRs: iNOS and COX2
    2.10 Regulation of Innate and Inflammatory Responses
    2.10.1 Positive Feedback Mechanism
    2.10.2 Negative Feedback Mechanism
    2.11 Harm Caused Due to Innate and Inflammatory Responses
    2.12 Evasion of Innate and Inflammatory Responses
    2.13 Key Concepts
    2.14 Summary
    Questions
    Bibliography
    Chapter 3 Adaptive Immunity
    3.1 Introduction
    3.2 Understanding Adaptive Immune Response
    3.3 Cells Involved in Adaptive Immune Response
    3.3.1 Lymphocytes
    3.3.2 Antigen Presenting Cells (APCs)
    3.4 Cell-Mediated Immunity
    3.4.1 What Happens When T-Cells Get Activated?
    3.5 Humoral Immunity
    3.5.1 Primary and Secondary Immune Response
    3.5.2 Passive Immunity
    3.5.2.1 Natural Passive Immunity
    3.5.2.2 Artificial Passive Immunity
    3.5.3 Active Immunity
    3.6 Comparison of Humoral and Cell-Mediated Immunity
    3.7 Behavior of Cells during Adaptive Immune Response
    3.7.1 Behavior of T-Cells during Adaptive Immune Response
    3.7.2 Behavior of B-Cells during Adaptive Immune Response
    3.8 Immune Dysfunctions
    3.8.1 Tolerance
    3.8.1.1 Central Tolerance and Development of Self-Reactive T-and B-Lymphocytes
    3.8.1.2 Peripheral Tolerance and Circulating Self-Reactive Lymphocytes
    3.8.2 Mechanisms involved in Tolerance
    3.8.2.1 T-Cell Anergy
    3.8.2.2 Apoptosis
    3.8.2.3 T-Regulatory Cells
    3.9 Some Common Autoimmune Diseases
    3.9.1 Acquired Immune Deficiency Syndrome (AIDS)
    3.9.2 Other Autoimmune Disorders
    3.9.2.1 Rheumatoid Arthritis
    3.9.2.2 Systemic Lupus Erythematosus (SLE)
    3.9.2.3 Myasthenia Gravis
    3.9.2.4 Multiple Sclerosis
    3.9.2.5 Goodpasture's Syndrome
    3.9.2.6 Wegener's Granulomatosis
    3.9.3 Factors Affecting Autoimmunity
    3.9.3.1 Environmental Factors
    3.9.3.2 Genetic Factors
    3.10 Interaction between Innate and Adaptive Immunity
    3.11 Key Concepts
    3.12 Summary
    Questions
    Bibliography
    Chapter 4 Antigens
    4.1 Introduction
    4.2 Antigenicity and Immunogenicity
    4.3 Immunogens
    4.4 Haptens
    4.5 Factors Influencing Immunogenicity
    4.5.1 Foreignness or Phylogenetic Unrelatedness
    4.5.2 Chemical Composition and Complexity
    4.5.3 Molecular Size
    4.5.4 Predisposition to Processing and Presentation by MHC
    4.5.5 Other Factors
    4.5.5.1 Genotype of the Host
    4.5.5.2 Dose and Route of Administration of Immunogen
    4.5.5.3 Presence or Absence of Adjuvants
    4.6 Adjuvants
    4.7 Epitopes
    4.8 B- and T-Lymphocytes Epitopes
    4.9 Exogenous and Endogenous Antigens
    4.10 Summary
    Questions
    Bibliography
    Chapter 5 Antibodies
    5.1 Introduction
    5.2 Antibody and Its Basic Structure
    5.2.1 Discovery of Antibody Molecule
    5.2.2 Structure Elucidation of Immunoglobulin
    5.2.3 Fine Structure of Immunoglobulin
    5.2.4 Immunoglobulin Ultrastructure: Multiple Domains with High Degree Organization
    5.2.5 Hinge Region
    5.2.6 Glycosylation
    5.3 Secreted and Membrane-Bound Antibody
    5.4 Antigenic Determinants of Immunoglobulins
    5.4.1 Isotypic Determinants
    5.4.2 Allotypic Determinants
    5.4.3 Idiotypic Determinants
    5.5 Antibody Half-Life
    5.6 Paratope vs Epitope vs Agretope
    5.7 Biological Functions and Structure of Immunoglobulin Classes
    5.7.1 Functions of Immunoglobulin
    5.7.1.1 Neutralization
    5.7.1.2 Opsonization
    5.7.1.3 Antibody-dependent Cell-mediated Cytotoxicity (ADCC)
    5.7.1.4 Activation of Complement System
    5.7.1.5 Transcytosis
    5.8 Immunoglobulin Classes
    5.8.1 Immunoglobulin G
    5.8.2 Immunoglobulin A
    5.8.3 Immunoglobulin M
    5.8.4 Immunoglobulin D
    5.8.5 Immunoglobulin E
    5.9 Monoclonal Antibodies
    5.9.1 Hybridoma Technology for MAb Production
    5.9.2 Monoclonal Antibody: Usage and Application
    5.10 Summary
    Questions
    Bibliography
    Chapter 6 Antigen–Antibody Interactions
    6.1 Introduction
    6.2 Strength of Antigen-Antibody Reaction
    6.3 Cross-Reactivity and Specificity
    6.4 Agglutination Reactions
    6.5 Immunoprecipitation Reactions
    6.5.1 Immunoprecipitation in Fluids
    6.5.2 Immunoprecipitation in Gel
    6.6 Immunoelectrophoresis
    6.7 Radioimmunoassay
    6.8 Enzyme Linked Immunosorbent Assay (ELISA)
    6.8.1 Types of ELISA
    6.8.1.1 Direct ELISA
    6.8.1.2 Indirect ELISA
    6.8.1.3 Sandwich ELISA
    6.8.1.4 Competitive ELISA
    6.9 Chemiluminescence
    6.10 ELISPOT Assay
    6.11 Immunofluorescence
    6.12 Western Blotting
    6.13 Summary
    Questions
    Bibliography
    Chapter 7 Major Histocompatibility Complex and Antigen Presentation
    7.1 Introduction
    7.2 Organization of Class I, Class II, and Class III Genes
    7.2.1 Genetic Organization of Human Leukocyte Antigens (HLA) Complex
    7.2.1.1 HLA Class I Molecules
    7.2.1.2 HLA Class II Molecules
    7.2.1.3 HLA Class III Molecules
    7.2.2 Genetic Organization of the Mouse H2 Locus
    7.3 Inheritance
    7.4 Genetic Polymorphism
    7.5 Cellular Distribution
    7.6 Regulation of MHC Genes
    7.7 The MHC Molecule: Structure and Function
    7.7.1 Class I MHC Molecule
    7.7.2 Class II MHC Molecule
    7.7.3 Class III MHC Molecule
    7.8 MHC and Antigen Presentation
    7.8.1 The Endogenous Pathway of Antigen Presentation
    7.8.2 The Exogenous Pathway of Antigen Presentation
    7.9 HLA Typing
    7.9.1 Serological Method
    7.9.2 Cellular Assays
    7.9.3 Flow Cytometry
    7.9.4 Genetic or Molecular Methods
    7.10 Clinical Importance of MHC
    7.10.1 Susceptibility to Disease
    7.10.2 Immune Responsiveness
    7.11 Minor Histocompatibility Antigens
    7.11.1 Genetic Organization
    7.11.2 Graft Rejection: Role of H Antigen
    7.11.3 Immunodominance
    7.12 Summary
    Questions
    Bibliography
    Chapter 8 Cytokines
    8.1 Introduction
    8.2 Theory
    8.3 Properties of Cytokine
    8.4 Cytokines and Hormones
    8.4.1 Similarities
    8.5 Classification of Cytokines
    8.5.1 Classification of Cytokines Based on Contribution in Innate Immunity
    8.5.2 Classification of Cytokines Based on Structure
    8.6 Cytokine Receptors
    8.7 Cytokine Antagonists and Agonists
    8.8 Cross-Regulation of Cytokines
    8.9 Cytokines in Health and Disease (Therapeutic Cytokines)
    8.10 Recent Advances in Cytokine
    8.11 Summary
    Questions
    Multiple Choice Questions
    Short Answer Questions
    Long Answer Questions
    True/False
    Bibliography
    Chapter 9 The Complement System
    9.1 History
    9.2 Components and Features of the Complement System
    9.3 The Three Complement Activation Pathways
    9.4 Activation of the Complement System
    9.4.1 Classical Pathway
    9.4.1.1 C1 Macromolecule
    9.4.1.2 Activation of Classical Complement Cascade System
    9.4.2 Antibody Independent Pathways of the Complement Activation
    9.4.2.1 The Lectin Pathway
    9.4.2.2 The Alternative Pathway
    9.4.3 Assembly of the Membrane Attack Complex
    9.5 Functions of the Complement System
    9.5.1 Cell Lysis
    9.5.2 Opsonization
    9.5.3 Inflammation
    9.5.4 Clearing of Immune Complexes from Circulation
    9.5.5 Augmenting Adaptive Humoral Responses
    9.5.6 Viral Infection Neutralization
    9.6 Complement System Regulation
    9.6.1 Regulation of C1 Component
    9.6.2 Regulation of C3 Convertases
    9.6.2.1 Inhibition of C3 Convertase Formation
    9.6.2.2 Inhibition after C3 Convertase Formation
    9.6.3 Regulation of Membrane Attack Complex Formation
    9.7 Deficiencies of Complement System
    9.7.1 Genetic Complement Deficiencies
    9.8 Summary
    Questions
    Bibliography
    Books
    Journals
    Chapter 10 Tolerance and Autoimmunity
    10.1 Introduction
    10.2 Mechanisms of Tolerance
    10.2.1 Central Tolerance
    10.2.2 Peripheral Tolerance
    10.2.3 Role of T[sub(reg)] Cells in Tolerance
    10.3 Autoimmune Diseases
    10.3.1 Organ Specific Autoimmune Diseases
    10.3.1.1 Autoimmune Anemias
    10.3.1.2 Goodpasture's Syndrome
    10.3.1.3 Hashimoto's Thyroiditis
    10.3.1.4 Insulin Dependent Diabetes Mellitus (IDDM)
    10.3.1.5 Graves' Disease
    10.3.1.6 Myasthenia Gravis
    10.3.2 Systemic Autoimmune Diseases
    10.3.2.1 Systemic Lupus Erythematosus (SLE)
    10.3.2.2 Multiple Sclerosis
    10.3.2.3 Rheumatoid Arthritis
    10.4 Summary
    Questions
    Bibliography
    Chapter 11 Hypersensitivity
    11.1 Introduction
    11.2 Type I Hypersensitivity
    11.2.1 Components Involved in Type 1 Reaction
    11.2.1.1 Allergen
    11.2.1.2 IgE Antibody
    11.2.1.3 Mast Cells and Basophils
    11.2.1.4 IgE-Binding Fc Receptor
    11.2.1.5 IgE Cross-Linkage Initiates Degranulation
    11.2.2 Mediators of Type I Reactions
    11.2.2.1 Primary Mediators
    11.2.2.2 Secondary Mediators
    11.2.3 Clinical Manifestations of Type I Reactions
    11.2.3.1 Systemic Hypersensitive Reactions
    11.2.3.2 Localized Hypersensitive Reactions
    11.2.3.3 Detection Methods
    11.2.3.4 Therapeutic Measures for Type I Hypersensitivities
    11.3 Type II Hypersensitivity
    11.3.1 ABO Blood Transfusion Reaction
    11.3.2 Hemolytic Disease of New Born (Erythroblastosis Fetalis)
    11.3.3 Drug-Induced Hemolytic Anemia
    11.4 Immune Complex– Mediated (Type III) Hypersensitivity
    11.4.1 Localized Type III Hypersensitivity Reaction
    11.4.2 Generalized Type III Hypersensitive Reaction
    11.5 Type IV or Delayed-Type Hypersensitivity (DTH)
    11.5.1 Phases of the DTH Response
    11.5.2 Mechanism of Type IV Hypersensitivity
    11.5.3 Examples of Type IV Hypersensitivity
    11.5.4 The Tuberculin Reaction/Mantoux Reaction
    11.6 Summary
    Questions
    Bibliography
    Chapter 12 Transplantation Immunology
    12.1 Introduction
    12.2 History of Transplantation
    12.3 Types of Transplantation
    12.3.1 Autograft
    12.3.2 Isograft
    12.3.3 Allograft
    12.3.4 Xenograft
    12.3.5 ABO Incompatible Transplantation
    12.3.6 Stem Cell Transplantation
    12.4 Cells, Tissues and Organs for Transplantation
    12.5 Types of Donors
    12.5.1 Living Donors
    12.5.2 Deceased Donors
    12.6 Possible Reasons for Organ Donations
    12.6.1 Living Relative Donors
    12.6.2 Paired Exchange
    12.6.3 Good Samaritan
    12.6.4 Financial Compensation
    12.6.5 Forced Donation
    12.7 Immune Response to Transplantation
    12.8 Mechanisms of Graft Rejection
    12.9 Transplantation Antigens
    12.9.1 Major Histocompatibility Complex (MHC)
    12.9.2 Minor Histocompatibility Antigens
    12.9.3 ABO Blood Group Antigens
    12.9.4 Monocytes and Endothelial Cell Antigens
    12.10 Graft-versus-Host Disease (GvHD) and Host-versus-Graft Disease (HvGD)
    12.11 Donor-Recipient Matching
    12.11.1 ABO Blood Group Compatibility
    12.11.2 Tissue-Typing
    12.11.3 Cross-Matching
    12.11.4 Panel Reactive Antibody (PRA) Test
    12.11.5 Serology Screening
    12.12 Immunosuppressive Drugs
    12.13 Summary
    Questions
    Bibliography
    Chapter 13 Vaccines
    13.1 Introduction
    13.2 Historical Background
    13.3 Routes of Vaccine Administration
    13.4 Components of a Vaccine
    13.4.1 Antigens
    13.4.2 Stabilizers
    13.4.3 Adjuvants
    13.4.4 Antibiotic
    13.4.5 Preservatives
    13.5 Active and Passive Immunity
    13.5.1 Innate Immunity
    13.5.2 Adaptive Immunity
    13.5.2.1 Active Immunity
    13.6 Types of Vaccines
    13.6.1 Mono-and Polyvalent Vaccines
    13.6.2 Combination Vaccines
    13.6.3 Live Attenuated Vaccines (LAV)
    13.6.3.1 Methods of Attenuation
    13.6.3.2 Mechanism of Action
    13.6.3.3 Safety and Stability of LAV
    13.6.4 Inactivated Whole-Cell Vaccines
    13.6.4.1 Mechanism of Action
    13.6.5 Subunit Vaccines
    13.6.5.1 Protein-Based Subunit Vaccines
    13.6.5.2 Polysaccharide-Based Subunit Vaccines
    13.6.5.3 Conjugate Subunit Vaccines
    13.6.6 Toxoid Vaccines
    13.6.6.1 Mechanism of Action
    13.6.6.2 Advantages
    13.6.6.3 Disadvantages
    13.6.7 DNA Vaccines
    13.6.7.1 Advantages
    13.6.8 Dendritic Cell-Based Vaccines
    13.6.9 Recombinant Vector Vaccines
    13.7 List of Currently Available Vaccines and Pipeline Vaccines
    13.8 Difficulties in Vaccine Development
    13.9 Key Concepts
    13.10 Summary
    Questions
    Bibliography
    Chapter 14 Generation of Receptor Diversity
    14.1 Introduction
    14.2 Immunoglobulin Multi-Gene Organization
    14.3 V Region DNA Rearrangement
    14.3.1 Mechanism of VDJ Recombination
    14.3.1.1 First Phase – Recognition of Specific DNA Sequence and Cleavage
    14.3.1.2 Second Phase – Processing Followed by Joining of Ends
    14.3.2 DNA Repair Machinery
    14.3.2.1 Canonical NHEJ (c-NHEJ) Pathway
    14.3.2.2 Alternative NHEJ (Alt-NHEJ) Pathway
    14.4 Diversification of Antibody Repertoire
    14.4.1 Somatic Hypermutation (SHM)
    14.4.2 Class Switch Recombination
    14.5 Summary
    Questions
    Bibliography
    Chapter 15 Biology of the B Lymphocyte
    15.1 Introduction
    15.2 Antigen-Independent Phase of B Cell Development
    15.2.1 B Cell Maturation
    15.2.1.1 Production of Immature B Cells
    15.2.1.2 Selection of Immature B Cells
    15.3 Antigen-Dependent Phase of B Cell Development
    15.3.1 B Cell Activation and Proliferation
    15.4 Humoral Response
    15.4.1 Primary Response
    15.4.2 Secondary Response
    15.5 Anatomical Distribution of B Cell Population
    15.5.1 B Cells in Lymph Nodes
    15.5.1.1 Antigen-Induced B-Cell Differentiation in Germinal Centres
    Summary
    Questions
    Bibliography
    Chapter 16 Biology of the T Lymphocytes
    16.1 Introduction
    16.2 T Cell Receptor (TCR)
    16.2.1 Structure of T Cell Receptor (TCR)
    16.2.2 T Cell Receptor Complex: TCR-CD3
    16.2.3 Self MHC Restriction of T Cell Receptor (TCR)
    16.2.3.1 Doherty and Zinkernagel's Experiment to Show Self MHC Restriction of T Cells
    16.3 T Cell Accessory Membrane Molecules
    16.3.1 CD4 and CD8 Co-Receptors
    16.3.2 Role of Other Accessory Molecules
    16.4 T-Cell Development
    16.4.1 Selection of T Cells in Thymus
    16.4.1.1 Positive Selection
    16.4.1.2 Negative Selection
    16.5 T H Cell Activation
    16.5.1 Co-Stimulatory Signals for T Cell Activation
    16.6 T Cell Differentiation
    16.7 Summary
    Questions
    Bibliography
    Chapter 17 Cell-Mediated Cytotoxic Responses
    17.1 Introduction
    17.2 Effector T Cells
    17.2.1 Properties
    17.2.2 Role of Cell Adhesion Molecules in TCR Interactions
    17.2.3 Effector Molecules Produced by T Cells
    17.3 Cytotoxic T Lymphocytes (CTLs)
    17.3.1 Generation of Effector CTLs
    17.3.2 CTL Mediated Response
    17.4 Natural Killer Cells
    17.4.1 Mechanism of NK Cell-Mediated Cytotoxicity
    17.5 NKT Cells
    17.6 Antibody-Dependent Cell-Mediated Cytotoxicity
    17.7 Summary
    Questions
    Bibliography
    Index