Elements of Immunology

Description

This book is designed to introduce readers to the exciting world of immunology, the people who populate it and foster a curiosity to question and know more. The book is supported by a consistent, colourful art programme. The detailed explanation of concepts and terms, and the deconstruction of complex molecular mechanisms into simple, easy-to-remember steps help students focus on the fundamentals without any distractions. Packed with extensive Web-based supplements, the book enables students to visualize concepts, thereby enriching the learning process. The book, comprising twenty chapters, has numerous pedagogical elements built into it. Margin snippets present interesting and relevant information without breaking the flow of the text. Margin definitions highlight the key terms for easy identification and recollection. Each chapter talks about a relevant molecular biology technique, thus providing an insight into the practical aspect of immunology as well. A glossary at the end of the book lists out the important terms used. Cover The Elements of Immunology Copyright Brief Contents Contents The Author Preface An Introduction to the Immune System Introduction The Components of Immunity Innate Immunity Mechanical Barriers Chemical Barriers Phagocytosis Fever Infl ammation Acute-phase Proteins Adaptive Immunity Cells of The Immune System B Lymphocytes T Lymphocytes Antigen-presenting Cell Natural Killer Cells Eosinophils Basophils and Mast Cells Mononuclear Phagocytes Neutrophils Antigens and Antigen Recognition Mhc and Antigen Presentation Processing of Endogenous Antigens Processing of Exogenous Antigens Types of Immune Response Antibody-Mediated Immunity Cell-Mediated Immunity Activation of the Immune Response Humoral Response Selective Activation of B Cells And Generation of Humoral Response Cell-Mediated Response Immune Disorders Autoimmunity Immunodeficiency Hypersensitivity Evolution of Immunity Cells and organs of the Immune System Haematopoiesis Regulation of Haematopoiesis Apoptosis Cells of the Immune System LymphocytesY Lymphocyte Development B Lymphocytes T Lymphocytes Natural Killer Cells/Null Cells Mononuclear Phagocytes Granulocytes Neutrophils Eosinophils Basophils and Mast Cells Platelets Phagocytosis Overcoming Phagocytic Defences Lymphoid Tissues Primary Lymphoid Organs Bone Marrow Thymus Thymic Education Secondary Lymphoid Organs And Tissues Lymph Nodes Spleen Mucosa-associated Lymphoid Tissue Nasal-associated Lymphoid Tissue Gut-associated Lymphoid Tissue Bronchus-associated Lymphoid Tissue Cutaneous-associated Lymphoid Tissue Lymphatic System Flow Cytometry Antigens Introduction General Properties of Antigens Molecular Size Self or Foreign Chemical Complexity Route of Entry B-Cell and T-Cell Epitopes Properties of B-Cell Epitopes Properties of T-Cell Epitopes Superantigens Haptens Adjuvants Gel Filtration Chromatography Antibodies Introduction Landmarks in the Elucidation of Antibody Structure Antibody Structure Hinge Region J Chain Disulphide Bonds Classes of Immunoglobulin Immunoglobulin G Immunoglobulin A Immunoglobulin M Immunoglobulin D Immunoglobulin E Antibody-Mediated Effector Functions Activation of complement system by igg and igm Cell-Mediated Cytotoxicity Targeted By Immunoglobulins Opsonization Mucosal Immunity Neonatal Immunity Antibodies Can be Antigens too Isotype Allotype Idiotype Immunoglobulin Superfamily Antigen–Antibody Interactions:Immunoprecipitation Generation of Antibody Diversity Introduction Genetic Organization of Immunoglobulin Genes Light-Chain Loci l-chain Family k-chain Family Heavy Chain Loci Rearrangement of Genes Heavy-Chain Gene Rearrangement Rearrangement of Genes at DNA Level Rearrangement of Genes at RNA Level Light-Chain Gene Rearrangement Rearrangement of Genes at DNA Level Rearrangement of Genes at RNA Level Rearrangement of V, (D), J Gene Segments 12/23 Rule Recombination Sequence-directed Joining of Gene Segments Mechanism of V, (D), J Gene-segment Rearrangement Defects in V, (D), J Recombination Allelic Exclusion Allelic Exclusion of Heavy Chains Allelic Exclusion of Light Chains The Generation of Diversity in Immunoglobulins Multiple Germ-Line Gene Segments V–J And V–D–J Recombination Junctional Diversity Gene Conversion Somatic Hypermutation Association of Varied Light and Heavy Chains Membrane-Bound and Secreted Immunoglobulins Generation Of Membrane-Bound Or Secreted Immunoglobulins co-expression of membrane-bound igm and igd Assembly and Secretion of Immunoglobulins Class Switching Regulation of Immunoglobulin Gene Transcription Immunodiffusion Major Histocompatibility Complex Introduction Class I Mhc Molecules Class Ii Mhc Molecules Class Iii Mhc Molecules Structure of Peptide-Binding Cleft Peptide–Mhc Interaction Gene Map of the Major Histocompability Complex Murine Mhc Loci Classical Murine Class I Loci Non-Classical Murine Class I Loci Murine Class Ii Mhc Loci I-Gene In H-2 Locus Human Mhc Loci Human Class I Mhc Loci Human Class II Mhc Loci Human Class III Loci Why The Name Hla? Mhc Polymorphism Distribution of Class I And Class Ii Mhc Molecules Transcriptional Regulation of Mhc Molecules Class I Mhc: Constitutive Expression Class I Mhc: Cytokine-Induced Expression Class Ii Mhc Expression Affinity Chromatography T-cell Receptors Introduction Structure of T-Cell Receptor T-Cell Receptors Are Related To Immunoglobulins Glycosylation of Tcr Chains Organization of T-Cell Receptor Genes in the Germ Line Mouse TcrGene Locus Mouse Tcr Gene Locus Human Tcr Gene Locus Human Tcr Gene Locus Mouse Tcr Gene Locus Mouse Tcr Gene Locus Human Tcr Gene Locus Human Tcr ™-Gene Locus Rearrangement of Genes to Form Mature & and â Gene Gene Rearrangement To Form Mature Tcr & Gene Rearrangement of Genes at DNA Level Splicing and Maturation of Primary Transcript Rearrangement Of &-Chain Genes Rearrangement of © and ™ Genes Allelic Exclusion of Tcr Genes Inhibition of Immunoglobulin Gene Rearrangement In T Cells Generation of Structural T-Cell Receptor Diversity Presence of Multiple Germ-Line V, D, And J Segments Junctional Diversity Imprecise Recombination P- And N-Nucleotide Addition Complementarity Determining Regions (Cdr) of T-Cell Receptor Tcr Genes do not Undergo Somatic Hypermutation Promoters, Enhancers and Silencers of T-Cell Receptors a Chain B Chain g AND ä CHAINS T-Cell Receptor Complex Cd3 Proteins Cd3 Complex g Chain of CD3 Complex d Chain of CD3 Complex e Chain of CD3 Complex z Chain of CD3 Complex Surface Expression Of Tcr Complex Function Of Cd3 Complex Accessory Molecules on T Cells Cd4 Accessory Molecules Cd8 Accessory Molecules Antigen–Mhc–T-Cell Receptor Complex Cross-Reactivity of T Cell With Allogeneic Mhc Transmission Electron Microscopy T-cell Development and Activation Introduction T-Cell Development Positive and Negative Selection Positive Selection Experimental Evidence of Positive Selection Negative Sele Experimental Evidence of Negative Selection Mechanisms of Positive and Negative Selection Activation of T Lymphocytes Recognition of Antigen–Mhc Complex and Signal Transduction By Tcr Costimulators and T-Cell Activation The Fall of T-Cell Response Superantigen-Induced T-Cell Activation T Lymphocytes Specificity of T Cells Func™Tions of T Cells Nkt Cells Scanning Electron Microscopy B-cell Developmentand Activation Introduction B-Cell Development Stages of B-Lymphocyte Development Negative Selection of B Cells B1 Subset of B Cells Activation of B Cells Antigen Recognition Signalling Through B-Cell Co-Receptor Complex Proliferation Phase Thymus-Dependent and Thymus-Independent Antigen Role of TH Cells in B-Cell Activation Antigen Presentation By B Cells To Th Cells CD40–CD40 Ligand Interaction Th cell’s Cytokine in B-cell Proliferation and Diff erentiation B-Cell Differentiation Into Effector Plasma Cells B-Cell Differentiation Into Memory B Cells Primary and Secondary Humoral Immune Response Role of TH Cells in Humoral Response Sites for Induction of Humoral Response Germinal-Centre Reactions Affinity Maturation of B Cells Somatic Hypermutation Selection of High-Affinity B Cells Regulation of Immune Response Regulation By Antigen Antibody-Mediated Regulation Regulation By Lymphocytes Regulation By Idiotypic–Anti-Idiotypic Network Double Diffusion Agar Assay The Complement System Introduction Classical Pathway Alternative Pathway The Mannan-Binding Lectin Pathway The Formation of Membrane-Attack Complex Biological Functions of Complement Proteins Cytolysis Anaphylatoxins and Inflammation C3b Generation and Promotion of Phagocytosis Solubilization of Immune Complexes or Immune Complex Clearance Neutratization of Viral Infection Induction of Immune Response Regulation of Complement Cascade Regulation of c1 Regulation of C3 Convertases Regulation of Membrane-Attack Complex Complement Deficiencies Complement Fixation Test Antigen Presentation and Processing Introduction Antigen-Presenting Cells Dendritic Cells Mononuclear Phagocytic Cells B Lymphocytes Non-Professional Antigen-Presenting Cells Two Processing and Presentation Pathways Presentation of Endogenous Pathogens to Class I Mhc Molecules Proteasome Complex Ubiquitination of Proteins Peptide Transport from Cytoplasm to ER Presentation of Peptides Derived from Membrane-bound and Secreted Proteins Evidence for Cytosolic Degradation of Membrane-bound and Secreted Proteins Binding of Class I MHC Molecules and Peptides Blockage of Endogenous Pathway by Viruses Presentation of Exogenous Antigen to Class Ii Mhc Molecules Endocytosis of Proteins Binding of Processed Peptides to Class IiMHC Molecules Role of Specialized Class Ii MHC-like Molecules — Hla-Dm Presentation of Non-Peptide Bacterial Antigens Gel Electrophoresis Cell-mediated Immunity Introduction Lymphocytes and Cell-Mediated Response Cytotoxic T Lymphocytes Mechanism of Cytotoxicity Natural Killer Cells Surface Markers on Nk Cells Mechanism of Nk-cell Cytotoxicity Antibody-Dependent Cell-Mediated Cytotoxicity Delayed-Type Hypersensitivity Sensitization and Effector Phases in Dth Response Sensitization or Activation Phase Eff ector Phase of DTH Cytokines and Dth Reaction Growth Factors/Cytokines Secreted By Macrophages Detection of Dth Reaction Significance of Dth Reaction Agglutination Hypersensitivity Introduction Gell and Coombs Classification Type I Hypersensitivity Reaction What Is An Allergen? Ige Basophils, Mast Cells and Eosinophils Mast Cells Eosinophils Receptors for Ige High-affi nity Receptor (FcεRI) Low-affi nity Receptor (FcεRII) Activation of Mast Cells and Basophils Events Leading to Mast-cell Activation Biological Mediators of Type I Reactions Primary Mediators Secondary Mediators Cytokines Clinical Consequences of Type I Hypersensitivity Features of Anaphylaxis Features of Atopy Allergic Rhinitis (Hay Fever) Asthma Food Allergies Atopic Dermatitis (Eczema) Late-Phase Reaction Tests For Diagnosis of Type I Hypersensitivity Skin Test Patch Test Radioimmunosorbent Test (RIST) Radioallergosorbent Test (RAST) Therapeutic Measures for Type I Hypersensitivity TYPE Ii HYPERSENSITIVITY: ANTIBODY-DEPENDENT CYTOTOXIC HYPERSENSITIVITY Drug-Induced Hypersensitivity Reaction Transfusion Reactions Rhesus Antigen Incompatibility TYPE Iii HYPERSENSITIVITY: IMMUNE COMPLEX– MEDIATED HYPERSENSITIVITY How Are Immune Complexes Removed in Normal Individuals? What Goes Wrong in Type III Hypersensitivity Reactions? Mechanism of Type Iii Hypersensitivity Reactions Localized Type Iii Reactions Generalized Type Iii Reactions Type iv HypersensitivityRreactions: Delayed-type Hypersensitivity Reaction Contact Hypersenstivity Tuberculin Reaction Granulomatous Hypersenstivity Immunoelectrophoresis Cell Migration and Inflammatory Response Introduction Cell-Surface Adhesion Molecules Immunoglobulin superfamily cams Selectins Integrins Mucin Family Cadherins Leukocyte Migration Chemotactic Molecules Chemokines Chemotactic Molecules Mediators of Inflammation Kinin System Clotting System Fibrinolytic System Complement System Inflammatory Cytokines Inflammatory Lipid Mediators The Process of Inflammation Acute Inflammatory Response localized infl ammation systemic acute-phase response Chronic Inflammatory Response Anti-Inflammatory Agents Anti-Cam Antibodies Corticosteroids Non-Steroidal Drugs Elisa —Indirect Assay Immune Response to Infectious Agents Introduction Immunity to Viruses Innate immune response to viruses viral neutralization by antibody and complement T-Cell-Mediated Antiviral Mechanism Virus Strategies For the Evasion of Host Immune Response Viral Avoidance of Immune Response Downregulating Cellular Protein Evasion of Antibody Detection Evasion of T-cell Response Hiding in Immune-privileged Sites Evasion by Inhibiting Host Immunity Viral Infections: Influenza The Influenza Virus Antigenic Drift And Antigenic Shift Immune Response To Influenza Infection Immunity to Bacterial Infections FIRST LINE of DEFENCE Immune Response to Extracellular Bacteria Innate Defence Adaptive Immune Response Immune Response to Intracellular Bacteria Innate Immune Response Adaptive Immune Response Evasion of Host Defences by Bacteria Antiphagocytic Mechanism Feigning of Antigen (Antigenic Disguise) Neutralization of Antibody Changing Antigens on Bacterial Surface Bacterial Infections Cornyebacterium Diphtheriae Mycobacterium Tuberculosis Lyme Disease: Borrelia Burgdorferi Protozoan Diseases Malaria Pathogenesis of Malaria Host Immune Response to Plasmodium Antimalarial Drugs and Vaccines African Sleeping Sickness Pathogenesis of Trypanosomiasis Host Immune Response Leishmaniasis Host Response to Leishmania spp. Diseases Caused by Parasitic Worms Host Immune Response Evasion of Immune Mechanism by Helminths Elisa —Antibody Sandwich Assay Vaccines Introduction Types of Vaccines Natural Live Vaccines Live Attenuated Vaccines Advantages of Attenuated Vaccines Disadvantages of Attenuated Vaccines Inactivated Vaccines Toxoid Vaccines Polysaccharide Vaccines Recombinant Antigen Vaccines Live Vector Vaccines Viral Vector Vaccine Bacterial Vector Vaccine Dna Vaccines New Vaccine Strategies Synthetic Vaccines Microencapsulation Delivery System Liposomes and Micelles Iscoms—Immune-Stimulating Complexes Solid Matrix-Antibody-Antigen Complexes (Smaa) Anti -Idiotype Vaccines Antigen-Cochelate What Should an Ideal Vaccine Have? Ion Exchange Chromatography Transplantation Immunology Introduction Transplantation Antigen Immunology of Allogeneic Transplantation Presentation of Allogeneic MHC to T Cells T-cell Response to Alloantigens in vitro: Mixed Leukocyte Reaction Cell-mediated Response to Allografts in vivo Types of Graft Rejection Hyperacute Rejection Chronic Rejection Immunosuppressive Therapy of Allograft Rejection Antigen-Non-Specific Immunosuppressive Agents Cyclosporin Fk-506 (Tacrolimus) Rapamycin Mycophenolate Mofetil (MMF) Corticosteroids Azathioprine/Cyclophosphamide Specific Immunosuppressive Agents Monclonal Antibodies to T-Cell Antigens Blocking Costimulatory Signals Immunology of Xenogeneic Transplantation Hyperacute Xenograft Rejection Delayed Xenograft Rejection T-Cell-Mediated Xenograft Rejection Transplants to Privileged Sites Organ Transplantation Kidney Transplantation Lung Transplantation Heart Transplantation Liver Transplantation Pancreas Transplantation Skin Transplantation Bone Marrow Transplantation Graft Versus Host Disease Immunofluorescence Cancer and the ImmuneSystem Introduction Malignant Transformation of Cells Oncogenes and Cancer Induction Induction of Cellular Proliferation Activation of Proto-oncogene to Oncogene Tumour Suppressor Genes Immortalization and Transformation Tumours of the Immune System Tumour Antigens Tumour-Specific Antigens Expression of Antigen in the Wrong Place Virus-induced Tumour-specifi c Antigens Mutated Cellular Gene Product as Tumour-specifi c Antigen Tumour-Associated Antigens Oncofoetal Tumour Antigen Oncogenic Product as Tumour Antigen Aberrantly Expressed Normal Cell Protein Altered Glycolipid and/or Glycoprotein Antigens Immune Response to Tumours T-Cell-Mediated Immunity Nk-Cell- and Macrophage-Mediated Immunity Evasion of Immune Response by Tumours Downregulation of Class I Mhc Molecules Blocking of Tcyt Response by Antibodies Modulation of Tumour Antigens Lack of Costimulators Suppression of anti-Tumour Immune Response Antigen Masking Preventing Inlammatory Responce Preventing Inflammatory Response Immunotherapy for Cancer Stimulation of Active Immunity Against Tumour Augmentation of Immune Response by Costimulators Stimulation by Cytokines Augmentation of Antigen Presentation Non-Specific Stimulation of the Immune System Passive Immunotherapy for Tumours Adoptive Cellular Immunotherapy Humoral Immunotherapy Immunoblotting Primary and Secondary Immunodeficiencies Introduction Primary Immunodeficiency Secondary or Acquired Immunodeficiency Primary Immunodeficiencies Lymphoid Cell Disorder Severe Combined Immunodefi ciency (SCID) Defects in B-cell Maturation Defects in T-cell Development Combined B-cell and T-cell Disorders Defects in Myeloid Lineage Chronic Granulomatous Disease Leukocyte Adhesion Defi ciency-1 (LAD-1) Chediak–Higashi Syndrome Neutropenia or Granulocytopenia Defects in the Complement System Treatment Approaches for Immunodeficiency Animal Models of Primary Immunodeficiency Nude Mouse Scid Mouse Cba/N Mouse Beige Mouse secondary immunodeficiency and Aids The Aids Epidemic The Hiv Virus The Genetic Composition of HIV The Life Cycle of HIV Hiv’s Mechanism of Immunosuppression Mechanism of Evasion Used by Hiv The Course of Hiv Infection and Aids Treatment and Prevention of Aids Development of Eff ective Drugs Development of an Eff ective Vaccine Radioimmunoassay Autoimmunity and Autoimmune Diseases Introduction Single-Organ Autoimmune Disease Autoimmune Diseases Due To Tissue Destruction Of Organs Chronic Thyroiditis (Hashimoto’s Thyroiditis) Pernicious Anaemia Autoimmune Haemolytic Anaemia Drug-induced Haemolytic Anaemia Thrombocytopenic Purpura Goodpasture Syndrome Insulin-dependent Diabetes Mellitus (Type I Diabetes) Autoimmune Diseases Induced By Antibody Binding Graves’ Disease (Hyperthyroidism) Myasthenia Gravis Systemic Autoimmune Diseases Systemic Lupus Erythematosus Rheumatoid Arthritis Multiple Sclerosis Scleroderma Guillian–Barre Syndrome Animal Models of Autoimmune Diseases Models of Spontaneous Autoimmunity Mechanism For Induction of Autoimmunity Failure of B-cell Tolerance Molecular Mimicry by Cross-reactive Microbial Antigens Availability of Sequestered Self-antigens Aberrant Expression of Class Ii MHC Molecules Therapeutic Approaches to Autoimmune Diseases Other Strategies Tolerance Induction Monoclonal Antibody Against Autoantigens Blockage Of Mhc Molecules Induction Of T-Cell Suppression Role Of Mhc, Th Cells and Tcr in Autoimmunity Elispot Role of Mhc Th Cells in Autoimmunity Role of T-Cell Receptors in Autoimmunity ELISPOT Glossary Icons Used in Books Index Feedback