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Immunology & Serology in Laboratory Medicine - E-Book

Immunology & Serology in Laboratory Medicine - E-Book

Mary Louise Turgeon

(2017)

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Abstract

Immunology & Serology in Laboratory Medicine - E-Book

Table of Contents

Section Title Page Action Price
Front Cover Cover
IMMUNOLOGY & SEROLOGY in Laboratory Medicine i
evolve page ii
Copyright iii
Dedication iv
REVIEWERS v
PREFACE vi
DISTINCTIVE FEATURES AND LEARNING AIDS vi
NEW TO THIS EDITION vi
Part I1397058884Basic Immunologic Mechanisms (Chapters 1-5) vi
Part II1397058884The Theory of Immunologic and Serologic Procedures (Chapters 6-14) vii
Part III1397058884Immunologic Manifestations of Infectious Diseases (Chapters 15-24) vii
Part IV1397058884Immune Disorders (Chapters 25-29) vii
Part V1397058884Transplantation and Tumor Immunology (Chapters 30 and 31) vii
Part VI—Vaccines (Chapter 32) vii
GENERAL, OVERALL IN-TEXT FEATURES viii
ANCILLARIES viii
For the Instructor viii
ABOUT THE AUTHOR ix
TABLE OF CONTENTS x
I - Basic ImmunologicMechanisms 1
1 - An Overview of Immunology 2
HISTORY OF IMMUNOLOGY 2
WHAT IS IMMUNOLOGY? 3
CELLS OF THE IMMUNE SYSTEM 3
FUNCTION OF IMMUNOLOGY 3
Microbiota 5
First Line of Defense 5
Second Line of Defense: Natural Immunity 5
Third Line of Defense: Adaptive Immunity 7
Humoral-Mediated Immunity 7
Cell-Mediated Immunity 9
COMPARISON OF INNATE AND ADAPTIVE IMMUNITY 10
Pathogen-Associated Molecular Patterns and Pattern Recognition Receptors 10
Pattern Recognition Receptors 10
CHAPTER HIGHLIGHTS 11
REVIEW QUESTIONS 12
BIBLIOGRAPHY 13
2 - Antigens and Antibodies 14
ANTIGEN CHARACTERISTICS 15
General Characteristics of Immunogens and Antigens 15
Histocompatibility Antigens 15
Major Histocompatibility Complex Regions 16
Classes of HLA Molecules 17
Autoantigens 17
Blood Group Antigens 17
CHEMICAL NATURE OF ANTIGENS 17
Adjuvant 18
PHYSICAL NATURE OF ANTIGENS 18
Foreignness 18
Degradability 18
Molecular Weight 18
Structural Stability 18
Complexity 18
GENERAL CHARACTERISTICS OF ANTIBODIES 18
IMMUNOGLOBULIN (IG) CLASSES 18
Immunoglobulin M 18
Immunoglobulin G 19
Immunoglobulin A 20
Immunoglobulin D 20
Immunoglobulin E 20
ANTIBODY STRUCTURE 20
Typical Immunoglobulin Molecule 21
Structures of Other Immunoglobulins 21
Immunoglobulin M 21
Immunoglobulin A 21
Immunoglobulin D 21
Immunoglobulin E 21
IMMUNOGLOBULIN VARIANTS 22
Isotype Determinants 22
Allotype Determinants 22
Idiotype Determinants 23
ANTIBODY SYNTHESIS 24
Primary Antibody Response 24
Secondary (Anamnestic) Response 24
FUNCTIONS OF ANTIBODIES 25
ANTIGEN–ANTIBODY INTERACTION: SPECIFICITY AND CROSS-REACTIVITY 25
Antibody Affinity 25
Antibody Avidity 26
Immune Complexes 26
MOLECULAR BASIS OF ANTIGEN–ANTIBODY REACTIONS 26
Types of Bonding 26
Hydrophobic Bonds 27
Hydrogen Bonds 27
Van der Waals Forces 27
Electrostatic Forces 27
Goodness of Fit 27
Detection of Antigen–Antibody Reactions 27
Influence of Antibody Types on Agglutination 28
MONOCLONAL ANTIBODIES 28
Discovery of the Technique 28
Monoclonal Antibody Production 28
Uses of Monoclonal Antibodies 28
CHAPTER HIGHLIGHTS 30
REVIEW QUESTIONS 31
BIBLIOGRAPHY 34
3 - Cells and Cellular Activities of the Immune System: Granulocytes and Mononuclear Cells 35
ORIGIN AND DEVELOPMENT OF BLOOD CELLS 36
GRANULOCYTIC CELLS 36
Neutrophils 36
Eosinophils and Basophils 37
Eosinophils 37
Basophils 37
PROCESS OF PHAGOCYTOSIS 38
Chemotaxis 38
Adherence 39
Engulfment 39
Digestion 39
Subsequent Phagocytic Activity 40
Neutrophil Extracellular Traps 40
MONOCYTES-MACROPHAGES 40
Mononuclear Phagocyte System 40
Host Defense Functions 41
Phagocytosis 42
Antigen Presentation and Induction of the Immune Response 43
Secretion of Biologically Active Molecules 43
ACUTE INFLAMMATION 43
SEPSIS 43
CELL SURFACE RECEPTORS 44
DISORDERS OF NEUTROPHILS 45
Noninfectious Neutrophil-Mediated Inflammatory Disease 45
Abnormal Neutrophil Function 45
Congenital Neutrophil Abnormalities 45
Chédiak-Higashi Syndrome 46
Chronic Granulomatous Disease 46
Complement Receptor 3 Deficiency 46
Myeloperoxidase Deficiency 46
Specific Granule Deficiency 47
MONOCYTE-MACROPHAGE DISORDERS 47
Gaucher’s Disease 47
Niemann-Pick Disease 48
DISEASE STATES INVOLVING LEUKOCYTE INTEGRINS 48
CHAPTER HIGHLIGHTS 50
REVIEW QUESTIONS 50
BIBLIOGRAPHY 52
4 - Cells and Cellular Activities of the Immune System: Lymphocytes and Plasma Cells 54
LYMPHOCYTES AND PLASMA CELLS 55
LYMPHOID AND NONLYMPHOID SURFACE MEMBRANE MARKERS 55
Sites of Lymphocyte Development 55
Primary Lymphoid Tissue 55
Secondary Lymphoid Organs 58
Circulation of Lymphocytes 60
VIRGIN OR NAÏVE LYMPHOCYTES 61
DEVELOPMENT OF T LYMPHOCYTES 62
Early Cellular Differentiation and Development 62
Double-Negative Thymocytes 62
Double-Positive Thymocytes 63
Later Cellular Differentiation and Development of T Lymphocytes 63
T-Lymphocyte Subsets 63
CD4 Lymphocytes 63
Subsets of CD4+ Effector T Lymphocytes 64
CD8+ Cytotoxic T Lymphocytes 66
Antigen Recognition by T Cells 69
T-Cell Activation 69
T-Independent Antigen Triggering 70
Antigen Processing and Antigen Presentation to T Cells 70
INNATE LYMPHOID CELLS 70
Natural Killer Cells 70
T-REGULATORY LYMPHOCYTES 71
B LYMPHOCYTES 72
Development and Differentiation of B Lymphocytes 72
Cell Surface Antigens 72
. B1 and B2 cells are B-cell subsets. One phenotypically distinct subset, designated B10 cells, has been shown to uniquely regul... 73
PLASMA CELL BIOLOGY 74
ALTERATIONS IN LYMPHOCYTE SUBSETS 74
Changes With Aging 75
IMMUNOLOGIC DISORDERS 75
Immune-Mediated Disease 75
CHAPTER HIGHLIGHTS 76
REVIEW QUESTIONS 76
BIBLIOGRAPHY 78
5 - Soluble Mediators of the Immune System 80
THE COMPLEMENT SYSTEM 81
Activation of Complement 81
Enzyme Activation 82
Complement Receptors 83
CLASSIC PATHWAY 83
RECOGNITION 83
Amplification of Proteolytic Complement Cascade 83
Membrane Attack Complex 83
ALTERNATIVE PATHWAY 84
MANNOSE-BINDING LECTIN PATHWAY 85
BIOLOGICAL FUNCTIONS OF COMPLEMENT PROTEINS 85
Biological Effects of Complement Activation 85
ALTERATIONS IN COMPLEMENT LEVELS 86
Elevated Complement Levels 86
Decreased Complement Levels 86
DIAGNOSTIC EVALUATION 88
OTHER SOLUBLE IMMUNE RESPONSE MEDIATORS 88
Biological Response Modifiers 88
Cytokines 88
Interleukins 91
Interferons 91
Tumor Necrosis Factor 92
HEMATOPOIETIC STIMULATORS 92
Stem Cell Factor (c-kit Ligand) 92
Colony-Stimulating Factors 92
Transforming Growth Factors 92
Chemokines 92
Assessment of Cytokines 92
ACUTE-PHASE PROTEINS 92
Overview 93
Synthesis and Catabolism 93
C-Reactive Protein 93
Other Acute-Phase Reactants 94
Laboratory Assessment Methods 94
CHAPTER HIGHLIGHTS 97
REVIEW QUESTIONS 97
BIBLIOGRAPHY 99
II - The Theory of Immunologicand Serologic Procedures 100
6 - Safety in the Immunology-Serology Laboratory 101
SAFETY STANDARDS AND AGENCIES 102
PATIENT SAFETY 102
PREVENTION OF TRANSMISSION OF INFECTIOUS DISEASES 103
SAFE WORK PRACTICES FOR INFECTION CONTROL 103
PROTECTIVE TECHNIQUES FOR INFECTION CONTROL 104
Selection and Use of Gloves 104
Facial Barrier Protection and Occlusive Bandages 104
Laboratory Coats or Gowns as Barrier Protection 104
HAND SANITIZING AND HANDWASHING 104
OTHER SAFETY PRACTICES 106
Nail Care 106
Shoes 106
Electronic Devices 106
SPECIMEN-PROCESSING PROTECTION 106
ADDITIONAL LABORATORY HAZARDS 106
DECONTAMINATION OF WORK SURFACES, EQUIPMENT, AND SPILLS 107
DISPOSAL OF INFECTIOUS LABORATORY WASTE 107
Containers for Waste 108
Biohazard Containers 108
Biohazard Bags 108
Final Decontamination of Waste Materials 108
DISEASE PREVENTION 108
Immunization and Vaccination 108
Screening Tests 108
Hepatitis B Surface Antigen 108
Rubella 108
Tuberculosis 108
Varicella 109
Postexposure Prophylaxis 109
Human Immunodeficiency Virus 109
BASIC FIRST AID PROCEDURES 110
CHAPTER HIGHLIGHTS 111
REVIEW QUESTIONS 111
BIBLIOGRAPHY 112
7 - Quality Assurance and Quality Control 113
CLINICAL LABORATORY REGULATORY AND ACCREDITING ORGANIZATIONS 114
NONANALYTIC FACTORS RELATED TO TESTING ACCURACY 114
Qualified Personnel 114
Established Laboratory Policies 114
Laboratory Procedure Manual 114
Test Requisitioning 114
Patient Identification, Specimen Procurement, and Labeling 114
Preventive Maintenance of Equipment 115
Appropriate Testing Methods 115
Inaccurate Results 115
ERRORS RELATED TO PHASE OF TESTING 115
QUALITY DESCRIPTORS 115
Definitions 115
Coefficient of Variation 116
Sensitivity and Specificity 116
Sensitivity 116
Specificity 116
Predictive Values 116
MONITORING QUALITY 117
Proficiency Testing 117
Control Specimens 117
REFERENCE RANGE STATISTICS 117
TESTING OUTCOMES 118
VALIDATING NEW PROCEDURES 118
Parallel Testing of Test Kits 118
Validation of a New Procedure Write-Up 118
CHAPTER HIGHLIGHTS 120
REVIEW QUESTIONS 121
BIBLIOGRAPHY 122
8 - Basic Serologic Laboratory Techniques 123
PROCEDURES MANUAL 124
BLOOD SPECIMEN PREPARATION 124
TYPES OF SPECIMENS TESTED 124
INACTIVATION OF COMPLEMENT 124
PIPETTES 124
Graduated Pipettes 125
Serologic Pipettes 125
Inspection and Use 125
PIPETTING TECHNIQUES 125
Manual Pipettes 125
Automatic Pipettes 126
Micropipettors 126
Automatic Dispensers or Syringes 127
Diluter-Dispensers 127
DILUTIONS 128
Diluting Specimens 128
Dilution Factor 128
Single Dilutions 128
Example of Calculation of Concentration of a Single Dilution 129
Use of Dilution Factors 129
Serial Dilutions 129
ANTIBODY TESTING 130
ANTIBODY TITER 130
CHAPTER HIGHLIGHTS 131
REVIEW QUESTIONS 131
BIBLIOGRAPHY 132
9 - Rapid Testing 133
TESTING CATEGORIES 133
Staff Competency 134
Quality Control 134
QUALITY CONTROL STANDARDS FOR MODERATE AND HIGH COMPLEXITY TESTING 134
EXAMPLES OF NON–INSTRUMENT-BASED TESTING 134
Malaria Testing 134
HIV Testing 135
Pregnancy Testing 135
?CASE STUDY 9.1 139
CHAPTER HIGHLIGHTS 140
REVIEW QUESTIONS 140
BIBLIOGRAPHY 141
10 - Precipitation and Particle Agglutination Methods 142
PRINCIPLES OF PRECIPITATION AND PARTICLE AGGLUTINATION ASSAYS 143
Precipitation Assays 143
Particle Agglutination Assays 144
LATEX AGGLUTINATION 144
PREGNANCY TESTING 145
Human Chorionic Gonadotropin 145
Agglutination Inhibition 147
FLOCCULATION TESTS 147
DIRECT BACTERIAL AGGLUTINATION 148
HEMAGGLUTINATION 148
Mechanisms of Agglutination 148
Sensitization 148
Lattice Formation 150
Methods of Enhancing Agglutination 150
Graded Agglutination Reactions 150
Microplate Agglutination Reactions 151
NEPHELOMETRY 151
Principle 151
Physical Basis 151
Optical System 153
Measuring Methods 153
Advantages and Disadvantages 154
Clinical Application: Cryoglobulins 154
CHAPTER HIGHLIGHTS 155
REVIEW QUESTIONS 155
BIBLIOGRAPHY 158
11 - Electrophoresis Techniques 159
ELECTROPHORESIS 159
SERUM PROTEIN ELECTROPHORESIS 160
Principle 160
Results 161
Reference Values 161
Clinical Interpretation 161
IMMUNOFIXATION ELECTROPHORESIS 161
Principle 162
Interpretation 162
Clinical Applications 163
Follow-Up Laboratory Testing 163
CAPILLARY ELECTROPHORESIS 163
?CASE STUDY 11.1 164
CHAPTER HIGHLIGHTS 164
REVIEW QUESTIONS 164
BIBLIOGRAPHY 165
12 - Labeling Techniques in Immunoassay 166
IMMUNOASSAY FORMATS 167
TYPES OF LABELS 167
Immunoassays 167
Radioimmunoassay 167
Solid-Phase Immunoassays 167
Antigen Detection 168
Antibody Detection 168
Noncompetitive Enzyme Immunoassay 168
Competitive Enzyme Immunoassay 168
Capture Enzyme Immunoassay 169
Multiple and Portable Enzyme-Linked Immunosorbent Assay 169
Enzyme Immunoassay Modification 170
CHEMILUMINESCENCE 170
Direct Labels 170
Indirect Labels 170
Specific Clinical Applications 170
IMMUNOFLUORESCENCE 171
Stage 1: Excitation 171
Stage 2: Excited-State Lifetime 171
Stage 3: Fluorescent Emission 171
Direct Immunofluorescent Assay 171
Inhibition Immunofluorescent Assay 172
Indirect Immunofluorescent Assay 172
ALTERNATIVE LABELING TECHNOLOGIES 173
Signal Amplification Technology 173
Magnetic Labeling Technology 173
Time-Resolved Fluoroimmunoassay 173
Fluorescence Polarization Immunoassay 174
Fluorescence In Situ Hybridization 174
CHAPTER HIGHLIGHTS 175
REVIEW QUESTIONS 175
BIBLIOGRAPHY 176
13 - Flow Cytometry 177
CHARACTERISTICS OF INSTRUMENTATION 177
FLOW CELL CYTOMETRY 178
Fundamentals of Laser Technology 178
Principles of Cell Cytometry 178
Fluorophores 178
Fluorochromes and Conjugated Antibodies 179
The Flow Process 179
The Use of Monoclonal Antibodies 179
Immunofluorescence 180
Tandem Dyes for Flow Cytometry 180
A Multicolor System 180
The Luminex Flow Cytometry System 181
Sample Preparation 182
Clinical Immunology Applications 182
Lymphocyte Subsets 182
Other Cellular Applications 182
CHAPTER HIGHLIGHTS 185
REVIEW QUESTIONS 185
BIBLIOGRAPHY 186
14 - Molecular Laboratory Techniques 187
CHARACTERISTICS OF NUCLEIC ACIDS 188
How Does Deoxyribonucleic Acid Replicate? 188
Forms of Ribonucleic Acid 189
AMPLICONS AND AMPLICON CONTROL MEASURES 189
Polymerase Chain Reaction 189
Modified Polymerase Chain Reaction Techniques 191
Reverse Transcriptase Polymerase Chain Reaction 191
Multiplex Polymerase Chain Reaction 191
Real-Time Polymerase Chain Reaction 191
Other Methods of Amplification 191
Transcription-Mediated Amplification 192
Strand Displacement Amplification 192
Nucleic Acid Sequence–Based Amplification 192
ANALYSIS OF AMPLIFICATION PRODUCTS 192
Conventional Analysis 192
Other Techniques 192
Deoxyribonucleic Acid Sequencing 192
Branched Deoxyribonucleic Acid 192
Hybridization Techniques 192
Blotting Protocols 193
Fluorescence In Situ Hybridization 194
Principle of the Fluorescence In Situ Hybridization Technique 194
Use of Fluorescence In Situ Hybridization in the Clinical Laboratory 194
Microarrays 194
NEXT-GENERATION SEQUENCING TECHNOLOGY 197
Target Enrichment Strategies 197
Steps of Next-Generation Sequencing 198
TARGETED SEQUENCING 198
Single Nucleotide Polymorphisms 199
MORE APPLICATIONS OF MOLECULAR DIAGNOSTIC TESTING 199
CHAPTER HIGHLIGHTS 200
REVIEW QUESTIONS 200
BIBLIOGRAPHY 201
III - Immunologic Manifestationsof Infectious Diseases 203
15 -\rInfectious Diseases: Traditional and Alternate Diagnostic Techniques 204
CHARACTERISTICS OF INFECTIOUS DISEASES 205
DEVELOPMENT OF INFECTIOUS DISEASES 205
TRADITIONAL INFECTIOUS DISEASES LABORATORY TESTING 205
TORCH Test Panel 205
BACTERIAL DISEASES 206
PARASITIC DISEASES 206
FUNGAL DISEASES 206
Histoplasmosis 207
Aspergillosis 207
Coccidioidomycosis 208
North American Blastomycosis 208
Sporotrichosis 208
Cryptococcosis 208
VIRAL, RICKETTSIAL, AND MYCOPLASMAL DISEASES 208
Dengue Fever 209
Herpesviruses 209
Herpes Simplex Virus 209
Congenital and Neonatal Infection 210
IV - Immune Disorders 363
25 - Hypersensitivity Reactions 364
WHAT IS HYPERSENSITIVITY? 365
WHAT IS AN ALLERGY? 365
TYPES OF ANTIGENS AND REACTIONS 365
Environmental Substances 365
Infectious Agents 365
Self Antigens 365
Food Allergies 365
TYPES OF HYPERSENSITIVITY REACTIONS 365
Type I Anaphylactic Reactions 366
Etiology 366
Immunologic Activity 366
Signs and Symptoms 367
Testing for Type I Hypersensitivity Reactions 368
Laboratory Evaluation of Allergic Reactions 368
Treatment 370
Type II Cytotoxic Reactions 370
Examples of Antibody-Dependent, Complement-Mediated Cytotoxic Reactions 371
Type III Immune Complex Reactions 373
Mechanism of Tissue Injury 373
Clinical Manifestations 374
Testing for Type III Hypersensitivity Reactions 374
Treatment 374
Type IV Cell-Mediated Reactions 374
Characteristics 375
Latex Sensitivity 375
Testing for Delayed Hypersensitivity 376
Treatment 376
Comparison of Types of Hypersensitivity 376
CHAPTER HIGHLIGHTS 379
REVIEW QUESTIONS 379
BIBLIOGRAPHY 381
26 - Immunoproliferative Disorders 382
GENERAL CHARACTERISTICS OF GAMMOPATHIES 383
Monoclonal Gammopathies 383
Polyclonal Gammopathies 383
MULTIPLE MYELOMA 383
Etiology 383
Pathophysiology 383
Epidemiology 385
Signs and Symptoms 385
Skeletal Abnormalities 385
Hematologic Features 385
Renal Disorders 385
Neurologic Features 387
Infectious Diseases 387
Immunologic Manifestations 387
Diagnostic Evaluation 387
Hematologic Assessment 387
Molecular Testing 387
Bence Jones Proteins 388
Free Light Chains 388
Immunologic Testing 389
Prognosis 390
Treatment 390
WALDENSTRÖM’S PRIMARY MACROGLOBULINEMIA 390
Etiology 390
Epidemiology 391
Signs and Symptoms 391
Skeletal Features 391
Hematologic Abnormalities 391
Renal Dysfunction 391
Ocular Manifestations 391
Neuropsychiatric Problems 391
Cardiopulmonary Abnormalities 391
Cutaneous Manifestations 391
Immunologic Manifestations 392
Diagnostic Evaluation 392
Hematologic Assessment 392
Immunologic Assessment 392
Treatment 392
OTHER MONOCLONAL DISORDERS 392
Monoclonal Gammopathy of Undetermined Significance 392
Light-Chain Disease 393
Heavy-Chain Disease 393
CHAPTER HIGHLIGHTS 394
REVIEW QUESTIONS 394
BIBLIOGRAPHY 396
27 - Tolerance, Autoimmunity, and Autoimmune Diseases 397
IMMUNOLOGIC TOLERANCE 398
Maintenance of Self-Tolerance 398
T-Cell Tolerance 398
B-Cell Tolerance 399
FACTORS INFLUENCING DEVELOPMENT OF AUTOIMMUNITY 399
Genetic Factors 399
Patient Age 399
Exogenous Factors 399
Immunopathogenic Mechanisms 399
MAJOR AUTOANTIBODIES 401
AUTOIMMUNE DISEASE 401
INNATE IMMUNE SYSTEM 401
ADAPTIVE IMMUNE RESPONSE 402
COMPARISON OF ORGAN-SPECIFIC AND ORGAN-NONSPECIFIC AUTOIMMUNE DISEASES 402
ORGAN-SPECIFIC AND MIDSPECTRUM DISEASES 403
Cardiovascular Diseases 403
Vasculitis 403
Carditis 403
Collagen Vascular Diseases 404
Progressive Systemic Sclerosis (Scleroderma) 404
Eosinophilia-Myalgia Syndrome 404
Endocrine Gland Diseases: Thyroid Disease 404
Lymphoid (Hashimoto’s) Chronic Thyroiditis 404
Immunologic Manifestations 405
Diagnostic Evaluation 405
Graves’ Disease 406
Pancreatic Diseases 406
Insulin-Dependent Diabetes Mellitus 406
Latent Autoimmune Diabetes in Adults 407
Autoimmune Pancreatitis 407
Adrenal Glands 408
Pituitary Gland 409
Parathyroid Gland 409
Polyglandular Syndromes 409
Reproductive Diseases 409
Exocrine Gland Disease 409
Sjögren’s Syndrome 409
Gastrointestinal Diseases 410
Atrophic Gastritis and Pernicious Anemia 410
Autoimmune Liver Disease 411
Idiopathic Biliary Cirrhosis 411
Inflammatory Bowel Disease 412
Immune Markers 412
Celiac Disease 412
Other Gastrointestinal Tract Immunologic Diseases 414
Autoimmune Hematologic Diseases 414
Autoimmune Lymphoproliferative Syndrome 414
Autoimmune Hemolytic Anemia 414
Idiopathic Thrombocytopenic Purpura 415
Neuromuscular Diseases 416
Amyotrophic Lateral Sclerosis 416
Inflammatory Polyneuropathies 416
Myasthenia Gravis 416
Multiple Sclerosis 416
Neuropathies 418
Renal Diseases 419
Renal Disease Associated With Circulating Immune Complexes 419
Membranoproliferative Glomerulonephritis 419
Renal Disease Associated With Anti–Glomerular Basement Membrane Antibody 419
Tubulointerstitial Nephritis 420
Skeletal Muscle Diseases 420
Inflammatory Myopathy 420
Skin Diseases: Bullous Disease and Other Conditions 421
CHAPTER HIGHLIGHTS 423
REVIEW QUESTIONS 423
BIBLIOGRAPHY 426
28 - Systemic Lupus Erythematosus 428
DIFFERENT FORMS OF LUPUS 429
Discoid Lupus 429
Systemic Lupus Erythematosus 429
Drug-Induced Lupus 430
Neonatal Lupus 430
ETIOLOGY 430
Genetic Predisposition 430
Environmental Factors 430
Hormonal Influences 431
Antibiotics 431
Vitamins 431
EPIDEMIOLOGY 431
SIGNS AND SYMPTOMS 432
Infection 432
Cutaneous Features 433
Renal Characteristics 433
Lymphadenopathy 433
Serositis 433
Cardiopulmonary Characteristics 434
Gastrointestinal Manifestations 434
Musculoskeletal Features 434
Neuropsychiatric Features 434
Late-Onset Lupus 434
IMMUNOLOGIC MANIFESTATIONS 434
Cellular Aspects 435
Humoral Aspects 435
Immunologic Consequences 435
DIAGNOSTIC EVALUATION 436
Histologic Changes 436
Hematologic and Hemostatic Findings 436
Hemostatic Testing 436
Serologic Findings 436
Complement 436
Antibodies 437
Antinuclear Antibodies 437
Laboratory Evaluation 438
Indirect Immunofluorescent Tests for Antinuclear Antibody 438
Indirect Immunofluorescent Technique 439
Rapid Slide Test for Antinucleoprotein 441
Autoimmune Enzyme Immunoassay 441
Automated Testing: Multiplex Immunoassay 441
TREATMENT 442
Rituximab 442
CHAPTER HIGHLIGHTS 445
REVIEW QUESTIONS 445
BIBLIOGRAPHY 446
29 - Rheumatoid Arthritis 447
ETIOLOGY 448
EPIDEMIOLOGY 448
SIGNS AND SYMPTOMS 448
ANATOMY AND PHYSIOLOGY OF JOINTS 448
IMMUNOLOGIC MANIFESTATIONS 450
DIAGNOSTIC EVALUATION 452
Rheumatoid Factor 452
Cyclic Citrullinated Peptide Antibodies 452
Other Markers 452
Immune Complexes 452
Complement Levels 453
V - Transplantation andTumor Immunology 461
30 - Transplantation: HLA, Solid Organ, and Hematopoietic Stem Cells 462
HISTOCOMPATIBILITY ANTIGENS 463
Nomenclature of Human Leukocyte Antigen Alleles 463
Major Histocompatibility Complex Regions 464
Classes of Human Leukocyte Antigen Molecules 464
Role of Major Histocompatibility Complex and Human Leukocyte Antigens 465
The Impact of Human Leukocyte Antigens 466
Evaluation of Potential Transplant Recipients and Donors 466
Human Leukocyte Antigen Techniques 466
Complement-Mediated Cytotoxicity 466
Solid-Phase Enzyme-Linked Immunosorbent Assay 467
Flow Cytometry 468
Molecular Techniques 468
Bead Technology 469
Donor-Specific Antibody Tests 469
TRANSPLANTATION TERMINOLOGY 469
GENERAL FACTS ABOUT TRANSPLANTATION 469
Organ Transplantation 469
Hematopoietic Stem Cells 470
TYPES OF TRANSPLANTS 470
Bone 470
Cornea 471
Heart 471
Heart Valves 471
Intestine 472
Kidney 472
Liver 472
Lung 472
Pancreas 472
Skin 473
Hematopoietic or Peripheral Blood Stem Cells 473
SOURCES OF STEM CELLS FOR TRANSPLANTATION 474
Bone Marrow 474
Peripheral Blood Stem Cells 474
Umbilical Cord Blood 474
Issue Related to Cord Blood Transplantation 475
Engraftment 475
The Impact of HLA Matching 475
GRAFT REJECTION 475
First-Set and Second-Set Rejections 476
Hyperacute Rejection 476
Accelerated Rejection 476
Acute Rejection 476
Chronic Rejection 478
MECHANISMS OF REJECTION 478
General Characteristics 478
Role of T Cells 478
Antibody Effects 479
Immunosuppression 479
Pharmacologic Activity of Representative Immunosuppressant Drugs 481
Azathioprine 481
Corticosteroids 481
Cyclosporine (Cyclosporin A) 481
Tacrolimus 481
Sirolimus 482
Mycophenolate Mofetil 482
Antilymphocyte (Antithymocyte) Globulin 482
Nulojix 482
Monoclonal Antibodies 482
Immunosuppressive Protocols 482
New Approaches in Immunosuppression 482
TRANSPLANTATION COMPLICATIONS 482
Post–Organ Transplantation 482
Infectious Diseases 482
Cancer 483
Osteoporosis 483
Diabetes 483
Hypertension 483
Hypercholesterolemia 483
Post–Stem Cell Transplantation 483
Xenotransplantation 483
BIOMARKERS FOR REJECTION 484
FOXP3 MRNA 484
GRAFT-VERSUS-HOST DISEASE 484
Etiology 485
Epidemiology 485
Signs and Symptoms 485
Immunologic Manifestation 485
Diagnostic Evaluation 486
Prevention 486
High-Risk Patients 486
Intermediate-Risk Patients 486
Low-Risk Patients 486
Effects of Radiation on Specific Cellular Components 487
CURRENT DIRECTIONS 487
CHAPTER HIGHLIGHTS 488
REVIEW QUESTIONS 489
BIBLIOGRAPHY 491
31 - Tumor Immunology and Up-to-Date Applications of Next-Generation Sequencing 493
CANCER STEM CELLS 494
TYPES OF TUMORS 494
Benign Tumors 494
Malignant Tumors 494
EPIDEMIOLOGY 495
Cancer in Adults 495
Cancer in Children 495
Risk Factors 496
CAUSATIVE FACTORS IN HUMAN CANCER 496
Environmental Factors 496
Microbial Carcinogens 497
Host Factors and Disease Associations 497
THE IMPACT OF SOMATIC MUTATIONS 498
Driver, Actionable, and Passenger Mutations 498
STAGES OF CARCINOGENESIS 498
CANCER-PREDISPOSING GENES 499
PROTO-ONCOGENES 499
p53 or tp53 gene 499
ROLE OF ONCOGENES 500
Mechanisms of Activation 500
Viral Oncogenes 500
Tumor-Suppressing Genes 500
BODY DEFENSES AGAINST CANCER 501
T Lymphocytes 501
Natural Killer Cells 501
Macrophages 502
Antibodies 502
TUMOR MARKERS 502
Categories of Tumor Antigens 504
Tumor-Specific Antigens 505
Tumor-Associated Antigens 505
Carcinofetal Antigens 505
Spontaneous Tumor Antigens 505
Classic Tumor Markers 505
Alpha-Fetoprotein 505
CA 125 505
Human Epididymis Protein 4 505
Thyroglobulin 506
Prostate-Specific Antigen and Prostatic Acid Phosphatase 506
Carcinoembryonic Antigen 506
CA 19-9 506
CA 15-3 506
CA 27.29: Breast Carcinoma–Associated Antigen 507
HER2 (HER2/neu) 507
Other Cancer Biomarkers 507
β-Human Chorionic Gonadotropin (β-Beta Subunit) 507
Miscellaneous Enzyme Markers 507
Miscellaneous Hormone Markers 507
Breast, Ovarian, and Cervical Cancer Markers 508
Epidermal Growth Factor Receptor 508
Molecular Diagnosis of Breast Cancer 508
Bladder Cancer 508
DNA MICROARRAY TECHNOLOGY 508
WHAT’S NEW IN CANCER DIAGNOSTIC TESTING? 509
Next-Generation Sequencing 509
Identification of Somatic Mutations 509
Detection of Low Levels of Genomic Alterations 509
Improved Management of Cancer Treatment 509
Continuous Field-Flow–Assisted Dielectropheresis 509
MODALITIES FOR TREATING CANCER 509
Chemotherapeutic Agents 509
Cell Cycle Active, Phase Specific 509
Cell Cycle Active, Phase Nonspecific 510
Non–Cell Cycle Active 510
Cytokines 510
Effects of Drug-Induced Immunosuppression 511
Monoclonal Antibody Therapy 511
What’s New in Therapy? 512
CHAPTER HIGHLIGHTS 514
REVIEW QUESTIONS 514
BIBLIOGRAPHY 516
VI - Vaccines 518
32 - Primer on Vaccines 519
THE GOAL OF VACCINATION 520
WHAT IS A VACCINE? 520
HISTORY OF VACCINES 520
TYPES OF VACCINES 520
Live, Attenuated Vaccines 520
INACTIVATED VACCINES 521
Subunit Vaccines 521
ADJUVANTS 521
Toxoid Vaccines 521
Conjugate Vaccines 521
DNA Vaccines 521
Recombinant Vector Vaccines 523
SITES OF VACCINE ADMINISTRATION 523
HOST RESPONSE TO VACCINATION 523
RATES OF VACCINATION 524
REPRESENTATIVE VACCINES 524
Chikungunya Vaccine 524
Dengue Fever Vaccine 524
Hay Fever Vaccine 524
Herpes Zoster (Shingle) Vaccine 525
HIV-AIDS 525
HIV 525
Vaccine Development 525
Vaccine Problems 525
Clinical Trials 526
Vaccine Expectations 526
Influenza 527
CANCER VACCINES 527
Prophylactic Vaccines 527
Gardasil 527
Cervarix 528
Cancer Treatment Vaccines 528
Clinical Trials 528
New Treatments 528
Leukemia 528
VACCINES IN BIODEFENSE 529
Smallpox 529
Category A Agents 529
Smallpox Vaccine 529
Vaccine Administration 529
Anthrax 529
SAFETY ISSUES 529
Concerns About Vaccines 529
Vaccine Side Effects and Adverse Events 530
Monitoring Adverse Events to Vaccines 530
CHAPTER HIGHLIGHTS 531
REVIEW QUESTIONS 531
BIBLIOGRAPHY 532
A - Answers to Case Study Multiple Choice Questions 533
CHAPTER 1: AN OVERVIEW OF IMMUNOLOGY 533
CHAPTER 2: ANTIGENS AND ANTIBODIES 533
CHAPTER 3: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM: GRANULOCYTES AND MONONUCLEAR CELLS 533
CHAPTER 4: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM: LYMPHOCYTES AND PLASMA CELLS 533
CHAPTER 5: SOLUBLE MEDIATORS OF THE IMMUNE SYSTEM 533
CHAPTER 6: SAFETY IN THE IMMUNOLOGY-SEROLOGY LABORATORY 533
CHAPTER 7: QUALITY ASSURANCE AND QUALITY CONTROL 533
CHAPTER 8: BASIC SEROLOGIC LABORATORY TECHNIQUES 533
CHAPTER 9: POINT-OF-CARE TESTING 533
CHAPTER 10: AGGLUTINATION METHODS 533
CHAPTER 11: ELECTROPHORESIS TECHNIQUES 533
CHAPTER 12: LABELING TECHNIQUES IN IMMUNOASSAY 533
CHAPTER 13: AUTOMATED PROCEDURES 533
CHAPTER 14: MOLECULAR TECHNIQUES 534
CHAPTER 15: THE IMMUNE RESPONSE IN INFECTIOUS DISEASES 534
CHAPTER 16: STREPTOCOCCAL INFECTIONS 534
CHAPTER 17: SYPHILIS 534
CHAPTER 18: VECTOR-BORNE DISEASES 534
CHAPTER 19: TOXOPLASMOSIS 534
CHAPTER 20: CYTOMEGALOVIRUS 534
CHAPTER 21: INFECTIOUS MONONUCLEOSIS 534
CHAPTER 22: VIRAL HEPATITIS 534
CHAPTER 23: RUBELLA INFECTION 534
CHAPTER 24: ACQUIRED IMMUNODEFICIENCY SYNDROME 534
CHAPTER 25: HYPERSENSITIVITY REACTIONS 534
CHAPTER 26: IMMUNOPROLIFERATIVE DISORDERS 535
CHAPTER 27: AUTOIMMUNE DISORDERS 535
CHAPTER 28: SYSTEMIC LUPUS ERYTHEMATOSUS 535
CHAPTER 29: RHEUMATOID ARTHRITIS 535
CHAPTER 30: SOLID ORGAN TRANSPLANTATION 535
CHAPTER 31: TUMOR IMMUNOLOGY 535
CHAPTER 32: VACCINES 535
B - Answers to Review Questions 536
CHAPTER 1: AN OVERVIEW OF IMMUNOLOGY 536
CHAPTER 2: ANTIGENS AND ANTIBODIES 536
CHAPTER 3: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM: GRANULOCYTES AND MONONUCLEAR CELLS 536
CHAPTER 4: CELLS AND CELLULAR ACTIVITIES OF THE IMMUNE SYSTEM: LYMPHOCYTES AND PLASMA CELLS 536
CHAPTER 5: SOLUBLE MEDIATORS OF THE IMMUNE SYSTEM 536
CHAPTER 6: SAFETY IN THE IMMUNOLOGY-SEROLOGY LABORATORY 537
CHAPTER 7: QUALITY ASSURANCE AND QUALITY CONTROL 537
CHAPTER 8: BASIC SEROLOGIC LABORATORY TECHNIQUES 537
CHAPTER 9: POINT-OF-CARE TESTING 537
CHAPTER 10: AGGLUTINATION METHODS 537
CHAPTER 11: ELECTROPHORESIS TECHNIQUES 537
CHAPTER 12: LABELING TECHNIQUES IN IMMUNOASSAY 537
CHAPTER 13: FLOW CYTOMETRY 537
CHAPTER 14: MOLECULAR TECHNIQUES 537
CHAPTER 15: INFECTIOUS DISEASES: TRADITIONAL AND ALTERNATE DIAGNOSTIC TECHNIQUES 537
CHAPTER 16: STREPTOCOCCAL INFECTIONS 537
CHAPTER 17: SYPHILIS 538
CHAPTER 18: VECTOR-BORNE DISEASES 538
CHAPTER 19: TOXOPLASMOSIS 538
CHAPTER 20: CYTOMEGALOVIRUS 538
CHAPTER 21: INFECTIOUS MONONUCLEOSIS 538
CHAPTER 22: VIRAL HEPATITIS 538
CHAPTER 23: RUBELLA INFECTION 538
CHAPTER 24: ACQUIRED IMMUNODEFICIENCY SYNDROME 538
CHAPTER 25: HYPERSENSITIVITY REACTIONS 538
CHAPTER 26: IMMUNOPROLIFERATIVE DISORDERS 538
CHAPTER 27: AUTOIMMUNE DISORDERS 538
CHAPTER 28: SYSTEMIC LUPUS ERYTHEMATOSUS 538
CHAPTER 29: RHEUMATOID ARTHRITIS 539
CHAPTER 30: TRANSPLANTATION:HLA, SOLID ORGAN, HEMATOPOIETIC STEM CELLS 539
CHAPTER 31: TUMOR IMMUNOLOGY AND UP-TO-DATE APPLICATIONS 539
CHAPTER 32: A PRIMER ON VACCINES 539
C - Origin and Immunoregulatory Activity of Cytokines 540
GLOSSARY 544
A 544
B 546
C 546
D 548
E 549
F 550
G 551
H 552
I 553
J 556
K 556
L 556
M 557
N 558
O 559
P 559
Q 561
R 561
S 562
T 564
U 565
V 565
W 565
X 565
Z 565
INDEX 566
A 566
B 568
C 569
D 570
E 571
F 571
G 572
H 572
I 574
K 577
L 577
M 578
N 580
O 580
P 581
Q 582
R 582
S 583
T 586
U 587
V 587
W 589
X 589
Y 589
Z 589