Cover -- Title Page -- Copyright Page -- Contents -- List of Contributors -- Preface -- About the Companion Website -- Section 1 A Primer for the Clinician -- Chapter 1 A Clinician's Guide to the Immune System: Innate and Adaptive Immunity -- 1.1 Introduction:Innate Versus Adaptive Immunity -- 1.2 The Innate Response -- An Immediate Front Line of Defense -- 1.2.1 Physical Barriers and Cells -- 1.2.2 Pathogen Recognition and Discrimination -- 1.2.3 Cellular Communication -- 1.2.4 The Complement System -- 1.3 TheAdaptive Response -Specialized Cells with Specificity and Memory -- 1.3.1 Generation of Diversity: Antigen Receptors -- 1.3.2 Antigen-Presenting Cells -- 1.3.3 T Cells -- 1.3.3.1 Origins and Importance -- 1.3.3.2 Phenotypic Diversity -- 1.3.4 B Cells -- 1.4 Blurringthe Lines Between Innate and Adaptive Immunity -- 1.5 Regulationof the Immune Response -- 1.6 CellDeath Mechanisms -- 1.7 Microbiotaand Immunity -- 1.8 Areas for Further Research -- Companion Website -- Key References -- Chapter 2 Pathophysiology of Immune-Mediated Disease -- 2.1 Introduction -- 2.2 A Brief History of Tolerance -- 2.3 Immune Tolerance in Clinical Medicine -- 2.3.1 Selection of T and B Cells -- 2.3.2 Regulatory T Cells -- 2.3.3 Regulation of Lymphocyte Activation -- 2.3.4 Innate Immune Tolerance -- 2.3.5 Regulation by Cytokines -- 2.3.6 Heterogeneity in Immune Tolerance -- 2.4 Clinical Spectrum of Immune-Mediated Diseases -- 2.4.1 Autoimmune Diseases -- 2.4.2 Autoinflammatory Diseases -- 2.4.3 Allergy and Anaphylaxis -- 2.5 Risk Factors for Autoimmune Disease -- 2.5.1 Genetic Predisposition -- 2.5.2 Epigenetic Landscape -- 2.5.3 Immune Tolerance and the Microbiome -- 2.5.4 Molecular Mimicry -- 2.5.5 Superantigens -- 2.6 Areas for Further Research -- Companion Website -- Key References -- Chapter 3 Immunogenetics: The Final Frontier -- 3.1 Introduction.

3.2 Types of Genetic Variation -- 3.2.1 Single Nucleotide Polymorphisms (SNPs) -- 3.2.2 Indels (Insertions and/or Deletions) -- 3.2.3 Copy Number Variants (CNVs) -- 3.2.4 Inversions and Chromosomal Rearrangements -- 3.3 Investigating Genetic Variation -- 3.3.1 Candidate Gene Study -- 3.3.2 Linkage Analysis -- 3.3.3 Genome-Wide Association Study (GWAS) -- 3.3.4 Next-Generation Sequencing Technology -- 3.4 Challenges in Understanding Genetic Risk in Complex Diseases -- 3.4.1 Complexity of Genetic Predisposition -- 3.4.2 The Role of the Environment -- 3.4.3 Phenocopies of Disease -- 3.4.4 Age-Matched, Healthy Control Samples for Case-Control Studies -- 3.4.5 Population Structure -- 3.4.6 The Concept of "Fixed Disease Risk" Within Certain Breeds or Populations -- 3.4.7 Knowledge of Normal Variation in the Canine and Feline Genome -- 3.4.8 Epigenetic Influences -- 3.4.9 Genes of the Major Histocompatibility Complex -- 3.5 The Canine MHC -- 3.6 The Feline MHC -- 3.7 Non-MHC Regions -- 3.7.1 Genetic Polymorphism in Cytokines, Chemokines, and Their Receptors -- 3.7.2 Transporters Associated with Antigen Processing -- 3.8 Clinical Examples of Genetic Influences -- 3.8.1 Immune-Mediated and Autoimmune Diseases -- 3.8.2 Onco-Immunology -- 3.8.3 Immunodeficiency -- 3.8.4 Innate Immune Responses to Pathogens -- 3.8.5 Infectious Disease Susceptibility -- 3.8.6 Vaccination Responses -- 3.8.7 Transplantation -- 3.9 Areas for Further Research -- Companion Website -- Key References -- Chapter 4 Vector-Borne Pathogens and Immune-Mediated Disease -- 4.1 Introduction -- 4.2 Mechanisms of Infection and Loss of Immune Tolerance -- 4.3 Vector-Borne Organisms as a Cause of Immune-Mediated Disease? -- 4.3.1 Overview -- 4.3.2 Immune-Mediated Hemolytic Anemia -- 4.3.2.1 Pathophysiology -- 4.3.2.2 Babesia species -- 4.3.2.3 Hemotropic Mycoplasma -- 4.3.2.4 Bartonella species.

4.3.2.5 Anaplasma species -- 4.3.2.6 Ehrlichia species -- 4.3.2.7 Other organisms -- 4.3.3 Immune Thrombocytopenia -- 4.3.3.1 Pathophysiology -- 4.3.3.2 Vector-borne Organisms -- 4.3.4 Immune-Mediated Polyarthritis -- 4.3.4.1 Classification -- 4.3.4.2 Pathophysiology -- 4.3.4.3 Leishmania species -- 4.3.4.4 Borrelia burgdorferi -- 4.3.4.5 Anaplasma phagocytophilum -- 4.3.4.6 Ehrlichia species -- 4.3.4.7 Bartonella species -- 4.3.4.8 Rickettsia rickettsii -- 4.3.4.9 Dirofilaria immitis -- 4.3.5 Protein-Losing Nephropathy (PLN) -- 4.3.5.1 Pathophysiology -- 4.3.5.2 Leishmania species -- 4.3.5.3 Dirofilaria immitis -- 4.3.5.4 Piroplasms -- 4.3.5.5 Ehrlichia canis -- 4.3.5.6 Borrelia burgdorferi -- 4.3.5.7 Anaplasma phagocytophilum -- 4.3.5.8 Bartonella species -- 4.4 Screening for Vector-Borne Pathogens -- 4.5 Consequences of Immunosuppression in Patients with Occult Vector-Borne Infections -- 4.6 Areas for Further Research -- Companion Website -- Key References -- Section 2 Diagnostic Approaches and Treatment -- Chapter 5 Diagnosing Immune-Mediated Disease: General Approach and Specific Tests -- 5.1 Introduction: General Approach -- 5.1.1 Clinical Reasoning -- 5.1.1.1 Introduction: Diagnostic Error and Clinical Reasoning -- 5.1.1.2 Types of Clinical Reasoning: Non-Analytical and Analytical -- 5.1.1.3 Problem-OrientedClinical Reasoning as an Analytical Reasoning Tool -- 5.1.1.4 Generating the Initial Problem List and Associated Differential Diagnoses -- 5.2 Specific Diagnostic Tests for Immune-Mediated Disease -- 5.2.1 General Concepts -- 5.2.2 Enzyme-Linked Immunosorbent Assays -- 5.2.3 Radioimmunoassays -- 5.2.4 Immunohistochemistry, Immunocytochemistry, and Immunofluorescent Assays -- 5.2.5 Flow Cytometry -- 5.2.6 Agglutination Assays -- 5.3 Specific Tests for Common Immune-Mediated Diseases -- 5.3.1 Immune-Mediated Hemolytic Anemia -- 5.3.1.1 Anemia.

5.3.1.2 Hemolysis -- 5.3.1.3 Anti-ErythrocyteAntibodies -- 5.3.2 Immune-Mediated Polyarthropathy (IMPA) -- 5.3.2.1 Synovial Fluid Cytology -- 5.3.2.2 Detection of Immunoglobulins -- 5.3.3 Immune Thrombocytopenia -- 5.3.4 Autoimmune Diseases Affecting the Neuromuscular System -- 5.3.4.1 Myasthenia Gravis -- 5.3.4.2 Masticatory Muscle Myositis (MMM) -- 5.3.5 Autoimmune Disease Affecting Multiple Organ Systems -- 5.3.6 Immune-Mediated Glomerulonephritis -- 5.3.7 Cutaneous Autoimmune Disease -- 5.3.8 Idiopathic Inflammatory Bowel Disease (IBD) -- 5.4 Areas for Further Research -- Companion Website -- Key References -- Chapter 6 Treating Immune-Mediated Disease: What to Use and When -- 6.1 Introduction -- 6.2 Systemic Immunosuppressive Therapy -- 6.2.1 Glucocorticoids -- 6.2.2 Cyclosporine -- 6.2.3 Mycophenolate Mofetil -- 6.2.4 Azathioprine -- 6.2.5 Leflunomide -- 6.2.6 Monitoring Response to Therapy -- 6.3 Targeted Organ Immunosuppression -- 6.3.1 Budesonide and Fluticasone -- 6.4 Immune-Mediated Blood Disorders: Other Treatment Considerations -- 6.4.1 Gastroprotectants -- 6.4.2 Human Intravenous Immunoglobulin (hIVIG) -- 6.4.3 Splenectomy -- 6.4.4 Therapeutic Plasma Exchange -- 6.4.5 Vincristine -- 6.5 Miscellaneous Anti-Inflammatory and Immunosuppressive Agents -- 6.6 Areas for Further Research -- Companion Website -- Key References -- Section 3 Specific Immune-Mediated Diseases -- Chapter 7 Blood and Hematopoietic System -- 7.1 Introduction -- 7.2 Pathobiology and Etiology -- 7.2.1 Immune-Mediated Hemolytic Anemia -- 7.2.2 Immune Thrombocytopenia -- 7.2.3 Immune-Mediated Neutropenia -- 7.3 Making a Diagnosis -- 7.3.1 Immune-Mediated Hemolytic Anemia -- 7.3.2 Immune Thrombocytopenia -- 7.3.3 Immune-Mediated Neutropenia -- 7.4 Immune-Mediated Blood Disorders: General Treatment Considerations -- 7.5 Areas for Further Research -- Companion Website.

Key References -- Chapter 8 Musculoskeletal System -- 8.1 Introduction -- 8.2 Pathobiology and Etiology -- 8.2.1 Immune-Mediated Polyarthritis -- 8.2.2 Polymyositis -- 8.2.3 Masticatory Muscle Myositis -- 8.3 Immune-Mediated Polyarthritis -- 8.3.1 Clinical Summary -- 8.3.1.1 Making a Diagnosis -- 8.3.1.2 Clinical Presentation -- 8.3.1.3 Classification -- 8.3.2 Treatment Options -- 8.3.2.1 MedicalTreatment -- 8.3.2.2 SurgicalTreatment -- 8.3.2.3 Monitoring for Treatment -- 8.3.3 Prognosis -- 8.4 Polymyositis -- 8.4.1 Clinical Summary -- 8.4.1.1 Making a Diagnosis -- 8.4.1.2 Clinical Presentation -- 8.4.2 Treatment Options -- 8.4.3 Prognosis -- 8.5 Masticatory Muscle Myositis -- 8.5.1 Clinical Summary -- 8.5.1.1 Making a Diagnosis -- 8.5.1.2 Clinical Presentation -- 8.5.2 Treatment Options -- 8.5.3 Prognosis -- 8.6 Areas for Further Research -- Companion Website -- Key References -- Chapter 9 Central and Peripheral Nervous System -- 9.1 Introduction -- 9.1.1 Pathobiology of the Nervous and Immune Systems -- 9.1.1.1 Relationships Between the Central Nervous and Immune Systems -- 9.1.1.2 Immune Surveillance During Homeostasis -- 9.1.1.3 Innate and Adaptive Immune Responses -- 9.1.1.4 Loss of Tolerance -- 9.1.1.5 The Concept of Neuroinflammation -- 9.1.1.6 The Immune System and Peripheral Nerves -- 9.1.2 Making a Diagnosis of Immune-Mediated Neurologic Disease -- 9.2 Specific Immune-Mediated Diseases of the Central Nervous System -- 9.2.1 Meningoencephalomyelitis in Dogs -- 9.2.1.1 Meningoencephalomyelitis of Unknown Origin -- 9.2.1.2 Granulomatous Meningoencephalitis, Necrotizing Meningoencephalitis and Necrotizing Leukoencephalitis -- Clinical Summary -- 9.2.1.3 Eosinophilic Meningoencephalitis -- 9.2.1.4 Meningoencephalitis in Greyhounds -- 9.2.1.5 Idiopathic Generalized Tremor Syndrome -- 9.2.2 Steroid-Responsive Meningitis-Arteritis.