Immune-Mediated Disease in Clinical Practice Flashcards
What are the traditional classifications of immune-mediated disease?
Primary = idiopathic
Secondary
What underlying factors need to be eliminated to determine a primary immune-mediated disease?
Drug usage, neoplasia or infection
What are some organ specific immune-mediated diseases?
Myasthenia gravis
Immune-mediated neutropaenia/anaemia
What is the pathogenesis of immune-mediated disease?
Immune system over-reacts to normal body tissues or harmless exogenous proteins otherwise known as a loss of tolerance
Both humoral and cellular mechanisms of tissue damage recognised
What are the potential trigger factors for immune-mediated disease?
Release of sequestered antigens Abnormal immunoregulation Molecular mimicry Polyclonal activation of T and B cells Exposure of cryptic epitopes or haptenisation of foreign moecules to self antigens
What is the role of infection in immune-mediated disease?
Breakdown of vascular/cellular barriers allowing exposure to self-antigens
Promotion of cell death by necrosis causing inflammation (bystander activation)
Polyclonal activation of T cells by bacterial superantigen
Molecular mimicry leading to cross reactivity
Vector borne pathogens may be important in some parts of the world
What is the aetiology of immune-mediated disease?
Unclear and likely to be multifactorial in most cases
Genetic, infectious and hormonal influences
Canine examples of SLE (genetics,C-type viruses), IMHA (vaccinal antigens) IMPA (vaccinal antigens)
Is there a typical signalment for immune-mediated disease?
Idiopathic immune-mediated disease over-represented in juvenile to middle-aged patients
What is a classic history and physical exam for a patient with immune-mediated disease?
Remission and exacerbation
Lameness, mucocutaneous junction lesions, lethargy, dyspnoea, weight loss, PU/PD, +/- seizures or behavioural changes
Effusive painful joints, cutaneous erythema, macules, papules, pustules, erosion, pallor +/- petechiae, cardiac arrhythmias, lymphadenomegaly +/- splenomegaly
What diseases can CBC can be useful in diagnosing immune-mediated disease?
Anaemia - regenerative = IMHA
Thrombocytopaenia = I-M thrombocytopenia
Leucopaenia - anti-leucocyte antibodies = SLE
Coagulation abnormalities = SLE/DIC
How can biochemistry aid diagnosis of immune-mediated disease?
Azotaemia, increase inorganic phosphate = chronic glomerular lesions
Hypoalbuminaemia/hypercholesterolaemia = PLN
Hyperbilirubinaemia = pre-hepatic/haemolysis
Hyperglobulinaemia = inflammatory disease/polyclonal B cell activation
Increase CK and lactate dehydrogenase = polymyositis/ myocarditis
How does urinalysis aid diagnosis of immune-mediated disease?
Proteinuria = PLN (rule out UTI/other infection)
Haematureia, pyuria, erythrocyte casts - rule out UTI, compatible with membranoproliferative GN
How are radiography and arthrocentesis helpful in diagnosing immune-mediated disease?
Joint lesions common in polysystemic I-M disease usually as a non-erosive pauciarthropathy
Erosive lesions suggest an overlap syndrome
Arthritis isn’t always clinically obvious
Synovial fluid - increase WBC/proportion of neutrophils +/- increase in protein content with decreased viscosity and poor mucin clot formation
What is Coombs’ test used to diagnose?
IMHA but false positives and negative possible
Antibodies to RBCs cause cells to agglutinate
What are AChR autoantibodies used to diagnose?
Acquired myasthenia gravis
Nocotinic AChR autoAb detected by immunoprecipitation RIA
What are antinuclear antibodies (ANA) used to diagnose?
SLE
Indirect immunofluorescence or immunoperoxidase test
What are biopsies useful in diagnosing?
Mucocutaneous lesions across interface with normal tissue
How is central tolerance achieved?
Thymic selection
What are the intrinsic methods of peripheral tolerance?
Ignorance
Deletion
Phenotypic skewing
Anergy
What are the extrinsic methods of peripheral tolerance?
Tolerogenic dendritic cells
Treg: Tr1, Th3, CD4+, CD25+
What is the type I Coombs and Gel response?
Priming of naive T cell by dendritic cell which then sensitises B cells to antigen
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What does the type I Coombs and Gel response result in?
Degranulation with inflammatory mediators, pruritis, bronchoconstriction, vasodilation, oedema and eosinophil chemotaxis
What is the type II Coombs and Gel response?
Complement mediated lysis by cytotoxicty of NK cells and phagocytosis by macrophages
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What is the type III Coombs and Gel response?
Immune complexes form on endothelial basement membrane causing complement activation, neutrophil and basophil activation, platlet and clotting factor activation and increased vascular permeability
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What is the type IV Coombs and Gel response?
Priming of naive T cell, Th1 effector function, Endothelial activation, Local inflammation
What are the different methods that tick borne diseases can cause immune-mediated disease?
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What is masticatory muscle myositis (MMM)?
Idiopathic immune-mediated disease of 2M myofibres directed specifically at myosin
Clinical signs - swelling +/- eventual atrophy of masticatory muscles
Diagnosis by demostrating autoAb to 2M myofibres
What is the antiplatelet antibody test?
Indirect immunofluorescence test with substrate comprising of PLTs from healthy donor and is considered when immune-mediated thrombocytopaenia is a DDx
What is rheumatoid factor?
Non-specific autoantibody to IgG that may be found at low titre in animals with a range of infectious, inflammatory and neoplastic diseases but high titres characterise rheumatoid arthritis
Why would thyroglobulin autoAb be tested for?
Lymphocytic thyroiditis is thought to represent an autoimmune disease and Ab against thyroid antigens are released during ensuing inflammation
