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Principles of Clinical Immunology > Immune-Mediated Disease in Clinical Practice > Flashcards

Immune-Mediated Disease in Clinical Practice Flashcards

1
Q

What are the traditional classifications of immune-mediated disease?

A

Primary = idiopathic

Secondary

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2
Q

What underlying factors need to be eliminated to determine a primary immune-mediated disease?

A

Drug usage, neoplasia or infection

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3
Q

What are some organ specific immune-mediated diseases?

A

Myasthenia gravis

Immune-mediated neutropaenia/anaemia

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4
Q

What is the pathogenesis of immune-mediated disease?

A

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

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5
Q

What are the potential trigger factors for immune-mediated disease?

A 
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
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6
Q

What is the role of infection in immune-mediated disease?

A

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

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7
Q

What is the aetiology of immune-mediated disease?

A

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)

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8
Q

Is there a typical signalment for immune-mediated disease?

A

Idiopathic immune-mediated disease over-represented in juvenile to middle-aged patients

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9
Q

What is a classic history and physical exam for a patient with immune-mediated disease?

A

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

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10
Q

What diseases can CBC can be useful in diagnosing immune-mediated disease?

A

Anaemia - regenerative = IMHA
Thrombocytopaenia = I-M thrombocytopenia
Leucopaenia - anti-leucocyte antibodies = SLE
Coagulation abnormalities = SLE/DIC

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11
Q

How can biochemistry aid diagnosis of immune-mediated disease?

A

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

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12
Q

How does urinalysis aid diagnosis of immune-mediated disease?

A

Proteinuria = PLN (rule out UTI/other infection)

Haematureia, pyuria, erythrocyte casts - rule out UTI, compatible with membranoproliferative GN

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13
Q

How are radiography and arthrocentesis helpful in diagnosing immune-mediated disease?

A

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

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14
Q

What is Coombs’ test used to diagnose?

A

IMHA but false positives and negative possible

Antibodies to RBCs cause cells to agglutinate

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15
Q

What are AChR autoantibodies used to diagnose?

A

Acquired myasthenia gravis

Nocotinic AChR autoAb detected by immunoprecipitation RIA

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16
Q

What are antinuclear antibodies (ANA) used to diagnose?

A

SLE

Indirect immunofluorescence or immunoperoxidase test

17
Q

What are biopsies useful in diagnosing?

A

Mucocutaneous lesions across interface with normal tissue

18
Q

How is central tolerance achieved?

A

Thymic selection

19
Q

What are the intrinsic methods of peripheral tolerance?

A

Ignorance
Deletion
Phenotypic skewing
Anergy

20
Q

What are the extrinsic methods of peripheral tolerance?

A

Tolerogenic dendritic cells

Treg: Tr1, Th3, CD4+, CD25+

21
Q

What is the type I Coombs and Gel response?

A

Priming of naive T cell by dendritic cell which then sensitises B cells to antigen
IMAGE

22
Q

What does the type I Coombs and Gel response result in?

A

Degranulation with inflammatory mediators, pruritis, bronchoconstriction, vasodilation, oedema and eosinophil chemotaxis

23
Q

What is the type II Coombs and Gel response?

A

Complement mediated lysis by cytotoxicty of NK cells and phagocytosis by macrophages
IMAGE

24
Q

What is the type III Coombs and Gel response?

A

Immune complexes form on endothelial basement membrane causing complement activation, neutrophil and basophil activation, platlet and clotting factor activation and increased vascular permeability
IMAGE

25
Q

What is the type IV Coombs and Gel response?

A

Priming of naive T cell, Th1 effector function, Endothelial activation, Local inflammation

26
Q

What are the different methods that tick borne diseases can cause immune-mediated disease?

A

IMAGE

27
Q

What is masticatory muscle myositis (MMM)?

A

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

28
Q

What is the antiplatelet antibody test?

A

Indirect immunofluorescence test with substrate comprising of PLTs from healthy donor and is considered when immune-mediated thrombocytopaenia is a DDx

29
Q

What is rheumatoid factor?

A

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

30
Q

Why would thyroglobulin autoAb be tested for?

A

Lymphocytic thyroiditis is thought to represent an autoimmune disease and Ab against thyroid antigens are released during ensuing inflammation

Principles of Clinical Immunology (4 decks)

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