Immune-Mediated Dz Overview Flashcards
What is Sjogrens syndrome?
- uncommon vet
- immune mediated attack of salivary gladns -> dry mouth and dry eye
What is myasthenia gravis?
- nicotinic muscarinic receptors ACh
What are the 3 underlying factors to r/o as causes of immune mediated dz before declaring it IDIOPATHIC??
- Previous tx
- Infection
- Neoplasia
What is the emchanism that breaks down leading to immune mediated dz?
Tolerance
What are the 2 types of immune response?
> humoral
- Antibody mediated
cell
- B and T cell mediated
Potential trigger factors -> pathogenesis of immune-mediated dz? -
- release of sequestered ag (not usually seen by imune celsl)
- abnormal imunoregulation
- molecular mimicry
- polyclonal activatioin of T and B cells (Bacteria can cause this)
- exposure of cryptic epitopes
- haptenisation (haptens = small molecules eg. penicillin) of foreign molecules to self antigen (stick onto big molecules and get them in trouble!)
How can infection influence autoimmune dz?
- breakdown of vascular /cellular barriers allowing exposure of self antigen - promotion of celll death by necorsis causing inflam -> bystander activation
- polyclonal activation of T cells - bacterial superantigens
- molecular mimicry (pathogens look like self antigen)
- vector-bourne pathogens may be important in some part of world (r/o) usually protozoal, rickettsial, bacterial
eg. vector-borne pathogen that can cause IM dz? Dxx?
- Babesia
- blood smear
> bilobed pyriform gaps in RBC
> inclusion bodies stuck on surface
Most common aetiology of IMD? egs of potential aetiologies:
- usually multifactorial
- genetic, infectious and hormonal influence (ex esp.)
- canine egs:
> SLE (genetics, viruses)
> IMHA (vaccinal ag)
> IMPA (vaccinal ag) - feline egs:
> rarer
What age is idiopathic immune mediated dx commonly seen?
youong animals
Which species are most afected by IMD?
- dogs
Which cats are predisposed to IMD?
- more exotic breeds (siamese, persians, persion-related)
What hx and clinical exam signs indicate IMD?
- remission and exacerbation fluctuating (beware coincidence of giving Abx and the dz remissing etc.)
> PE - lamess, mucocutaneous lesions (ddepigmentation of nasal planum, lethargy, dyspnoea, weight loss, PUPD, +- seizures, behaviour,
- effusive painful joints, cutaneous erythema, macular, papules, pustules, eroise, pallor +- petichiae, cardiac arythmia
- lymphadenomegaly +- splenomegaly
Ddx of depigmentation of the nasal planum??
- drug eruption
- aspergillosis
What are the most important aspects of work up for IMD?
History and PE
- DO NOT RELY ON DXX TESTS!!
Potential findings on CBC/coag with IMD?
> anaemia - regenerative (IMHA) - non-regenerative (infection, uraemia, chronic bleeding, attack of precursors) > thrombocytonpenia (MARKED) - IM thrombocytopenia 150,000 > leucopenia - anticonvulsants esp. - anti-leucocyte Abs eg. SLE, IM neutropenia > coagulation abnormlalitis - ^ APTT, PT, anticoagulant Ab (SLE) - DIC less common but poss - hyPER coagulability d/t surface g stimulation coagulation
What findings may be seen on blood smear with regenerative anaemia IMD?
- spherocytes (lack of central pallor, smaller cells, more apparent in the dog than cat) indicate extravascular destruction
- polychromatophils
- ghost cells (intravascular haemolysis)
- rubriocytes (red cell precursors)
What breed are pdf IMHA?
cocker spaniels
What diagnostic tests on biochem would be relevant for IMD?
> azotaemia, ^ inorganic phosphate - chronic glomerular lesions > hypoalbumenaemia, hypercholesterolaemia - PLN > hyperbilirubinaemia - pre-hepatic/haemolysis > hyperglobulininaemia - inflam dz, polyclonal B cell activation[lupus] > ^CK and lactate dehydrogenase - polymyositis and or myocarditis
What proceses can cause ^ CK? ECHO
- anorexia
- muscular dystrphy
What should be looked for on urinalysis dxx?
> proteinuria
- PLN (r/o UTI and occult infection)
eg. dirofilaria immitis, ehrlichia canis, anaplasma phagocytophilum, borrellia burgderfori, rickettsia rickettsiae, bartonella spp
haematuria, pyuria, erythrocyte casts
- r/o UTI and infection
- compatible with membranoproliferative GN
Which funghi are present in the uk?
- aserpgillus
- cryptococcus
Dxx for locomotor affected IMD?
> joint lesions common in polysystemic IM dz (usually non-erosive pauciarthropathy)
- erosive lesions suggest overlap syndrome
- arthritis not always clinically obvious
synovial fluid
- ^ WBC
- ^ protein content
- ^ neutrophils
- v viscosity (d/t loss of GAGs)
- culture
- poor mucin clot formation
PUO think…
JOINTS
Where is arthrocentesis of the carpus performed? ECHO
- Antiebrachial-carpal region
- lateral to:
- medial to:
Give examples of tests of IMD that oculd be used to r/o specific path
- coombs test
- anti-platelet Ab
- RF
- T3, T4, TG autoAb
- Ach R autoantibody
- 2M Myofibre autoAb
- antinuclear Ab
- biopsies
What is the coombs test? What other tests can be used for this dz?
- test for IMHA
- antibodies associated with Ag on RBC clumps/agglutinates
- titre down to lowest conc
- if acute IMHA suspected, in-saline agglutination and osmotic fragility tests can also be performed
> primary reagent : polyvalent canine/feline IgG, IgM, C3 antiserum (direct antiglobulin) - false + and - occour
> monovalent better (send off)
What test r/o myasthenia gravis?
- AChR autoAb (immunoprecipitation RIA of nicotinic AChR autoAb)
- very good sensitivity and specificity (rare false +-)
Forms of myasthenia gravis?
- focal
- generalised
- acute fulminating
- paraneplastic
Best PE test for myasthenia gravis?
- repeat palpebral response
> will tire and not be able to blink
What test can r/o SLE?
- ANA (antinuclear antibodies)
- indirect (patient serum not cells, apply to tissue sample) Immunofluorescence/immunoperoxidase
- fair senstivity and specificity, some false results
When would biopsy be useful? What tissue should be sampled?
> mucocutaneous dz
- sample junction NOT centre
lesions may nto be specific for one dz
- immune deposits in lesional tissue may be demonstrated by immunoperoxidase or immunoflueorescence techniques
Why is IMD a problem?
Not common
- BUT severely affected and can be rapidly fatal
Which vector borne diseases are present in the UK?
ECHO
What do neutrophils indicate?
Infection (sepsis) OR immune-mediated dz
What does an air broncho-gram suggest?
- consolidatino of lung and pulmonary pattern
What does fluffiness on thoracic rads indicate?
Interstitial pattern
What is central and perpheral tolerance?
> central
- thymic selection
peripheral
- intrinsic (ignorance, deletion phenotypic skewing)
~ anergy
- extrinsic (tolerogenic dendritic cells, Tregs)
What are the 2 types of Coombes and gel response
> type 1 (MHC2) - Dendritic cell primes naive T cells - TH2 cell interaction with B cells - sensitisation - degranulation > Type 2 - NK cell (complement mediated lysis) - target cell (cytotoxicity and phagocytosis) - macrophages > Type 3 - Neutrophil and basophil activation - complement activation and immune complexes > Type 4 - Denrditic cell primes naive T cells - TH1 effector function - endothelial activation and local inflammation
How can vector borne diseases initiate immune-mediated problems?
- immune complex deposition -> vasculitis
- cross-reactive antibodies
- hypergammaglobulinaemia
- autoantibodies
> other info on slide
What causes masticatory myofibre autoAb? (MMM) Clinical signs? Dx?
- idiopathic immune-mediated disease of 2M myofibres (myosin)
- swelling +- eventual atrophy of muscles of mastication
- Dx: demonstrate autoAb against 2M myofibres of temporalis m. in immunocytochemical assay
What test should be considered when immune-mediaed thrombocytopenia is on the ddx list?
- antiplatelet antibody test
- indirect immunofluorescence test (substrate comprises PLTs from healthy donor)
- reagent = fluorescenated goat anti-dog or anti-cat IgG antiserum (icroscopic and flowcytometric assays poss)
- false +- possible
What test r/o erosive arthrittis causes?
Rheumatoid factor
- non-specific autoAb to igG (may be found in a range of infectious/inflam/neoplastic dz)
- high titres seen with RA
- assayed by ELISA/Rose-Waeler test
> RF agglutinates IgG-coated substrate RBCs
When is T3, T4 thyroglobulin autoAb test indicated?
- lymphocytic thyroiditis
- Ab against thyroid antigen
> 50-60% hypothyroid dogs have TG-autoAb
> 20% euthyroid dogs with TG-autoAb develop signs in a year
> T3-autoAb observed in 33% hypothyroid dogs, T4 15%
What are SCE recommednations for interpretting T3/T4/TG autoAb results?
- normal FT4D and TSH => healthy euthyroid
- low TT4/FT4D w/ ^TSH => hypothyroid
- TGautoAb w/ NAD => impedning hypothyroid?
- low TT3 limited diagnostic value, except SIGHT HOUNDS, which have low TT4 and FT4D based on generic canine ref ranges.
What is the spectrum of immune-mediated dz?
> non-organ specific (usually d/t vasculiltis related effects)
- SLE
- Sjogren’s syndrome
- RA
- canine familiar dematomyositis
- DIscoid lupus erythematosus
- pemphigus-pemphigoid complex
- glomerelonephritis
- easinophilic myositis
- non-erosive PA
- feline progressive PA
- immune-mediated anaemia, thrombocytonpenia, neutropenia
- myasthenia gravis
