Immune-Mediated Dz Overview Flashcards Preview

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Flashcards in Immune-Mediated Dz Overview Deck (46):

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??

1. Previous tx
2. Infection
3. Neoplasia


What is the emchanism that breaks down leading to immune mediated dz?



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


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
> 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...



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?



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)
- 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