Flashcards in Immune-Mediated Dz Overview Deck (46):
1
What is Sjogrens syndrome?
- uncommon vet
- immune mediated attack of salivary gladns -> dry mouth and dry eye
2
What is myasthenia gravis?
- nicotinic muscarinic receptors ACh
3
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
4
What is the emchanism that breaks down leading to immune mediated dz?
Tolerance
5
What are the 2 types of immune response?
> humoral
- Antibody mediated
> cell
- B and T cell mediated
6
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!)
7
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
8
eg. vector-borne pathogen that can cause IM dz? Dxx?
- Babesia
- blood smear
> bilobed pyriform gaps in RBC
> inclusion bodies stuck on surface
9
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
10
What age is idiopathic immune mediated dx commonly seen?
youong animals
11
Which species are most afected by IMD?
- dogs
12
Which cats are predisposed to IMD?
- more exotic breeds (siamese, persians, persion-related)
13
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
14
Ddx of depigmentation of the nasal planum??
- drug eruption
- aspergillosis
15
What are the most important aspects of work up for IMD?
History and PE
- DO NOT RELY ON DXX TESTS!!
16
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
17
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)
18
What breed are pdf IMHA?
cocker spaniels
19
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
20
What proceses can cause ^ CK? ECHO
- anorexia
- muscular dystrphy
21
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
22
Which funghi are present in the uk?
- aserpgillus
- cryptococcus
23
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
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PUO think...
JOINTS
25
Where is arthrocentesis of the carpus performed? ECHO
- Antiebrachial-carpal region
- lateral to:
- medial to:
26
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
27
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)
28
What test r/o myasthenia gravis?
- AChR autoAb (immunoprecipitation RIA of nicotinic AChR autoAb)
- very good sensitivity and specificity (rare false +-)
29
Forms of myasthenia gravis?
- focal
- generalised
- acute fulminating
- paraneplastic
30
Best PE test for myasthenia gravis?
- repeat palpebral response
> will tire and not be able to blink
31
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
32
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
33
Why is IMD a problem?
Not common
- BUT severely affected and can be rapidly fatal
34
Which vector borne diseases are present in the UK?
ECHO
35
What do neutrophils indicate?
Infection (sepsis) OR immune-mediated dz
36
What does an air broncho-gram suggest?
- consolidatino of lung and pulmonary pattern
37
What does fluffiness on thoracic rads indicate?
Interstitial pattern
38
What is central and perpheral tolerance?
> central
- thymic selection
> peripheral
- intrinsic (ignorance, deletion phenotypic skewing)
~ anergy
- extrinsic (tolerogenic dendritic cells, Tregs)
39
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
40
How can vector borne diseases initiate immune-mediated problems?
- immune complex deposition -> vasculitis
- cross-reactive antibodies
- hypergammaglobulinaemia
- autoantibodies
> other info on slide
41
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
42
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
43
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
44
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%
45
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.
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