Immune-Mediated Dz Overview Flashcards Preview

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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

24

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.

46

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