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Lymphoreticular > Immune-Mediated Dz Overview > Flashcards

Immune-Mediated Dz Overview Flashcards

1
Q

What is Sjogrens syndrome?

A
  • uncommon vet

- immune mediated attack of salivary gladns -> dry mouth and dry eye

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2
Q

What is myasthenia gravis?

A
  • nicotinic muscarinic receptors ACh
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3
Q

What are the 3 underlying factors to r/o as causes of immune mediated dz before declaring it IDIOPATHIC??

A
  1. Previous tx
  2. Infection
  3. Neoplasia
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4
Q

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

A

Tolerance

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5
Q

What are the 2 types of immune response?

A

> humoral
- Antibody mediated
cell
- B and T cell mediated

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6
Q

Potential trigger factors -> pathogenesis of immune-mediated dz? -

A
  • 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!)
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7
Q

How can infection influence autoimmune dz?

A
  • 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
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8
Q

eg. vector-borne pathogen that can cause IM dz? Dxx?

A
  • Babesia
  • blood smear
    > bilobed pyriform gaps in RBC
    > inclusion bodies stuck on surface
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9
Q

Most common aetiology of IMD? egs of potential aetiologies:

A
  • usually multifactorial
  • genetic, infectious and hormonal influence (ex esp.)
  • canine egs:
    > SLE (genetics, viruses)
    > IMHA (vaccinal ag)
    > IMPA (vaccinal ag)
  • feline egs:
    > rarer
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10
Q

What age is idiopathic immune mediated dx commonly seen?

A

youong animals

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11
Q

Which species are most afected by IMD?

A
  • dogs
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12
Q

Which cats are predisposed to IMD?

A
  • more exotic breeds (siamese, persians, persion-related)
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13
Q

What hx and clinical exam signs indicate IMD?

A
  • 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
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14
Q

Ddx of depigmentation of the nasal planum??

A
  • drug eruption

- aspergillosis

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15
Q

What are the most important aspects of work up for IMD?

A

History and PE

- DO NOT RELY ON DXX TESTS!!

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16
Q

Potential findings on CBC/coag with IMD?

A 
> 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
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17
Q

What findings may be seen on blood smear with regenerative anaemia IMD?

A
  • 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)
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18
Q

What breed are pdf IMHA?

A

cocker spaniels

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19
Q

What diagnostic tests on biochem would be relevant for IMD?

A 
> 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
Q

What proceses can cause ^ CK? ECHO

A
  • anorexia

- muscular dystrphy

21
Q

What should be looked for on urinalysis dxx?

A

> 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
Q

Which funghi are present in the uk?

A
  • aserpgillus

- cryptococcus

23
Q

Dxx for locomotor affected IMD?

A

> 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
Q

PUO think…

A

JOINTS

25
Q

Where is arthrocentesis of the carpus performed? ECHO

A
  • Antiebrachial-carpal region
  • lateral to:
  • medial to:
26
Q

Give examples of tests of IMD that oculd be used to r/o specific path

A
  • coombs test
  • anti-platelet Ab
  • RF
  • T3, T4, TG autoAb
  • Ach R autoantibody
  • 2M Myofibre autoAb
  • antinuclear Ab
  • biopsies
27
Q

What is the coombs test? What other tests can be used for this dz?

A
  • 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
Q

What test r/o myasthenia gravis?

A
  • AChR autoAb (immunoprecipitation RIA of nicotinic AChR autoAb)
  • very good sensitivity and specificity (rare false +-)
29
Q

Forms of myasthenia gravis?

A
  • focal
  • generalised
  • acute fulminating
  • paraneplastic
30
Q

Best PE test for myasthenia gravis?

A
  • repeat palpebral response

> will tire and not be able to blink

31
Q

What test can r/o SLE?

A
  • ANA (antinuclear antibodies)
  • indirect (patient serum not cells, apply to tissue sample) Immunofluorescence/immunoperoxidase
  • fair senstivity and specificity, some false results
32
Q

When would biopsy be useful? What tissue should be sampled?

A

> 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
Q

Why is IMD a problem?

A

Not common

  • BUT severely affected and can be rapidly fatal
34
Q

Which vector borne diseases are present in the UK?

A

ECHO

35
Q

What do neutrophils indicate?

A

Infection (sepsis) OR immune-mediated dz

36
Q

What does an air broncho-gram suggest?

A
  • consolidatino of lung and pulmonary pattern
37
Q

What does fluffiness on thoracic rads indicate?

A

Interstitial pattern

38
Q

What is central and perpheral tolerance?

A

> central
- thymic selection
peripheral
- intrinsic (ignorance, deletion phenotypic skewing)
~ anergy
- extrinsic (tolerogenic dendritic cells, Tregs)

39
Q

What are the 2 types of Coombes and gel response

A 
> 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
Q

How can vector borne diseases initiate immune-mediated problems?

A
  • immune complex deposition -> vasculitis
  • cross-reactive antibodies
  • hypergammaglobulinaemia
  • autoantibodies
    > other info on slide
41
Q

What causes masticatory myofibre autoAb? (MMM) Clinical signs? Dx?

A
  • 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
Q

What test should be considered when immune-mediaed thrombocytopenia is on the ddx list?

A
  • 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
Q

What test r/o erosive arthrittis causes?

A

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
Q

When is T3, T4 thyroglobulin autoAb test indicated?

A
  • 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
Q

What are SCE recommednations for interpretting T3/T4/TG autoAb results?

A
  • 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
Q

What is the spectrum of immune-mediated dz?

A

> 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

Lymphoreticular (31 decks)

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