Immune-mediated disease - overview Flashcards Preview

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Flashcards in Immune-mediated disease - overview Deck (54):
1

What is the spectrum of immune-mediated disease?

- organ specific to non-organ specific (vasculitis)
- primary ('idiopathic') vs secondary

2

What underlying factors should be eliminated when considering immune-mediated disease?

- drug use
- neoplasia
- infxn

3

Example - non-organ specific immune dz

SLE

4

Example: organ specific immune dz

Myasthenisa gravis (MG)

5

What goes wrong in immune-mediated dz?

Immune system (I.S.) overreacts to normal body tissues or harmless exogenous protein. aka loss of tolerance
- humoral and cellular mechanisms
- loss of self-tolerance needed to perpetuate +/- start dz

6

Trigger factors - immune-mediated dz

- release of sequestered Ag
- abnormal immunoregulation
- molecular mimicry
- polycloncal activation of BCs and TCs
- exposure of cryptic epitopes or haptenisation of foreign molecules to self antigens

7

What is haptenisation?

small molecules bind to larger carreir molecules and these complexes elicit an immune response, directed against the carrier molecule.

8

How is infxn thought to influence autoimmune dz?

- breakdown of vascular/cellular barriers allowing exposire of self-antigens
- promotion of cell death by necrosis, causes inflammation --> bystander sactionation
- polyclonal activation of TCs by bacterial superantigens
- molecular mimicry leading to cross-reactivity
- vector-borne pathogens may be important in some parts of the world (r/o by different tests)

9

Name 3 main vector-borne pathogens that can be important in influencing autoimmune dz

- protozoa
- rickettsia
- bacteria

10

Aetiology - autoimmune dx

- of many is unclear, likely mutlifactorial often
- genetic, infectious, hormonal influences

11

Give canine autoimmune dz examples of aetiology

- SLE: genetics (DLA-A7, C4,4), c-type viruses (retroviruses)
- IMHA: vaccinal Ag?
- IMPA: vaccinal Ag?

12

Signalment - idiopathic immune-mediated disease

- over-represented in juvenile to middle-aged patients
- any age or dog/cat though
- SLE: Dogs 2mo-13yo, GSD, shelties, collies, beagles, poodles. Cats 1-11 yo, Siamese, Persian, Persian-related breeds

13

Hx and PE - immune-mediated dz characteristics

- remission and exacerbation
- lameness, mucocutaneous lesions, lethargy, dyspnoea, wt loss, PUPD, +/- seizures or behavioural changes
- effusive, painful joint, cutaneous erythema, macules, papules, pustules, erosion etc, pallor +/- petechiae, cardiac arrhythmias, lymphadenomegaly +/- splenomegaly
* Hx and PE are PIVOTAL to a DIAGNOSIS

14

How can CBC/coags tests help make diagnosis? 4

- ANAEMIA: regenerative (IMHA) or non-regenerative (ifxn, uraemia, chronic bleeding, attack of precursors)
- THROMBOCYTOPAENIA: I-M thrombocytopaenia
- LEUCOPAENIA? anti-leukocyte Abs (e.g. SLE, I-M neutropaenia)
- COAGULATION ABNORMALITIES: increased APTT, PT, anticoagulant Ab (SLE), DIC

15

On a blood smear, what is the hallmark of extravascular haemolysis?

spherocytes

16

What do chromatophils suggest on smear?

rengerative anaemia

17

What is rubricytosis?

- presence of immature RBCs
- suggests regenerative anaemia

18

What do ghost cells represent on a smear?

intravascular haemolysis

19

How can biochem. help make I-M dz diagnosis? 5

- AZOTAEMIA, increased inorganic phosphate (chronic glomerular lesions)
- HYPOALBUMINAEMIA, HYPERCHOLESTEROLAEMIA: e.g. PLN
- HYPERBILIRUBINAEMIA: pre-hepatic/ haemolysis
- HYPERGLOBULINAEMIA; inflammatory disease, polyclonal BC activation
- INCREASED CK and (LACTATE DEHYDROGENASE); polymyositis and/or myocarditis

20

How can UA make an I-M diagnosis?

- PROTEINURIA: with PLN r/o UTI and occult infections
- HAEMATURIA, POLYURIA, ERYTHROCYTE CASTS: r/o UTI and occult infxn, compatible with membranoproliferative glomerulonephritis (GN)

21

Features - radiography for I-M dz

- erosive lesions suggest an overlap syndrome
- arthritis is not always clinically obvious

22

Define pauciarthropathy

where a few joints are affected, >1 but

23

How common are joint lesions in polysystemic I-M dz?

- common
- usually a non-erosive pauciarthropathy

24

Describe synovial fluid of I-M dz

- increased WBC
- increased neutrophil %
+/- increased protein content
- decreased viscosity
- poor mucin clot formation

25

Describe synovial fluid of I-M dz

- increased WBC
- increased neutrophil %
+/- increased protein content
- decreased viscosity
- poor mucin clot formation

26

Which joint space do you aim for in carpus?

- antebrachial joint as this is the 1st joint space and this is the largest joint space
- aim for middle (to avoid nn, tendons, BVs)

27

List some tests for specific I-M dz

- coomb's test
- anti-platelet Ab
- rheumatoid factor
- T3, T4, TG autoAb
- ACh receptor autoAb
- 2M myofibre autoAb
- ANA
- biopsies

28

What to do if IMHA is suspected

- in-saline agglutination and ostmotic fragility tests to be performed
- Ab associated with surface of RBC may also be detected with Coomb's test
- primary reagent: polyvalent anti-dog or anti-cat IgG, IgM and C3 antiserum (direct antiglobulin test)
- false positive and negatives may occur

29

What is the commonest I-M neuromuscular disorder?

Acquired MG (various forms: focal, generalised, acute fulminating, paraneoplastic)

30

Gold standard diagnosis for acquired MG

- documentation of nicotinic AChR autoAb by immunoprecipitation RIA

31

Sensitivity/specificity of nicotinic AChR autoAb by immunoprecipitation radioimmunoassay (RIA)

- false positives v rare: 2% dogs with generalised MG may be seronegative

32

What part of PE may cause you to suspect MG?

you will be able to fatigue the palpebral response in MG patients after 10-20 stimulations

33

Outline antinuclear antibodies (ANA)

- serum ANA = hallmark of human/canine/feline SLE, occasional ANA-negative cases
- indirect immunofluorescene or immuno-peroxidase test
- substrate tissues have included rat liver, vero and Hep-2 cells: various patterns of staining
- false positives /negatives may occur

34

How are biopsies useful for I-M dz?

- often signal immune mediation of lesionsin organ-specific and polysystemic diseases
- mucocutaneous lesions should be sampled across interface with normal tissue
- lesions may not be specific for one disease but helps you localise lesion (e.g. dermis vs. epidermis)
- immune deposits in lesional tissue may be demonstrated by immunoperoxidase or immunofluorescence techniques.

35

T/F: I-M dz are a major cuse of morbidity and mortality in SA

True

36

T/F: various vector-borne dz have immunopathological sequelae

True

37

Define anergy

the absence of a normal immune response to a particular Ag

38

What determines central tolerance?

thymic selection

39

What determines peripheral tolerance?

- intrinsic and extrinsic components

40

What can be the physiological response to degranulation?

- inflammatory mediators
- pruritus
- bronchoconstriction
- vasodilation
- oedema
- eosinophil chemotaxis

41

Define MMM

Masticatory Muscle Mysositis

42

What is MMM?
CS?
Dx?

- idiopathic I-M dz of 2M myofibres, directed specifically at myosin
- CS include swelling +/- eventual atrophy of mm of mastication
- Dx by demonstrating autoAb against 2M myofibres of temporalis mm in immunocytochemical assay

43

What is the anti-platelet Ab test?

- considered when I-M thrombocytopaenia is a ddx
- indirect immuofluorescence test: substrate comprises PLTs from healthy donor
- reagent is fluoresceinated and goat anti-dog or anti-cat IgG antiserum: micrscopic and flow cytometric assays are described
- false positive/negatives may occur

44

What is rheumatoid factor?

- considered when erosive arthritis documented
- RF is a non-specific autoAb to IgG that may be found at low titre in animals with a range of infectious, inflammatory neoplastic diseases
- high titres characterise RA
- assayed by ELISA or Rose-Waaler test, in which RF agglutinates IgG-coated substrate RBCs

45

What are T3, T4 and thyroglobulin autoAb used for?

- lymphocytic thyroiditis thought to represent an autoimmune disease: Ab against thyroid Ag are released during ensuing inflammation
- 50-60% hypothyorid dogs have TG-autoAb
- 20% euthyroid dogs with TG-autoAb develop additional signs within a year
- T3-autoAb observed in 33% hypothyroid dogs, T4-autoAb observed in 15% cases

46

Define TT4

total T4

47

Define fT4d

free T4 by dialysis (baseline)

48

What is suggested with normal FT4D and TSH

healthy euthyroid

49

What is suggested with low TT4 or FT4D with increased TSH

hypothyroidism

50

What is suggested by TG-autoAb with no other abnormalities?

impending hypothyroidism?

51

What does low TT3 suggest?

it is of limited diagnositic value, except in sight hounds, which have low TT4 and FT4D based on generic canine reference ranges

52

What can be the physiological response to degranulation?

- inflammatory mediators
- pruritus
- bronchoconstriction
- vasodilation
- oedema
- eosinophil chemotaxis

53

Define MMM

Masticatory Muscle Mysositis

54

What is MMM?
CS?
Dx?

- idiopathic I-M dz of 2M myofibres, directed specifically at myosin
- CS include swelling +/- eventual atrophy of mm of mastication
- Dx by demonstrating autoAb against 2M myofibres of temporalis mm in immunocytochemical assay

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