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

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