Immunology 1A: Autoimmune and auto-inflammatory diseases 2

Question 1

Which antibodies do systemic diseases produce?

Answer 1

ANA

Question 2

Graves’ disease pathophysiology

Answer 2

IgG antibodies to TSH receptor –> uncontrolled production of thyroid hormones which cannot be overrided by negative feedback

Question 3

What kind of hypersensitivity is Grave’s?

Answer 3

Type II

Question 4

Which thyroiditis is associated with a high T4 and which with low?

Answer 4

High; Viral thyroiditis (de quervain’s)

Low: Hashimoto’s thyroiditis

Question 5

clinical features of hashimoto’s

Answer 5

Constipation, lethargy cold intolerance etc

GOITRE - irregular

Question 6

Autoantibody in Hashimoto’s

Answer 6

anti-TPO and anti-thyroglobulin

Question 7

Why is it not useful to measure autoantibodies in Hashimotos?

Answer 7

They are present in many women who do not exhibit any symptoms

Question 8

Hypersensitivtiy type of Hashimoto’s

Answer 8

Type II and IV

Question 9

Pathophysiology of T1DM? Therefore what hypersensitivity is it?

Answer 9

CD8+ T cells recognise autoantigens on pancreatic B cells

Type IV-mediated

Question 10

On 1st presentation of T1DM, what else do you screen for?

Answer 10

Coeliac’s, TFTs and LFTs

Question 11

What autoantigens are recognised by T cells in T1DM?

Answer 11

GAD and IA2

Question 12

Antibodies seen in T1DM (often predate symptoms but not used diagnostically)

Answer 12

Anti-GAD
Anti-islet cell
anti-insulin
anti-IA2

Question 13

Clinical fx of B12 deficiency

Answer 13

Subacute degeneration of cord
Optic neuropahty
Peripheral neuropathy

Question 14

Pernicious anaemia autoantibodies

Answer 14

Autoantibodies to gastric parietal cells and intrinsic factor

Question 15

Myasthenia gravis autoantibodies

Answer 15

Autoantibodies to ACh receptor

Question 16

Special test for diagnosis

Answer 16

Tensilon test

Question 17

MG type of hypersensitivity?

Answer 17

Type II

Question 18

Offending antibody in Goodpasture’s

Answer 18

antibody vs alpha3 subunit of type IV collagen

Question 19

Immunohistochemistry for anti-GBM, what is a +ve result?

Answer 19

Linear IgG deposition along basement membrane

Question 20

What is seen on biopsy in GBM?

Answer 20

Cresentic nephritis

Question 21

Goodpasture’s hypersensitivity

Answer 21

Type II

Question 22

Rheumatoid arthritis HLA ASSOCIATIONS

Answer 22

HLADR4/HLADR1 (Bind to citrullinated peptides with higher affinity)

Question 23

Which is the most SPECIFIC autoantibody in RA?

Answer 23

Anti-CCP

Question 24

2 GENETIC predispositions to RA?

Answer 24

HLAdR4/DR1

PAD2 + 4 polymorphisms (deamination of arginine to citrulline)

Question 25

What infection is associated with RA and why?

Answer 25

Porphyromonas gingivalis - expresses PAD enzyme thus promoting citrullination

Question 26

Why does smoking increase RA risk?

Answer 26

Erosion and increased citrullination

Question 27

What is rheumatoid factor

Answer 27

IgM antibody targeted against Fc region of IgG antibody

Question 28

B cell involvement in rheumatoid arthritis - give 2 ways

Answer 28

Type II - Antibodies bind to citrullinated peptides --> complement activation, macrophage activation and NK cell activation with ADCC Type III response - immune complex formation by anti-CCP and anti-RF + deposited --> complement activation

Question 29

How is the joint affected macroscopically in RA?

Answer 29

Increased synovial fluid Inflamed synovial tissue --> pannus Pannus invades articular cartilage and adjacent bone

Question 30

4 Diseases associtaed with ANA +ve

Answer 30

SLE Sjogrens Systemic sclerosis Dermato/polymyositis

Question 31

Which cells are used to test for aNAs?

Answer 31

Stain Hep2 cells

Question 32

Pathogenesis of SLE

Answer 32

Antibodies against intracellular proteins IMMUNE COMPLEXES formed + deposited in tissues Complement activation + activation of cells expressing Fc receptors (type III hypersensitivity)

Question 33

Is ANA specific to autoimmune diseases?

Answer 33

No, present in normal population

Question 34

How does the staining pattern / immunofluorescence differ in SLE and Goodpasture's?

Answer 34

``` Goodpasture's = linear, smooth SLE = Lumpy bumpy due to immune complex deposition ```

Question 35

Which antigens involved in SLE?

Answer 35

DNA, histones and RNP

Question 36

You request an anti nuclear antibody test on two patients with joint pain Patient A’s result is 1:640 Patient B’s result is 1:80 Based on this information, which has the “strongest” (i.e most positive) antibody?

Answer 36

Patient A's

Question 37

4 ribonuclear ANAs

Answer 37

Ro,La, Sm, U1RNP

Question 38

Which autoantibody test is highly specific for SLE?

Answer 38

Anti-dsDNA

Question 39

anti-ENA vs anti-dsDNA antibodies Which one is useful in monitoring disease activity, and in which disease?

Answer 39

Anti-dsDNA in SLE

Question 40

homogenous staining of the nucleus is associated with..?

Answer 40

anti-dsDNA

Question 41

speckled staining of the nucleus is associated with antibodies to...?

Answer 41

ENA (Ro,La,Sm, U1RNP)

Question 42

aNTI-ro, ANTI-LA?

Answer 42

Sjorgens

Question 43

Antibodies in diffuse CREST

Answer 43

Anti-topoisomerase (Anti-Scl70)

Question 44

Antibodies in limited CREST

Answer 44

Anti-centromere

Question 45

What other investigation can be done in SLE?

Answer 45

Measure complement

Question 46

Which complement factor depleted first in SLE?

Answer 46

C4 first then C3

Question 47

C3 and C4 levels in inactive, moderate and very active lupus

Answer 47

inactive = normal C3 + C4 Moderate = low C4, normal C3 Severe/v active = Low C4 ADN C3

Question 48

Antiphospholipid syndrome antibodies

Answer 48

Anti-cardiolipin Lupus anticoagulant Anti-B2 glycoprotein 1

Question 49

Symptoms of APLS

Answer 49

Clots, obstetric complications, livedo reticularis recurrent venous or arterial thrombosis

Question 50

Thickening around the mouth, microstomia

Answer 50

Systemic sclerosis

Question 51

What does CREST stand for?

Answer 51

``` Calcinosis Raynaud's Eosophageal dysmotility Sclerodactyly Telangiectasia ```

Question 52

Diffuse cutaneous scleroderma symptoms

Answer 52

CREST + more severe GIT involvement + interstitial pulmonary disease + renal problems

Question 53

Differentiating between diffuse and limited cutaneous scleroderma (CREST)

Answer 53

Diffuse: skin involvement progresses BEYOND the forearms (Does not progress in CREST, involved PERI-ORAL SKIN)

Question 54

Immunofluorescence findings in diffuse cutaneous scleroderma

Answer 54

Nucleolar pattern

Question 55

Antibodies found in diffuse cutaneous scleroderma

Answer 55

Anti-topoisomerase (Scl70), RNA pol I,II,III and Fibrillarin

Question 56

Antibodies found in CREST syndrome

Answer 56

Anti-centromere

Question 57

As well as CREST, what other symptom is found in CREST syndrome?

Answer 57

primary pulmonary HTN

Question 58

weakness, malaise, periorbital heliotropic rash, Gottron’s papules

Answer 58

Dermatomyositis

Question 59

Dermatomyositis clinical features

Answer 59

Periorbital Heliotrope rash + Gottron's papules

Question 60

Dermatomyositis hypersensitivity type

Answer 60

Type 3, immune complex mediated vasculitis

Question 61

Polymyositis hypersensitivity type

Answer 61

Type 4 - CD8 cells kill myofibers via perforin/granzymes

Question 62

Antibodies in myositis

Answer 62

Dermatomyositis + polymyositis: Anti-Jo-1 DM >PM Anti-Mi-2 PM - Anti-SRP

Question 63

3 types of small vessel associated ANCA vasculitis

Answer 63

Granulomatosis with polyangiitis (GPA - Wegner's) Eosinophilic granulomatosis with polyangiitis (Churg Strauss) microscopic polyangiitis

Question 64

cANCA antibodies to...

Answer 64

Proteinase 3

Question 65

pANCE antibodies to...

Answer 65

Myeloperoxidase

Question 66

Staining in cANCA and pANCA

Answer 66

cANCA - cytoplasmic fluorescence | pANCA - perinuclear staining pattern

Question 67

pANCA - which diseases?

Answer 67

MPA and eGPA

Question 68

What is ANA used for?

Answer 68

Connective tissue disease screening

Question 69

What is ANCA used for?

Answer 69

Small vessel vasculitis including MPA, GPA, eGPA