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Immu > Immu 2: Autoimmune And Auto-inflammatory Disorders 2 > Flashcards

Immu 2: Autoimmune And Auto-inflammatory Disorders 2 Flashcards

1
Q

Patient presents with nervousness, diarrhoea, heat intolerance and on examination has exophthalmos. What is the most likely auto-immune disease causing this ?

A

Grave’s disease

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2
Q

What causes hyperthyroidism in Grave’s disease ?

A

IgG antibodies that stimulate TSH receptors

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3
Q

What type of hypersensitivity reaction is Grave’s disease ?

A

Type 2

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4
Q

What is a goitre ?

A

Enlarged thyroid due to T and B cell infiltration

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5
Q

What causes hypothyroidism in Hashimoto’s Thyroiditis ?

How common is this condition as a cause of hypothyroidism?

A

Anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies

(most common cause of hypothyroidism in iodine-replete areas)

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6
Q

What type of hypersensitivity reaction is hashimoto’s thyroiditis ? (2 option)

A

Type 2 and type 4

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7
Q

List 2 of the auto-antigens presented by MHC class 1 molecules to cytotoxic CD8+ T cells that causes destruction of the Beta cells of the pancreas in Type 1 diabetes mellitus

A

islet antigen 2 (IA2)
Glutamic acid dehydrogenase (GAD)

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8
Q

List the 4 antibodies associated with T1DM ?

A

Anti-islet cell antibodies
Anti-GAD antibodies
Anti-insulin antibodies
Anti-IA2 antibodies

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9
Q

Which auto- antibodies are associated with pernicious anaemia ?

A

Anti-IF antibodies (Intrinsic factor)

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10
Q

Pernicious anaemia is an example of a …………. anaemia

A

Macrocytic

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11
Q

Aetiology of pernicious anaemia

A
  • patients develop antibodies against intrinsic factor, which leads to failure of absorption of vitamin B12
  • Vitamin B12 deficiency can also lead to subacute degeneration of the spinal cord
  • Other neurological features include peripheral neuropathy and optic neuropathy
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12
Q

Pernicious anaemia can cause subacute …………

A

Subacute degeneration of the spinal cord

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13
Q

Apart from anti IF antibodies which other auto-antibodies are seen in pernicious anaemia ? (1)

A

Anti-parietal cell antibodies

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14
Q

Patient presents with drooping eyelids and weakness which is worse at the end of the day. What is the likely diagnosis ?

A

Myasthenia gravis

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15
Q

Deficiency of which vitamin causes subacute degeneration of the spinal cord ?

A

Vitamin B12

Seen in pernicious anaemia

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16
Q

Which Autoantibodies cause Myasthenia gravis?

How does this result in the aetiology?

A

Nicotinic acetylcholine receptor antibodies (nAChR)

  • subsequent failure to depolarise the receptors and do NOT get muscle action potential
  • get fluctuating weakness
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17
Q

Which test is used to diagnose Myasthenia Gravis ?

A

Tensilon test - give very short-acting acetylcholinesterase - causes rapid improvement in symptoms

*type II hypersensitivity reaction

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18
Q

What type of hypersensitivity reaction is mysasthenia gravis?

A

Type 2

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19
Q

Which autoimmune disease causes haematuria, proteinuria and pulmonary haemorrhage ?

A

Goodpasture’s syndrome

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20
Q

What Histological finding on renal biopsy suggests Goodpasture’s syndrome ?

How does the test work?

A

Crescentric nephritis

Test works by: detected using fluorescein conjugated anti-human immunoglobulin

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21
Q

Which auto-antibodies are associated with Goodpasture’s syndrome ?

A

Anti-basement membrane antibodies

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22
Q

Patient presents with Pain and stiffness of multiple joints in the hands. He also has a normocytic anaemia and elevated ESR and CRP. What is the most likely diagnosis ?

A

Rheumatoid arthritis

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23
Q

Which HLA polymorphisms are associated with Rheumatoid arthritis ?

A

HLA DR4
HLA DR1

(others = PTPN22, those affecting TNF, IL1, IL6, IL10, PA2 + PD4)

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24
Q

Which bacterial gum infection is associated with Rheumatoid arthritis ?

A

Porphyromonas gingivalis (expresses PDA)

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25
Q

Is smoking associated with increased or decreased risk of rheumatoid arthritis ?

A

Increased

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26
Q

Which antibodies are characteristically seen in rheumatoid arthritis ?

A

Anti-cyclic Citrullinated Peptide Antibodies (anti-CCP) antibodies (95% specific)
Anti-Rheumatoid factor (IgM anti IgG variant)

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27
Q

Which 3 types of hypersensitivity reactions occur in Rheumatoid arthritis ?

A

Hypersensitivity 2- antibody binds to CCP (peptides) causing complement activation (classical pathway), Macrophage and NK cell activation

Hypersensitivity 3- Immune complexes deposit

Hypersensitivity 4- APCs present peptides (citrulinated, self) to CD4+ T cells causing release of IFN gamma and IL-17 which activate macrophages and fibroblasts. MMPs and TNF-alpha are then released

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28
Q

What is a ‘Pannus’ in Rheumatoid arthritis ?\

A

Inflammed synovial cartilage which invades the articular cartilage and adjacent bone structures
Increase in synovial fluid volume

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29
Q

What happens to the joint in rheumatoid arhtritis?

A
  • In rheumatoid arthritis, the synovium becomes very inflamed forming a pannus
  • This invades the articular cartilage and adjacent bone
  • There is also an increase in synovial fluid volume
30
Q

Which auto-antibodies are characteristic of connective tissue diseases ?

A

ANA

31
Q

Antibody found in each condition:

  • Goodpasture’s disease
  • Myasthenia gravis
  • Graves’ disease
  • Pernicious anaemia
  • Diabetes Mellitus
  • Hashimoto’s thyroiditis
  • Rheumatoid arthritis
A
  • Goodpasture’s disease – Anti-basement membrane antibody
  • Myasthenia gravis – Anti-AChR antibody
  • Graves’ disease – Anti-TSHR antibody
  • Pernicious anaemia – Anti-IF antibody
  • Diabetes Mellitus – Anti-GAD antibody
  • Hashimoto’s thyroiditis – Anti-thyroglobulin antibody
  • Rheumatoid arthritis – Anti-cyclic citrullinated antibody
32
Q

What is the role of anti-nuclear antibodies (ANA)?

A
  • These are a group of antibodies that bind to nuclear proteins
  • They are tested by staining Hep-2 (Human epidermoid cancer line) cells
33
Q

List 6 pathologies seen in SLE ?

A

SOAP BRAIN MD

Serositis
Oral or nasal ulcers
Arthritis in > 2 joints
Photosensitivity

Blood disorders
Renal
ANA
Immunologic
Neurologic symptoms

Malar rash
Discoid rash

(abnormalities in clearing apoptotic cells. Antibodies bind to antigens forming immune complexes, deposit in tissues eg skin, joints, kidneys)

34
Q

Aetiology of SLE

A
  • Abnormalities in clearing apoptotic cells
  • Abnormalities in cellular activation
  • B cell hyperactivity and loss of tolerance occurs
  • Antibodies directed particularly at intracellular proteins
  • Antibodies bind to antigens forming immune complexes, which deposit into small blood vessels of tissues (e.g. kidneys, skin, joint)
  • Immune complexes can activate complement via the classical pathway
35
Q

Histology of the kidney shows “Lumpy bumpy” pattern of immunoflourescence.

Which disease is more likely:
A) SLE
B) Goodpasture’s disease

A

A- SLE

causes lumpy bumpy pattern due to immune complex deposition (type 3 hypersensitivity reaction)

36
Q

Which Auto-antibody is useful for monitoring disease severity in SLE ?

Which antibody is used for diagnosis?

A

Anti- dsDNA - disease monitoring

ANA used in diagnosis

37
Q

Which of these Auto-antibodies is not often seen in SLE ?

A) ANA
B) dsDNA
C) topoisomerase (Scl70)
D)smith
E)Ro
D)La

A

C- Anti- topoisomerase (Scl70) is seen in Diffuse Cutaneous Systemic Sclerosis and not in SLE

All the other antibodies can be seen in SLE
Ro and La are more present in Sjögren’s syndrome

38
Q

SLE (type 3) vs Goodpasture’s (type 2) presentation

A
  • GP: get antibody binding in a linear fashion at the basement membrane
  • SLE: immune complex deposition leads to a lumpy-bumpy distribution of antibody formation
39
Q

Association between SLE and complement + how does this link to disease activity?

A
  • Formation of antibody-antigen immune complexes will activate complement via the classical pathway (expose the binding site for C1q)
  • Complement components (C3 and C4) become depleted if constantly consumed
  • Quantification of C3 and C4 acts as a surrogate marker for DISEASE ACTIVITY
40
Q

What is the Triad for Antiphospholipid syndrome ?

A

Recurrent venous or arterial thrombosis
Recurrent miscarriage
Thrombocytopenia

41
Q

List the 2 main antibody tests in antiphospholipid syndrome?

A

Anti-Cardiolipin antibody
Lupus anticoagulant test- coagulation dependent on phospholipids is prolonged

42
Q

List the 6 pathologies seen in Limited Cutaneous Systemic Sclerosis (NB think about the mnemonic) ?

A

CREST-P

Calcinosis
Raynauds
Esophageal dysmotility
Sclerodactyly
Telangectasia
Primary pulmonary hypertension

43
Q

Which features of LIMITED cutaneous Systemic Sclerosis are different to DIFFUSE cutaneous Systemic Sclerosis?

A

Skin involvement goes beyond forearm
Renal involvement: scleroderma kidney/renal cysts
more extensive GI disease
Interstitial pulmonary disease
Also has all the other features of CREST

ANA staining is an important prognostic indicator in SS

44
Q

Which 2 antibodies allows differentiation of LIMITED cutaneous Systemic Sclerosis from Diffuse cutaneous Systemic Sclerosis ?

A

LIMITED cutaneous Systemic Sclerosis - Anti-centromere antibodies
Diffuse cutaneous systemic sclerosis - Anti-Topoisomerase antibodies (Scl70)

45
Q

Which disease causes weakness, malaise, peri-orbital heliotrope rash and gottron’s papules ?

A

Dermatomyositis

46
Q

How is polymyositis different to dermatomyositis ?

A

There is no rash in Polymyositis

47
Q

Name 1 autoantibody seen in dermatomyositis ?

A

Anti-aminoacyl tRNA synthetase antibody (anti-Jo1)

Anti- Mi2 is more common in DM than PM

48
Q

Name 1 autoantibody seen in Polymyositis ?

A

anti-signal recognition peptide antibody

49
Q

Patient presents with recurrent nosebleeds and breathlessness. Examination reveals collapse of the nose bridge. X ray shows cavitation get lesions. What is the likely cause ?

A

ANCA (Anti-neutrophil cytoplasmic antibodies) associated vasculitis (small vessel)

50
Q

List 3 types of small vessel vasculitis (ANCA associated vasculitis) ?

A

Microscopic polyangitis (MPA)
Granulomatosis with polyangitis (GPA) (aka wegener’s)
Eosinophilic granulomatosis with polyangitis (eGPA) (Churg-Strauss syndrome)

51
Q

Which type of ANCA is associated with granulomatosis with polyangitis ?

A) cANCA
B) pANCA

A

A (cANCA) - suggests Granulomatosis with polyangitis with renal involvement

(pANCA suggests MPA or eGPA)

52
Q

Which auto-antibodies can be seen in Primary sclerosis cholangitis / Autoimmune hepatitis ?

A

Anti- SMA

(Autoimmune hepatitis can also have anti-LMK-1)

53
Q

Which type of ANCA is associated with eosinophilic granulomatosis with polyangitis (Churg-strauss syndrome) ?

What is presentation of this syndrome?

A

P-ANCA

54
Q

Which antibodies are associated with Primary billiard cirrhosis ?

A

Anti-mitochondrial antibodies

55
Q

Patient presents with blurry vision and weakness in her legs. CSF shows Oligoclonal bands of IgG on electrophoresis.

Most likely diagnosis ?
What type of hypersensitivity reaction is this ?

A

Multiple sclerosis (MS)

Optic neuritis and demyelination.

Type 4 hypersensitivity reaction targeting oligodendrocyte and myelin proteins.

56
Q

Which antibody is characteristic of Pemphigus vulgaris ?

A

Anti- Demoglein 3

57
Q

Which disease is suggested by a +ve Nikolsky’s sign ?

A

Pemphigus vulgaris

Bullae rupture easily

58
Q

Skin histology shows acantholytic cells (separation of keratinocytes caused by loss of intercellular cadherin connections). Leading to blistering.

Most likely diagnosis ?

A

Pemphigus vulgaris

59
Q

Immunofluorescence shows A linear pattern of IgG and C3 at the basement membrane. Causes blistering.

Most likely diagnosis ?

A

Bullous pemphigoid.

60
Q

List 2 diseases for which interferon Beta is a treatment ?

A
  • Relapsing MS
  • Bechets
61
Q

for which disease is inteferon gamma used as a treatment ?

A

Chronic granulomatous disease

62
Q

Describe complement profiles in SLE

A

formation of antibody-antigen immune complexes will activate the classical pathway
complement becomes depleted

active disease - low C4
severe active disease - low C3 + C4

63
Q

features of systemic sclerosis

A

inflammation with Th2 and Th17 cells
cytokines lead to activation of fibroblasts and the development of fibrosis
loss of B cell tolerance to nuclear antigens

64
Q

list 3 idiopathic inflammatory myopathies

A

dermatomyositis - within muscle, immune complex mediated vasculitis (type III response)
polymyositis - within muscle, type IV response

65
Q

list 2 large vessel vascilituses

A

Takayasu’s arteritis
Giant cell arteritis/ polymyalgia rheumatica

66
Q

list 2 medium vessel vasculituses

A

anti-GBM disease
IgA disease
Cryoglobulinaemia

67
Q

ANA+ve, Anti-dsDNA +ve, Low C3 and C4, High ESR. Negative results for:

Ro, La, Sm, RNP, Scl70, Centromere, Jo1. What is the diagnosis?

A

SLE

68
Q

What are Anti-neutrophil cytoplasmic antibody (ANCA)?

A
  • Antibodies specific for antigens located in primary granules within the cytoplasm of neutrophils
  • Inflammation may lead to expression of these antigens on the cell surface of neutrophils
69
Q

c-ANCA (Anti-neutrophil cytoplasmic antibodies) vs p-ANCA in terms of where in the cell they stain

A

c-ANCA: cytoplasm

p-ANCA: Perinuclear staining

70
Q

c-ANCA vs p-ANCA in terms of which antibody they are associated with

A
  • c-ANCA: antibodies to the enzyme proteinase 3
  • p-ANCA: antibodies to myeloperoxidase
71
Q

ANA vs ANCA in terms of what they screen for

A
  • ANA= Screening test for a connective tissue disease
  • ANCA= associated with a small subset of small vessel vasculitides including MPA, GPA and eGPA
    • Microscopic polyangiitis
    • Granulomatosis with polyangiitis

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