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JL Musculoskeletal > Immunology > Flashcards

Immunology Flashcards

1
Q

Name one monogenic autoimmune disease?

A

IPEX syndrome (fatal autosomal recessive disorder presenting early in childhood)

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2
Q

What is IPEX syndrome?

A

Immune dysregulation, polyendocrinopathy, enteropathy and x-linked inheritance syndrome

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3
Q

Give 5 symptoms of IPEX syndrome?

A
  1. Early onset insulin dependent diabetes mellitus
  2. Severe malabsorption syndrome
  3. Eczema
  4. Autoimmune thyroid disease, autoimmune haemolytic anaemia
  5. Severe infections
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4
Q

What is the pathogenesis of IPEX syndrome?

A

Mutation in FOXP3 gene - essential for development of regulatory T-cells (regulatory T cells are essential in protection against autoimmunity)

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5
Q

What do most autoimmune diseases result from?

A

Complex genetic interplay

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6
Q

Name three immune response genes that most autoimmiune diseases result from?

A

HLA (human leukocyte antigen complex)
Cytokine genes
Costimulatory molecules

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7
Q

In autoimmunity - what recognises foreign antigens?

A

T lymphotcytes

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8
Q

During recognition of a foreign antigen - what do T cells see peptides exhibited on?

A

A defined HLA framework

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9
Q

What do all nucleated cells express on the cell surface?

A

Class I (HLA-A, HLA-B, HLA-C)

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10
Q

What do specialised antiven-presenting cells also express on their surface?

A

Class II (HLA-DR, HLA-DQ, HLA-DP)

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11
Q

What can help maintenance of diversity?

A

Polymorphism in HLA molecules

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12
Q

What is the susceptible allele for - Ankylosing spondylitis?

A

HLA B27

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13
Q

What is the susceptible allele for - Goodpastures syndrome?

A

HLA DR2

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14
Q

What is the susceptible allele for - Grave’s disease?

A

HLA DR3

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15
Q

What is the susceptible allele for - SLE?

A

HLA DR3

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16
Q

What is the susceptible allele for - type 1 diabetes?

A

HLA DR3/DR4

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17
Q

What is the susceptible allele for - RA?

A

HLA-DR4

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18
Q

What can alter the course of some autoimmune diseases?

A

Pregnancy

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19
Q

What is there sex bias in?

A

Predisposing genetic factors

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20
Q

What environmental factor contributes to autoimmune disease?

A

iNFECTION

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21
Q

What reaction is an immune response that results in bystander damage to the self?

A

Hypersensitivity

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22
Q

Name two IMMUNE COMPLEX MEDIATED autoimmune diseases?

A
  1. SLE

2. RA

23
Q

Name an autoimmune disease which is a prototypic multisystemc disease, 1:2000, has female preponderance and genetic predisposition?

A

SLE

24
Q

What is the fundamental abnormality in SLE?

A

Disturbed regulation of B cell activity characterised by antibodies to nuclear proteins

25
Q

In SLE because it is mediated by immune complexes - what mediates inflammation?

A

Complement

26
Q

Give three antibodies produced against contents of cell nuclei in SLE?

A
  1. Anti-DNA
  2. Anti-nuclear
  3. Antibodies to extractable nuclear antigens
27
Q

Give four non-specific clinicakl features of SLE?

A

Malaise, fatigue, myalgia and fever

28
Q

What disease can patients present with mouth ulcers, malar rash and photosensitivity?

A

SLE

29
Q

What is the speckled antibody associated with and more specific for?

A

Associated with antibodies to extractable nuclear antigens

More specific for SLE and Sjorgrens

30
Q

What pattern of ANA antibody is very specific for limited Scleroderma (CREST) and binds to chromosomes?

A

Anti-centromere antobdy

31
Q

What ANA antibody pattern is associated with scleroderma and proteins associated with nucleolar RNA including fibrillarin, U1RNP?

A

Nucleolar ANA

32
Q

Antibodies to extractable nuclear antigens: give the disease association for anti-centromere antibody?

A

CREST variant of scleroderma, occasionally found in primary Raynaud’s syndrome

33
Q

Antibodies to extractable nuclear antigens: give the disease association for anti-Jo-1 (anti-histidyl-tRNA syndthease)?

A

Polymyositis, dermatomyositis or polymyositis-scleroderma, particularly associated with interstitial lung disease in these conditions

34
Q

Antibodies to extractable nuclear antigens: give the disease association for Anti-La antibody?

A

Sjogrens syndrome, SLE

35
Q

Antibodies to extractable nuclear antigens: give the disease association for Anti-ribonucleoprotein antibody (anti-RNP)?

A

Mixed connective tissue disease

SLE

36
Q

Antibodies to extractable nuclear antigens: give the disease association for Anti-Ro antibody?

A

SLE: associated with photosensitivity, thrombocytopaenia and subacute cutaneous lupus. Maternal anti-Ro are associated with neonatal lupus and congenital heart block
Sjorgrens syndrome

37
Q

Antibodies to extractable nuclear antigens: give the disease association for Anti-Smith antibody?

A

SLE

38
Q

Antibodies to extractable nuclear antigens: give the disease association for Anti-topoisomerase I antibody?

A

Diffuse scleroderma: associated with severe organ involvement, including pulmonary fibrosis

39
Q

What do anti-DNA binding antibodies measure antibodies against?

A

Double stranded DNA

40
Q

What are very high titres of Anti-DNA antibodies often associated with?

A

SLE: more severe including renal or CNS involvement

41
Q

What does formation of antibody-antigen immune complexes activate and cause?

A

Complement cascade via classical pathway

Inflammation of tissues in immune complexes are deposited

42
Q

When measuring complement proteins what type do we measure?

A

UNACTIVATED COMPLEMENT PROTEINS

43
Q

Quantitation of what acts as a surrogate marker of disease activity?

A

C3 and C4

44
Q

Give three type III hypersensitivity investigations?

A
  1. Specific IgG to putative antigen
  2. Low serum complements
  3. Characteristic biopsy features
45
Q

Describe the deposition of IgG in glomerulonephritis associated with SLE?

A

Deposition of IgG and complement C3 in granular lumpy-bumpy pattern

46
Q

Describe the deposition of IgG in glomerulonephritis associated with Goodpastures?

A

Linear deposition of IgG along the glomerular basement membrane

47
Q

Name the criteria for classification of SLE?

A 
Serositis - pleurisy or pericarditis
Oral ulcers
Arthritis
Photosensitivity
Blood disorders
Renal involvement
Antinuclear antibodies
Immunologic phenomena - anti-DNA, anti-Smith
Neurologic disorder
Malar rash
Discoid rash
48
Q

What two pharmacological things are used to decrease inflammation and decrease production of antibody in type III hypersensitivity?

A

Corticosteroids

Immunosuppressive agents - anti-proliferative

49
Q

Name three anti-proliferative agents?

A

Azathiprine
Mycophenolate
Cyclospohsphamide

50
Q

Name a type IV hypersensitivity disease?

A

RA

51
Q

What is the immunopathogenesis of RA?

A

Infiltration of synovium by CD4+ T cells

Secondary involvement of activated b CELLS AND ANTIBODY

52
Q

What four things happen when the synovium is infiltrated by activated CD4 cells in RA?

A
  1. production of cytokines
  2. recruitment of phagocytes
  3. recruitment of activated B cells
  4. activation of synovial fibroblasts
53
Q

In an RA joint what destroys cartilage and bone?

A

Matrix metalloproteases

54
Q

Give an example of an antibody which blocks attachment of cytokine to receptor in RA ?

A

Anti-TNF - infliximab and adalimumab

JL Musculoskeletal (35 decks)

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