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LCRS 2 > Pathogenesis of Autoimmune Disease > Flashcards

Pathogenesis of Autoimmune Disease Flashcards

1
Q

Define Rheumatoid Arthritis.

A

Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis of synovial joints

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2
Q

What is the site of inflammation in rheumatoid arthritis?

A

Synovium

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3
Q

What are the two main autoantibodies that are associated with rheumatoid arthritis?

A

Rheumatoid factor

Anti-cyclic citrullinated peptide antibody

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4
Q

Other than at joints, where else is synovium found?

A

Around tendons (tenosynovium)

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5
Q

Define Ankylosing Spondylitis.

A

Chronic spinal inflammation that can result in fusion and deformity

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6
Q

What is the site of inflammation in ankylosing spondylitis?

A

Entheses – where a ligament or a tendon inserts into bone

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7
Q

What family of diseases is ankylosing spondylitis a part of?

A

Seronegative spondyloarthropathies

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8
Q

Define Systemic Lupus Erythematosus (SLE).

A

Chronic tissue inflammation in the presence of antibodies directed at self-antigens
NOTE: it is inflammation of sterile tissue

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9
Q

Lupus causes multi-site inflammation but state some sites that are particularly badly affected.

A

Joints, Skin and Kidneys

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10
Q

What are the two autoantibodies that are associated with lupus?

A

Anti-nuclear antibodies

Anti-double stranded DNA antibodies

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11
Q

What family of diseases is lupus a part of?

A

Connective tissue diseases

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12
Q

On which chromosome is HLA encoded?

A

Chromosome 6

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13
Q

A change in which class of MHC is associated with rheumatoid arthritis, ankylosing spondylitis and SLE?

A

Ankylosing spondylitis = Class 1

Rheumatoid Arthritis + SLE = Class 2

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14
Q

Which cells express class I MHC and which cells recognise this class of MHC?

A

All nucleated cells (they display endogenous antigens)

They are recognised by CD8+ T cells

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15
Q

Which cells express class II MHC and which cells recognise this class of MHC?

A

Antigen presenting cells e.g. macrophages, dendritic cells (they display exogenous antigens)
Recognised by CD4+ T cells

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16
Q

How does HLA-B27 cause ankylosing spondylitis?

A

Ankylosing spondylitis is independent of CD8+ T cells
HLA-B27 has a propensity to misfold, which causes cellular stress and triggers the release of IL-23 and IL-17 by adaptive immune cells and innate immune cells
The release of chemical mediators leads to inflammation
The cellular stress is most likely to occur in innate immune cells and these are present in the entheses – hence why ankylosing spondylitis causes enthesitis

17
Q

What is the difference in the specificity of the autoantibodies in SLE?

A

Anti-nuclear antibodies are found in all cases of SLE but isn’t specific to SLE
Anti-dsDNA antibodies are specific to SLE – serum level of this antibody correlates with disease activity

18
Q

How is the presence of anti-nuclear antibodies detected?

A

Some cells are permeabilised so the antibodies can enter the cell andthen the patient’s serum is washed over the cells
If there are anti-nuclear antibodies, they will bind to the nuclearantigens

19
Q

What are the features of a sick lupus patient in terms of complement levels and serum levels of anti-dsDNA antibodies?

A

Low complement levels

High serum levels of anti-dsDNA antibodies

20
Q

Blockage of which cytokine with biological therapy has proven to be very effective in reducing some of the negative effects of rheumatoid arthritis?

A

TNF-alpha- blocks lymphocyte recruitment and angiogenesis

21
Q

Other than cytokine blockade, what else can be targeted to improve symptoms in rheumatoid arthritis?

A

B cell depletion (B cell hyperactivity is a key feature of SLE)

22
Q

Name a monoclonal antibody that targets RANKL.

A

Denusomab

23
Q

State two drugs that deplete B cells and specify what they target.

A

Rituximab – anti-CD20 monoclonal antibody

Belimumab – anti-BLYS monoclonal antibody (BLYS is a B cell survival factor)

24
Q

MHC association of rheumatoid arthritis

A

HLA-DR4

25
Q

MHC association of ankylosing spondylitis

A

HLA-B27

26
Q

MHC association of systemic lupus erythematosus

A

HLA-DR3

27
Q

Importance of NSAIDS in SLE treatment

A

Interfere with arachidonic acid metabolism so reduce inflammation and pain from prostaglandins

28
Q

What are seronegative spondlyoarthropathies

A

Diseases with no autoantibodies

LCRS 2 (44 decks)

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