Pathogenesis of Autoimmune Disease :part 2

Question 1

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

Answer 1

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

Question 2

What do glucocorticoids inhibit?

Answer 2

Phospholipase A2

Question 3

What is RANKL produced by and what does it do?

Answer 3

RANKL is produced by T cells and synovial fibroblasts It stimulates osteoclast formation

Question 4

How is the presence of anti-nuclear antibodies detected?

Answer 4

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

Question 5

What is the key autoantibody in: a. Diffuse systemic sclerosis b. Limited systemic sclerosis c. Dermatomyositis/Polymyositis d. Mixed connective tissue damage

Answer 5

a. Diffuse systemic sclerosis Anti-Scl-70 antibody b. Limited systemic sclerosis Anti-centromere antibody c. Dermatomyositis/Polymyositis Anti-tRNA transferase antibody d. Mixed connective tissue disease Anti-U1-RNP antibody

Question 6

What can upregulate RANKL production?

Answer 6

IL-17 IL-1 TNF-alpha PTH-related peptide

Question 7

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

Answer 7

Rituximab – anti-CD20 monoclonal antibody Belimumab – anti-BLYS monoclonal antibody (BLYS is a B cell survival factor)

Question 8

How do antinuclear antibodies react with nuclear antigens, which are found within the nucleus?

Answer 8

Apoptosis leads to the translocation of nuclear antigens onto the surface of the cell so that they are accessible to the immune system In lupus, apoptotic cells are not cleared normally This impaired clearance enables abnormal presentation to the immune system The immune response is amplified through B cells

Question 9

What are the effects of prostaglandins produced by COX?

Answer 9

Vasodilation, inhibit platelet aggregation, bronchodilation, uterine contraction

Question 10

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

Answer 10

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

Question 11

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

Answer 11

TNF-alpha

Question 12

What decoy receptor antagonises the action of RANKL?

Answer 12

Osteoprotegrin

Question 13

What are the effects of leukotrienes produced by lipooxygenase?

Answer 13

Leukocyte chemotaxis, smooth muscle contraction, bronchoconstriction, mucous secretion

Question 14

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

Answer 14

Low complement levels High serum levels of anti-dsDNA antibodies

Question 15

How does HLA-B27 cause ankylosing spondylitis?

Answer 15

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

Question 16

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

Answer 16

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

Question 17

Name a monoclonal antibody that targets RANKL.

Answer 17

Denusomab

Question 18

State some important cytokines in rheumatology.

Answer 18

IL-1 – produced by macrophages and activates T cells, fever + pro-inflammatory IL-2 – produced by T cells – activates T + B cells IL-6 – produced by T cells – activates B cells + acute phase response TNF-alpha – produced by macrophages – similar to IL-1 but more destructive Gamma-IFN – produced by T cells – activates macrophages