Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Musculoskeletal > Pathogenesis of AI disease > Flashcards

Pathogenesis of AI disease Flashcards

1
Q

Define Rheumatoid Arthritis.

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the site of inflammation in rheumatoid arthritis?

A

Synovium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

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

A

Rheumatoid factor

Anti-cyclic citrullinated peptide antibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Other than at joints, where else is synovium found?

A

Around tendons (tenosynovium)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Define Ankylosing Spondylitis.

A

Chronic spinal inflammation that can result in fusion and deformity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the site of inflammation in ankylosing spondylitis?

A

Entheses – where a ligament or a tendon inserts into bone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What family of diseases is ankylosing spondylitis a part of?

A

Seronegative spondyloarthropathies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which other diseases are Seronegative spondyloarthropathies?

A

Reiter’s syndrome and reactive arthritis
Psoriatic arthritis
Enteropathic synovitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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

A

Joints, Skin and Kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the two autoantibodies that are associated with lupus?

A

Anti-nuclear antibodies

Anti-double stranded DNA antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What family of diseases is lupus a part of?

A

Connective tissue diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What other diseases are connective tissue diseases?

A

Systemic sclerosis (diffuse and localised)
Polymyositis/Dermatomyositis
Sjogren’s syndrome
Mixed connective tissue disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is Sjogren’s syndrome?

A

An autoimmune disease that targets the exocrine glands (e.g. lacrimal glands)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the MHC associations of rheumatoid arthritis, ankylosing spondylitis and SLE?

A

Rheumatoid arthritis – HLA-DR4
SLE –HLA-DR3
Ankylosing spondylitis – HLA-B27

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

On which chromosome is HLA encoded?

A

Chromosome 6

17
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

18
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

19
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

20
Q

What is a theory about HLA-B27 causing 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

21
Q

What is the key autoantibody in:

a. Diffuse systemic sclerosis
b. Limited systemic sclerosis
c. Dermatomyositis/Polymyositis
d. Mixed connective tissue damage

A

Diffuse systemic sclerosis - Anti-Scl-70 antibody

Limited systemic sclerosis - Anti-centromere antibody

Dermatomyositis/Polymyositis - Anti-tRNA transferase antibody

Mixed connective tissue disease - Anti-U1-RNP antibody

22
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

23
Q

How is the presence of anti-nuclear antibodies detected?

A

Some cells are permeabilised so the antibodies can enter the cell and then the patient’s serum is washed over the cells

If there are anti-nuclear antibodies, they will bind to the nuclear antigens

24
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

25
Q

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

A

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

26
Q

State some important cytokines in rheumatology.

A

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

27
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

28
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)

29
Q

What is RANKL produced by and what does it do?

A

RANKL is produced by T cells and synovial fibroblasts

It stimulates osteoclast formation

30
Q

What can upregulate RANKL production?

A

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

31
Q

What decoy receptor antagonises the action of RANKL?

A

Osteoprotegrin

32
Q

Name a monoclonal antibody that targets RANKL.

A

Denusomab

33
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)

34
Q

What are the effects of prostaglandins produced by COX?

A

Vasodilation, inhibit platelet aggregation, bronchodilation, uterine contraction

35
Q

What are the effects of leukotrienes produced by lipooxygenase?

A

Leukocyte chemotaxis, smooth muscle contraction, bronchoconstriction, mucous secretion

36
Q

What do glucocorticoids inhibit?

A

Phospholipase A2

Musculoskeletal (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions