Organ-specific immunity: JOINT & BONE Flashcards

1
Q

What is the synovial membrane made up of?

A

Type A (mAcrophage) and type B (fibroBlast) synoviocytes

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

What are the layers of the joint lining?

A

The sublining, lining (fibroblast and barrier-forming macrophages) and the synovial fluid)

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

How are type A synoviocytes connected?

A

Tight junctions

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

What happens to the Type A lining during arthritis?

A

The lining is disrupted, enabling infiltration of myeloid cells

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

What is the sublining composed of?

A

Different types of macrophages and fibroblasts (than those of the lining).

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

What happens (disease-wise) in early RA?

A

Immune infiltration and proliferation of the synovial lining, blood vessel formation.

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

What happens (disease-wise) in established RA?

A

Synovial lining is overlaying the cartilage, produced enzymes lead to cartilage and bone destruction

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

What are chondrocytes?

A

Cartilage cells

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

What do macrophages do in arthritis?

A

They release a lot of inflammatory cytokines as well as IL-10 and TGFß (to try to dampen the whole thing) and interact with T and B cells through soluble factors and direct contact

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

What causes RA?

A

Environmental factors (smoking, stress, microbes) and genetic predisposition are involved

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

What happens before clinical symptoms?

A

Pre-arthritis, which is a bit auto-immune like but not yet arthritis.

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

Can pre-arthritis be detected?

A

Yes, there are some antibodies that can be detected in some patients, such as IgG-RF and/or anti-CCP

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

What are ACPAs directed against and what does binding do?

A

Citrullinated protein on osteoclast precursors. This causes further activation and maturation of osteoclasts and IL-8 production

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

What do osteoclasts usually do?

A

Bone resorption which is necessary for maintenance, repair and remodeling

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

How do ACPAs induce pain?

A

IL-8 produced by mature osteoclasts can interact with (sensory) nociceptor.
Recruitment of neutrophils can lead to inflammation and progression, which is also painful

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

What does knocking out IL-12 in RA patients do, and why does knocking out IFNy not have the same effect?

A

Dampens symptoms, while knocking out IFNy makes symptoms worse.

15
Q

So what is driving RA autoimmune processes?

A

IL-17/IL-23 (so Th17), not Th1

16
Q

What does Th17 have an effect on?

A

Monocytes, B cells and fibroblasts

17
Q

What is the proportion of IL-17 in early RA patients, and why?

A

Higher compared to healthy controls, due to a CCR6 polymorphism

18
Q

What is the pro-inflammatory loop in RA?

A

Th17 ->TNFα and L-17 ->fibroblast ->IL6 and IL8 which act on Th17 and so on.

19
Q

Is Th17 plastic?

A

Yes

20
Q

What are possible treatments?

A

Rituximab, CD80/86 inhibitors, JAK inhibitors, TNF inhibitors, IL6R inhibitors

21
Q

What are the two kinds of RA?

A

Activating complement and binding to Fc receptors on macrophages

22
Q

What is RF?

A

Rhematoid factors are autoantibodies directed against IgG Fc that can form enormous immune complexes

23
Q

What is ACPA?

A

Antibodies (general) against Citrullinated Protein antigens

24
Q

What is anti-CCP?

A

Anti-cyclic citrullinated Peptide, which is an artificial peptide used to measure ACPA using ELISA (so anti-ACPA)

25
Q

What is citrullination?

A

Totally normal. Post-translational amino acid modification (arginine -> citrulline), can occur in every protein

26
Q

Why is smoking a risk factor for RA?

A

Inflammation (lungs) results an increase citrullination and breakdown of tolerance in genetically predisposed individuals

27
Q

What is fine specificity in ACPA?

A

ACPA is very specific for specific citrullinated proteins