Brainscape's Knowledge GenomeTM

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


See full index

LCRS Musculoskeletal > Pathogenesis of autoimmune disease > Flashcards

Pathogenesis of autoimmune disease Flashcards

1
Q

What is rheumatoid arthritis?

A

Chronic joint inflammation in the synovium that can result in joint damage

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

What are the main autoantibodies of rheumatoid arthritis?

A

Rheumatoid factor

Anti-cyclin citrullinated peptide (Anti CCP antibodis0

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

What is ankylosing spondylitis?

A

Chronic spinal inflammation in the enthesis that can result in spinal fusion and deformity

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

What is the enthesis?

A

Where a ligament inserts to the bone

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

How does ankylosing spondylitis tend to present?

A

Spontaneously but it’s associated with a strong genetic predisposition

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

Where are enthuse found in the spine?

A

Between the vertebrae- in the annulus fibrosis, entheses join it to the bone above and bone below

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

What is the normal structure of an intervertebral disc?

A

They have a soft nucleus pulpous and tough fibrous annulus fibrosus around the outside

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

What can the inflammation between the vertebral bodies lead to if untreated?

A

Calcified fusion of the vertebrae

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

What are ankylosing spondylitis cases often referred to as?

A

Seronegative spondyloarthropathies

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

Why are they seronegative?

A

There are no autoantibodies

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

What is systemic lupous erythematous (SLE)

A

Chronic tissue inflammation (of sterile tissue- not infected) in the presence of auto-antibodies

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

How do the autoantibodies lead to inflammation in SLE?

A

They activate the complement via the classical pathway- inflammatory cells have Fc receptors so if autoantibodies are mobilised on these, you can trigger inflammation

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

Why do you see widespread inflammation in SLE?

A

Formation of immune complexes doesn’t immediately indicate that one particular part of the body is inflamed

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

In lupus you get widespread organ inflammation but which organs are commonly affected?

A

Skin and kidneys

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

What autoantibodies is lupus associated with?

A

Antinuclear antibodies

Antidouble stranded DNA antibodies

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

What family of diseases does lupus belong to?

A

Connective tissue diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does Sjogrens syndrome attack?

A

Exocrine glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

For the aforementioned autoimmune diseases, where are the strongest genetic associations within?

A

Within the MHC which is encoded by the HLA gene locus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does MHC class 1 have a genetic association with?

A

Ankylosing spondylitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does MHC class II have a genetic association with?

A

Rheumatoid arthritis and SLE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the MHC molecule responsible for?

A

Antigen presentation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which T cells recognise antigens presented by MHC class I?

A

CD8+ T cells- cell killing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which T cells recognise antigens presented by MHC class II?

A

CD4+ T cells- antibody response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Why is MHC so important in antigen recognition?

A

T cells can only see an antigen when it’s being presented by MHC

25
Q

What happens in regards to MHC in an autoimmune disease?

A

You get self antigen binding to the MHC molecule and it’s able to trigger an immune reaction

26
Q

What HLA is involved in ankylosing spondylitis?

A

HLA-B27- it allows the binding of some sort of antigen and triggering of class 1 response

27
Q

When rats were made to express HLA-B27, what happened?

A

Ankylosing spondylitis type effects

28
Q

What was thought to be the reason for ankylosing spondylitis type effects in the rats?

A

Interactions between CD8+ T cells and HLA-B27 molecules

29
Q

Why was the theory about CD8+ T cells proved wrong?

A

Experiment was repeated but CD8+ T cells were removed and rats still showed disease so ankylosing spondylitis is independent of CD8+ T cells

30
Q

What new theory was suggest for the link between HLA-B27 and ankylosing spondylitis?

A

HLA-B27 has a propensity to misfold which causes cellular stress that triggers IL-23 release and triggers IL-17 production by:
Adaptive immune cells e.g. CD4+ and innate immune cells e.g. CD4- and CD8-

31
Q

Why don’t you get inflammation everywhere in ankylosing spondylitis?

A

Chemical stress is more likely to occur in innate immune cells and these innate cells are present in entheses

32
Q

What are antinuclear antibodies?

A

Directed against the nucleus

33
Q

What is the amount of autoantibodies used for?

A

To give an estimate of the severity of disease

34
Q

How many nuclear antigens are there that react with anti-nuclear antibodies in lupus and what does this mean?

A

<100 nuclear antigens of a huge number so lupus ANAs only react with relatively few

35
Q

How is the presence of autoantibodies detected?

A

By permeabilising cells on a glass slide to allow entry of autoantibodies
The patient’s serum is then placed over the cells and if there are antinuclear antibodies, they will bind to the nucleus and can be detected by fluorescence

36
Q

What are the complement levels and serum levels of anti-ds-DNA antibodies like in a lupus patient?

A

Low complement

High serum levels of anti-ds-DNA antibodies

37
Q

What does apoptosis normally cause in terms of antigens?

A

Apoptosis results in translocation of certain nuclear antigens to surface of apoptotic cell so nuclear antigens are accessible to immune response

38
Q

What happens in lupus in terms of apoptotic cells?

A

They aren’t cleared normally so this impaired clearance enables abnormal presentation to the immune system and the immune response is amplified through B cells

39
Q

What is biological therapy?

A

Manipulation of cytokines and switching them off by using monoclonal antibodies

40
Q

What cytokines are there and what effect do they have?

A

y-IFN- activates macrophages
IL-1- activates T cells, fever and pro-inflammatory
IL2- Activates T and B cells
IL-6- Activates B cells, acute phase response
TNF-alpha- Similar to IL-1 but more destructive

41
Q

Why is anti-TNF treatment so successful and commonly used?

A

TNF alpha is produced by many cells- mainly macrophages and anti-TNF treatment is so successful because these macrophages that produce TNF-alpha are causing many of the negative effects

42
Q

What negative effects does TNF alpha that is released by activated macrophages have?

A 
Proinflammatory cytokine release
Hepcidin induction
PGE2 production
Osteoclast activation
Chondrocyte activation
Angiogenesis
Leukocyte accumulation 
Endothelial cell activation
Chemokine release
43
Q

Apart from TNF alpha blockade what else is available in clinics?

A

IL-6 and IL-1

44
Q

What else can be done in addition to cytokine blockade?

A

We can deplete B cells in rheumatoid arthritis by parenteral administration of an antibody that acts against a B cell surface antigen- this antibody is called rituximab

45
Q

What effect will blocking RANKL have?

A

Decreased osteoclast activity

46
Q

What is RANKL produced by?

A

T cells and synovial fibroblasts

47
Q

What upregulates RANKL?

A

Interleukin-1, TNF-alpha
Interleukin-17
PTH-related peptide

48
Q

What does RANKL stand for?

A

Receptor activator of nuclear factor kB ligand

49
Q

What is denusomab?

A

Monoclonal antibody against RANKL

50
Q

What is denusomab used to treat?

A 
Osteoporosis
Bone metastases
Multiple myeloma
Giant cell tumours 
-Not rheumatoid arthritis
51
Q

What is B cells hyperactivity a key feature of?

A

SLE

52
Q

What biological therapies target B cells in treatment of SLE?

A

Rituximab- chimeric anti-CD20 antibody that is used to deplete B cells
Belimumab- Monoclonal antibody against a B cell survival factor called BLYS (B-lymphocyte stimulator)

53
Q

What are prostaglandins?

A

Lipid mediators of inflammation that act on platelets, endothelium, uterine tissue and mast cells

54
Q

What are prostaglandins synthesised from?

A

Essential fatty acids: phospholipase A2 generates arachidonic acid from diacylglycerol in cell membranes

55
Q

What are the two pathways that arachidonic acid enters?

A

Cyclooxygenase pathway- Arachidonic acid -> Prostaglandins

Lipooxygenase pathway- Arachidonic acid -> leukotrienes

56
Q

What do glucocorticoids inhibit that is involved with prostaglandins?

A

Phospholipase A2

57
Q

What do NSAIDs?

A

COX

58
Q

What are NSAIDs used to generally deal with?

A

Pain

LCRS Musculoskeletal (7 decks)

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