Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Molecular Basis of Disease > Pathogenesis of RA in the young > Flashcards

Pathogenesis of RA in the young Flashcards

1
Q

Adult conditions cannot happen in children

TRUE or FALSE

A

FALSE

Any adult condition can manifest in children

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

What is the name given to arthritis that presents in children?

A

Juvenile idiopathic arthritis

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

What is the cause of JIA?

A

Idiopathic

Believed to be caused from a combination of genetic and environmental factors

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

How common is JIA?

A

Affects 1 in 1000 children

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

What is the age cutoff for JIA?

A

The patients must be younger than 16 years old

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

What is a characteristic for JIA needed for diagnosis?

A

Have arthritis in one joint for longer than 6 weeks

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

What is the underlying mechanism of JIA?

A

Autoimmunity

Formulation of an uncontrollable immune response against self

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

What is secondary arthritis?

A

Arthritis caused by an underlying condition

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

Are monogenic inherited conditions more common in childhood or adulthood?

A

Onset is much more common in childhood

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

What genes are associated with JIA?

A

IL-10

MIF

IL-23R

TNF-a

IL-2Ra

PTPN22

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

What is the significance of an IL-10 polymorphism?

A

Protective

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

How does GWAS provide us information regarding JIA?

A

Allows us to look at the expression of different inflammatory molecules

Can help determine which are protective and which are causative

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

Which genes are the most significant in JIA?

A

MHC I and MHC II genes

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

What is another name for the MHC I and MHC II complexes?

A

Human transplant genes

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

What is the role of MHC I?

A

Present peptides to cytotoxic T cells

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

Which cells express MHC I?

A

On the majority of self cells

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

Where are MHC I found?

A

Cytosolic

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

What is the role of MHC II?

A

Present peptides

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

Which cells express MHC II?

A

Professional antigen presenting cells

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

Where are MHC II found?

A

Extracellularly

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

What is a common polymorphism of MHC I?

A

In the B27

Increase risk of developing autoimmunity

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

What is a common polymorphism of MHC II?

A

DR1

Increase the risk of developing autoimmunity

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

Why is it important to understand the genetics of JIA?

A

Will give us insight into the disease mechanisms

Allows doctors to preduct treatment responses

Allows doctors to predict the outcome of a patient

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

Why are the genetics of JIA complex?

A

There are multiple genes associated with the condition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What does epigenetics refer to?
Explains how the expression of genes can be altered through many different mechanisms
26
What are ways by which the expression of genes can be altered?
Toxins Infections Diet Parental exposures can affect the risk in offspring
27
What, apart from genetics, is an important aspect of JIA we need to understand?
The immunology of arthritis
28
What causes inflammation to become pathogenic?
When the immune response is too strong or persists for too long
29
What are important traits in autoimmune diseases?
Faulty immune response is not localised Relies on the interactions of many subgroups of cells in both the adaptive and innate immune responses
30
What is the main site of inflammation in JIA?
The synovium
31
Which cells are seen to have infiltrated the synovial fluid in JIA?
T cells Dendritic cells Plasma cells
32
What is the most predominant immune cell in the joint?
T cells
33
What is the marker for T cells?
CD3
34
What are destructive molecules often seen in the synovial joint?
Pro inflammatory cytokines Osteoclasts MMPs
35
What do MMPs do in synovial joints?
Damage cartilage
36
What are the two types of patients seen in JIA?
The type that undergo spontaneous remission The type that have severe polyarthritis resistant to therapy
37
What is the function of cytokines in JIA?
Destroy bone Attract damage causing cells
38
What is the benefit of targeting treatment to cytokines?
They are easy to target
39
Which cytokines are released by innate cells?
IL-6 IL-1 TNFa
40
What cytokine is released by adaptive cells?
TNFa
41
What is the disadvantage of blocking TNFa as a therapy for JIA?
Increases the risk of developing cancer
42
What is the relationship between IL-6 and JIA?
There are high levels of IL-6 in JIA Levels rise and fall with fever
43
What does IL-6 cause in JIA patients?
Contributes to anaemia, osteoporosis and growth retardation
44
How effective is blocking IL-6 as a therapy for JIA?
Very effective
45
What is the relationship between IL-17 and JIA?
Immunohistochemistry shows prevalence of these in the joint synovial fluid Levels are increased
46
What is the relatioship between Th17 cells and JIA?
Levels are increased in JIA patients
47
What is the relatioship between Treg cells and JIA?
An increased concentration of these cells is related milder forms of JIA
48
What is the marker for Treg cells?
Foxp3+
49
What is the correlation between Th17 and Treg cells in JIA?
Inverse correlation The higher the Treg population, the lower the Th17 cell population
50
What happens to the balance of immune complexes in JIA patients?
It is broken Favours the pro-inflammatory cells/cytokines
51
Examples of pro-inflammatory cytokines
TNF-a IL-22 IL-21
52
Examples of inhibitory cytokines
IL-10 IL-35
53
Examples of pro-inflammatory cells
Th17 Th1
54
What is the relationship between gut flora and JIA?
Remains unclear Questions about whether we can target the gut microflora using probiotics to improve the disease course in JIA patients
55
What bacterial gut microflora population was shown to be dysregulated in JIA?
Prevotella copri Found in 76% of new onset RA compared to only 21% in controls
56
What has the discovery of new sequencing machinery allowed us to do?
Discover new monogenic diseases
57
Examples of monogenic diseases recently discovered through next gen sequencing
Polyarteritis nodosa Interferonopathies Proteaosome deficiencies
58
Which gene is mutated in polyarteritis nodosa?
ADA2 aka CECR1
59
On what chromosome is the mutation responsible for polyarteritis nodosa found?
p.P251L
60
Type of mutation is responsible for polyarteritis nodosa
Homozygous
61
Consequence of mutation in polyarteritis nodosa
Loss of function
62
What cells are affected by polyarteritis nodosa
Endothelium
63
What are the symptoms of polyarteritis nodosa?
B cell immunodeficiency Aplastic anaemia Neuropathy Opthalmic involvement Ulcers
64
How does the gene mutation in polyarteritis nodosa cause disease?
Reduces the concentration of signalling molecules Triggers M1 macrophages to make inflammatory cytokines M2 macrophages apoptose Less IL-10 and TGF-b leads to the breakdown of the endothelium due to the lack of growth factors
65
What is a sybtype of polyarteritis nodosa?
Monogenic polyrteritis nodosa
66
What is the disease presentation of monogemnic polyarteritis nodosa?
Range of presentations Asymptomatic Cutaneous vasculitis Systemic polyarteritis nodosa
67
What is the age of onset of monogenic polyarteris nodosa?
Ranges from childhood to adulthood
68
What treatment is effective in polyarteritis nodosa?
Anti-TNF
69
What causes interpheronopathies?
Mutation of interferon genes
70
What types of mutations cause interpheronopathies?
Gain of function mutations
71
What leads to the symptoms of interpheronopathies?
Since the gene encoding for interferon 1 is constantly activated, the immune cells are constantly active
72
What condition is an interferonopathy?
STING-associated vasculopathy with onset in infacy
73
When does STING-associated vasculopathy present?
Early life
74
What are the symptoms of STING-associated vasculopathy ?
Scaling lesions of fingers, toes, nose and ears Acral necrosis in some patients Pulmonary inflammation and ILD Fever Failure to thrive
75
What are proteasome deficiencies?
Caused by mutations to the proteasome
76
What is the proteasome?
Complex structure Targets proteins for degradation Through the process of ubiquitination
77
What happens when the proteasome becomes aberrant?
Cells become stressed Release cytokines like IFN-g Leads to the activation of immune modulators
78
Examples of proteasome deficiencies
CANDLE JMP Nakajo-Nishimura syndrome PSMB8 mutation
79
What are the pathogenic mechanisms that develop following PSMB8 mutations?
Reduced proteasome activity Increase in cellular proteins Increase in cellular stress Activation of IFN signalling Increase in IFN genes
80
Which macrophages are increased following PSMB8 mutations?
CD68 CD14 CD163
81
Which cells are decreased following PSMB8 mutations?
CD3+ cells

Molecular Basis of Disease (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions