Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

I&I WC2 > Auto-immune disease > Flashcards

Auto-immune disease Flashcards

1
Q

What are the pathological processes in early RA? (4)

A
  1. Capillary formation
  2. Hyperplastic synovial membrane
  3. Hyperthropic synoviocytes
  4. Influx of immune cells into the joint
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which immune cells can be found in the joint in early RA? (3)

A
  1. Neutrophils
  2. T-cells
  3. B-cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the pathological processes in established RA? (5)

A
  1. Plasma cells in the joint
  2. Synovial villi formation
  3. Extensive angiogenesis
  4. Bone erosion
  5. Pannus formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which two cell types are the main contributors to the production of RA-related cytokines?

A
  1. Macrophages
  2. T-cells (Th17)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which cytokines are the main cytokines in RA? (6) Are they pro- or anti-inflammatory? By which cell types are they produced?

A

Pro-inflammatory:
1. TNF-α = macrophage
2. IL-6 = macrophage
3. IFN-γ = Th17
4. IL-17A = Th17

Anti-inflammatory:
1. TGF-β = macrophage
2. IL-10 = macrophage

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

Various RA-related diseases have involvement of the same pathways, with a different predominant cytokine. What is the central cytokine in all these diseases?

A

TNF-α

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

If TNF-α is combined with IL-17/IL-23, which group of (3) diseases can occur? On which cell-type is the pathogenesis of this cluster dependent?

A
  1. Spondylarthritis ankylopoietica (SpA)
  2. Psoriasis
  3. Psoriatic arthritis (PsA)

T-cell dependent

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

Which cytokine(s), in addition to TNF-α, is/are involved in the pathogenesis of spondylarthritis ankylopoietica (SpA)?

A

IL-17/IL-23

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

Which cytokine(s), in addition to TNF-α, is/are involved in the pathogenesis of psoriasis?

A

IL-17/IL-23

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

Which cytokine(s), in addition to TNF-α, is/are involved in the pathogenesis of psoriatic arthritis (PsA)?

A

IL-17/IL-23

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

If TNF-α is combined with IL-6, which group of (2) diseases can occur? On which pathological process is this cluster dependent?

A
  1. Rheumatoid arthritis (RA)
  2. Giant cell arteritis (CGA)

Early phase T-cell-dependent, late phase inflammasome-dependent

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

Which cytokine(s), in addition to TNF-α, is/are involved in the pathogenesis of rheumatoid arthritis (RA)?

A

IL-6

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

Which cytokine(s), in addition to TNF-α, is/are involved in the pathogenesis of giant cell arteritis (CGA)?

A

IL-6

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

If TNF-α is combined with IL-1, which group of (3) diseases can occur? On which pathological process is this cluster dependent?

A
  1. Gout
  2. Juvenile idiopathic arthritis (JIA)
  3. Other auto-inflammatory diseases

Inflammasome-mediated

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

Which cytokine(s), in addition to TNF-α, is/are involved in the pathogenesis of gout?

A

IL-1

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

Which cytokine(s), in addition to TNF-α, is/are involved in the pathogenesis of juvenile idiopathis arthritis (JIA)?

A

IL-1

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

How can knowledge of involved cytokines aid the treatment of auto-immune/auto-inflammatory disease?

A

The cytokines or their downstream signalling can be targeted as a therapeutic intervention

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

Which four main ways are there to target cytokine signalling?

A
  1. Monoclonals against cytokines
  2. Soluble receptors to catch cytokines
  3. Monoclonals against cytokine receptors
  4. Blocking of downstream receptor signalling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

In which pathological processes in RA is IL-6 involved? (4)

A
  1. B-cell differentiation -> antibody production
  2. Mediation of chronic inflammation through activation of immune cells
  3. Osteoclast activation -> bone resorption -> bone/joint destruction
  4. Synoviocyte activation -> pannus formation -> joint destruction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Which two types of IL-6 signalling can be distinguished?

A
  1. Classical IL-6 signalling
  2. Trans IL-6 signalling (trans-signalling)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the configuration of the IL-6 receptor?

A

IL-6R supported by 2 gp130 chains

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

What is classical IL-6 signalling?

A

Surface-bound IL-6R supported by 2 gp130 chains gets activated by IL-6

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

What is IL-6 trans-signalling?

A

Soluble IL-6R activates IL-6 signalling pathways in cells lacking IL-6R, but expressing gp130

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

Joint destruction in RA is a two-step process. What are the two steps?

A
  1. Cartilage destruction
  2. Bone erosion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the processes involved in cartilage destruction in RA? (3)

A
  1. Matrix metalloproteases (MMPs) released under inflammatory conditions break down cartilage
  2. Invasion of synovial fibroblasts into the cartilage -> pannus formation
  3. Chondrocyte death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Which cells are the main producers of matrix metalloproteases (MMPs) in cartilage destruction in RA?

A

Chondrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the first step in cartilage destruction by matrix metalloproteases (MMPs) in RA? Is this step reversible?

A

Proteoglycan loss; still reversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the first step of irreversible damage in joint destruction in RA?

A

Chondrocyte death during cartilage destruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Which cytokines are involved in cartilage destruction in RA? (3) What is their role?

A
  1. IL-1 -> activation of synovial fibroblasts
  2. IL-17 -> activation of synovial fibroblasts
  3. TNF-α -> production of MMPs by chondrocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Which cytokines activate synoviocytes in cartilage destruction in RA? (2) What is the effect of synoviocyte activation? (2)

A

IL-1 & IL-17

Synoviocyte activation leads to:
1. Pannus formation
2. Production of TNF-α

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Which cytokines are involved in driving the release of MMPs by chondrocytes in cartilage destruction in RA? (2)

A

IL-1 & TNF-α

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the main process of bone destruction in RA?

A

Osteoclast activation -> bone resorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What kind of cell type are osteoclasts?

A

Myeloid-derived cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Which receptor is the main activating receptor of osteoclasts? What is its ligand?

A

RANK, stimulated by RANK-ligand (RANK-L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is the role of OPG in the regulation of osteoclast activation?

A

OPG = RANK-L decoy receptor -> blocks RANK-RANKL signalling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Which cytokine cascasde leads to increased expression of RANK on osteoclasts in bone resorption in RA?

A

IL1 -> TNF-α -> IL-17 -> increased RANK expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Which cytokines can downregulate osteoclast activity, downregulating bone resorption? (2)

A

IL-4 & IL-10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is the prototypic JAK/STAT signalling pathway? (5)

A
  1. Activation of receptor by ligand
  2. JAK phosphorylation
  3. STAT phosphorylation & dimerization
  4. Nuclear translocation
  5. Modification of gene transcription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

How many different JAKs and STATs are there?

A

JAKs: 4
STATs: 6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

How can a limited number of JAKs and STATs lead to a plethora of different responses to receptor activation?

A

JAKs and STATs can be combined, giving rise to a higher number of possibilities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What are the main JAK/STAT pathways involved in RA? (2)

A
  1. IL-6R -> JAK1/JAK2 -> STAT3/STAT3 -> Th17 phenotype
  2. IL-2R -> JAK1/JAK3 -> STAT5/STAT5 -> blocking of Th17 phenotype by blocking of STAT3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is the main effect of JAK/STAT mutations?

A

Auto-immune disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

How can knowledge of JAK/STAT signalling be used to control auto-immune disease?

A

JAK-inhibitors can block downstream receptor signalling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Into which rough groups can auto-immune disease be grouped?

A
  1. Organ-specific
  2. Systemic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What are the antigens of organ-specific auto-immune disease? What are examples of such diseases?

A

Organ-specific antigens

Examples: DM1, thyroid disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What are the antigens of systemic auto-immune disease? What are examples of such diseases?

A

Antigens that occur throughout the body (such as blood vessels, collagens)

Examples: SLE, RA, vasculitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What are the three main processes preventing auto-immunity?

A
  1. Central tolerance -> deletion of auto-reactive T-cells
  2. Peripheral tolerance -> anergy & Tregs
  3. Seclusion of auto-antigens
48
Q

What is the main cause of a disruption in central tolerance?

A

AIRE mutations

49
Q

Which mechanisms may cause breakdown in peripheral tolerance? (7)

A
  1. Activation by superantigens
  2. Polyclonal activation
  3. Molecular mimicry
  4. Bystander activation
  5. Neoantigens
  6. Release of secluded auto-antigens
  7. Drugs (immune checkpoint inhibitors)
50
Q

Which four groups of vasculitis can be distinguished, based on the size of the vessels involed?

A
  1. Large artery
  2. Medium artery
  3. Small artery
  4. Arteriole/capillary venule
51
Q

Why is a classification of vasculitis based on vessel size useful? (3)

A
  1. Different clinical presentation
  2. Different pathogenic mechanism
  3. Different treatment
52
Q

What are examples of diseases in the category of large artery vasculitis? (2)

A
  1. Takayasu
  2. Giant cell arteritis
53
Q

What are examples of diseases in the category of medium artery vasculitis? (2)

A
  1. Polyarteritis nodosa
  2. Kawasaki
54
Q

What are examples of diseases in the category of small artery vasculitis? (3)

A
  1. Wegener’s granulomatosis
  2. Microscopic polyangiitis
  3. Churg-Strauss
55
Q

What are examples of diseases in the category of arteriole/capillary venule vasculitis? (2)

A
  1. Cryglobulinaemia
  2. Henoch-Schönlein
56
Q

Which group of vasculitis is most common?

A

Small vessel vasculitis

57
Q

What is the target of large vessel vasculitis?

A

Vessel wall of the vasa vasorum

58
Q

What is the pathological process leading to large vessel vasculitis? (3)

A
  1. DCs in the vasa vasorum in the adventitia of the large vessels become activated
  2. DCs don’t migrate to the lymph node, but locally activate passing lymphocytes
  3. Local auto-immune reaction against the vessel wall
59
Q

What is the effect of the local immune reaction against the vessel wall in large artery vasculitis? (2)

A
  1. Internal bleeding due to weakening of the vessel wall
  2. Ischaemia due to oblitteration of blood vessels
60
Q

Why are small vessels exempt from the pathological process occurring in large vessel vasculitis?

A

These vessels don’t have DCs in their adventitia -> no possibility of local activation

61
Q

What are the two possible pathogeneses of small vessel vasculitis?

A
  1. Immune complex deposition
  2. ANCA-associated vasculitis
62
Q

What can lead to immune complexes being deposited in small vessels?

A

High numbers of immune complexes cannot be sufficiently cleared by phagocytes in the bloodstream, leading to deposition in the vessels with the slowers blood flow

63
Q

How does deposition of immune complexes in small vessels lead to an inflammatory reaction (vasculitis)?

A

Complement activation

64
Q

What are the main treatment strategies that can be considered in case of auto-immune disease? (6)

A
  1. Replace function of the damaged organ
  2. General immune suppression
  3. Specific eradication of cells involved in the disease
  4. Drugs that block involved cytokine pathways
  5. Blocking pathogenic cells from reaching target organs
  6. Bone marrow transplant (last resort)
65
Q

What is the most frequently used form of general immunosuppression in auto-immune disease?

A

Corticosteroids

66
Q

Why is myositis paired with an elevated creatine kinase (CK)?

A

CK is highly present in muscles -> muslce damage causes release into the circulation

67
Q

What is the first-line treatment of myositis? What are second line treatments?

A

First line: corticosteroids
Second line: IVIG and/or JAK-inhibitors

68
Q

True or false: myositis is one disease

A

False: myositis is a heterogeneous group of disorders

69
Q

Which organs can be involved in myositis (5)? How can this present itself?

A
  1. Muscles: weakness/myositis
  2. Skin: rash
  3. Joints: arthritis
  4. Lungs: ILD
  5. Systemic: fever
70
Q

True or false: the different auto-antibodies that are characteristic for certain types of myositis are used for diagnostics

A

False: while most types of myositis are characterized by specific auto-antibodies, only one of these is actually used in diagnostics

71
Q

Which four groups of myositis can be identified?

A
  1. Overlap myositis, including anti-synthetase syndrome
  2. Dermatomyositis
  3. Immune-mediated necrotizing myositis
  4. Inclusion body myositis
72
Q

On which criteria is myositis classification based? (6)

A
  1. Age of onset
  2. Type of muscle weakness
  3. Type of skin manifestations
  4. Other clinical manifestations
  5. Laboratory measurements
  6. Muscle biopsy features
73
Q

What are the laboratory measurements used in myositis diagnostics? (4)

A
  1. Elevated creatine kinase (CK)
  2. Elevated lactate dehydrogenase (LDH)
  3. Elevated transaminases (ASAT/ALAT)
  4. Anti-Jo-1 auto-antibodies
74
Q

What is the target of anti-Jo-1-antibodies? Of which type of myositis are they characteristic?

A

Histidyl-tRNA synthetase

Characteristic of anti synthetase syndrome

75
Q

What are MSAs, and how do they differ with MAAs? (in the context of myositis)

A

MSA = myositis-specific antibody
MAA = myositis-associated antibody

76
Q

In how many % of myositis is anti-Jo-1 positive?

77
Q

What is the result of anti-Jo-1 antibodies?

A

Target histidyl-tRNA synthetase -> interference with protein synthesis

78
Q

How are anti-Jo-1 antibodies detected? (2)

A
  1. Enzyme immune-assay (EIA)
  2. Immunoblot
79
Q

What is ANA immunofluorescence?

A

Testing patient serum for anti-nuclear antibodies, which are present in many auto-immune diseases

80
Q

What can MSAs and MAAs be associated with, in addition to myositis? (3)

A
  1. Malignancy
  2. ILD
  3. Other diseases
81
Q

True or false: all auto-antibodies in myositis give prognostic information

A

False: some auto-antibodies do give prognostic information, but most do not

82
Q

What is the main challenge in the use of antibodies to detect/diagnose myositis?

A

Interpretation of clinically less/non-relevant antibody types or titres -> how to interpret these?

83
Q

What is the main way to estimate whether detected auto-antibodies are clinically relevant in myositis?

A

If no characteristic pattern in indirect immunofluorescence assays -> likely not clinically relevant

84
Q

Anti-synthetase syndrome is a myositis variant. What the possible presentations of this disease? (4)

A
  1. Myositis
  2. ILD
  3. Non-erosive arthritis
  4. Raynaud phenomenon
85
Q

True or false: muscle involvement is always part of myositis

A

False: muscle involvement is not always present and/or clear

86
Q

What is the hallmark of sarcoidosis?

A

Formation of granulomas

87
Q

How are granulomas built up?

A

Core of epithelioid cells & macrophages, surrounded by T-lymphocytes

88
Q

Granulomas can produce hormones and enzymes. Which are the two main ones, and what is their effect?

A
  1. Active vitamin D -> increased Ca2+ in blood
  2. ACE -> increased blood pressure
89
Q

What is the trigger for sarcoidosis?

A

Haha, got you there: the trigger is unknown!

90
Q

What are the stages of sarcoidosis, and the pathological processes during these stages?

A

Early stage: inflammatory response - (temporary) organ dyfunction
Late stage: fibroblast triggering -> fibrosis -> tissue damage

91
Q

Sarcoidosis is a multi-organ disease. What is the main target organ, and which other organs can be involved (4)?

A

Main target: lungs

Manifestations can also occur in:
1. Eyes
2. Skin
3. Heart
4. Brain/CNS

92
Q

What is the treatment of sarcoidosis?

A

Immunosuppression

93
Q

What are the treatment lines of immunosuppression for sarcoidosis? (3)

A
  1. Prednisone
  2. Methotrexate
  3. Anti-TNF (adalimumab, infliximab)
94
Q

Hypogammaglobulinaemia is [typical/atypical] for sarcoidosis

A

Atyptical -> usually (clonally) increased hypergammaglobulinaemia

95
Q

What causes hypergammaglobulinaemia in sarcoidosis?

A

Elevated levels of BAFF

96
Q

True or false: sarcoidosis is related to an increased risk of infections

A

False, sarcoidosis patients typically do not have an increased risk of infections

97
Q

Which pathogen forms an exception to the rule that sarcoidosis patients typically do not have an increased infection risk?

A

Cryptococcus

98
Q

What can cause sarcoidosis patients to have a higher risk of opportunistic infections?

A

Immunosuppression (steroids)

99
Q

What are primary antibody deficiences? (definition)

A

Antibody deficiency with low IgG, IgM & IgA

100
Q

What are important antibody deficiencies? (2)

A
  1. X-linked agammaglobulinaemia
  2. Common variable immunodeficiency (CVID)
101
Q

What is the cause of X-linked agammaglobulinaemia (XLA)?

A

BTK mutations, causing a complete block in B-cell maturation

102
Q

True or false: XLA is always diagnosed during childhood

A

True; XLA causes such a severe increase in infection risk that it is (nearly) always diagnosed during childhood

103
Q

True or false: CVID is always diagnosed during childhood

A

False; CVID does not necessarily cause such an increased infection risk that it is always diagnosed during childhood

104
Q

What are the main complications of CVID? (4)

A
  1. Recurrent infections
  2. Auto-immune complications
  3. Auto-inflammatory complications
  4. Increased risk of haematological malignancies
105
Q

What are the main types of infections commonly seen in CVID patients? (2)

A
  1. Gastrointestinal
  2. Respiratory
106
Q

What is the main determinant of prognosis in CVID patients?

A

Non-infectious complications such as auto-immunity and haematological malignancy

107
Q

Why are infections not the factor determining prognosis in CVID?

A

Can be effectively prevented/treated using (prophylactic) antibiotics & IVIG

108
Q

True or false: the majority of CVID patients have granulomatous disease

A

False: granulomatous disease occurs in 8-25% of CVID patients

109
Q

In CVID patients with granulomatous disease, granulomatous disease often presents [before/after] presentation of antibody deficiency

A

Before -> granulomatous presents before antibody deficiency

110
Q

Granulomatous disease [does/does not] affect prognosis in CVID patients

A

Does -> granulomatous severely worsens prognosis of CVID patients

111
Q

Granulomas in CVID patients typically form in [different/the same] locations as in sarcoidosis patients

A

Same locations

112
Q

What is the trigger of granuloma formation in granulomatous disease in CVID?

A

Haha, got you again! This is also unknown, although it is kikely infectious

113
Q

What is the treatment of granulomatous disease in CVID?

A

No standardized treatment

114
Q

What makes treatment of granulomatous disease in CVID difficult?

A

Immunosuppression is necessary to decrease granuloma formation, but this severely increases the risk of infection in these already immunodeficient patients

115
Q

How can histological characteristics of granulomas be used to develop treatments?

A

Differences in size, structure & involved cells generally give information about the origin of the granuloma, which can be used to target treatment

I&I WC2 (18 decks)

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