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I&I WC1 > Dermatology > Flashcards

Dermatology Flashcards

1
Q

What is the skin-gut axis?

A

Due to the skin and gut having the same homing factors, there is a strong immunological connection between them

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2
Q

What are examples of the skin-gut axis? (2)

A
  1. Food allergies that cause dermatological symptoms
  2. IBD causes dermatological symptoms
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3
Q

How many % of IBD patients has erythema nodosum?

A

15%

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4
Q

What are the main skin functions? (6)

A
  1. Protection & defence
  2. Signal reception
  3. Thermoregulation
  4. Communication
  5. Secretion
  6. Absorption
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5
Q

In which ways is the skin involved in protection and defence? (2)

A
  1. Mechanical
  2. Immunological
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6
Q

In which ways is the skin involved in signal reception? (4)

A
  1. Tactile
  2. Pressure
  3. Temperature
  4. Pain
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7
Q

In which ways is the skin involved in thermoregulation? (2)

A
  1. Sweating
  2. Vasoconstriction & dilatation
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8
Q

In which ways is the skin involved in communication? (2)

A
  1. Skin tint
  2. Odor
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9
Q

Which substances are secreted by the skin? (3)

A
  1. Sweat
  2. Sebum
  3. Milk
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10
Q

What does the skin absorb? (2)

A
  1. Light
  2. Pharmaceuticals
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11
Q

What are the three layers of the skin?

A
  1. Epidermis
  2. Dermis
  3. Hypodermis
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12
Q

What structures can be found in the dermis? (6)

A
  1. Connective tissue
  2. Fibroblasts
  3. Hair follicles
  4. Sweat glands
  5. Sebaceous glands
  6. Vasculature
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13
Q

What structures can be found in the hypodermis? (2)

A
  1. Blood vessels
  2. Adipocytes
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14
Q

Which 5 layers of keratinocytes can be found in the dermis (basal to apical)?

A
  1. Stratum basale
  2. Stratum spinosum
  3. Stratum granulosum
  4. Stratum lucidum
  5. Stratum corneum
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15
Q

Which cells populate the stratum basale? (4)

A
  1. Basal cells
  2. Keratinocyte precursors
  3. Merkel cells
  4. Melanocytes
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16
Q

What is the function of Merkel cells?

A

Touch sensation

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17
Q

What is the function of melanocytes?

A

Melanin production

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18
Q

Why does the stratum spinosum appear spiny?

A

Due to the presence of desmosomes joining the cells

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19
Q

What is the main function of keratin in the epidermis?

A

Prevention of water loss

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20
Q

Where are the Langerhans cells of the skin found?

A

In the stratum spinosum of the epidermis

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21
Q

What is the appearance of keratinocytes in the stratum granulosum?

A

Flattened with high levels of keratin present, thickened membrane

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22
Q

What is the stratum lucidum made up of? What is its function?

A

Keratinocytes filled with protein (eleidin), as an extra protection against abrasion

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23
Q

In which type of skin is the stratum lucidum present?

A

Thick skin

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24
Q

What is the stratum corneum made out of?

A

Dead, anuclear keratinocytes

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25
Q

What is the function of the stratum corneum?

A

Protection against microbes, dehydration & abrasion

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26
Q

By which process are the anuclear keratinocytes in the stratum corneum produced?

A

Specialized form of programmed cell death, in which nucleus and organelles disintegrate

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27
Q

Why do hair follicles form an area of close contact between microbiota and keratinocytes?

A

They are not keratinized

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28
Q

Where can thick skin be found?

A

Hairless skin on the soles of feet and palms/fingertips of the hand

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29
Q

What are the properties of thick skin? (4)

A
  1. Contains no sweat/sebaceous glands
  2. Thick stratum corneum
  3. Stratum lucidum visible due to presence of eleidin
  4. Dermis thinner than thin skin dermis
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30
Q

What are the properties of thin skin? (3)

A
  1. Follicles & glands are non-keratinized
  2. Thin epidermis due to a thin stratum corneum and absence of the stratum lucidum
  3. Thick dermis
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31
Q

How do keratinocytes adhere to the basal membrane?

A

Hemidesmosomes

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32
Q

Which kinds of fibres can be found in hemidesmosomes? (2)

A

Collagen & integrins

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33
Q

Between which layers is the basal membrane of the skin located?

A

Epidermis & dermis

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34
Q

Which kinds of fibres can be found in the basal membrane of the skin? (3)

A
  1. Type IV collagen
  2. Laminin
  3. Proteoglycans
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35
Q

How are keratinocytes interconnected?

A

Through desmosomes

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36
Q

How are desmosomes made up?

A

Extracellular cadherins are connected to intracellular keratin fibres

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37
Q

Of which structures the epidermal tight junctions made up? (3)

A

Claudin, JAM and occludin

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38
Q

What is the size limit for passive uptake through the skin? How can larger molecules be taken up?

A

<500 Da
Larger molecules can be taken up through active uptake via cytoplasm

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39
Q

True or false: keratin in the skin is the same throughout all layers

A

False; there are multiple types of keratin that are specific to specific layers/cell types

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40
Q

How are keratin fibres made up structurally?

A

Heterodimers of keratin filaments

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41
Q

What are the functions of keratin in the skin? (2)

A
  1. Barrer integrity by interacting with keratinocytes
  2. Aid in metabolic functions
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42
Q

When is regulation of keratin expression disrupted?

A

Disruption of homeostasis

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43
Q

Where is skin pigmentation produced?

A

By melanocytes in the stratum basale

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44
Q

What is the embryonic origin of melanocytes?

A

Neural crest -> differs from skin, which is derived from the ectoderm

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45
Q

What are the functions of melanocytes? (2)

A
  1. Pigmentation
  2. Thermoregulation
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46
Q

How does melanin end up in keratinocytes? When is it transported intracellularly by keratinocytes?

A

It is exocytosed by melanocytes in melanosomes, which are absorbed by keratinocytes. Exposure of keratinocytes to UV-light causes them to relocate to the top of their nucleus to shield if from UV.

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47
Q

What induces production of melanin by melanocytes?

A

UV light

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48
Q

In which type of skin are Merkel cells especially present?

A

Thick skin

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49
Q

Which two rough layers can be distinguished in the dermis?

A
  1. Papillary dermis
  2. Reticular dermis
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50
Q

What are the properties of the papillary dermis? What kind of connective is present?

A

Superficial layer, invading deep into the dermis, made up out of loose and highly vascular connective tissue

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51
Q

What are the properties of the reticular dermis? What kind of connective tissue is present?

A

Deep layer forming the bulk of the dermis, made up out of dense connective tissue

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52
Q

Which cells can be found in the dermis? (5)

A
  1. Fibroblasts
  2. Macrophages
  3. Dermal DCs
  4. Mast cells
  5. Adaptive immune cells
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53
Q

Which ECM components are highly abundant in the dermis? (2)

A
  1. Collagen
  2. Elastin
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54
Q

How many layers of blood vessels can be discerned in the dermis? What kind of vessels do they contain?

A
  1. Superficial of the papillary dermis, containing capillaries
  2. Middle layer, containing arterioles, venules and lymphatics
  3. Deep layer, containing arteries and veins
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55
Q

In which homeostatic processes is skin vasculature important? (3)

A
  1. Thermoregulation
  2. Immune surveillance
  3. Transport of nutrients and paracrine factors
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56
Q

What are the first immune barriers of the skin?

A

Physical barriers

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57
Q

The physical barriers of the skin are an active barrier. Why?

A

They are formed by an interplay between microbiota, keratinocytes, fibroblasts, adipocyes, Langerhans cells, dermal DCs and ILCs

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58
Q

How do skin-resident microbiota deter pathogens? (2)

A
  1. Production of AMPs
  2. Interaction with keratinocytes and dermal immune cells, shaping homeostatic immune cell function of the skin
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59
Q

What are the functions of fibroblasts in skin immunity? (2)

A
  1. Express a wide range of TLRs, allowing them to detect pathogens and produce AMPs and cytokines
  2. Attraction of immune cells & modulation of their functions
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60
Q

How do fibroblasts produce IL-1β?

A

Through their NLRP3 inflammatsome

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61
Q

What are Langerhans cells?

A

DCs that populate the dermis

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62
Q

What are Langerhans cell markers? (2)

A

CD1a/c & CD207

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63
Q

How are Langerhans cells replaced under physiological vs. pathogical conditions?

A

They are self-renewing under physiological conditions, but can be repopulated by moDCs in case of homeostasis disruption

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64
Q

Where are the cell bodies and where are the dendrites of Langerhans cells located?

A

Cell body: stratum spinosum
Dendrites stretch into the stratum corneum

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65
Q

Langerhans cells are more closely related to [DCs/macrophages]. Why? (3)

A

Macrophages, because they have macrophage-like characteristics:
1. Embryonic origin
2. Self-renewing population
3. Requires tissue-derived signals

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66
Q

Which tissue-derived signals are required for correct Langerhans cell function?

A

TGF-β

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67
Q

What do Langerhans cells do after sensing antigen? What happens in physiological/pathogenic circumstances?

A

Migrate to LN to interact with T-cells
Physiological circumstances: induction of Tregs through release of IL-10
Pathogenic conditions: induction of inflammatory cytokines

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68
Q

Which intracellular pathway is upregulated by keratinocytes in inflammation? What does this lead to?

A

STAT3-signaling is upregulated, leading to IL-23 production by LCs -> Th17-response induced

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69
Q

How do Langerhans cells migrate out of the skin?

A

Through lymphatic vessels in the deeper dermis

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70
Q

The majority of the cells in the dermis are [mesenchymal cells/leukocytes]

A

Leukocytes -> 70% of the cells in the dermis are leukocytes

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71
Q

What is the largest population of leukocytes in the dermis? How many % of total leukocytes?

A

Macrophages (~55%)

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72
Q

How many % of cells in the dermis are non-phagocytes? Which cell types does this concern? (3)

A

5%, consisting of:
1. T-cells
2. ILCs
3. Mast cells

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73
Q

Which three populations of phagocytes can be identified in the skin?

A
  1. Macrophages
  2. CD14+ DCs
  3. CD1a+ DCs
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74
Q

What are the characteristics of macrophages in the skin? (2)

A
  1. No migration upon stimulus
  2. High phagocytic capacity
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75
Q

What are the characteristics of CD14+ DCs of the skin? (2)

A
  1. Migration can be induced
  2. Phagocytic capacity lower than macrophages
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76
Q

What are the characteristics of CD1a+ DCs of the skin? (2)

A
  1. Migration can be induced
  2. Phagocytic capacity lower than macrophages
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77
Q

How do APCs interact with the PNS?

A

PNS produces factors that influence moDC function (immune regulatory)

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78
Q

Which neurotransmitter is released by the PNS to intact with APCs?

A

CGRP

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79
Q

What are the homeostatic functions of dermal mast cells? (2)

A
  1. Induction of differentiation & proliferation of immune cells, keratinocytes & fibroblasts
  2. Mediation of vasodilatation & constriction
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80
Q

Mast cells are involved in the defence against many types of pathogens. Against which types, and is their function benefical or detrimental? (3)

A
  1. Antibacterial = benefical
  2. Antiviral = mixed beneficial/detrimental
  3. Antiparasitic = mixed beneficial/detrimental
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81
Q

What are the antibacterial functions of dermal DCs? (2)

A
  1. Direct killing of bacteria through NETs, AMPs & phagocytosis
  2. Recruitment of neutrophils
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82
Q

What are the benefical (2) and detrimental (2) effects of mast cells in case of viral infection?

A

Beneficial:
1. Inhibition of viral replication of several viruses
2. Recruitment of NK-cells & T-cells

Detrimental:
1. Mast cells can be infected by viruses, faciltating viral migration
2. Degranulation can result in viraemia

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83
Q

What are the beneficial (3) and detrimental (1) effects of mast cells in case of parasitic infection?

A

Beneficial:
1. Direct killing of parasites through NO-production
2. Killing of parasites through extracellular traps
3. Recruitment and activation of DCs

Detrimental: cause vascular leakage -> allows parasites to spread

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84
Q

What are the types of ILC present in the skin?

A

ILC1, ILC2, ILC3

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85
Q

What is the signature transcription factor of ILC1s?

A

T-bet

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86
Q

What is the signature transcription factor of ILC2s?

A

Gata3

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87
Q

What is the signature transcription factor of ILC3s?

A

RORγT

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88
Q

Which two markers are expressed by dermal ILCs?

A
  1. CCR6
  2. CCR10
89
Q

What are the functions of CCR6 on dermal ILCs? (2)

A
  1. Facilitation of barrier function
  2. Facilitation of microbiome homeostasis
90
Q

What are the functions of CCR10 on dermal ILCs?

A

Facilitation of effector and regulatory T-cell homeostasis

91
Q

Which cytokines do dermal ILC2s produce? (2)

A

IL-5, IL-13

92
Q

In which physiological (2) and pathological (1) processes are ILC2s involved?

A

Physiological: tissue repair & barrier integrity
Pathological: progression of atopic inflammation

93
Q

Which cytokines do dermal ILC1s produce? (2)

A

IFN-γ, TNF

94
Q

In which pathological processes are ILC1s involved?

A

Contact hypersensitivity

95
Q

Which cytokines do dermal ILC3s produce? (2)

A

IL-17, IL-22

96
Q

In which pathological processes are ILC3s involved?

A

Psoriatic inflammation

97
Q

Which micro-organisms make up the skin microbiome?

A

Bacteria, viruses, fungi

98
Q

The skin virome is largely [site-dependent/host-dependent]

A

Host-dependent -> differs from person to person

99
Q

The skin microbiome (bacteria) is largely [site-dependent/host-dependent]

A

Site-dependent

100
Q

In which ways do commensal microbiota play an important role in shaping host immune responses? (2)

A
  1. Induction of a TLR2 response in keratinocytes, resulting in steady-state production of AMPs
  2. Interaction with DCs, shaping adaptive immune responses
101
Q

To which bacterium does the immune system never develop tolerance?

A

S. aureus

102
Q

S. aureus causes keratinocytes to produce IL-1 and other cytokines, resulting in: (3)

A
  1. Production of AMPs by keratinocytes
  2. Attraction of neutrophils
  3. NK- and γδ-T activation
103
Q

How big are antimicrobial peptides?

A

15-50 amino aicds

104
Q

What are two important families of AMPs produced in the skin?

A
  1. Defensins
  2. Cathelicidins
105
Q

By which cell type are cathelicidins produced?

A

Adipocytes

106
Q

What are mechanisms of action of AMPs? (2)

A
  1. Creating holes in bacterial walls
  2. Sequestering of Fe
107
Q

In psoriatic skin, the production of AMPs is [increased/decreased]. Therefore, psoriatic skin contains [low numbers of bacteria/high numbers of bacteria]

A

Increased -> psoriatic skin contains low numbers of bacteria

108
Q

In atopic dermatitis, the production of AMPs is [increased/decreased]. Therefore, atopic skin contains [low numbers of bacteria/high numbers of bacteria]

A

Decreased -> atopic skin contains high numbers of bacteria, increasing the risk of bacterial infection

109
Q

Which T-cell subsets can be found in the skin? (4)

A
  1. Th1
  2. Th2
  3. Th3
  4. Treg
110
Q

Which cytokines induce Th1 cells? (4)

A
  1. IL-27
  2. IL-12
  3. IL-18
  4. IFN-γ
111
Q

What is the signature transcription factor of Th1-cells?

A

T-bet

112
Q

What are the major cytokines produced by Th1-cells? (4)

A
  1. IFN-γ
  2. IL-2
  3. IL-10
  4. TNF-α
113
Q

What is the physiological function of Th1-cells?

A

Defence against intracellular micro-organisms

114
Q

Which cytokine induces Th2-cells?

A

IL-4

115
Q

What is the signature transcription factor of Th2-cells?

A

Gata3

116
Q

What are the major cytokines produced by Th2-cells? (6)

A
  1. IL-4
  2. IL-5
  3. IL-9
  4. IL-10
  5. IL-13
  6. IL-25
117
Q

What is the physiological function of Th2-cells?

A

Defence against parasitic infections

118
Q

Which cytokines induce Th17-cells? (3)

A
  1. IL-1
  2. IL-6
  3. TGF-β
119
Q

What is the signature transcription factor of Th17-cells?

A

RORγT

120
Q

What are the major cytokines produced by Th17-cells? (3)

A
  1. IL-17 (A/F)
  2. IL-21
  3. IL-22
121
Q

What is the physiological function of Th17-cells?

A

Defence against extracellular bacteria & fungi

122
Q

Which cytokines induce Tregs? (2)

A
  1. IL-2
  2. TGF-β
123
Q

What is the signature transcription factor of Tregs?

A

FoxP3

124
Q

What are the major cytokines produced by Tregs? (3)

A
  1. IL-10
  2. TGF-β
  3. IL-35
125
Q

What is the physiological function of Tregs?

A

Tolerance & suppression of auto-immunity, auto-inflammation & allergy

126
Q

Which Th-subsets are inhibited by Th1?

A

Th2, Th17

127
Q

Which Th-subsets are inhibited by Th2?

A

Th1, Th17

128
Q

Which Th-subsets are inhibited by Tregs?

A

Th1, Th2, Th17 (all subsets)

129
Q

Which Th-subsets are inhibited by Th17?

A

None

130
Q

What is meant when we talk about plasticity when it comes to Th-subsets?

A

Capacity to produce cytokines of another subset (but not a complete switch to another subset)

131
Q

What is the term for a complete switch of a Th-cell from one subset to another?

A

Transdifferentiation

132
Q

What are the histopathologic features of psioriasis? (6)

A
  1. Acanthosis
  2. Hyperkeratosis
  3. Parakeratosis
  4. Papillomatosis
  5. Hypogranulosis
  6. Influx of immune cells
133
Q

What is acanthosis?

A

Thickening of the skin

134
Q

What is hyperkeratosis?

A

Increased proliferation of keratinocytes, leading to increased shedding of skin

135
Q

What is parakeratosis?

A

Retention of nucleated keratinocytes in the stratum corneum (normally these are all anuclear)

136
Q

What is papillomatosis?

A

Elongation of rete ridges -> elongation of the epidermis into the papillary dermis

137
Q

What is hypogranulosis?

A

Loss of the stratum granulosum

138
Q

Which immune cells can be seen to infiltrate the skin in histopathology of psoriasis? (2)

A
  1. T-cells
  2. Neutrophils
139
Q

What do neutrophils in psoriatic skin form?

A

Munro’s micro abcscesses

140
Q

What causes psoriasis?

A

A combination of environmental factors & susceptibility genes

141
Q

What happens during the initiation phase of psoriasis?

A

Pro-inflammatory crosstalk between injured/stressed keratinocytes, leading to release of nucleic acids and LL-37, which recruit various types of immune cells

142
Q

Which cells are recruited by the pro-inflammatory crosstalk between keratinocytes in the initiation phase of psoriasis? (3) What is each of their effects?

A
  1. Plasmacytoid DCs -> production of IFN-α
  2. Activated dermal DCs -> travel to LN and activate Th1/Th17s
  3. Inflammatory dDCs -> cause a local inflammatory environment
143
Q

Which mediators do dDCs excrete in the initiation phase of psoriasis, creating a pro-inflammatory environment? (3)

A
  1. IL-23
  2. TNF
  3. NO
144
Q

What is the effect of the release of IL-23 released by dDCs during the initiation phase of psoriasis?

A

Activation of Th17/Tc17-cells

145
Q

Which factors are produced by Th17-cells that have effects during the initiation phase of psoriasis? (2) What are their effects?

A
  1. IL-17 -> promotes induction of T-cells and neutrophils
  2. IL-22 -> induces epidermal hyperplasia by impairing keratinocyte terminal differentiation

Both also cause production of AMPs

146
Q

Which cytokine axis is most important for psoriasis?

A

IL-23/IL-17 (=Th17)

147
Q

How can knowledge of cytokines involved in psoriasis lead to treatments?

A

These can be targeted to block pathogenic processes

148
Q

Which cytokines are being targeted in psoriasis treatments? (4)

A
  1. IL-12
  2. IL-23
  3. TNF
  4. IL-17A/F
149
Q

What is the beneficial effect of IL-12 blocking in the treatment of psoriasis?

A

Downregulation of factors that promote Th1-cells

150
Q

Which drug is used to block IL-12 in psoriasis? Which cytokine is also targeted by this drug, and why?

A

Ustekinumab, also targets IL-23 because IL-12 and IL-23 have a shared subunit

151
Q

What is the beneficial effect of IL-23 blocking in the treatment of psoriasis?

A

Downregulation of factors that promote Th17-cells

152
Q

Which drugs are used to block IL-23 in psoriasis? (4) Which of them also targets another cytokine?

A
  1. Ustekinumab (also targets IL-12)
  2. Guselkumab
  3. Tildrakizumab
  4. Risankizumab
153
Q

What is the beneficial effect of TNF blocking in the treatment of psoriasis?

A

Downregulation of inflammation

154
Q

Which drugs are used to block TNF in psoriasis? (3)

A
  1. Etanercept
  2. Infliximab
  3. Adalimumab
155
Q

What is the beneficial effect of IL-17A/F blocking in psoriasis?

A

Blocking of the effector cytokines of Th17-cells

156
Q

Which drugs are used to block IL-17A signaling? (2) Which to block IL17-A/F signaling? (2)

A

IL-17A:
1. Secukinumab
2. Ixekizumab

Both IL17-A/F
1. Bimekizumab
2. Brodalumab (blocks IL-17R)

157
Q

Targeting of which cytokine has proven to be especially effective in psoriasis? Why?

A

IL-17 -> leads to almost complete PASI reduction

158
Q

How many % of patients don’t respond to TNF, IL-12 and IL-23?

A

~20%

159
Q

What is the main risk factor for atopic dermatitis?

A

Genetic susceptibility

160
Q

Which gene has the strongest association with atopic dermatitis?

A

Filaggrin (FLG)

161
Q

Genes involved in which functions can predispose for atopic dermatitis? (4)

A
  1. Epidermal barrier
  2. Environmental sensing
  3. Immune regulation
  4. Tissue response
162
Q

What iniates atopic dermatitis?

A

Defective skin barrier, leading to permability -> triggers production of inflammatory cytokines

163
Q

Which cytokines are involved in the initial phase atopic dermatitis? (4) Which type of reaction do they induce?

A
  1. IL-1
  2. TSLP
  3. IL-25
  4. IL-33

Induce a type II reaction

164
Q

Which cells are recruited by the cytokines produced by keratinocytes in the initiation phase of atopic dermatitis? Which cytokines do they produce? (4)

A

Th2/Th22/ILC2, producing
1. IL-4
2. IL-5
3. IL-13
4. IL-31

165
Q

What are the effects of the release of IL-4, IL-5, IL-13 and IL-31 in atopic dermatitis? (3)

A
  1. Activation of mast cells & eosinophils
  2. IL-31 drives itching
  3. B-cell class switch to IgE
166
Q

What is the effect of mast cells & eosinophils in atopic dermatitis?

A

Release of histamine, causing redness and itch

167
Q

What are the stages of atopic dermatitis? (4)

A
  1. Healty skin
  2. Non-lesional skin
  3. Acute lesional skin
  4. Chronic lesional skin
168
Q

What causes atopic dermatitis to progress?

A

Recruitment of additonal Th2-, Th22-, Th17- and Th1-cells, leading to a further loss of barrier function

169
Q

Which two types of itch can be identified in atopic dermatitis?

A
  1. Histamine-dependent itch
  2. Histamine-independent itch
170
Q

What is the mechanism of histamine-dependent itch?

A

Histamine activates processes in the brain through C-fibres

171
Q

What is the mechanism of histamine-independent itch? Which cytokine is mainly responsible?

A

JAK-STAT pathways in neurons triggered, leading to itch-processes in the brain
Mainly caused by IL-31

172
Q

Which groups of drugs are used in atopic diseases? Which are effective in atopic dermatitis? (7)

A
  1. Anti-IL-4 = low effect in AD
  2. Dual anti-IL-4/13 = effective in AD
  3. Anti-IL-13
  4. Anti-IL-5 = low effect in AD
  5. Anti-IgE = low effect in AD
  6. Corticosteroids = effective in AD
  7. Antihistamines
173
Q

What is the beneficial effect of blocking IL-4 in atopic disease?

A

Stops Th2 activation/differentiation

174
Q

Which drugs can be used to block IL-4? (2) Are they used in atopic dermatitis?

A
  1. Altrakincept
  2. Pascolizumab

Development discontinued due to low effect

175
Q

Which dual IL-4/IL-13 blocker is used against atopic diseases? What is its effect on AD?

A

Dupilumab -> very effective against atopic diseases, including AD

176
Q

What is the beneficial effect of blocking IL-13 in atopic disease?

A

Inhibits B-cell class switch to IgE

177
Q

Which drugs are used to block IL-13 in atopic disease? (2) In which circumstances are they effective?

A
  1. Tralokinumab
  2. Lebrikizumab -> effective in Th2-high subgroups of asthma
178
Q

What is the beneficial effect of blocking IL-5 in atopic disease?

A

Reduces eosinophil recruitment

179
Q

Which drugs are used to block IL-5 in atopic disease? (3) Are they effective agains AD?

A
  1. Mepolizumab
  2. Reslizumab
  3. Benralizumab

Effective in asthma, not in AD

180
Q

What is the beneficial effect of blocking IgE in atopic disease?

A

Lower triggering of mast cells

181
Q

Which drug is used to block IgE in atopic disease? Is it effective in AD?

A

Omalizumab -> effective in allergic asthma, not in AD

182
Q

What is the effect of corticosteroids in atopic disease?

A

Non-specific immmunosuppression -> effective against all atopic diseases

183
Q

What is the downside of using corticosteroids for the treatment of atopic disease?

A

Toxic effects

184
Q

Auto-inflammatory disease of the skin is [less/more] common than auto-immune disease of the skin

A

Less common -> auto-immune disease of the skin is more common than auto-inflammatory

185
Q

What is a characteristic feature of all auto-inflammatory diseases?

A

Recurrent, generalized inflammation with episodic fever

186
Q

What is the most prevalent auto-immune disease of the skin?

A

Atopic dermatitis

187
Q

Why is the skin especially sensitive when it comes to sensations such as burning, itching, pain, etc.?

A

It contains high amounts of sensory neurons

188
Q

What is often times a trigger of auto-immune/-inflammatory disease of the skin in susceptible individuals?

A

Damage to the skin, such as infection, wounds, etc.

189
Q

True or false: most auto-immune or auto-inflammatory diseases of the skin are clearly fully adaptive (auto-immune) or innate (auto-inflammatory)

A

False; there are few ‘pure’ auto-immune/-inflammatory diseases -> most are mixed-pattern diseases

190
Q

Which compartment of the immune system is dysregulated in auto-inflammatory disease? What are the predominant cell types? (3)

A

Innate compartment
1. Monocytes
2. Macrophages
3. Neutrophils

191
Q

What is the pathogenesis of organ damage in auto-inflammatory disease?

A

Neutrophil/macrophage-mediated damage

192
Q

Which compartment of the immune system is dysregulated in auto-immune disease? What are the predominant cell types? (2)

A

Adaptive compartment
1. T-cells
2. B-cells

193
Q

What is the pathogenesis of organ damage in auto-immune disease?

A

Auto-antibody or auto-reactive T-cell mediated

194
Q

How many auto-inflammatory diseases are currently known?

A

~110

195
Q

True or false: auto-inflammatory disease is inherited

A

False; they can be inherited as well as acquired

196
Q

Which treatments can be used for auto-inflammatory diseases? (4)

A
  1. NSAIDs
  2. Colchicine
  3. Steroids
  4. Biologicals interfering with pathogenic cytokines
197
Q

Which four major groups of auto-inflammatory diseases can be identified? (4)

A
  1. Inflammasomopathies and other disorders with abrrant IL-1 signaling
  2. Type I interferonopathies
  3. Disorders of NF-κB and/or aberrant TNF-activity
  4. Diseases caused by other miscellaneous mechanisms
198
Q

What is the most common auto-inflammatory disease?

A

Mediterranean fever

199
Q

What is the difficulty in diagnosing Mediterranean fever?

A

Looks very similar to erysipelas = bacterial skin infection

200
Q

What is the cause of Mediterranean fever?

A

TNF-receptor defects

201
Q

Auto-inflammatory diseases form a risk for a specific group of diseases. Which group, and why?

A

Haematological diseases such as myelodysplastic syndrome and leukaemia, due to chronic stimulation of the bone marrow

202
Q

Auto-inflammatory diseases can predispose for leukaemia. Why does this lead to particular difficulties in the clinical management of these diseases?

A

The sypmtoms of malignancy can overlap with auto-inflammatory symptoms -> hard to know whether you are dealing with auto-inflammation or leukaemia

203
Q

What are mechanisms of neutrophil-induced damage in auto-inflammatory disease? (6)

A
  1. Cytokine release
  2. Phagocytosis
  3. Oxidative burst
  4. Ectodomain shedding
  5. NETosis
  6. Degranulation
204
Q

Where do non-active neutrophils typically reside?

A

Bone marrow

205
Q

Neutrophils in the blood follow a circadian rythm. How?

A

During the day, they are released by the bone marrow into the circulation. At night, they again home into the bone marrow.

206
Q

How can disturbances in circadian rythm or stress cause exacerbation of auto-inflammatory disease?

A

Increased release of neutrophils from the bone marrow

207
Q

What are the three main types of auto-immune disease of the skin?

A
  1. Th1-mediated
  2. Th2-mediated
  3. Th17-mediated
208
Q

What is the function of Th22-cells?

A

Repair of tissue damage caused by other Th-subsets

209
Q

On which locations on the skin does psoriasis tend to occur? How is this for atopic dermatitis? What is the likely cause of this difference?

A

Psoriasis: outside of elbows/knees
Atopic dermatitis: inside of elbows/knees

Most likely caused by different microbiota in these locations

210
Q

What can exacerbate psoriasis?

A
  1. Injury
  2. Infections
  3. Drugs
211
Q

Which drugs are notorious for causing psoriasis exacerbation? (2)

A
  1. β-blockers
  2. lithium
212
Q

What are common comorbidities of psoriasis? (4)

A
  1. Arthritis
  2. Cardiovascular disease
  3. Metabolic syndrome
  4. Higher risk of depression & psychiatric disorders
213
Q

How many % of psoriasis patients develop arthritis psoriatica?

A

~20%

214
Q

What causes a higher risk of depression & psychiatric disorder in psoriasis patients?

A

IL-17

215
Q

True or false: the severity of psoriasis correlates with the chance of comorbidities

A

True -> the more severe the psoriasis, the higher the chance of comorbidities

216
Q

What is vitiligo?

A

Skin depigmentation disease caused by type II auto-immune disease attacking melanocytes

217
Q

What is immune alopecia?

A

Hair loss due to immunological attack on hair follicles

218
Q

Which cells are important in maintaining immune tolerance to hair follicles? Why is this tolerance needed?

A

Tregs -> tolerance needed to protect stem cells of the hair follicles from inflammation

I&I WC1 (20 decks)

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