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MK ACVD Exam > Atopy and hypersensitivity > Flashcards

Atopy and hypersensitivity Flashcards

1
Q

What is the term for secreted proteins that bind to specific receptors and play a role in intercellular communication among leukocytes?

A

Interleukins

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2
Q

What cytokines are produced by Th2 cells?

A

IL-4, 5, 13, 31

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3
Q

What cytokines contribute to the development and intensity of Th2 responses/inflammation?

A

TSLP
IL-25
IL-31
IL-33

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4
Q

What immune cells are the primary producers of IFN-gamma?

A

Th1 cells

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5
Q

What type of cell produces cytokines that are important in the immune response to helminths?

A

Th2

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6
Q

What cytokines are produced by Th17 cells?

A

IL-17A
IL-17F
IL-6
IL-8
TNF-alpha
IL-22
IL-26

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7
Q

What is the major role of Treg cells in hypersensitivity?

A

Allergen tolerance

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8
Q

Where are ILCs active?

A

Mucosal surfaces

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9
Q

What cytokines are produced by epithelial cells when they sense allergens?

A

IL-1alpha
IL-25
IL-33
TSLP
GM-CSF

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10
Q

What cytokines are produced when epithelial cells sense viruses?

A

type I interferons
GM-CSF
RANTES

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11
Q

What is the role of IL-1RA?

A

Anti-inflammatory via inhibition of IL-1 signaling (it acts as a “dummy” IL-1)

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12
Q

What two interleukins can produce high levels of IFN-gamma when combined?

A

IL-12
IL-18

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13
Q

What cytokine downregulates filaggrin expression and can impair barrier function?

A

IL-33

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14
Q

Is IL-38 pro- or anti-inflammatory?

A

Anti

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15
Q

What cytokine is essential for the development of Treg cells?

A

IL-2

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16
Q

What cytokine serves as a major stimulus of Th2 cell development?

A

IL-4

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17
Q

What is the effect of IL-4 on type I immunity?

A

It suppresses type I immunity

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18
Q

The receptor for which cytokine serves as a marker for ILCs?

A

IL-7

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19
Q

What is the effect of IL-9 on Th1 cells?

A

Reduces Th1 cytokine secretion

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20
Q

What is the effect of IL-9 on B-cells?

A

Promotes IgE production

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21
Q

Is IL-10 pro- or anti-inflammatory?

A

Anti

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22
Q

What is the effect of IL-10 on B cells?

A

Promotes their survival and proliferation
Increases IgG production

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23
Q

What is the effect of IL-20 on the skin?

A

Hyperkeratosis, epidermal thickening

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24
Q

What cells express IL-24?

A

Melanocytes
T-cells
Monocytes

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25
Q

What is the major function of IL-24?

A

Tumor suppression

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26
Q

What type 2 cytokine contributes to proliferation and activation of eosinophils?

A

IL-5

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27
Q

What cytokine is found in bronchoalveolar lavage fluid in asthmatic patients?

A

IL-5

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28
Q

What cells produce IL-31?

A

Activated CD4+ T-cells (CD8+ T-cells produce lower levels)

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29
Q

What cells express the IL-31 receptor?

A

KCs
epithelial cells
dorsal root ganglia
eos
basophils
monocytes

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30
Q

What cytokine does TSLP resemble structurally?

A

IL-7

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31
Q

What type of inflammatory response is promoted by TSLP?

A

Th2

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32
Q

What is the major function of IL-8?

A

activation and recruitment of neutrophils

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33
Q

Is IL-17 pro- or anti-inflammatory?

A

Pro

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34
Q

IL-14 promotes proliferation of what cell type?

A

B-cells

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35
Q

In what organ is IL-34 most abundant?

A

spleen

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36
Q

Does IFN-gamma promote a Th1 or Th2 cell response?

A

Th1

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37
Q

What cytokine plays a role in embryonic development?

A

TGF-beta

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38
Q

What cytokine plays a key role in the defense against intracellular pathogens?

A

TNF-alpha

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39
Q

A local increase in which cytokine causes the 5 cardinal signs of inflammation?

A

TNF-alpha

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40
Q

What is the average size of cytokines?

A

25 kDa

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41
Q

Are cytokines usually found in circulation?

A

No (rare)

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42
Q

Do cytokines act in a widespread or local manner?

A

Local

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43
Q

What cytokine shares similar properties to IL-4?

A

IL-13

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44
Q

What are the primary roles of Th17 cytokines?

A

Inflammation
Extracellular pathogens

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45
Q

What are the major roles of Th1 cytokines?

A

Viruses
Intracellular pathogens

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46
Q

What are the major roles of Th2 cytokines?

A

Parasites (extracellular organisms)
Allergy

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47
Q

What is the role of DC1 dendritic cells?

A

Anti-tumor activity

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48
Q

What T cell subset can be activated by DC1 dendritic cells?

A

Th1

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49
Q

What cytokines are produced by DC1 dendritic cells?

A

IL-1alpha
IL-1beta
IL-6
IL-12
IL-23

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50
Q

What T-cell subset is activated by DC2 dendritic cells?

A

Th2

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51
Q

What cytokines are produced by DC2 dendritic cells?

A

IL-4
IL-5
IL-10

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52
Q

What cytokines/chemokines are produced when Langerhans cells are stimulated by TSLP?

A

IL-16
IL-8
CCL22/MDC
CCL17/TARC

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53
Q

What chemokine is considered a biomarker for atopic dermatitis?

A

CCL17/TARC

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54
Q

What receptor does TARC bind to attract Th2 cells?

A

CCR4

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55
Q

What cells produce TARC?

A

Langerhans cells
Keratinocytes

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56
Q

What cells produce MDC/CCL22?

A

Macrophages
T-cells
Langerhans cells

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57
Q

What cytokines induce CCL2 expression?

A

IL-4
IL-13

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58
Q

What cells produce IL-8?

A

Langerhans cells
Endothelial cells
Macs

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59
Q

What is the function of IL-16?

A

CD4+ T-cell chemotaxis

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60
Q

What cytokine binds to nerves to stimulate itch?

A

TSLP

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61
Q

What cells are activated by IL-33?

A

ILC2
Eos
Basophils
Mast cells
Macs

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62
Q

What cells are activated by IL-33?

A

Mast cells
Th2 cells

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63
Q

What cytokines have receptors on peripheral nerves?

A

TSLP
IL-25

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64
Q

What cytokine is critical in equine allergy?

A

IL-5

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65
Q

What pro-inflammatory cytokine is a major inducer of acute phase proteins in the liver?

A

IL-6

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66
Q

What cytokine has similar activities to IL-1?

A

IL-6

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67
Q

What are the 3 primary pro-inflammatory cytokines?

A

IL-1
IL-6
TNF-alpha

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68
Q

What is the major function of IL-17?

A

Activation of neutrophils

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69
Q

Is IFN-gamma a type I or type II intereron?

A

Type II

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70
Q

What cell type makes IFN-alpha?

A

Leukocytes

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71
Q

What cell type makes IFN-beta?

A

Fibroblasts

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72
Q

What cell types produce IFN-gamma?

A

T-cells (Th1)
NK cells
Macs

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73
Q

What are two major anti-inflammatory cytokines?

A

TGF-beta
IL-10

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74
Q

What T-cell subset produces TGF-beta

A

Treg

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75
Q

What cytokine is heavily implicated in canine leishmaniasis?

A

IL-17

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76
Q

What cytokines are produced by damaged keratinocytes and serve as alarmins?

A

IL-25
IL-33
TSLP

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77
Q

Is atopic dermatitis primarily Th1 or Th2-driven?

A

Th2

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78
Q

How does adult-onset AD differ from pediatric-onset AD?

A

Pediatric: low Th1, high Th2, preserved FLG expression
Adult: more upregulation of Th1 and Th17, less pronounced barrier defect

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79
Q

What ethnicity has the highest Th17 activation in AD?

A

Asian

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80
Q

What cytokines are considered the main drivers of AD pathogenesis?

A

IL-4
IL-13

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81
Q

What is the effect of IL-13 on dermal fibroblasts and how does this contribute to AD lesions?

A

It stimulates them to produce collagen –> AD-related skin fibrosis

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82
Q

Besides atopy, which condition is associated with increased IL-1 expression in the skin of humans?

A

Alopecia areata

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83
Q

What JAK subsets mediate signaling of IL-13?

A

JAK 1, JAK 2, TYK2

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84
Q

What JAK subsets mediated signaling of IL-31?

A

JAK1, JAK2

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85
Q

What receptor for IgE is over-expressed in AD skin?

A

FCεR1

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86
Q

What fibers are stimulated by histamine, triggering itch?

A

unmyelinated C fibers

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87
Q

Are cannabinoids considered agonists or antagonists of TRPV1?

A

Antagonists

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88
Q

What is released when C fibers are activated by TRPV1?

A

substance P

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89
Q

What are the keratinocyte-derived cytokines involved in AD?

A

TARC/CCL17
MDC/CCL22
TSLP
IL-33

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90
Q

What cytokine is constitutively expressed in epithelial tissues?

A

IL-33

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91
Q

True or false: TSLP is currently considered a relevant therapeutic target in cAD

A

False

91
Q

What is the primary effect of TARC?

A

Recruitment of Th2 cells to the skin

92
Q

What cytokine correlates with AD disease severity?

A

CCL17/TARC (this is why it is a biomarker for AD)

93
Q

What is the receptor for CCL22/MDC?

A

CCR4 (same as CCL17/TARC)

94
Q

What are the primary functions of IL-4?

A

Leukocyte survival in Th2 responses
IgE class-switching of B-cells

95
Q

Is IL-4 considered more prominent in acute or in chronic AD?

A

Acute

96
Q

When does IL-31 expression in the skin peak after allergen challenge?

A

24-48 hours

97
Q

True or false: IL-31 expression in the skin and blood are highly correlated

A

False

98
Q

What cytokines induce IFN-gamma secretion?

A

IL-12
IL-15
IL-18

99
Q

What happens if IL-18 is present in the absence of IL-12?

A

Stimulates Th2 response (normally IL-18 + IL-12 stimulates Th1)

100
Q

What are the representative cytokines produced by Treg cells (i.e. “immunosuppressive cytokines”)

A

IL-10
TGF-β

101
Q

True or false: IL-10 and TGF-β secretion significantly change with ASIT

A

False (previously these were thought to be involved in the MOA of ASIT but a 2021 paper found no significant change in plasma levels of these cytokines after 1 year of ASIT)

102
Q

What is the function of IL-22?

A

Activates keratinocyte proliferation

103
Q

What cytokine is suspected to be involved in the lichenification seen in chronic cAD?

A

IL-22

104
Q

How does IL-34 in human AD differ from canine AD?

A

IL-34 is decreased in the epidermis of humans with AD
IL-34 is higher in the serum of dogs with AD (but remained high despite clinical improvement so may play less of a role in dogs)

105
Q

What medication serves as a NK-1R antagonist and decreased pruritus and skin lesions in cats?

A

Maropitant

106
Q

Which neuropeptide is blocked from binding to its receptor by maropitant?

A

Substance P

107
Q

What dog breeds are predisposed to cAD worldwide?

A

Boxer
Bulldog
Lab
Pug
WHWT

108
Q

What short, single-stranded RNA molecules are suspected to play a role in the pathogenesis of allergies?

A

microRNAs (miRNA)

109
Q

Name 4 environmental factors that are considered protective against AD in humans

A

Rural environment
Diet rich in fiber
High food diversity
Early contact with peers

110
Q

What environmental factors have been associated with a decreased risk of developing cAD?

A

Rural environment
Walking in woods
Living with another dog
Living in detached house
Non-processed meat-based diet early in life
Birth in current household

111
Q

What is the effect of D. farinae serine protease on cytokine expression?

A

Increased IL-33 expression

112
Q

How is a “major” allergen defined?

A

If >=50% of patients allergic to the parent allergen have detectable positive IgE on serology or skin test

113
Q

What are 5 known major allergens in dogs?

A

D. farinae (Der f2, Der f15, Der f18, Zen1)
Japanese cedar (Cry j1, Cry j3)
short ragweed (Amb a1)
M. pachydermatis
Ctenocephalides felis (Cte f1)

114
Q

What is the most common cause of cAD worldwide?

A

House dust mites

115
Q

What are the major HDM allergens for cAD?

A

Der f2
Der f15
Der f18
Zen1

116
Q

What parameter has been most commonly used to indirectly assess the skin barrier?

A

TEWL

117
Q

What 4 measurements have higher sensitivity when combined to assess the skin barrier integrity?

A

TEWL
pH
erythema
hydration

118
Q

What is the correlation between pH and clinical sign severity in cAD?

A

Negatively correlated

119
Q

What ceramides are usually altered in AD as compared to healthy controls?

A

ceramide 1
ceramide 9
cer[NP]

120
Q

How is the structure of lipid packing in AD different from that of unaffected dogs?

A

In AD there is hexagonal lipid packing (instead of orthothrombic)

121
Q

What structural protein is known to be mutated in humans with AD?

A

Filaggrin

122
Q

What tight junction proteins are reduced in atopic dogs and may be involved in the cAD pathogenesis?

A

claudin-1
occludin

123
Q

What species of Malassezia predominates on the skin of non-atopic dogs?

A

M. globosa

124
Q

What species of Malassezia predominates on the skin of atopic dogs?

A

M. pachydermatis

125
Q

What bacterial organisms are more abundant in the ears of atopic dogs?

A

Staphylococcus spp.
Ralstonia spp.

126
Q

What bacterial organism is more abundant in the ears of non-atopic dogs?

A

Escherichia spp.

127
Q

Is the expression of host defense peptide genes higher or lower in atopic dogs compared to healthy dogs?

A

Higher (though this does not correlate to increased protein expression of these peptides)

128
Q

Describe the reaction patterns consistent with allergic dermatitis in cats

A

Miliary dermatitis
Self-induced alopecia
Eosinophilic granuloma complex
Head and neck excoriations

129
Q

True or false: There is strong evidence for allergen avoidance for FASS cats

A

False

130
Q

What steroid is considered particularly diabetogenic in cats?

A

Dexamethasone

131
Q

True or false: There is sufficient evidence to support the use of CsA for treatment of feline asthma

A

False

132
Q

What antihistamine has some support for its efficacy as a first-line H1R-antihistamine in cats?

A

Chlorpheniramine

133
Q

What bred of cat is predisposed to FASS?

A

Abysinnian (Persian, Siamese, Maine Coon also suspected)

134
Q

Is there a sex predilection for FASS?

A

Yes- females overrepresented

135
Q

How does BAL fluid in asthmatic cats differ from that in cats with chronic bronchitis?

A

Asthma: eosinophils predominate
Chronic bronchitis: neutrophils predominate

136
Q

What does IDAT detect?

A

Allergen-specific IgE bound to cutaneous mast cells

137
Q

What does ASIS detect?

A

Circulating allergen-specific IgE

138
Q

What is the withdrawal time for antihistamines prior to IDAT?

A

7 days (2 days minimum)

139
Q

What is the withdrawal time for short-acting oral/topical glucocorticoids prior to IDAT?

A

14 days

140
Q

What is the withdrawal time for long-acting injectable glucocorticoids prior to IDAT?

A

28 days

141
Q

In comparison to dogs, what extracutaneous sign may be seen more commonly in cats with atopy?

A

Asthma

142
Q

Does the definition of feline atopic skin syndrome include food and flea allergy?

A

No - environmental only

143
Q

Does pentoxifylline need to be withdrawn prior to IDAT?

A

No

144
Q

What is the most widely used positive control for IDAT and at what concentration?

A

histamine at 1:100,000 w/v (1:10,000 w/v also accepted)

145
Q

What lesion types are assessed by the CADESI-4?

A

erythema
lichenification
excoriation/alopecia

146
Q

What 20 body sites are evaluated in the CADESI-4?

A
147
Q

What are the 4 points on the CADESI-4 severity scale?

A

None
Mild
Moderate
Severe

148
Q

Besides the CADESI, what other scoring system has been validated for lesions of AD?

A

CADLI

149
Q

Does cAD have a known sex predilection?

A

No

150
Q

What body region is most commonly affected in WHWT and SharPeis with cAD?

A

Dorsolumbar

151
Q

What body regions are most commonly affected in GSDs with cAD?

A

Elbows
Hindlimbs
Thorax

152
Q

What body region is most commonly affected in Dalmatians with cAD?

A

Lips

153
Q

What is the prevalence of conjunctivitis in allergic dogs?

A

21-30%

154
Q

What is the prevalence of rhinitis in allergic dogs?

A

7%

155
Q

Is FLG considered a primary mutation in WHWT with cAD?

A

No

156
Q

What two candidate genes are proposed to be involved in cAD pathogenesis in WHWT?

A

PTPN22
cytochrome p450 26B1

157
Q

What candidate gene is proposed to be involved in cAD pathogenesis in Glden Retrievers?

A

RAB3C

158
Q

What candidate gene is proposed to be involved in cAD pathogenesis in GSDs?

A

PKP2

159
Q

How do Group 1 mite allergens increase epithelial permeability?

A

They are cysteine proteases –> degrade occludin, claudin, and zona occludens

160
Q

Which groups of allergens are serine proteases?

A

Groups 3, 6, 9

161
Q

Where are mast cells highest in number on canine skin?

A

Pinnae, ventral interdigital

162
Q

Describe the presence of macrophages in atopic vs healthy canine skin

A

Atopic: macs present in lesional and non-lesional skin
Healthy: macs not present

163
Q

What is the name of the high-affinity IgE receptor?

A

FcεRI

164
Q

What proteins can induce IgE-independent mast cell degranulation?

A

Proteases, stem cell factor

165
Q

The binding of which TLRs to their ligands can increase TSLP expression?

A

TLR3, TLR4 (whereas TLR2 and TLR7 do not increase TSLP expression)

166
Q

What cell types express cannabinoid receptors?

A

KCs
Endothelial cells
Mast cells

167
Q

PEA (palmitoylethanolamide) is an agonist of what type of receptor?

A

Cannabinoid

168
Q

True or false: total serum IgE levels are strongly associated with atopic status in dogs

A

False (it’s allergen-specific IgE that matters)

169
Q

What is the term for atopic-like dermatitis in humans?

A

Intrinsic atopic dermatitis

170
Q

Besides IgE, which other antibody is suspected to have some role in atopy?

A

IgG

171
Q

What type of lymphocyte are a major component of the inflammatory infiltrate in cAD skin?

A

CD3+ T-cells

172
Q

What type of lymphocyte typically predominates in the epidermis of normal skin?

A

CD8+ T-cells

173
Q

What type of lymphocyte typically predominates in the dermis of normal skin?

A

CD4+ T-cells

174
Q

What receptor on T-cells allows them to be recruited to atopic skin?

A

CCR4 (binds TARC)

175
Q

Do Th1 cytokines induce humoral or cell-mediated immunity?

A

Cell-mediated

176
Q

Do Th2 cytokines induce humoral or cell-mediated immunity?

A

Humoral

177
Q

What type of T-helper cell response predominates during acute lesions of AD and during sensitization?

A

Th2

178
Q

What are 3 regulatory cytokines in cAD?

A

IL-10
TGFβ
FOXP3

179
Q

What is the role of S100A8 protein in atopy?

A

Induces chemotaxis of neutrophils

180
Q

Describe the body distribution of lice and Cheyletiella in dogs

A
181
Q

Describe the body distribution of Sarcoptes in dogs

A
182
Q

Describe the body distribution of trombiculiasis in dogs

A
183
Q

Describe the body distribution of demodicosis in dogs

A
184
Q

Describe the body distribution of Malassezia in dogs

A
185
Q

What are the most common food allergens in dogs?

A

Beef
Dairy
Chicken
Wheat
(lesser: soy lamb, pork, fish, corn)

186
Q

Describe the distribution of clinical lesions in different breeds with cAD

A
187
Q

Name Favrot’s criteria

A

1) Age of onset <3 years
2) Mostly indoor
3) Corticosteroid-responsive pruritus
4) Chronic or recurrent yeast infections
5) Affected front feet
6) Affected ear pinnae
7) Non-affected ear margins
8) Non-affected dorsolumbar area

188
Q

What is the minimum numer of Favrot’s criteria that should be fulfilled to help with the diagnosis of cAD?

A

5

189
Q

Within how many months after peak allergy season should IDAT be done?

A

2 months (>60 days is too late)

190
Q

How many minutes after intradermal injection should a reaction be read?

A

15-20 min

191
Q

What are the most common methods for serum allergy testing?

A

Solid phase ELISA using a monoclonal anti-canine IgE Ab
FcεRIα receptor assay

192
Q

What sedatives should be avoided prior to IDAT?

A

Ketamine
Oxymorphone
Acepromazine
Morphine

193
Q

What sedatives can be safely used for IDAT?

A

Xylazine
Dexmedetomidine
Tiletamine/zolazepam
Halothane
Isoflurane
Methoxyfluorane

194
Q

What percent of dogs with CAFR should respond to an 8 week elimination diet trial?

A

90%

195
Q

Where are IL-31 receptors highest?

A

Dorsal root ganglia

196
Q

What cytokine is rapidly induced after exposure to Staph superantigens?

A

IL-31

197
Q

What are the receptor subunits for IL-31?

A

IL-31RA
OSMR

198
Q

What cytokine is constitutively produced by KCs?

A

IL-1alpha

199
Q

What cells produce IL-2?

A

Th1 cells
Macs

200
Q

What is the function of IL-3?

A

Stimulates hematopoiesis

201
Q

What cytokine is a homolog for IL-2?

A

IL_7

202
Q

What cytokine is critical for the survival of memory T-cells?

A

IL-7

203
Q

What cytokines have been shown to be significantly elevated in the blood of atopic dogs compared to controls?

A

IL-7
IL-8
IL-13
IL-15
IL-17
IL-31
IL-34

204
Q

What cytokine is produced by macrophages in response to microbial infection?

A

IL-12

205
Q

What cytokine is produced by macrophages during phagocytosis of neutrophils?

A

IL-23

206
Q

What cytokine lives in the nuclei of keratinocytes and is only released when the cell is injured?

A

IL-33

207
Q

What is another name for CCL5?

A

RANTES

208
Q

What chemokine attracts B-cells?

A

CCL3

209
Q

Is IFN-gamma found more in chronic or acute lesions?

A

Chronic

210
Q

What cytokine’s primary biological function is to induce a cytotoxic effect on tumor cells?

A

TNF-alpha

211
Q

TGF-beta induces the production of which antibody?

A

IgA

212
Q

Which cytokine is important in wound healing due to its role in collagen synthesis?

A

TGF-beta

213
Q

What T-cell subset is CD3+?

A

All T-cells

214
Q

What T-cell subset is CD4+?

A

Helper T-cells

215
Q

What T-cell subset is CD8+?

A

Cytotoxic T-cells

216
Q

What T-cell subset is CD4+CD8+?

A

Memory T-cells

217
Q

What T-cell subset is CD4+CD25+FoxP3+?

A

Tregs

218
Q

What T-cell subset is CD4+IFNgamma+?

A

Th1

219
Q

What T-cell subset is CD4+IL4+?

A

Th2

220
Q

What cytokines support differentiation of Th1 cells?

A

IL-12
IL-27
IFN-gamma

221
Q

What cytokines support differentiation of Th2 cells?

A

IL-4
IL-25
IL-33
TSLP

222
Q

What is the master regulator (i.e. transcription factor) of Th1 responses?

A

Tbet

223
Q

What is the master regulator (i.e. transcription factor) of Th2 responses?

A

GATA3

224
Q

What cytokines are important in the differentiation of Th17 cells?

A

IL-1
IL-6
IL-23
TGF-beta

225
Q
A

MK ACVD Exam (11 decks)

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