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2019 Added Cards COPY > Atopy, Food Allergy, Contact > Flashcards

Atopy, Food Allergy, Contact Flashcards

1
Q

T/F Food-induced and nonfood-induced atopic dermatitis can be distinguished based on clinical signs alone.

A

False. Food-induced and nonfood-induced atopic dermatitis cannot be distinguished based on clinical signs alone.

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2
Q

What is the definition of canine AD?

A

Genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE antibodies, most commonly directed against environmental allergens.

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3
Q

What does CADESI stand for?

A

Canine Atopic Dermatitis Extent and Severity Index

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4
Q

What does CADLI stand for?

A

Canine Atopic Dermatitis Lesion Index

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5
Q

The majority of dogs develop signs of AD before the age of __.

A

3 years

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6
Q

Which dog breeds develop AD earlier in life than other breeds?

A

French bulldogs and shar-pei dogs

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7
Q

How does the age of onset for food-induced AD differ from environmental AD?

A

Dogs with food-induced AD were more likely to be very young (<1 year) or older (>6 years).

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8
Q

What dog breeds are predisposed to AD?

A

WHWT, Labrador, golden, boxer, french bulldog, GSD, and cocker spaniel.

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9
Q

T/F Canine AD does not exhibit sex predilection.

A

True. However, one study reported that female boxers and male golden retrievers are more frequently affected.

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10
Q

What percentage of dogs exhibit seasonal signs?

A

15-62%, median 30%

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11
Q

In which season do the majority of seasonally affected AD dogs exhibit clinical signs?

A

Spring and/or summer

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12
Q

What is the term for pruritus that precedes other clinical signs?

A

Pruritus sine materia

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13
Q

Shar-peis and WHWT exhibit a breed-specific phenotype of pruritus in which area of the body? What about GSDs?

A

Shar-pei and WHWT - dorsolumbar

GSD - elbows, hindlimb, thorax

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14
Q

What are the most common clinical lesions seen in canine AD?

A

Erythema, erythematous macular and papular eruptions, self-induced alopecia, excoriations, hyperpigmentation and lichenification.

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15
Q

What are some less-common clinical manifestations of canine AD? In what breeds are you more likely to see these manifestations?

A

Urticaria - boxer
Hot spots - GSD, goldens, labs
Hyperhidrosis and seborrhea oleosa - WHWT and GSD
Interdigital fistulae - Labrador retrievers

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16
Q

What are two noncutaneous conditions associated with canine AD?

A

Rhinitis and conjunctivitis

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17
Q

What are the common histopathologic findings of canine AD?

A

Epidermal hyperplasia, orthokeratotic and parakeratotic hyperkeratosis, hypergranulosis, spongiosis, melanosis and lymphocytic and eosinophilic exocytosis.
Superficial perivascular to interstitial mononuclear dermatitis with neutrophils and eosinophils. Mast cell and eosinophil degranulation present upon allergen challenge.

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18
Q

What does the “outside-inside” theory propose?

A

An abnormal skin barrier in atopic patients facilitates the penetration of allergens (and microbes) through the epidermis, increasing their contact and exposure to epidermal immune cells.

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19
Q

What does the “outside-inside-outside” theory propose?

A

A primary defect in the epidermal barrier leads to a higher penetration of allergens and microbes that overstimulate the local immunity (innate and adaptive). This excessive stimulation triggers the release of inflammatory mediators that further exacerbate the barrier dysfunction.

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20
Q

Significant decreases in TEWL have been reported in dogs supplemented with ______ _____.

A

Significant decreases in TEWL have been reported in dogs supplemented with linoleic acid.

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21
Q

Ceramides are waxy lipid molecules composed of one ______ and one ____ ____.

A

Ceramides are waxy lipid molecules composed of one sphingosine and one fatty acid.

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22
Q

`A subset of dogs with AD have increased/decreased filaggrin expression.

A

`A subset of dogs with AD have decreased filaggrin expression. Suggests loss-of-function mutations in the C-terminus portion.

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23
Q

Greater/fewer bacterial species were identified in samples from dogs with AD.

A

Fewer bacterial species identified. Suggests that decreased microbial diversity seen in humans with AD may also be present in affected dogs.

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24
Q

Is colonization and infection of atopic skin associated more with bacterial virulence factors or host factors? Why do we think this?

A

Colonization and infection of atopic skin is associated more with host factors. Staphylococcal isolates from atopic and healthy skin exhibit identical adhesion to fibronectin, cytokeratin and fibrinogen in vitro. These molecules (along with P-selectin) are expressed on the skin surface and stratum corneum in inflamed skin.

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25
Q

Increased levels of antistaphylococcal ____ antibodies were found in atopic dogs compared with nonatopic dogs with pyoderma, healthy dogs and specific pathogen-free dogs. Levels of antistaphylococcal ____ antibodies are comparable in atopic and nonatopic dogs.

A

Increased levels of antistaphylococcal IgE antibodies were found in atopic dogs compared with nonatopic dogs with pyoderma, healthy dogs and specific pathogen-free dogs. Levels of antistaphylococcal IgG antibodies are comparable in atopic and nonatopic dogs.

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26
Q

Which toxins from which Staphylococcus species are able to alter the skin barrier, stimulate the immune system and trigger atopic lesions in humans?
What are these molecules called?

A

Enterotoxins and exfoliative exotoxins produced by S. aureus, S. pseudintermedius and S. hyicus.

Superantigens!

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27
Q

What are some effects of superantigens in humans?

A
  • Activation of keratinocytes
  • Induction of cutaneous leukocyte antigen expression on T cells
  • Induction of MCH II, IL-1, TNF-α, IL-4 and IL-12 by mononuclear cells
  • Decreased IFNƔ production
  • Upregulation of ICAM-1 and VCAM-1
  • Stimulation of Staphylococcus-specific IgE, which binds mast cells or Langerhans cells

Overall, leads to exacerbation of clinical signs of AD.

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28
Q

About what percentage of canine S. pseudintermedius strains are able to produce superantigens?

A

Up to 25%

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29
Q

Production of _____________ (which is able to disrupt a host’s cell membranes) is a possible initiating factor for Malassezia dermatitis secondary to AD.

A

Production of phospholipase A2 (which is able to disrupt a host’s cell membranes) is a possible initiating factor for Malassezia dermatitis secondary to AD.

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30
Q

Which cytokines are Malassezia spp. able to induce in normal human keratinocytes?

A

IL1-β, IL-6, IL-8 and TNFα

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31
Q

How does Malassezia contribute both directly and indirectly to the inflammation associated with canine AD?

A

Directly - induction of inflammatory cytokines

Indirectly - acts as an allergen

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32
Q

What are the main functions of β-defensins and cathelicidins? (Think broad, not specific)

A
  1. Direct antimicrobial activity against variety of micro-organisms
  2. Modulate innate and adaptive immune reponses
33
Q

What is the role of antimicrobial peptides in the pathogenesis of canine AD?

A

Unclear. Requires further study. No correlation between AMP expression and staph colonization or clinical severity has been consistently established.

34
Q

T/F The filaggrin (FLG) locus is not likely to be associated with AD in WHWTs.

A

True

35
Q

What two intronic SNPs have been significantly associated with AD in golden retrievers?

A

PROM1 and RAB3C

RAB3C is a gene coding for a transporting protein found on lipid anchors.

(maybe too detailed, but who knows?)

36
Q

There is a strong positive correlation between AD and low/high IgA

A

There is a strong positive correlation between AD and low IgA

37
Q

Which desmosomal protein represents a relevant candidate gene for AD?

A

Plakophilin 2 (PKP2)

38
Q

What is the ‘hygiene hypothesis’?

A

Early-life exposure to “normal” childhood infections could protect against the development of allergic disease later in life.

39
Q

Group 1 mite allergens (Der f 1 and Der p 1) are potent _______ proteases.

A

Group 1 mite allergens (Der f 1 and Der p 1) are potent cysteine proteases.

40
Q

How do cysteine proteases from mite allergens increase epithelial permeability?

A

Degradation of occludin, claudin and the tight junction protein zone occludens 1.

41
Q

How do Group 1 mite allergens induce inflammation in humans?

A
  • Activation of basophils and mast cells in an IgE-independent manner
  • Induce release of IL-4 (Th2 cytokine)
  • Inhibit negative feedback from IgE by cleaving the low-affinity IgE receptor (FcεRII, CD23) from surface of B cells
  • Inhibit effective Th1 response by removal of the α-chain on the IL-2 receptor, CD25, and by impairing IL-12 secretion from DCs (by removing CD40 and DC-SIGN)
42
Q

How do Group 1 mite allergens induce inflammation in dogs?

A

Der f 1 has been found to enhance production of GM-CSF, IL-8/CXCL8 and TNFα from canine keratinocytes.

43
Q

What type of proteases are Group 3, 6 and 9 allergens?

A

Group 3 - trypsin like serine protease
Group 6 - chymotrypsin like serine protease
Group 9 - collagenase like serine protease

44
Q

T/F Group 2 allergens (like Der f 2 and Der p 2) are major allergens in humans and dogs.

A

False. Group 2 proteins are major allergens in humans bu their relevance to canine AD is somewhat controversial.

45
Q

Ragweed pollen grains have been shown to induce intracellular markers of _________ ________ in human bone marrow-derived DCs.

A

Ragweed pollen grains have been shown to induce intracellular markers of oxidative stress in human bone marrow-derived DCs.

It is associated with the release of IL-8, IL-6 and TNFα, as well as up regulation of surface markers of maturity (CD80, CD86, CD83, and HLA-DR).

46
Q

What are two pieces of evidence that support the role of oxidative stress in the pathogenesis of AD in dogs?

A
  1. Increased serum levels of malondialdehyde (formed during lipid peroxidation) in dogs with AD.
  2. Decreased expression of methionine sulfide reductase A, which plays a key role in repairing oxidative tissue damage.
47
Q

How might understanding the genotype of AD help clinicians in regards to treatment?

A
  • Some dogs may respond well to skin barrier therapy, whereas others would benefit more from ASIT.
  • May be able to identify dogs that may have a poor response or an increased risk of AEs to certain drugs.
  • Atopic genotypes identified in young dogs could allow management of environmental factors to minimize risk of developing clinical AD.
48
Q

In atopic dogs, both epidermal dendritic cells (Langerhans cells) and dermal dendritic cells (DCs) have been shown to be increased/decreased/the same as compared to healthy dogs.

A

In atopic dogs, both epidermal dendritic cells (Langerhans cells) and dermal dendritic cells (DCs) have been shown to be increased as compared to healthy dogs.

49
Q

Explain how the conditions in which DCs encounter antigen determine their future responses.

A

Antigen encountered in conditions of minimal or no inflammation is generally not sufficient to induce DC activation and migration.
Alternatively, co-exposure to certain microbial factors, such as proteases or PAMPs can induce potent cellular activation and migration to lymphoid tissue for presentation to naive T cells.

50
Q

Activation of canine DCs in the presence of microbial LPS increases expression of which cytokines?

A

IL-1β, IL-10, IL-12, IL-13 and TNF α

51
Q

Which inflammatory mediator produced by keratinocytes when exposed to microbial antigens and other inflammatory stimuli is a potent activator of epidermal dendritic cells (LCs)?

A

Thymic stromal lymphopoeitin.

52
Q

Production of thymic stromal lymphopoeitin by primary canine keratinocytes is induced by stimulation of which PRRs?

A

TLR3 and TLR4

53
Q

What inflammatory mediators have been shown to be released from mast cells?

A 
Histamine
TNFα
Eicosanoids (PGD2, PGE2, and leukotriene B4 and C4)
Neutral proteases (chemise and tryptase)
Matrix metalloproteinase 9
IL-3
IL-4
IL-6
IL-13
GM-CSF
CCL5 (RANTES)
CCL2 (monocyte chemotactic protein 1)
CCL3 (macrophages inhibitory protein 1α)
54
Q

Cross-linking of which canine dermal mast cell high-affinity IgE receptor results in the release of inflammatory mediators?

A

FcεRI

55
Q

Which chemokine is produced by canine keratinocytes that recruits T cells?
Which chemokine receptor is involved on T cells?

A

TARC - thymus and activation regulated chemokine is produced by keratinocytes and recruits T cells bearing the CCR4 chemokine receptor.

56
Q

Co-culture of canine keratinocytes with Der f 1 has been shown to increase expression of which cytokines?

A

IL-8, TNF-α, and GM-CSF

57
Q

T/F Mast cell degranulation has been demonstrated to increase L-selectin and ICAM-1 expression in canine endothelial cells.

A

False.

Mast cell degranulation has been demonstrated to increase P-selectin and ICAM-1 expression in canine endothelial cells.

58
Q

What are Heat Shock Proteins?

A

Family of cell chaperones considered to be part of the acute-phase response. They modulate inflammatory responses by regulating tolerance to heat, mediating protein folding, unfolding and degradation.

59
Q

What type of response do heat shock proteins induce in the skin of healthy dogs? Atopic dogs?

A 
HSPs induce a regulatory or mixed regulatory-T helper 1 response in healthy canine skin.
Atopic skin (particularly lesional skin), is refractory to HSP regulation.
60
Q

What changes in complement have been seen in the skin of atopic dogs?

A

Increased mRNA expression of:

  • C3
  • C5aR1 - receptor for the chemotactic C5a fragment
  • CFP - complement factor properdin, involved in positive feedback of the alternative complement pathway
61
Q

What role does sphingosine-1-phosphate (S1P) play in cutaneous homeostasis?

A

Maintenance of epidermal barrier
Regulation of ingress and egress of inflammatory cells
Regulates LN trafficking of T cells in humans and mice
Modulates the retention of inflammatory cells in skin

62
Q

What changes are seen to sphingosine-1-phosphate levels in the lesional skin and serum of atopic dogs?

A

Increased, possibly secondary to enhanced metabolism.

63
Q

Canine mast cell activation results in release of which leukotrienes?

A

LTB4 and LTC4

64
Q

Which two enzymes critical in leukotriene synthesis have been shown to have significantly greater mRNA expression in the skin of dogs with AD?

A

5-lipoxygenase and 5-lipoxygenase-activating protein

65
Q

What is the role of leukotrienes in the blood or skin of dogs with AD?

A

Insufficient evidence to draw any clear conclusions.

66
Q

Labrador retrievers with low vitamin __ levels have an increased risk of developing mast cell tumors.

A

Labrador retrievers with low vitamin D levels have an increased risk of developing mast cell tumors.

67
Q

IgE has been demonstrated to be expressed on the surface of which cells in the epidermis of atopic (but not nonatopic) dogs, where is may play a role in allergen capture and processing?

A

IgE has been demonstrated to be expressed on the surface of Langerhans cells in the epidermis of atopic (but not nonatopic) dogs, where is may play a role in allergen capture and processing?

68
Q

What is atopic-like dermatitis?

A

Disease in which all clinical criteria for AD are fulfilled, but there is no allergen-specific skin reactivity or increased levels of total or allergen-specific IgE.

69
Q

T/F Serum food-allergen-specific antibodies may be identified in atopic dogs in the absence of clinical food-reactive disease.

A

True

70
Q

What is oral allergy syndrome?

A

Oral or perioral pruritus and inflammation following ingestion of a food item that cross-reacts with an aeroallergen to which the patient is sensitized.

71
Q

Where do CD4 and CD8 lymphocytes usually predominate in normal canine skin?

A

CD8 usually predominates in the epidermis

CD4 usually predominates in the dermis

72
Q

What is CCR4?

A

Receptor for T-cell chemotactic factor TARC (thymus and activation regulated chemokine, aka CCL17)

73
Q

T cells expressing CCR4 have been shown to be increased/decreased in spontaneously allergic and experimentally sensitized dogs.

A

T cells expressing CCR4 have been shown to be increased in spontaneously allergic and experimentally sensitized dogs.

74
Q

T/F CD25 can be used as a marker for Treg cells.

A

False. CD25 represents the α-subunit of the IL-2 receptor present on the surface of thymus-derived Treg cells. However, it is also unregulated on activated T cells, and thus the mere presence of CD25 expression cannot be relied upon to identify a Treg phenotype.

75
Q

T/F Canine and human AD are not considered strictly Th2 polarized immune responses.

A

True. However, evidence does suggest that T2-type cytokines are involved in the development and perpetuation of AD, particularly in the early phases and in acute lesions.

76
Q

Atopic canine skin exhibits increased/decreased transcription of thymic stromal lymphopoietin (TSLP) compared to healthy skin.

A

Atopic canine skin exhibits increased transcription of thymic stromal lymphopoietin (TSLP) compared to healthy skin.

77
Q

Which cells produce TSLP? What does TSLP do?

A

Produced by keratinocytes.
Induces maturation and activation of DCs and mast cells.
DC activation in the presence of TSLP fosters a TH2-promoting phenotype.

78
Q

Production of TSLP by primary canine keratinocytes is induced by stimulation with which ligands?

A

Production of TSLP by primary canine keratinocytes is induced by stimulation with ligands for TLR 3 and 4, but not TLR2 or 7.

2019 Added Cards COPY (9 decks)

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