Atopic disease Flashcards
What’s the difference between “atopy”, “atopic dermatitis”, and “atopic like dermatitis”?
Atopy refers to an individual who produces specific IgE antibodies following exposure to common environmental allergens, and is “sensitized” to that allergen.
Atopic dermatitis is a clinical syndrome that not all patients with atopy manifest.
Atopic-like dermatitis is an inflammatory and pruritic skin disease with clinical features identical to those seen in CAD in which an IgE response to an environmental or other alleged cannot be documented”. This acknowledges that IgEs are not necessary for manifestation of the disease.
T/F: some dog with clinical presentations of atopic dermatitis do not ave measurable IgE against environmental allergens.
T. some dogs that have typical clinical presentation of AD do not have measurable IgE against environmental allergens.
What is the hygiene theory?
decreased exposure to bacteria, parasites in conjunction with increased practices of excessive bathing and use of antibacterial detergents that can harshly affect the skin barrier may be responsible for the increased occurrence of AD.
These associations do not prove causality but do support that certain environmental factors may influence the development of CAD.
Which of these is the most recently discovered loss-of-function mutation in the human ___ gene, associated with abnormal epidermal differentiation?
A) R501X
B) 22Derf1
C) 2282derl14
d) RU486
Filaggrin gene;
A and B: R501X and 2282derl4
These mutations have been strong predisposing factors for early-onset extrinsic AD
T/F: Development of clinical disease of AD is not predicted by the level of IgE.
T. The development of clinical disease is not predicted by the level of IgE.
Which of these are not genes that have been investigated in canine AD?
a) Protein tyrosine phosphatase non receptor type 22
b) Kallikrein
c) Filaggrin
d) Melanin
d. Protein tyrosine phosphatase non receptor type 22 has been identified as a potential candidate gene for canine AD.
Kallikrein has been investigated, but unfortunately no significant association was identified.
A single-nucleotide polymorphism within Filaggrin in WHWT has been associated with CAD, but not in all dogs.
Which of these have shown structural defects in skin of dogs with AD?
a) Collagen VIII
b) Collagen IV
c) intercellular lipid lamellae
d) laminin 332
C; intercellular lipid lamella have exhibited structural defects in the stratum corneum of dogs with AD. Lamellar lipid delamination (“rollup”) was common as was widening of lipid lamellae in sensitized dogs.
T/F: Total IgEs are mildly different between normal and atopic dogs and a good way to differentiate an atopic dog from a normal one.
F; Total IgEs are nor significantly different between normal and atopic dogs.
T/F: Total IgEs are mildly different between normal and atopic dogs and a good way to differentiate an atopic dog from a normal one.
F; Total IgEs are nor significantly different between normal and atopic dogs. Allergen-specific IgGs occur in both normal and atopic dogs.
What are the two types of IgE that are proposed to exist, and which is hypothesized to cause disease and which is non pathogenic?
IgE+: causing disease
IgE-: not pathogenic
Discuss the biphasic pattern of cytokine expression that appears to be a critical determinant in AD lesions of both humans and mouse models:
Acute skin lesions: CD4+ TH2 lymphocytes, eosinophils, release of IL-4, IL-13. These lead to high IgE levels and increased survival and maturation of eosinophils. Th2 cells preferentially express CCR3, CCR4, CCR8. In humans, chemotaxis of cells expression CCR4 is induced by TARC, resulting in selective migration of Th2 cells into the skin. IL-6 has been shown to play a role in early reactions followed by an increase in IL-13 and TARC. Th2-cell subsets are activated during the initiation phase.
Chronic lesions show predominance of macrophages and are associated with TH1 type cytokines (IL-2, IL-12, IFN-gamma, IL-18). Th1 cells predominantly express CCR5, CXCR3. Th1-cell subsets are activated after Th2, to account for the persistence of inflammation.
Which of these chemokine have been found at increased levels in both cutaneous lesions of AD and sera of affected patients:
a) Regulated on activation, normal T-cell expresses and secreted (RANTES)
b) Monocyte chemoattractant protein-4 (MCP-4)
c) Eotaxin
d) Macrophage-derived chemokine (MDC)
e) Thymus and activation-regulated chemokine (TARC)
f) all of the above
g) none of the above
F, all of the above.
CAD has been proposed to be associated with an increase/decrease of IL-4 and tolerance may be related to increase/decrease of TGF-b and increase/decrease of TARC and increase/decrease in IFN-gamma.
increase, increase, increase, decrease.
CAD has been proposed to be associated with an increase of IL-4 and tolerance may be related to increase of TGF-b and increase of TARC and decrease in IFN-gamma.
Which adhesion molecule has been increased in lesional skin of atopic dogs?
A) L-Selectin
B) LFA-1
C) P-selectin
D) ICAM-1
c) p-selectin. Upregulation of P-selectin was accompanied by signs of functional changes such as increased cell margination and membrane-associated protein expression.
Although expression of ICAM-1 and TNF-a was not enhanced in lesional vs nonlesional skin, there was a Trend toward a correlated up regulation of both molecules.
T/F: all dogs with elevated IgE levels benefit from antihistamines.
F, controversial. Correlation between histamine release and IgE levels is not clear-cut. The importance of histamine as a major mediator of canine AD is controversial.
