Allergy textbook Flashcards
T/F: Staph can reduce the efficacy of glucocorticoids.
TRUE – likely through action of superantigens
What are superoxide dismutase enzymes?
neutralize toxic reactive oxygen species generated in mitochondria by the process of oxidative phosphorylation
What do fungi cell walls contain?
chitin and beta-glucans
T/F: Der f 1 is the most common aeroallergen in the dog.
False – is the major Df allergen in humans and is almost never recognized by dogs sensitized to Df
What is the mechanism of action of capsaicin?
binds to a receptor on neurons and leads to a neuronal depletion of substance P, which is involved in pain and neurogenic inflammation
How do dendritic cells contribute to inflammatory processes?
activation of antigen-specific T cells
How are ceramides released into the extracellular space?
during differentiation of keratinocyes, lamellar granules containing glucosylceramides and sphingomyelins move to the apex of granular cells, fuse with the plasma membrane, and secrete the contents into the extracellular space of the stratum granulosum-stratum corneum boundaries; they are then converted back to ceramides by enzymes
T/F: In acute allergic responses, Th2 predominates, but in the chronic phase, Th1 response predominates
TRUE
T/F: Staphylococcal enterotoxin B is an inducer of IL-31.
TRUE
T/F: Staphylococcus can induce atopic dermatitis by itself.
TRUE – thought to be through increased proinflammatory cytokine production
T/F: Most tricyclic antidepressants can also produce antihistaminic and anticholinergic effects.
TRUE
A (decrease/increase) in the expression of kallikrein-related peptidase 7 (KLK7) has been reported in humans with AD.
increase; increased protein expression –> increased degradation of corneodesmosomal proteins in stratum corneum
How is pentoxifylline metabolized?
by liver and red blood cells - extensive enterohepatic recirculation
What are exfoliative toxins? What strains produce them?
virulence factors produced by pathogenic staphylococci that can produce blister formation in the skin. S. aureus, S. hyicus, S. pseudintermedius
T/F: There is no significant difference in the number of circulating Tregs between dogs with CAD and healthy dogs.
TRUE– however dogs undergoing ASIT will have an increase in their Tregs
What tricyclic antidepressants have been used in treatment of atopic dermatitis?
cyproheptadine (no effect), amitriptyline (some benefit), hydroxyzine (30% effective), doxepin (30% effective)
What are the intracellular proteins of corneocytes? What are their functions?
filaggrin and keratin; provide mechanical strength to cells and may hamper percutaneous entry of foreign bodies
What is TSLP?
thymic stromal lymphopoietin; modulates the function of dendritic cells – can trigger Th2 inflammatory responses
Why would anti-IgE antibodies (e.g. omalizumab) take longer to demonstrate clinical improvement with atopic dermatitis?
IgE is more stable on skin mast cells
What is the role of filaggrin in the stratum corneum?
aggregation of keratin intermediate filaments into tight bundles –> leads to collapse of the cells –> flattened appearance & mechanical strength
What is the mechanism of action of leukotriene inhibitors?
either block the synthesis or inhibit the action of leukotrienes; leukotrienes are produced from arachidonic acid & involved in mediating inflammation
IgE binds to the FceRI on what cells?
mast cells and basophils –> inflammatory mediator and cytokine release, eosinophils, dendritic cells/langerhans cells
Cross-antigenicity can occur between Ctenocephalides felis felis and what other insects?
Blatella germanica (cockroach)
T/F: Allergic skin has increased concentrations of histamine
TRUE
A single nucleotide polymorphism with the filaggrin gene is associated with atopic dermatitis in what breed?
UK Labradors
T/F: Langerhans cells express the high-affinity IgE receptor, FceRI.
TRUE
T/F: IgG antibodies develop higher levels of affinity than IgE.
True – through somatic hypermutation of the variable region gene & multiple iteration of clonal selection
What are pyrrolidone carboxylic and urocnic acids? What is their role?
degraded products of filaggrin monomers, are natural moisturizing factors
What are the main storage mites involved in allergy?
Acarus siro, Glycyphagus destructor, Tyrophagus putrescentiae, and Lepidoglyphus sp.
T/F: The presence of a dog greatly increases the number of mites in house dust.
FALSE
What are proposed mechanisms of action of pentoxifylline?
effects on leukocyte deformability and decreases platelet activation, decreases endothelial leukocyte adnesion, neutrophil degranulation, production of cytokines such as TNF, and inhibits T and B-cell activation
Atopic dermatitis
genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features, associated with IgE antibodies most commonly directed against environmental allergens
What is the mechanism of action of misoprostol?
synthetic prostagalndin E1 analogue; blocks one of the COX inflammatory pathways
What are the three major lipid constituents of the extracellular lipid lamellae in the mammalian stratum corneum?
ceramides, cholesterol, free fatty acids
What are reported side effects of misoprostol?
vomiting and diarrhea
What conditions are favored for storage mites?
humidity and heat
A (decrease/increase) in expression of claudin-1 gene has been reported in humans with AD.
decrease – claudin-1 is a major constituent in tight junctions
What specific virulence mechanism of staphylococci can cause lesions that mimic pemphigus foliaceus?
exfoliative toxins (EXI and ExpB) – cause epidermal splitting mediated through desmoglein-1
TEWL may be influenced by what factors?
impaired barrier function, edema, excoriation of inflamed skin
What is role of TARC?
thymus and activation-regulated chemokine; chemoattractant of Th2 cells
IFN-gamma is (increased/decreased) in atopic animals compared to healthy animals.
decreased
What are staphylococcal superantigens? How do they work?
exotoxins exhibiting polyclonal T-lymphocyte proliferating activity, enterotoxins and toxic shock syndrome toxin; can recruit T cells to the skin
______ are sphingoids consisting of sphongoid bases that are amide-linked to fatty acids.
Ceramides
T/F: When the amount of disease-related, allergen-specific IgE is small in comparison to total IgE, efficacy of omalizumab is higher.
TRUE
Atopy
Genetically predisposed tendency to develop IgE-mediated allergy to environmental allergens
T/F: Transepidermal water loss in non-lesional skin of dogs with AD is equal to that of healthy dog skin.
False – TEWL is higher in both lesional & non-lesional skin of dogs with AD (though it is higher in lesional skin)
What are the three major aeroallergens defined in the dog?
Derived from Dermatophagoides farinae (Der f 15, Der f 18, and Zen 1) & pollen of Japenese cypress trees
What is affinity maturation with respect to IgE?
increase in binding affinity of antibodies for an allergen epitope that occurs during B cell clonal selection as a function of hypermutation in the immunoglobulin gene variable region
What is RANTES?
CCL5 – chemokine that induces leukocyte migration, specifically eosinophils; part of Th1 response
What cells release TSLP?
keratinocytes
What do house dust and storage mites eat?
protein-rich substrates like dandruff, hair, nail, feathers, and mold
T/F: Cross-sensitization can occur between house dust mites and Sarcoptes.
True – as well as Cheyletiella and Otodectes
What role do superantigens play in atopic disease?
able to promote Th2 polarized skin inflammation, IgE production, T-regulatory cell subversion, expansion & migration of skin-homing T cells, and IgE antisuperantigen production
T/F: Dogs and humans are both colonized by M. pachydermatis.
False - only dogs
T/F: Animals sensitized to house dust mites will also have a positive IgE to Sarcpotes scabiei.
False – though they can be sensitized to Sarcoptes as well
What is the major constituent in keratohyalin granules?
profilaggrin (precursor protein of filaggrin)
What is the mechanism of action of tacrolimus?
calcineurin inhibitor – binds intracellular protein and forms complex with calcium, calmodulin and calinceurin which inhibits phosphatase activity of calcineurin – blocks activation of nuclear factor of activated T cells
What is the role of IL-23?
development of Th17 lymphocytes, secreted by activated dendritic cells, monocytes, and macrophages
What is the proposed mechanism of serotonin uptake inhibitors and pruritus?
serotonin is one of the preformed inflammatory mediators released with mast cell degranulation
____ activity has recently been identifid as a candidate virulence factor in M. pachydermatis infection in dogs.
phospholipase
What does S. pseudintermedius bind to in the dog’s skin?
corneocytes, fibronectin & fibrinogen
Where are antimicrobial peptides stored in the keratinocyte? When are they released?
stored in lamellar bodies, released in the upper layers of the epidermis in the course of keratinization
Atopic-like dermatitis
inflammatory and pruritic skin disease with clinical features identifical to CAD but an IgE response cannot be documented with serology or IDAT
How can staphylococcal superantigens promote a hypersensitivty reaction?
SAGs can promote IgE production
IS the activity of anti-microbial peptides increased or decreased with staphyloccal skin infections?
decreased – staph can produce proteases that break down AMPs
T/F: Both gamma-IFN and IL-4 inhibit Th17 differentiation.
TRUE– but they stimulate Th1 and Th2 differentiation
What is the optimal micoclimate for domestic house dust and storage mites?
20-30ºC and 80-90% humidity
Besides inciting pruritus, what other role can histamine play in allergic disease?
recruitment of leukocytes, enhancement of secretion of proinflammatory cytokines (IL-1 and IL-6) and chemokines (RANTES and IL-8), promotes activation of dendritic cells
T/F: Canine and human AD have been associated with loss-of-function filaggrin mutations and altered filaggrin expression.
TRUE
What surface cell markers are displayed on Tregulatory cells involved in the pathogenesis of allergic disease?
CD4+, CD25+, Foxp3+: all suppress the Th2 response to allergens
What does omalizumab target?
the epitope on IgE that is bound by FceRI
