Hypersensitivity Disorders Flashcards
In atopic dermatitis, initially, the immune response is dominated by TH2 cells and involves which cytokines?
such as IL-4, IL-5, IL-6, IL-13, and IL-31.
In atopic dermatitis, Development of chronic inflammation, however, involves a mix of what T-cell mediators?
TH1, TH2, TH17, and TH22
In general, _____ cells protect against intracellular pathogens (eg, viruses) and participate in cancer surveillance. The _____ cells support antibody production and im-munoglobulin class switching. Also, ____ cells protect against multicellular parasites through their ability to activate the production of IgE and to activate eosinophils;
TH1
TH2
TH2
The _____ cells are critical for neutrophil effector function, and this cell subset is believed to protect against extracellular pathogens, particularly at epithelial surfaces.
TH17
The _____ cells promote and regulate tissue inflammation and repair; they are be- lieved to promote epithelial proliferation in the skin.
TH22
The most recent set of diag-nostic criteria for atopic dermatitis that have been developed include:
- Initial itching without lesions in young dogs (≤ 3 years old)
- An indoor lifestyle
- Affected feet and concave aspects of the pinnae.
- Initial responsiveness to glucocorticoid administration,
- Caudal region of the dorsum and ear margins are not affected.
Strong breed associations support a genetic ba- sis for atopic dermatitis in dogs, although the predi- lection varies among regions. Mean heritability in British guide dogs (Labrador Retrievers and Golden Retrievers) is ___, indicating that nearly ____ of the risk of developing atopic dermatitis is determined by an individual’s genotype
0.47
50%
What is TSLP?
Thymic stromal Lymphopoetin, a proinflammatory cytokine produced by keratinocytes. Other specific proteins that have been identified in humans with atopic der- matitis remain to be identified in dogs with atopic dermatitis.
Findings of 3 genomic studies in what breed suggests that the gene for filaggrin is not involved in development of atopic dermatitis, whereas the filaggrin gene is associated with atopic dermatitis in what breed?
West Highland White Terriers
Golden Retrievers.
To date, only the gene for the ______ appears to be involved in atopic dermatitis in dogs of all studied breeds
TSLP receptor
*** A change in the expression or affinity of the TSLP receptor might allow this proinflammatory cytokine to bind more tightly, thereby stimulating more inflammation.
What cytokine produced by keratinocytes following epidermal damage? It initiates TH2-cell responses and stimulates itching.
Thymic stromal lymphopoietin
Other genes potentially involved include a protein _______ that modulates T- and B-cell responses to an- tigens and plakophilin 2, a protein involved in epidermal adhesion.
tyrosine phosphatase
Staphylococci and Malassezia organisms can stimulate the release of pruritogenic and inflammatory cytokines from skin cells. Those microbes also produce conventional allergens that result in what three immunologic processes?
IgE-mediated mast cell degranulation
superantigen-induced clonal T-cell activation
protease-associated damage of the skin barrier.
Compared with healthy dogs, there is _____ biodiversity among the cutaneous microbiota with a notable _____ in the number of staphylococci in dogs with atopic dermatitis.
decreased
increase
*The proportion of staphylococci appears to correlate with disease severity
Acute itching and inflammation are associated with cytokines produced by which TH2 lymphocytes and by which cytokines known to promote the differentiation or activation of TH2 lymphocytes?
IL-4, IL-5, IL-10, IL-13, and IL-31
TSLP, IL-25, and IL-33
Increased allergen penetration of the skin facilitates uptake, processing, and presentation of the allergen as major histocompatibility complex class II peptides by _______ cells, which further promotes the TH2-cell response, thereby leading to a vicious cycle of inflammation and sensitization to multiple allergens.
Langerhan cells
In an experimental model of atopic dermatitis in dogs, removal of the stratum corneum by tape stripping enhanced expression of what surface molecules on Langerhans cells and promoted allergic sensitization?
major histocompatibility complex class II, CD86, CD40, CD54 (ICAM1), and CD11c
Self-trauma and damage of the skin barrier trigger the release of ______, which polarizes skin dendritic cells to stimulate a TH2-cell response.
epidermal TSLP
The proteolytic activity of house dust mite allergens is able to activate _____ and impair the skin barrier by reducing expression of stratum corneum adhesion proteins, such as corneodesmosin and claudin-1
PAR2
***The expression of tight junction proteins is also de- creased by PAR2, which results in further degradation of the skin barrier.
_______ is a ceramide precursor, and it is hypothesized (but not yet proven) that topical application increases ceramide concentration in the skin.
phytoshingosine
AD is extremely common in dogs, affecting between ______ of the canine population or up to ____ of dogs affected by skin diseases.
3% and 15%
58%
What receptor are found on smooth muscle, endothelium, and CNS tissue. Binding of this molecule causes vasodilatation, bronchoconstriction, bronchial smooth muscle contraction, separation of endothelial cells (responsible for hives), and pain and itching in response to an insect sting. The receptors of this molecule are the primary receptors involved in the clinical signs of allergic rhinitis and motion sickness.
H1 histamine
Studies showed that atopic dogs have a ____- dominated cytokine response in nonlesional atopic skin in which ____ is overexpressed. This cytokine is known to be a major regulatory factor in the production of IgE.
Th2
IL-4
Atopic dogs also have low mRNA expression of the immunosuppressive cytokine, ________, compared with clinically normal dogs
transforming growth factor-β
Atopic skin is more prone to be colonized by Staphylococcus spp, and this may occur because of a variety of factors, ranging from decreased anti- microbial peptides to increased adherence due to the overexpression of Th2 cytokines. Colonization can result in an increase in ____ and ____ from cutaneous T cells. This increase in ____ can induce the production of fibronectin, which can contribute to the adherence of Staphylococcus spp to keratinocytes.
IL-4 , IL-13
IL-4
What is the high–molecular weight D farinae allergen?
Der-f-15
What protein is produced by skin cells that degrades into amino acids during skin cell maturation and that is essential for maintaining moisture in the outer layers of intact skin.
filaggrin protein
Canine keratinocytes have already been shown to produce pro-inflammatory agents such as ____, _______ and ______ in response to allergen and bacterial components such as Der f1 and lipopolysaccharide, respectively
granulocyte macrophage colony-stimulating factor, IL-8, and tumor necrosis factor-α in response to allergen
Thymic stromal lymphopoietin is an _____ -like cytokine that stimulates dendritic cells to induce naïve T cells to differentiate into Th2-like cells.
IL-7
**In lesional skin of humans with AD, and it can stimulate naïve T cells to produce pro-allergic cytokines such as IL-4, IL-5, and IL-13
How do antimicrobial peptides acting as anti- microbial agents?
They kill a broad spectrum of microbes
Microbe resistance is essentially absent because their mechanism of action is via physical interaction with microbial membranes through their cationic charge and hydrophobic amino acids.
What is the relationship between vitamin D3 and antimicrobial peptides?
Vitamin D3 regulates cathelicidin expression in keratinocytes
Recently, human dermal dendritic cells have been shown to produce _____, a member of the IL-17 cytokine family. This cytokine induces the production of Th2-associated cytokines and reduces the production of filaggrin by keratinocytes. It also stimulates the production of IL-4.5. and 13.
IL-25
In AD, macrophages play a key role in the initiation, propagation, and resolution of inflammation and have great capacity to produce proinflammatory mediators such as ___, ____, ____ and ____as well as cytokines that aid in the resolution of inflammation (eg, transforming growth factor-β)
IL-1, IL-6, IL-18, and tumor necrosis factor-α
____ is a cytokine produced by Th1 cells in humans and appears to be involved in a variety of inflammatory processes in the skin, such as enhanced proliferation and function of natural killer cells, lymphocytes, and keratinocytes, differentiation of B-cells into plasma cells; differentiation of naïve T cells into T-helper type 17 cells and suppression of regulatory T-cell function.
IL-21
What molecule binds to a heterodimeric receptor consisting of the IL-31 receptor A and the oncostatin-M receptor β.128,129 These receptors are found on a variety of cells such as keratinocytes, macrophages, and eosinophils and participate in regulating immune responses in these cell types
IL-31
What helper T cells not only appear to play a role in protective immunity against extracellular pathogens but can also be potent inducers of tissue inflammation. These CD4+ T cells have been shown to produce cytokines such as IL-17, IL-22, and IL-25.
Th17
What cytokine appears to be expressed in acute lesions in AD but is largely absent in chronic AD lesions,
IL-17
What cytokine that is upregulated in chronic AD skin lesions and has been shown to downregulate genes involved in terminal differentiation of the skin, which could lead to epidermal hyperplasia.
IL-22
What cytokine plays an important role in driving Th2 polarization and has been shown to induce the production of IL-4, IL-5, and IL-13
IL-25
What is a serine protease that may play a key role in urticaria, inducing edema through an increase in vascular permeability, mast cell activation and degranulation, and production of the anaphylotoxin C5a.
Thrombin
_____ can be clinical assessed by measuring transepidermal water loss (TEWL).
Barrier function
True/False Total IgE levels are not significantly different between normal and atopic dogs.
True
It has been suggested that this lack of difference may be because dogs have very high levels of IgE compared to humans, possible due to parasite exposure.
Chronic AD changes show a predominance of macrophages and are associated with the presence of which cytokines?
Th1 cytokines
IL-2, iL-12, IFN and IL-18
Similar to what is found in atopic humans, there is an increase in the endothelial cell expression of _____ but not MHCII in atopic ogs.
ICAM1
Lesional skin from atopic dogs has relatively more ____ and gamma-delta T cells than human atopic. these obevations support the concept of percutaneous allergen activation of atopic disease and a similar pathogenesis in both dogs and humans.
CD8 cells
Dendritic cells expressing the molecule ____ have tolerogenic function at mucosal sites.
CD103
Natural T regs are characterized by the production of the cytokine ____ and expression of the transcription factor ___.
IL-10
Foxp3
Allergen specific B cells can not be fully activated until they receive co-stimulatory signals ____ and ____ from allergen specific Th2 cells that migrate from the paracortex into the follicles to permit this interaction
IL4, IL13
Allergen specific IgE (and to the lesser extent the IgG subclasses) circulates in the bloodstream and engages with ____ receptors on the surface of circulating basophils and mast cells
Fce
