Hypersensitivity Disorders Flashcards
1
Q
In atopic dermatitis, initially, the immune response is dominated by TH2 cells and involves which cytokines?
A
such as IL-4, IL-5, IL-6, IL-13, and IL-31.
2
Q
In atopic dermatitis, Development of chronic inflammation, however, involves a mix of what T-cell mediators?
A
TH1, TH2, TH17, and TH22
3
Q
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;
A
TH1
TH2
TH2
4
Q
The _____ cells are critical for neutrophil effector function, and this cell subset is believed to protect against extracellular pathogens, particularly at epithelial surfaces.
A
TH17
5
Q
The _____ cells promote and regulate tissue inflammation and repair; they are be- lieved to promote epithelial proliferation in the skin.
A
TH22
6
Q
The most recent set of diag-nostic criteria for atopic dermatitis that have been developed include:
A
- 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.
7
Q
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
A
0.47
50%
8
Q
What is TSLP?
A
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.
9
Q
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?
A
West Highland White Terriers
Golden Retrievers.
10
Q
To date, only the gene for the ______ appears to be involved in atopic dermatitis in dogs of all studied breeds
A
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.
11
Q
What cytokine produced by keratinocytes following epidermal damage? It initiates TH2-cell responses and stimulates itching.
A
Thymic stromal lymphopoietin
12
Q
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.
A
tyrosine phosphatase
13
Q
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?
A
IgE-mediated mast cell degranulation
superantigen-induced clonal T-cell activation
protease-associated damage of the skin barrier.
14
Q
Compared with healthy dogs, there is _____ biodiversity among the cutaneous microbiota with a notable _____ in the number of staphylococci in dogs with atopic dermatitis.
A
decreased
increase
*The proportion of staphylococci appears to correlate with disease severity
15
Q
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?
A
IL-4, IL-5, IL-10, IL-13, and IL-31
TSLP, IL-25, and IL-33
16
Q
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.
A
Langerhan cells
17
Q
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?
A
major histocompatibility complex class II, CD86, CD40, CD54 (ICAM1), and CD11c
18
Q
Self-trauma and damage of the skin barrier trigger the release of ______, which polarizes skin dendritic cells to stimulate a TH2-cell response.
A
epidermal TSLP
19
Q
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
A
PAR2
***The expression of tight junction proteins is also de- creased by PAR2, which results in further degradation of the skin barrier.
20
Q
_______ is a ceramide precursor, and it is hypothesized (but not yet proven) that topical application increases ceramide concentration in the skin.
A
phytoshingosine
21
Q
AD is extremely common in dogs, affecting between ______ of the canine population or up to ____ of dogs affected by skin diseases.
A
3% and 15%
58%
22
Q
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.
A
H1 histamine
23
Q
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.
A
Th2
IL-4
24
Q
Atopic dogs also have low mRNA expression of the immunosuppressive cytokine, ________, compared with clinically normal dogs
A
transforming growth factor-β
25
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
26
What is the high–molecular weight D farinae allergen?
Der-f-15
27
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
28
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
29
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
30
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.
31
What is the relationship between vitamin D3 and antimicrobial peptides?
Vitamin D3 regulates cathelicidin expression in keratinocytes
32
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
33
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
34
____ 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
35
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
36
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
37
What cytokine appears to be expressed in acute lesions in AD but is largely absent in chronic AD lesions,
IL-17
38
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
39
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
40
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
41
_____ can be clinical assessed by measuring transepidermal water loss (TEWL).
Barrier function
42
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.
43
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
44
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
45
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
46
Dendritic cells expressing the molecule ____ have tolerogenic function at mucosal sites.
CD103
47
Natural T regs are characterized by the production of the cytokine ____ and expression of the transcription factor ___.
IL-10
| Foxp3
48
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
49
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
50
The clinical manifestation of allergy becomes apparent on the next occasion that the sensitized individual is exposed to the same allergen. At this time, allergen that pentrates the epithelial barrier encounters what cell?
IgE-coated mast cells
51
True/False: Strength of IgE affinity for an allergen, rather than the concentration of allergen-specfic IgE measured (regardless of affinity), can be useful in more accurate identification of trigger allergens may be an important consideration for improvement serologic testing in AD and in establishing a prognosis in allergic diseases
True
52
What are the two principle receptors, both membrane bound and soluble forms, responsible for the interactions between IgE and effector cells?
They are the high affinity Fc epsilon receptor and the so called low affinity IgE receptor (CD23)
53
It is likely that the proposed role of FcERI bearing ____ is a highly potent antigen presenter to T cells and source of cytokines driving the Th2 response
dendritic cell
54
IgE is bound by the ____ of the high affinity receptor that is present in cell surface tetrameric FcERI on mast cells and basophils, and in trimeric FcERI (lacking beta chain) present on eosinophils, antigen resenting cells sch as dendritic cells and Langerhans cells, and on epithelial cells
alpha chain
55
Human anti-IgE IgG antibodies have been shown mainly of the ____ subclass and recognize most often an epitope on the IgE episilon chain, which include amino acids 341-353 and thus may inhibit IgE binding to FceRI.
IgG1
56
Epidermal langerhans cells express a ____ receptor for IgE which allows Langerhans cells to carry out Fc receptor mediated uptake of allergens.
high-affinity
57
Th17 cells differentiate under a specific cytokine environment. A major factor in the development of Th17 cells is IL-___ which is predominantly secreted by dendritic cells, monocytes and macrophages and maintains IL-17 producing T-cells.
23
58
Th-17 cells serve a very important function in antimicrobial immunity at epithelial and mucosal barriers. These cells also secrete ___ and ___ which stimulate epithelial cells to produce antimicrobial proteins.
IL-21 and IL-22
* IL-22 belongs to the IL-10 family and binds to a receptor hat is shared with IL-10.
* The receptor for IL-22 is present on keratinocytes
* TH22 cells play a role in chronic skin diseases such as psoriasis and AD by promoting the synthesis of proinflammatory cytokines.
59
IL-22 is a cytokine expressed not only by Th17 cells but also by NK cells and a subset of T cells that express IL-22 independently of IL-17. These T cells are called Th22 cells and are under the control of what cells?
Langerhans cells
60
Describe T-regs
* Tregs, previously called supressor T cells, are a subpopulation of T cells which modulate the immune system maintaining tolerance to self-antigen and abrogating autoimmune dusase.
* Tregs may be present in different forms but the ones expressing CD4, CD25 and Foxp3 have been the most studied.
61
In ketatinocytes, antimicrobial peptides are stored in _____ and released during keratinization.
lamellar bodies
62
The most commonly involved tree pollen in Europe is what?
Birch
63
Ragweed (Ambrosia) and Artemisia are the main members if the _____ family
Composacea
Ragweed is an invasive weed which produces a very allergenic pollen.
Signs usually develop late summer and Autumn.
64
What are the three major D. Farinae allergens in dogs?
The major Df allergens in dogs worldwide are Der F 15, Der f 18 and Zen I, as 80-90% of dogs sensitized to Df extracts recognize these fractions.
Derf 2 allergen seems to be a major allergen in Japan and not in the USA.
65
Pollens can also act directly on the immune system through release of what compound that displays Th2 polarizing capacities (in vivo). These are one of the arguments for frequency bathing.
water-soluable phytoprostanes
66
Beside increased IgE levels, most human patients with AD do have higher allergen-specific IgG4 compared to healthy individuals and specific IgG1 can be elevated as well
* Hill et al. (1995) showed that total IgG concentrations were significantly higher in atopic dogs compared to healthy controls.
* Fraser et al. (2004) have recently shown that concentrations of total IgG1 are higher in atopic dogs than in healthy dogs, suggesting that the atopic state also leads to activation of IgG subclass production in addition to IgE.
* Fraser et al. (2004) have shown that concentrations of total IgG1 can increase following allergen-specific immunotherapy.
67
Oral tolerance develops with repeated low-dose exposure to antigen and is mediated by what regulatory T cells?
CD8 cells, Th3 cells, Tr1 cells, CD4 CD25 cells and NK1.
o These cells migrate to the local lymph nodes and stimulate the production of suppressive cytokines such as IL-10 amd TGF-b.
o High-dose antigen exposure can also induce tolerance if T-cell receptors engage in the absence of co-stimulation.
68
Gastrointestinal immune function may vary with age, ____, a marker for T regulatory cell expression, was found to be reduced in juvenile and older animals when compared with healthy middle aged dogs.
FoxP3
69
What breed has been reported to have a dietary hypersensitivity to gluten?
Irish setters
70
The protein sources most often to be suitable based on the previous dietary history include
lamb, venison, duck, rabbit, kangaroo, and ostrich
71
What are the four criteria of food hypersensitivity?
o Resolution or improvement of clinical signs on an elimination diet
o Relapse on subsequent challenge with the original diet
o Resolution on re-introduction of elimination diet
o Demonstration of an immunological basis for the adverse response
72
What nutients are most commonly deficient when feed home cooked diet?
calcium, phosphors, protein thiamine, taurine and vitamins E, A and D.
73
What are the most common nutrients that are fed in excess during diet trials?
vitamin A and D
74
Ensuring that a hydrolysate that has no peptides greater than _____ would give the greatest chance of eliminating any residual allergens
1kDa
75
In addition to alterations in ceramide production in the dermis, atopic dogs appear to have altered fatty acid metabolism, presumably in the liver. Atopic dogs appear to have reduced _________ activity, suggesting the impaired ability to produce long-chain desaturated fatty acids.
fatty acid desaturase
76
What is the major flea allergen?
Ctef1, with a molecular weight of 18k was identified, cloned and characterized. The recombinant allergen was recognized by 100% of the sera from sensitized dogs; but, only 80% of client owned dogs
77
Describe the immunopathogensis of FAD
* FAD involved both immediate (IgE) and delayed (cell-mediated) hypersensitivity. In response to flea bites or an IDT, most allergic animals react with clearly demarcated erythematous wheals within 15 minutes.
* The presence of immediate hypersensitivity should be demonstrable by both IDT and serology.
* Most emphasis is usually placed on the role of IgE as this is more readily quantified, but in one extensive survey of flea allergic dogs, 33% showed delayed reactions only.
78
Describe the histopathology of FAD
• There is generally mild to moderate superficial edema accompanied by a perivascular dermatitis comprising mast cells, eosinophils and mononuclear cells,
• Intraepidermal eosinophilic pustules may be seen
• The sequential pathological changes:
o Dogs that showed both strong immediate and delayed reactions were chosen for the study and biopsies were performed 2,4,24 and 48 hours.
Edematous reaction manifested by separation of collagen fibers was evident and peaked at 15 minutes and waned past 48 hours.
Eosinophils were the predominant cell type up to 4 hours.
Mononuclear cells were present starting at 4 hours and peaked at 24.
Neutrophils were present throughout.
Mast cells were present after 15 minutes.
79
What cells are increasingly recognized as being a major important in FAD. in FAD, these cells can be subdivided according to their protease content. Those that contain: typtase, chymase or both.
Mast cells
***When sensitized dogs were exposed to fleas, there was a significant increase in the proportion of chymase-staining cells and a concomitant decrease in the number of typtase-staining cells.
80
What cell are not routinely observed in skin biopsies following formalin fixation and H and E staining. Special preservatives are needed.
Basophils
81
Wuersch et al examined mRNA for a range of cytokines in flea-allergic and normal dogs, using skin biopsies and peripheral blood mononuclear cells when the response of the PBMC to flea antigen was examined, mRNA production of what cytokines was significantly increased in the allergic group prior to flea exposure when compared to the controls?
IL-4, IL-5 and IL-13
82
What test is a research tool used as the gold standard for determining the diagnostic value of various assays, including ELISA and intradermal testing?
The life flea challenge test
83
What is the recommended concentration for testing with whole body flea extract?
1/1000 w/v
This concentration is non-irritating to the majority of normal dogs but will still produce a strong response in the majority of confirmed flea-allergic dogs.
84
Flea adulticides
* The modern monthly residual flea adulticides have enhanced our flea control efforts primarily because of their prolonged residual activity and more rapid residual speed of kill, thus having a much greater impact on continue flea reproduction.
* The development of the modern monthly neurotoxic residual flea adulticides such as dinotefuran, fipronil, imidacloprid, indoxacarb, metaflymizone, pyriprole, selamectin, and spinosad has dramatically changed the way flea control is conducted
85
An effective integrated program should involve:
o Education of the veterinary staff and pet owners on the biology of fleas infesting pets
o Implementation of mechanical control measures
o Application of insect growth regulatory
o Administration of flea adulticides
86
Insect growth regulators
* Incorporation of topical or systemic IGR in a flea control program provides for potent ovidicial activity.
* These compounds can generally be grouped into either juvenile hormone analogues, which block development to adults, such as a Methoprene or pyriproxyfen or chitin synthesis inhibitors such as lufenuron.
* Systemic IGR are effective in preventing fleas from laying viable eggs. When a single oral dose of lufenuron was administered to dogs, it almost completely inhibited all eggs and larvae from developing into adult fleas for 1 month following administration.
87
Regarding fleas, what are important points for client education?
* Flea counts can escalate in the fall
* Treat every single pet
* Humidifiers help sustain flea infestations
* Set owner expectations
88
What is the predominant bacterial pathogen in canine skin infection
Staphylococcus pseudintermedius
o It has been isolated from 90% of superficial pyoderma cases and up to 60% of deep pyoderma cases.
o Lab recognition of S. pseudintermedius for diagnostic purposes is mainly based on identification of white circular colonies with a characteristic double zone of hemolysis on sheep blood agar.
Gram positive staining, positive reactions for coagulase, catalase and mannitol fermentation.
89
Contact allergy is caused by an aberrant repines to small molecules called _______?
Haptens
Haptens are too small to be allergenic on their own and need to be conjugated with other proteins in order to elicit an immunologic response.
Causes of contact allergy have included topical antibiotics (neomycin), propylene glycol, shampoos, flea products, carpets, metals and plants.
Commelineceae family have been reported to cause immediate reactions in dogs.
90
Contact allergy is mediated by activation of ______ T cells specific for haptens in contact with the skin,
CD8 cytotoxic
91
In contact allergy, what inflammatory molecule is rapidly released from Langerhans cells and keratinocytes after hapten exposure and stimulated the expression of E selectin and VCAM1 on endothelial cells, facilitating the movement of T cells?
TNFA
92
Several regulatory CD4T cell subsets, _______, are involved in immunological tolerance and regulation to haptens through the production of immunosuppressive cytokines IL10 and TGFbeta.
CD4CD25 natural Tregs cells
93
Venomous insect hypersensitivity
* There are various types of stinging insects that can elicit a hypersensitivity reaction.
* Hymenoptera are an order of insect class that includes bees, wasps, hornets, yellow jackers and fire ants.
* Hymenoptera sp. Are the most fatal group from the animal kingdom to cause death in humans.
94
There are different classifications grades for systemic anaphylactic reactions and most use a I-IV grading scale
Grade I involves generalized skin symptoms of urticaria, pruritus, angioedema and flushing.
Grade II additionally includes pulmonary, cardiovascular and/or gastrointestinal symptoms such as vomiting, diarrhea, dizziness and or chest construction.
Grade II additionally includes dyspnea, wheezing, weakness, confusion, or loss of consciousness.
Grade IV includes fall in blood pressure, collapse, cardiac arrest and/or apnea.
o Angioedema is the most common presentation in dog.
95
The major components of venom from honeybee, wasps, hornets and yellow jacks are primarily carious types of ______?
glycoproteins
96
Venom from honeybees contains what components?
ellitin, phospholipase A, hyaluronidase, biogenic amines, acid phosphatease, apamin and mast cell degranulating peptides.
97
Mellitin
is a major protein component of venom.
It hydrolyzes cell membranes thus altering their permeability. It is thought to be responsible for the pain associated with the sting and for histamine and catecholamine release.
98
What are the main enzymes of bee venom and are believed to be the major allergens triggering anaphylaxis?
Hyaluronidase and PLAs
99
Hyaluronidase in venom
causes hydrolysis of the hyaluronic acid thus disrupting the dermal connective tissue matrix and allowing the venom to disperse in the tissue.
100
Mast cell degranulating peptide
peptide (peptide 401) is a protein found in both bee and wasp venom and is the major cause of NON-IgE mediated histamine release following stings from these insects.
101
Thaumetropoeine
which is present in the hairs of processionary caterpillars, is also a mast cell degranulating agent.
102
Urticatia pigmentosa
Different than classical urticaria, is a form of cutaneous mastocytosis in which excessive proliferation of mast cells occurs due to mutations in c-kit.
o Urticaria pigmentosa is recognized in Devon Rex and sphynx cats, which have increase numbers of dermal mast cells identified on histopathology, although it is currently not clear is this represents a specific entity or a reaction pattern associated with allergic skin disease.
In 2019, it was reported in DSH cat by Pieper and Lara!
103
What is the Prausnitz Kustner test?
is an immunologic test formerly used by physicians to determine if a patient has an allergic reaction to a specific antigen. The test has been replaced by the safer skin prick test.
The PK test involves transferring serum from the test subject to another healthy person, essentially using the second person as a mixing vessel for antibodies and antigen.
104
RANTES
is a chemokine produced by many cell types and induced chemotaxis and activation of eosinophils, also memory T cells and monocytes.
105
TARC
induced its own production in keratinocytes and stimulates a Th2 dominated inflammatory reaction.
106
In cats with eosinophilic plaques increased ______ and _____ expression was described.
RANTES
| TARC
107
What do feline eosinophils contain?
major basic protein, and granule proteins have peroxidase, ribonuclease and bactericidal activities.
108
What is the different in protease content between healthy and FAD cats?
Changes in protease content of mast cell granules in lesional and non-lesional skin are found, indicated a generalized effect of mast cells in FAD.
o In FAD cats, a significantly lower number of mast cells was observed with typtase staining compared to staining for chymase and Astra blue staining.
o In healthy cat skin, all mast cells stained positive for typtase and around 90% stained positive for chymase.
109
It is considered that the staphylococcal group ______ and ______, both coagulase negative species with similar biochemical properties, has a resident status, being isolated form skin and mucosal sites in both healthy and diseased cats
S.felis and S.Simulans,
S. pseudinmedius and S. Aureus are coagulase positive species most often isolated form healthy cats and from cats with skin lesions.
110
What is the immunopathogenesis of feline asthma?
o Aeroallergens are taken up by APC that sample antigens from the airway lumen. Allergens are then processed and presented in conjunction with MHCII to naïve T helper cells in them mucosal inductive sites below the epithelial surface.
o A polarized TH2-mediated immune response results in production of cytokines, which orchestrate the allergic inflammatory response.
o Key cytokines include IL5 (eosinophil maturation, differentiation, and survival and IL4, 6, and 13 which allow B cells to undergo a class switch and terminally differentiate into IgE secreting plasma cells,
Allergen specific IgE is bound to the high affinity FCeRI receptors on mast cells and basophils, which upon re-exposure to allergen leads to degranulation and further exacerbation of the inflammatory cascade.
Chronically, the cat develops features of asthma: eosinophilic airway inflammation, airway hyper-responsiveness/airflow obstruction and airway remodeling.
111
Imidicloprid
High affinity for the nicotinergic acetylcholine receptors in the post-synaptic region of the CNS in insects. Inhibition of cholinergic transmission in insects’ results in paralysis and death of the parasite.
It is effective against adult fleas, requiring 8 hours of contact. It also has, in common with most insecticidal products, a larvicidal effect.
112
Nitenpyram
is a fast-acting, orally administered flea treatment. Like imidacloprid, it acts on the nicotinic acetylcholine receptor channel.
It is readily absorbed with peak plasma levels reached within 20 minutes and half-life of about 8 hours.
113
Dinotefuran
is a third generation neonicotinoid; it was synthesized with acetylcholine as the lead compound whereas imidacloprid as based on nicotine.
It is also a fast-killing insecticide, effective for 20 days following application.
It is available for cats as a spot on combined with pyriproxyfen (Vectra)
In dogs it is also combined with permethrin (Vectra)
114
Phenylpyrazol
block GABA-gated chloride channels of neurons in the central nervous system, sharing a common binding site with cyclodienes.
• Fipronil
115
Avermectins
• Selamectin is believed to bind to glutamate-gated chloride channels in the parasites’ nervous system, increasing permeability and allowing th rapid and continued influx of chloride ions into the nerve cells.
o This inhibits nerve activity thereby causing paralysis.
• Topical application was over 98% effective after 24 hours in cats.
• Activity against internal and external parasites.
116
Metaflumizone
• Metaflumizone is derived form pyrazoline and acts by binding the voltage-dependent sodium channels in insects.
117
Spinosad
* Spinosad is an aerobic fermentation product of the soil bacterium, Saccharopilyspora spinosa. Spinosad kill insects through activation of the acetylcholine nervous system through nicotinic receptors.
* A chewable tablet is indicated for the treatment and prevention of flea infestations cause by C. felis.
* It is excellent efficacy against flea and its rapid killing effect that is observed in dogs are also reported in ats.
118
Oxadiazine
* Indoxacarb is a novel oxadiazine insecticide which has food field activity against a number of pests including Leptidoptera, as well as certain Homoptera and Coleoptera.
* Its main mode of action is via blocking of sodium nerve channels.
* Following application, indoxacarb is taken up by flea where it is converted into a highly active metabolite. This metabolite causes flea to stop feeding and they die within hours. Mammals mainly convert indoxacarb into non-toxic metabolites so they are not exposed to the active insecticide.
119
Juvenile hormone analogues
* The pharmacological properties of juvenile hormone analogues are characterized by mimicking the juvenile hormones of insects resulting in interference with metamorphosis and reproduction.
* Prevention of larval development breaks the flea life cycle. Due to the specificity of juvenile hormone for insects, pyriproxyfen has virtually no effects on mammals.
120
Insect developmental inhibitors
* Lufenuron is a systemic insect developmental inhibitor which interferes with chitin synthesis, polymerization and deposition.
* Lufenuron has not affect on adult fleas.
* Excreted in flea faces, it prevents normal pupation of larvae feeding on those flea feces.
121
Mosquito bite exposure with what species on lesional and unaffected skin in allergic cats showed wheals within 20 minutes.
Aedes albopictus
In general, Aedes spp. are active during the daytime while house mosquitoes, including Culex and Anopheles spp are active during the night time.
122
The combination of the haplotypes ___ and ____ was found to be present more frequently in atopic versus healthy dogs
DLA-A3, R15
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What is the role of endotoxins and developing of canine AD?
he suggested protective effect of endotoxins may be explained by their immunoregulatory capabilities. Exposure to Gram-nega- tive bacteria as a source of endotoxins, especially during early childhood, will augment the stimulation of helper T cells type 1 (Th1). These Th1 cells will in turn inhibit the generation of helper T cells type 2 (Th2), which play an important role in the develop- ment of allergic diseases (Gereda et al., 2000). Besides the classical Th1–Th2 balance, regulatory T cells are also stimulated by endo- toxin exposure and may suppress the allergic inflammatory reac- tion
