Atopy and Hypersensitivity 18% Flashcards
1
Q
What are 5 proposed mechanisms of action of allergen specific immunotherapy?
A
Effects can be “allergen specific” and “nonspecific”
1) Reduction in effector cell (mast cell, basophil, eosinophil) activity
2) Suppression of helper T-cell responses and long-term immunologic shift from a Th2 to a Th1-biased response
3) Increase in T-regulatory cells and in cytokines including TGF-beta and IL-10
4) Decrease in allergen-specific IgE by effector B-cells
5) Increase in in allergen-specific IgG
2
Q
How is the immunologic response between SCIT and SLIT differ?
A
- Mucosal area under the tongue is a privileged immunologic site
- High concentration of dendritic cells and T-cells and low concentration of mast cells, basophils and eosinophils
- presence of oromucosal dendritic cells, which are very proficient at inducing tolerance.
3
Q
What is the primary immunologic mechanisms behind urticaria and angioedema
A
Type I hypersensitivity involving degranulating mast cells and basophils as well as a type III hypersensitivity reaction
- Can be caused by vaccines, drugs, foods, stinging and biting insects
4
Q
What are some non-immunologic causes of urticaria and angioedema?
A
- Pressure, sunlight, heat, cold, exercise, stress, various chemicals, activation of the coagulation cascade
- Thrombin 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 anaphylotoxin C5a.
5
Q
Whats is the definition of a) atopic dermatitis and b) atopic-like dermatitis?
A
a) a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE most commonly directed against environmental allergens
b) an inflammatory and pruritic skin disease with clinical features identical to those seen in canine atopic dermatitis in which an IgE response to environmental or other allergens can not be documented.
6
Q
List 3 possible causes for diagnosing an animal with atopic-like dermatitis?
A
1) IgE’s may not be necessary for manifestation of the disease and an alternative mechanism of disease may lead to dermatitis that is clinically indistinguishable from classic AD
2) The wrong allergens were selected for the test
3) Cases may represent early cases of classic AD in which development of clinical signs precedes detection of allergen specific IgE
7
Q
What is the hygiene hypothesis?
A
Decreased exposure to bacteria and parasites, in conjunction with increased practices of excessive bathing and use of antibacterial detergents that could harshly affect the barrier function of the skin, may be responsible for the increased occurrence of AD.
- There may be a protective effect of high indoor endotoxin exposure on the development of the condition.
8
Q
What are the two loss of function mutations of filaggrin in humans that predispose to atopic dermatitis?
A
- R501x and 2282derL4
9
Q
Whats it the biphasic pattern of cytokine release in
A
- acute skin lesions are characterized by CD4+ Th2 lymphocytes and eosinophils that release IL-4 and IL-13; these cytokines play an important role in the development of high levels of IgE and lead to increased survival and maturation of eosinophils
- Chronic lesions show a predominance of macrophages and associated with Th1 cytokines (IL-2, IL-12, IFN-gamma, IL-18)
10
Q
What chemokine have been associated with atopic dermatitis?
A
- Chemokines are key regulators of selective leukocyte migration
- Increased expression of the following chemokines has been associated with AD:
1) RANTES (regulated on activation, normal T-cell expressed and secreted)
2) Eaton
3) Monocyte chemoattactant protein -4 (i.e. MCP-4)
4) Macrophage-derived chemokine (i.e. MDC); a ligand for CCR4
5) Thymus and activation regulated chemokine (TARC); a ligand for CCR4 - TARC levels correlated with disease severity in humans and considered a marker of disease
- Chemotaxis of cells expressing CCR4 is induced by TARC, resulting in selective migration of Th2 cells into lesional skin of human AD.
- TARC mRNA and the gene encoding for CCR4 are selectively expressed in lesional skin of atopic dogs but not in nonlesional atopic skin or normal skin.
11
Q
What chemokine receptors do Th1 and Th2 cells predominately express?
A
Th1: CCR5, CXCR3
Th2: CCR3, CCR4, CCR8
12
Q
What supports the percutaneous allergen activation of atopic disease in dogs?
A
- In clinically normal Atopic skin, there is an increased number of Langerhans cells
- There is increased expression of endothelial cell expression of ICAM-1 but not MHC II in atopic dogs
- There are increased number of T cells in lesional skin of atopic dogs with an increase in CD4:CD8 T cell ratio and increased numbers of alpha beta T cells
- In lesional skin from atopic dogs, there are relatively more CD8+ cells and gamma delta T cells than human atopics
13
Q
What is the role of Staphylococcal super antigens in atopic dermatitis?
A
- The role of super antigens in epithelial presentation of allergen to Th2 cells
- Promotion of Th2 inflammation
- IgE production
- T-regulatory cell subversion
- Expansion and migration of skin-homing T cells
- Modulation of chemokines
- IgE anti-superantigen production
14
Q
What are criteria for being considered a “probiotic”? What immunologic benefit may probiotics provide?
A
- ability to resist acid and bile
- ability to adhere to intestinal epithelial cells and persist in the digestive tract for long enough to produce antimicrobial agents and modulate immune responses
- Resist technological processing
- Improvemebt with AD severity and probiotic treatment may be associated with significant increases in the capacity for Th1 IFN-gamma responses and altered responses to skin and enteric flora
15
Q
What breeds of dog are pre-disposed to developing canine atopic dermatitis?
A
- Beauceron
- Boston terrier
- Boxer
- Cairn terrier
- Chinese Shar-Pei
- Cocker spaniel
- Dalmation
- English bulldog
- English setter
- Fox terrier
- Irish setter
- Labrador retriever
- Labrit
- Lhasa apso
- Miniature schnauzer
- Pug
- Scottish terrier
- Seakyham terrier
- West highland white terrier
- Wire-haired fox terrier
- Yorkeshire terrier
16
Q
What is the primary eruption of canine atopic dermatitis?
A
- Some have described there is no primary eruption, just pruritus; others have described macular erythema, plaques, and papules
- Erythema is the most commonly noted clinical sign
- Papules smaller than what is seen in pyoderma and contact allergy
17
Q
What are Favrot’s nine criteria for diagnosing canine atopic dermatitis?
A
1) Age of onset <3 years old
2) Mostly indoors
3) Corticosteroid-responsive pruritus
4) Chronic or recurrent yeast infections
5) Affected front feet
6) Affected pinnae
7) Non-affected ear margins
8) Non-affected dorso-lumbar region
9) Pruritus with no visible lesions at onset
18
Q
What is Euroglyphus maynei?
A
A species of house dust mite this is reported to be very common in houses in England
19
Q
What is Blomia tropicalis?
A
it is a glyciphagig house dust mite found in tropical and subtropical climates; dominant house dust species in Brazil.
20
Q
What are 8 factors that could lead to a false negative intradermal test result?
A
1) Subcutaneous injections
2) Too little allergen (testing with mixes, outdated allergens, allergens too dilute, too small volume injected)
3) Drug interference (glucocorticoids, antihistamines, tranquilizers, progestational compounds, any drugs that lower blood pressure)
4) Anergy (testing during peak of hypersensitivity reaction)
5) Inherent host factors (stress, estrus, pseudopregnancy)
6) Endoparasitism or ectoparasitism?
7) Off-season testing (testing more than 1 - 2 months after clinical signs have disappeared)
8) Histamine hyporeactivity
21
Q
What are 8 causes that could lead to a false positive intradermal test result?
A
1) Irritant test allergens (especially those containing glycerin)
2) Contaminated test allergens (bacteria, fungi)
3) Skin-sensitizing antibody only (prior clinical or present subclinical sensitivity)
4) Poor technique (traumatic placement of needle)
5) Substances that cause nonimmunologic histamine release
6) Irritable skin
7) Dermatographism
8) Mitogenic allergen
22
Q
How long should corticosteroids be withdrawn prior to allergy testing?
How long should antihistamines be withdrawn prior to intradermal allergy testing?
A
- 3 weeks for oral glucocorticoids
- 8 weeks for injectable glucocorticoids
- 2 weeks for topical glucocorticoids
- 14 days for antihistamines
23
Q
What sedatives and anaesthetics do NOT affect intradermal skin test responses?
A
- Xylazine hydrochloride
- Medetomidine
- Tiletamine/zolazepam
- Thiamylal
- Halothane
- Isoflurane
- Methoxyflurane
24
Q
What sedatives and anaesthetics can adversely affect skin test reactivity?
A
- Oxymorphone
- Ketamine/diazepam
- Acepromazine
- Propofol
25
What are the commonly tested concentrations for allergens?
- 1000 PNU/ml for pollens and molds
- 1/50,000 w/v for house dust mites
- 1000 PNU/ml for insects
- 250 - 500 PNU/ml for wool or feathers
- 1: 10,000 w/v histamine
26
What are 5 advantages of serologic ELISA testing over intradermal testing?
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27
What are 5 advantages of serologic ELISA testing over intradermal testing?
1) No patient risk (no need to sedate, no risk of anaphylactic reactions)
2) Convenience (no need to clip or chemically restrain)
3) Lower likelihood that results will be influenced by prior drug therapy
4) Ability to use in a patient with widespread dermatitis or dermatographism
5) Similar results of hyposensitization therapy in carefully clinically diagnosed atopic dogs
28
What are the histologic features of acute and chronic atopic dermatitis?
- Acute AD lesions: spongiotic dermatitis with eosinophilic exocytosis; superficial perivascular dermatitis with lymphocytic exocytosis; increased numbers of CD4+ and CD8+ T cells; increased numbers of epidermal langerhans cell counts
- Late phase responses: neutrophils and activated eosinophils; influx of alpha beta T lymphocytes and dermal dendritic cells observed in later stages
- Mononuclear cells increase significantly at 6 hours and are predominant cell type at 24 hours after allergen exposure
- Accumulation of CD1c+ dendritic cells noted in lesional atopic skin.
29
What are the histologic features of acute and chronic atopic dermatitis?
- Acute AD lesions: spongiotic dermatitis with eosinophilic exocytosis; superficial perivascular dermatitis with lymphocytic exocytosis; increased numbers of CD4+ and CD8+ T cells; increased numbers of epidermal langerhans cell counts
- Late phase responses: neutrophils and activated eosinophils; influx of alpha beta T lymphocytes and dermal dendritic cells observed in later stages
- Mononuclear cells increase significantly at 6 hours and are predominant cell type at 24 hours after allergen exposure
- Accumulation of CD1c+ dendritic cells noted in lesional atopic skin.
30
Threshold of pruritus
Presence of a multitude of stimuli (i.e. bacteria, yeast_ that might contribute to the level of itch of the individual patient
- any individual is able to tolerate some pruritic stimulus without becoming clinical; after threshold is exceeded, clinical manifestation of pruritus ensures.
- Pruritic threshold is variable among individuals and may be lowered by stress and environmental factors
31
Threshold of pruritus
Presence of a multitude of stimuli (i.e. bacteria, yeast_ that might contribute to the level of itch of the individual patient
- any individual is able to tolerate some pruritic stimulus without becoming clinical; after threshold is exceeded, clinical manifestation of pruritus ensures.
- Pruritic threshold is variable among individuals and may be lowered by stress and environmental factors
32
What are the three main grass families (which do not cross-react very well with one another)?
- Eragrostoideae (Bermuda grass)
- Festucoideae (common northern pasture grasses)
- Panicoideae (Johnson and Bahia)
33
What are the histologic features of feline allergic dermatitis?
- Infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells
- This pattern mimics the dermal inflammation that occurs in the chronic phase of canine and human AD
34
What sedatives are oftentimes used to perform intradermal skin tests in cats?
- Diazepam and ketamine
- Ketamine
- Zolazepam/Tiletamine
- General gas anesthetic
35
How are feline intradermal skin tests different than dogS?
- Feline skin is thin so you need to take extra care to ensure that the injections are intradermal and not subcutaneous.
- Test site should be examined as early as 5 minutes post infection because feline reactions sometimes occur and fade rapidly
- Reactions, including those to histamine, are often much subtler with less erythema and turgidity than those in dogs
- Without sedation, cats produce a marked increase in the concentration of plasma cortisol, corticotropin and alpha-melanocyte stimulating hormone which may suppress wheal formation.
36
What are histologic features of feline atopic dermatitis?
- Infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells
- Clinically non-inflammatory alopecia: normal to slightly hyper plastic epidermis with mild superficial perivascular dermatitis where lymphocytes or mast cells predominate
- Inflammatory lesions: epidermal hyperplasia, spongiosis. serocellular crusts, erosions/ulcerations, variable degrees of superficial or deep perivascular dermatitis wherein eosinophils are usually the dominant inflammatory cell
37
Contact hypersensitivity
- a type IV hypersensitivity reaction
- Immunologic reactions to haptens (small, chemically reactive, lipid-soluble molecule)
- A cell-mediated response also referred to as hasten-type delayed hypersensitivity
- Epidermal langerhans cells play a key role in the sensitization phase which capture and process haptens and migrate the local draining lymph nodes and present the antigens in the paracortical region to T cells.
- Emigration from skin to lymph node may be initiated by TNF-alpha
38
Hapten sensitization induces which two populations of hasten-reactive T cells?
- CD8+ T cells producing IFN-Y which mediate the response
| - CD4+ T cells producing IL-4 and IL-10 which function to limit the magnitude and the duration of the response
39
Which cell-types play a major role in the a) sensitization phase and b) elicitation phase of allergic contact dermatitis?
A) Langerhans cells
| B) activated memory T cells
40
Memory T cells are recruited to the site of happen exposure in allergic contact dermatitis why expression of which adhesion molecules on the vascular endothelium?
- VCAM-1; stimulated by release of TNF-alpha
- E-selectin; stimulated by release of TNF-alpha
- ICAM-1
41
What cytokines are primarily involved in allergic contact dermatitis?
- TNF-alpha
- IL-6
- MIP
- IFN-gamma, IL-1, IL-12
42
What is the receptor for the followings chemokine ligands:
a) CCL2
b) IP-10, Mig, IP-9, ICAM-1, HLA-DR
A) CCR10; important during allergic contact dermatitis
| B) CXCR3; chemokine IP-10 exclusively expressed in allergic contact dermatitis
43
What are some histologic features of allergic contact dermatitis?
- Typically non-diagnostic
- Epidermal necrosis
- Neutrophilic granulocytes present in the epidermis of skin that did and did not have necrosis
- Spongiosis was occasionally observed
- Dermal infiltration with granulocytes and edema found in all biopsies but number of lymphocytes small
- Possible eosinophilic inflammation
- Histology is primarily lymphocytic
44
What breeds are predisposed to allergic contact dermatitis?
- Dependant on geographic location and the presence of plants likely to cause allergic contact dermatitis.
- Short-coated breeds including the Boston Terrier, Pit Bull, Boxer, Dachshund and Weimeraner
45
What are some plants and allergens reported to induce contact hypersensitivity?
- Tradescantia fluminensis (wandering jew plant)
- Commelina diffusa (spreading dayflower)
- Murdannia nudiflora (doveweed)
- Asian jasmine
- Hippeastrum (Amaryllidaceae) leaves and bulbs
- Dandelion
- Cedar wood
- Carpet deodorizer
- Cement
- Thiuram mix
- Cobalt chloride
- Nickel sulfate
- quinoline mix
- Colophony
- Black rubber mix
- Wood alcohols
- Epoxy resin
- Balsam of Peru
- carba mix
- Formaldehyde
- Fragrance mix
- ethylenediamine
- Primin
- Wood tar
- Napthyl mix
- Neomycint
- Propylene glycol
- Poison ivy
- Poison oak
46
What family of plants is a common cause of allergic contact hypersensitivity in dogs?
Commenlinaceae
47
What are the skin lesions and the the distribution of lesions seen in allergic contact dermatitis?
- macular erythema, papules and rarely vesicles
- confined to hairless of sparsley haired areas of skin in contact regions
- Ventral aspect of interdigital areas, ventral abdomen, thorax, ventral tail, neck, scrotum, perineal area, muzzle, concave aspect of pinnae
- If allergen is in a topical medicaement in liquid or aerosol or powder form, cutaneous reactions may be visible in haired regions at the site of contact
- Reactions to rubber or plastic dishes and rawhide chew toys are typically confined to lips and nose
48
What are treatment recommendations for contact allergy?
- lifelong sensitivity
- Identification and avoidance of allergens
- Consider treatment of environment with weed-killers as plants of the Commenlinaceae are frequent offenders
- Topical/oral glucocorticoids
- Pentoxifylline (given before prior to known exposure); can inhibit TNF-alpha release which appears to be an important player in the elicitation phase of allergic contact dermatitis
- Calcineurin inhibitors
49
What are treatment recommendations for contact allergy?
- lifelong sensitivity
- Identification and avoidance of allergens
- Consider treatment of environment with weed-killers as plants of the Commenlinaceae are frequent offenders
- Topical/oral glucocorticoids
- Pentoxifylline (given before prior to known exposure); can inhibit TNF-alpha release which appears to be an important player in the elicitation phase of allergic contact dermatitis
- Calcineurin inhibitor
50
What is food intolerance?
Individual specific and may include pharmacologic, metabolic or idiosyncratic mechanisms.
51
What immunologic mechanisms are believed to underly immunological adverse food reactions?
- Type 1 hypersensitivity
- Type III hypersensitivity
- Type IV hypersensitivity
52
What are proposed mechanisms by which allergic responses to food develop rather than tolerance?
Alterations in:
- Epithelial cells
- Intercellular permeability
- Dendritic cell function (antigen-presenting)
- M cells from Peyer patches
- Elements that intervene in immune defense (Th3 Tr1, CD4+ CD25+ cells)
- comprpomised barrier function of the gut may lead to an increased risk for intolerance; damaged intestinal tract allows excessive penetration of food allergens leading to an overload of the gut mononuclear phagocytic system
53
What plays a vital role in the induction and maintenancer of immunologic tolerance to food and other innocuous antigens?
- Bacteria, bacterial components and/or products, antigen presenting cells and T cells in the intestinal mucosa
- Bacteria modulate T-cell immunoglobulin-domain and mucin-domain (TIM) proteins; transmembranse cell surface proteins
- Th2 polarized and allergic responses can be abolished by blocking TIM-4 or its ligand TIM-1 on T cells, suggesting a new mechanism for intestinal bacterial superantigen in the induction of food allergy
54
How could helminth's have a protective role against developing allergic reactions?
- T-reg responses induced by helminths
- Non-specific IgE induced by helminths may protect from mast cell or basophil degranulation by saturating IgE binding sites
55
Known food allergens are typically a)______ between b)__ kD and __ kD
a) glycoproteins that are resistant to processing, cooking and digestion
b) 10-70 kD
56
What are some examples of allergens homologous to pathogensis-related proteins?
PR protein homologs:
- Chitinases (PR-3 family) from avocado, banana and chestnut
- Antifungal proteins such as the thaumatin-like proteins (PR-5) from cherry and apple
- Proteins homologous to the major birch pollen allergen Bet v 1 (PR-10) from vegetables and fruits
- Lipid transfer proteins (PR-14) from fruits and cereals
57
What are the major groupings of food allergens?
- Pathogenesis-related protein homologs
- Inhibitors of alpha-amylases and trypsin from cereal seeds
- Profillins from fruits and vegetables
- Seed storage proteins from nuts amd mustard sees
- Proteases from fruits
58
What are panallergens?
- Phylogenetically similar proteins that occur in all species
59
What are panallergens?
- Phylogenetically similar proteins that occur in all species
60
What are the most common food allergens in dogs?
- -> Mean number of food allergens per dog is 2.4
- Beef
- Chicken
- Dairy Products
- Eggs
- Wheat
- Soy
- Corn
- Fish
61
What is oral-allergy syndrome? What has it been documented in?
- Cross reactivity between cedar and tomato in one dog
62
How frequent are GI disturbances in animals with food allergies and what signs might be noticed?
- Concurrent GI disturbances have been reported in 10-15% of dogs with adverse food reactions
- Vomiting
- Diarrhea
- Increased number of bowel movements
- Flatulence
- Fecal mucus and blood
- Tenesmus
- Food allergens have also been noted to induce erythema multiforme, vasculitis, urticaria, seizures and behavioral changes as well as respiratory signs.
63
How frequent are GI disturbances in dogs with food allergies and what signs might be noticed?
- Concurrent GI disturbances have been reported in 10-15% of dogs with adverse food reactions
- Vomiting
- Diarrhea
- Increased number of bowel movements
- Flatulence
- Fecal mucus and blood
- Tenesmus
- Food allergens have also been noted to induce erythema multiforme, vasculitis, urticaria, seizures and behavioral changes as well as respiratory signs.
64
While complete remission of clinical signs of cutaneous adverse food reaction may take 10 weeks or longer, a positive response should be seen by most, if not all, by XXX weeks of feeding ?
6 weeks; if there is no improvement by the 6 week mark, it is unlikely there will be any improvement moving forward.
65
What are the proposed benefits of performing a home-cooked diet to screen for adverse food reaction?
- They are free of additives including coloring, falvorings and preservatives
- Avoids contamination from processing in equipment used to make other foods
- Avoids sources of animal fats that could have been contaminated by animal proteins
66
What does hydrolyzed mean?
Protein is made to be hypoallergenic by reducing the size of the protein and thus minimizing the ability to cross-link IgE and mast cell degranulation
- Not all dogs suffer from type I hypersensitivity reactions, these diets may not be the solution in all cases.
67
What are some potential problems of hydrolyzed protein diets?
- poorly palatable
- hyposmotic diarrhea
- reduced nutritional value
- Persistent allergenicity
68
What does cutaneous adverse food reaction in dogs look like histologically?
- Superficial perivascular dermatitis (pure, spongiotic, hyperplastic) with mononuclear cells or neutrophils usually predominating
- Secondary pyoderma, malassezia dermatitis, or both are common
- Occassionally, eosinophils are present and an eosinophilic vasculitis may also occur in rare cases
69
What does cutaneous adverse food reaction look like histologically?
- Superficial perivascular dermatitis (pure, spongiotic, hyperplastic) with mononuclear cells or neutrophils usually predominating
- Secondary pyoderma, malassezia dermatitis, or both are common
- Occassionally, eosinophils are present and an eosinophilic vasculitis may also occur in rare cases
70
What are examples of a) constituents of the innate immune system and b) adaptive immune system?
Compare and contrast the innate and adaptive immune system.
a) Macrophages dendritic cells, natural killer cells, polymorphonuclear leukocytes (i.e. granulocyte), physical barriers (skin, mucosa), soluble factors (complement), antimicrobial peptides, chemokines, cytokines - rapid response; used pattern recognition receptors to identify phylogentically conserved regions of invading pathogens; secrete cytokines and costimulatory molecules to instruct/direct/prompt adaptive immune system; direct response for host defense (phagocytosis, antimicrobial activity); generated no memory
b) T and B lymphocytes - slow response; through gene rearrangement and clonal expansion respond with T and B cells that have receptors specific to the pathogen; develop memory
71
What are the three complement pathways and what triggers their initiation?
1) Classical complement pathway - requires antibody triggering
2) Alternative complement pathway - spontaneously activated by microbial surfaces in the absence of specific antibodies
3) Lectin-dependent pathway -
72
What are antimicrobial peptides ?
- Part of the innate immune system
- Amphipathic (containing both hydrophobic and hydrophilic surfaces)
- Believed to be antimicrobial by binding membranes of microbes through hydrophobic surface and form pores in the membranes leading to microbial killing
- Examples in HUMANS include beta-defensins, cathelicidin, psoriasin, RNase 7 (all produced by keratinocytes) and dermicidin which is secreted by human sweat.
73
What are beta-defensins?
- A type of antimicrobial peptide
| - Cysteine-rich, cationic, low-molecular-weight antimicrobial peptides
74
What are cathelicidins?
- Cationic peptides with a structurally variable antimicrobial domain at the C terminus
- produced by keratinocytes, mast cells, neutrophils, ductal cells of eccrine glands.
- antibacterial, antifungal and antiviral properties
- downregulated in human atopic dermatitis patients by Th2 cytokines
75
What are cathelicidins?
- Cationic peptides with a structurally variable antimicrobial domain at the C terminus
- produced by keratinocytes, mast cells, neutrophils, ductal cells of eccrine glands.
- antibacterial, antifungal and antiviral properties
- downregulated in human atopic dermatitis patients by Th2 cytokines
76
What are pathogen recognition receptors?
- A small set of receptors encoded by the germ-line utilized by cells of the innate immune system that recognize conserved molecular patterns that are shared by a large group of pathogens (bacteria, fungi, viruses)
- These receptors mediate innate immune responses in host defence
- Toll like receptors are a type of pathogen recognition receptor
- Once stimulated, the TLR's induce signalling pathways that stimulate production of antimicrobial effector molecules, promote the expression of costimulatory molecules and release cytokines and augment the adaptive response.
- IL-4 acts to downregulate TLR expression which suggests that T helper 2 adaptive immune responses might inhibit TLR activation.
77
What breed of cat is predisposed to adverse food reaction? What age does adverse food reaction manifest in cats?
- Siamese
| - half of cats manifest before the age of 2; others say between 4-5
78
What percentage of cats with dermatologic signs from adverse food reaction have concurrent GI signs?
10-15%
79
What are histologic findings of feline adverse food reaction?
- The most common reaction pattern is a superficial or deep perivascular dermatitis wherein eosinophils are the dominant inflammatory cell
- Some cases lack eosinophils whereas others are primarily composed of a dense infiltrate of mast cells that may be misinterpreted as mast cell neoplasia
- Eosinophilic folliculitis and furunculosis is occasionally a feature of feline food hypersensitivity
80
What is a major allegen in canine flea bite hypersensitivity?
- the 18kda flea salivary proten Ctef1
81
What is a major allegen in canine flea bite hypersensitivity?
- the 18kda flea salivary proten Ctef1
82
What tends to lead towards more severe clinical signs in canine flea allergy dermatitis?
A) intermittent flea exposure
B) continuous flea exposure
Intermittent flea exposure
83
```
what are the withdrawal times of
a) Injectable corticosteroids
b) oral corticosteroids
c) antihistamines
prior to performing intradermal allergy testing in dogs?
```
a) 8 weeks
b) 2 weeks
c) 2 weeks
84
What are some histologic features of canine flea allergy dermatitis?
- Nondiagnostic
- Revealing varying degrees of superficial, perivascular (pure, spongiotic or hyperplastic) to interstitial dermatitis with eosinophils often being a predominant cell type
- Eosinophilic intraepidermal microabscesses in associaion with epidermal edema and necrossi may be visible
- Secondary pyoderma is common
85
What is the order and families most known to cause allergic reactions?
Order Hymenoptera; families:
1) Apidae (Beeds)
2) Vespidate (yellow jackets, wasps, hornets)
3) Formicidae (ants)
86
- Black ant, black fly, cockroach and fly have been shown to have significant cross-reactivity
- Otodectes and Sarcoptes may cross-react; possibly also react with house dust and storage mite
- Uncertain whether these cross-reactivities are clinically relevant
d
87
What kind of hypersensitivity reactions can insects cause?
Type I, Type III and Type IV
| - can cause vasculitis like lesions
88
Household mites can be broken down into which two categories?
1) Pyroglyphid mites - i.e. the house dust mites
2) Nonpyrogliphid mites - i.e. the storage mites including Acarus siro, T. putrescentieae and various species of Lepidoglyphus, Blomia, Aleuroglyphus, Glycyphagus and Suidasia
- Predominant species of storage mite depends on the geogrphic location; Lepidoglyphys destructor is the dominant species in Europe wheres Blomia tropicalis is most prevalent in South America
- Storage mites may cross react with house dust mites
89
Household mites can be broken down into which two categories?
1) Pyroglyphid mites - i.e. the house dust mites
2) Nonpyrogliphid mites - i.e. the storage mites including Acarus siro, T. putrescentieae and various species of Lepidoglyphus, Blomia, Aleuroglyphus, Glycyphagus and Suidasia
- Predominant species of storage mite depends on the geogrphic location; Lepidoglyphys destructor is the dominant species in Europe wheres Blomia tropicalis is most prevalent in South America
- Storage mites may cross react with house dust mites
90
Canine eosinophilic furunculosis
- Sudden onset, affects the face, very responsive to glucocorticoids
- Suspected secondary to arthropod or insect bite; most cases have exposure to fire ants, bees or wasps
- papules, nodules, crusts, exudative lesions, exudative
- Pruritus may be severe, may be painful
- Some healthy, others systemically unwell (fever, anorexia, malaise)
- Young large breed dogs overrepresented
- Bridge of the nose and muzzle
- Cytology: lots of eosinophils
- Histo: Infiltrative eosinophilic mural folliculitis, luminal eosinophilic folliculitis and eosinophilic furunculosis
- Marked dermal and subcutaneous mucinosis typically present
- Dermal hemorrhage and flame figures are common
91
Intestinal parasite hypersensitivity
- Intestinal parasites (ascardis, Coccidia, hookworks, taperworms, whipworms) of dogs and cats can be associated with a pruritic dermatosis and type I hypersensitivity reaction
- Pruritic papulocrustous dermatitis, seborrhea, occassionally urticaria
92
Hormonal hypersensitivity
- Very rare, pruritic papulocrustous dermatitis
- Hypersensitivity reactions to sex hormones
- Suggest type I and type IC hypersensitivity reaction to endogenous estrogen, progesterone or testosterone
- Over 90% of cases occur in intact female dogs
- Dogs have history of repeated pseudopregnancy, irregular estrus cycles or both
- Dermatologic signs: pruritic, erythematous often papulocrustous eruption that begins on dorsal rump, perineal, genital, and caudomedial thigh regions
- Bilaterally symmetric, progresses cranially
- feet, face, ears commonly affected
- Signs usually coincide with estrus or pseudopregnancy; non-seasonal pruritus in male dogs
- you can perform IDT with progersterone, estrogen, and testosterone however aqueous forms are unavailable at this time so Dx. based on clinical signs and timing between signs and estrous cycle
- Histo: superficial perivascular dermatitis (pure, spongiotic, hyperplastic) with neutrophils or mononuclear cells
- Poorly respond to glucocorticoids
- Recommend neutering; could consider repositol testosterone in females and oral estrogen in males
93
What species of fungi have been proposed to induce a hypersensitivity reaction?
- Malassezia
| - Fungal kerions and dermatophytes are thought to be hypersensitivity reactions to dermatophytes
94
What are ceramides composed of?
A sphingosine base and fatty acid
95
What is one of the most important lipids in the intercellular lipid bilayer?
Sphingomyelin
