Immune Function and Immune-Mediated Diseases 9% Flashcards
1
Q
What are cross-reactive carbohydrate determinants (i.e. CCD’s)?
A
IgE-binding carbohydrate structures common to plant and insect species; in people, they are thought to be clinically irrelevant but have the potential to confound serologic IgE test intepretation.
2
Q
Ischemic dermatopathy is a general designation for the following 5 vasculopathic syndromes that a united by similar clinical and histopathologic features.
A
1) Canine familial dermatomyositis
2) Dogs with juvenile-onset ischemic dermatopathy that is identical to dermatomyositis but without proven breed predilection/familial predisposition
3) Postrabies vaccination panniculits
4) Generalized vaccine-induced ischemic dermatopathy (GVIID)
5) Generalized idiopathic ischemic dermatopathy (GIID)
3
Q
The 5 vasculopathic syndromes that make up “ischemic dermatopathy” are united by what histologic feature?
A
Cell-poor vasculitis
4
Q
What are the clinical features of ischemic dermatopathy?
A
Alopecia, crusting, post-inflammatory, mottled pigmentary change, erosion, ulceration, scarring. Rare, transient papules, pustules and vesicles, claw dystrophy, claw sloughing
5
Q
What body sites are affected with ischemic dermatopathy?
A
Over bony prominences, muzzle, perioribital region, personal, forum, distal phalanges, distal extremities, pressure points, pinnae (especially tips), pinnal folds, claw folds, tip of the tail
6
Q
What are the primary histologic findings of ischemic dermatopathy?
A
- scattered degeneration (vacuolated or apoptotic) of basal cells; follicular epithelium to isthmus more affected than basal epidermis
- Very mild, diffuse dermal inflammation that loosely encircles follicles; lymphocytes and histiocytes predominate
- Increased prominence of the connective tissue surrounding the external root sheath of the atrophic hair follicle
- Diffuse pallor of the dermis; pale-staining, smudged collagen that has lost fibrillar character
- Hair follicles are severe atrophied (i.e. “faded”)
7
Q
What is canine familial dermatomyositis?
A
A vasculopathic syndrome reserved for those dogs with clinical and histopathologic evidence of a juvenile onset heritable inflammatory disease affecting the skin and muscle
8
Q
What may trigger a relapse of ischemic dermatopathy?
A
Photo-aggravation, trauma and estrus
9
Q
IN CASES OF ISCHEMIC DERMATOPATHY, MAKE SURE TO CHECK
A
- FOR A VACCINE SITE
- PINNAL MARGINS AND PINNAE
- TAIL TIP
- CLAWS AND CLAW FOLDS
- PAW PADS
- FACE
10
Q
What breeds seem to be at higher risk for postrabies vaccination panniculitis?
A
long haired toy or miniature breeds seem to be at greater risk but it can happen to any breed.
11
Q
What breeds appear predisposed to developing DLE?
A
Collie, Shetland Sheepdog, German Shepherd (especially White German Shepherds), Siberian Husky
12
Q
What are the histopathologic features of discoid lupus erythematosus?
A
- Basal cell degeneration, both apoptotic and vacuolar, creates an irregular and indistinct dermal-epidermal junction that is obscured by interface inflammation
- Secondary erosion/ulceration and superficial pustulation and crusting are observed in severe cases
- Moderate acanthosis
- Epidermal atrophy may be present; the basement membrane may be markedly thickened in some cases
- Dermis usually has a lichenoid/band-like mild to moderate inflammatory infiltrate that includes lymphocytes/macrophages/plasma cells and neutrophils
- Inflammation often obscures the dermal-epidermal junction and best termed “lichenoid-interface”
- Pigmentary incontinence
- There can be a zone of superficial laminar hypocellularity with/without laminar fibrosis termed a “Grenz zone” subtended by a deeper zone of lichenoid inflammation
13
Q
What are the cutaneous manifestations of systemic lupus erythematosus (which can occur in < 20 % of dogs with SLE)?
A
Erythema, scaling, crusting, depigmentation, alopecia, bullae –> ulcers involving the skin, mucocutaneous junctions and mucous membranes
- Generalized exfoliative dermatitis, ulcers of the pawpads, panniculitis and lesions closely mimicking DLE
- Face, ears and distal extemities are common sites of involvement
14
Q
What are the histologic features of cutaneous lesions of SLE?
A
- Basal cell vacuolation and apoptosis of basal cells occurs, leading to dermal-epidermal separation and ulceration; superficial hair follicles to the level of the isthmus may be similarly affected
- Vasculitis may occur
- Other forms of lupus erythematosus and erythema multiforme are the principal differential diagnosis; lupid drug reactions are essentially identical in appearance
- DLE tends to have more intense band-like dermal infiltrate and less severe basal degeneration than SLE; EM shows more prominent individual keratinocyte necrosis at all levels of the epidermis
15
Q
What are the histologic features of pemphigus erythematosus?
A
- Superficial pustulation as seen in pemphigus foliaceus but has an interface component
- A pemphigus-lupus crossover disease
- Superficial inflammation composed of lymphocytes, histiocytes and plasma cells that obscures the dermal-epidermal interface, resembling DLE
- Mild to moderate pigmentary incontinence
- Using immunofluorescence or IHC, deposition of immunoglobulin along the basement membrane in addition to the typical intercellular deposition of PF
16
Q
Erythema multiforme
A
Believed to be a host-specific T cell mediated hypersensitivity in which the cellular immune response is directed against various keratinocyte-associated antigens, including those associated with drug administration, infection, neoplasia, and connective tissue disease. Lymphocytes bind to the antigenically altered keratinocytes and trigger cell death via apoptosis.
17
Q
Define erythema multiforme minor and erythema multiforme major
A
Erythema multiforme minor: Target lesions, no more than one mucosal surface affected and less than 10% of the body surface area affected
EM major: more than one mucosal surface affected, 10 - 50 % of the body surface affected, with less than 10% epithelial detachment.
Stevens-Johson syndrome: severe EM with >50% body surface affected, with epithelial detachment ranging between 10-30%.
Toxic epidermal necrolysis: separate syndrome, over 30% of epidermal detachment
SJS-TEN overlap: features of both TEN and SJS with 10-30% epithelial detachment
18
Q
What are some triggers for Erythema multiforme in small animals?
A
- Drug hypersensitivity (TMS, penicillins, cephalosporins)
- Neoplasia
- Infection
- Dyes, preservatives, stabilizers in pet foods may act as”drugs”
19
Q
What is the most common cause of EM in humans?
A
Herpesviral infection
20
Q
What is the distribution of lesions in EM?
A
Ventrum (groin and axillae), oral cavity, mucocutaneous junctions, concave pinnae and pawpads
21
Q
Describe the clinical lesions of erythema multiforme
A
- acute onset of erythematous, annular macules, elevated circular plaques and papules, that progress rapidly into partially symmetrical patterns
- Early lesions may appear urticarial
- Crusting becomes more noticeable as lesions evolve
- Some lesions become targetoi with multiple concentric circular zones of erythema, blanching and exfoliation
- Adjacent lesions may coalesce to form distinctive arciform-serpiginous patterns
- In more severe forms, ulceration can become severe
- Old dog EM: exudative and proliferative lesions and predominately involve the face and ears
- Mucosal lesions: vesicles and bullae –> ulcers
22
Q
What are the histologic features of erythema multiforme?
A
- Apoptosis with lymphocyte satellitosis
- Interface dermatitis
- Lesions extend to superficial hair follicles
- Lymphocytes and macrophages are grouped along the dermal-epidermal junction and partially obscure it
- Dermal inflammation is usually mild but can approach band-like
- There is vacuolation of the basement membrane zone , often with a bubbling pattern, individual basal cell apoptosis may be present
- In EM, apoptosis is more prominent and seen in all levels of the epidermis; lupus has apoptosis that is typically distributed to the basal cell layer ; feline thymoma associated exfoliative dermaitits has less severe transepidermal apoptosis than EM.
23
Q
Where are mast cells found in highest numbers?
A
Skin, lung, gastrointestinal tract
24
Q
What are the basic function of mast cells?
A
Antigen-specific role in the development of allergic inflammation, innate defense against helminths and bacteria, wound healing
25
What cell types produce TNF-alpha?
macrophages, activated T cells, NK cells, and mast cells
26
What cell types produce IL-1?
Macrophages, endothelial cells, keratinocytes
27
Describe the effects of TNF-alpha and IL-1
Both are general pro-inflammatory cytokines; both activate endothelial cells to enable inflammatory cell recruitment to sites of injury, activate neutrophils, stimulate the production of acute phase proteins
28
What cell types produce IL-12?
Macrophages, dendritic cells
29
What are the effects of IL-12?
What are the effects of IL-12?
30
What are some precipitating triggers for toxic epidermal necrolysis?
- Adverse drug reaction (sulfonamides, anticonvulsants and NSAIDs are primarily implicated in humans)
- Infection
- Vaccination
- Sequela to graft vs. host disease
- Accompanying diseases of enhanced immune function
- Visceral neoplasia
31
What is the pathomechanism of TEN?
Largely unknown, but believed to be induction of overwhelming apoptosis of keratinocytes mediated by T cells and mononuclear cells. Thought there to be a drastic overexpression of TNF-alpha
32
What are X differential diagnoses for dogs with TEN?
- Severe erythema multiforme
- Pemphigus vulgaris
- Bullous pemphigoid
- Mucous membrane pemphigoid
- Epidermolysis bullosa acquisita
- Toxic shock syndrome
- Sterile pustular erythroderma of miniature schnauzers
- vasculitis
- Ischemic necrosis
- Burns
- SLE
33
What is toxic shock syndrome?
- Life-threatening multisystemic disease
- Caused by the staphylococcal exotoxins: toxic shock syndrome toxin-1 (TSST-1), enterotoxin B, enterotoxin C
- Disease results from both exotoxin as well as cytokine induction
- Exotoxins stimulate the release of TNF-alpha and IL-1
34
What are the clinical signs of toxic shock syndrome?
- Generalized macular erythema of the trunk and legs often accompanied by marked edema particularly of the legs
- Vesicles and ulcers sometimes observed
- Variable crusting
- Fever, severe malaise, anorexia
- DIC is a consistent finding
35
What is the dominant immunophenotype underlying dermatomyositis in humans?
- Type I interferons characteristic of a Th1 inflammatory response
36
Cephalexin
- 1st generation cephalosporin
- Covers methicillin susceptible staphylococci, streptococci and aerobes
- Some activity against gram-negative aerobes
- Unpredictable efficacy against anaerobes
-
37
Cefpodoxime
- Third generation cephalosporin
- Activity primarily against gram-negative bacteria
- Approved for use in skin and soft-tissue infections
38
Cefovecin
- Third generation cephalosporin
- Activity primarily against gram-negative bacteria
- Approved for use in skin and soft-tissue infections
- Highly protein bound slowly clearance, resulting in a very long-half life
- One dose lasts at least 14 days in cats and 7-14 days in dogs depending on the pathogen; injections can be administered every 14 days as needed in dogd
39
Ceftazidime
- Third generation cephalosporin
| - Activity primarily against gram-negative bacteria
40
Alopecia Areata
- TRICOHYALIN IS A MAJOR ANTIGEN FOR ALOPECIA AREATA
- Results in non-scarring alopecia
- Results from selective and reversible damage to anlagen hair follicles
- Circulating anti-hair hair follicle IgG autoantibodies to multiple hair follicle proteins including TRICOHYALIN and other inner root sheath proteins
- Infiltration of cytotoxic T lymphocytes, helper T cells, and dendritic antigen presenting cells.
- Lesions most commonly first appear on the face
- Alopecia and variable hyperpigmentation
- In multicolored breeds, lesions may be restricted to hair of one color with dark brown or black affected preferentially
- German shepherds and Dachshunds may be affected preferentially
- In early lesions, lymphocytes and neutrophils invade anagen hair bulbs; inflammation may be mild to severe.
- histiocytes, plasma cells, and sometime eosinophils may encircle the affected bulb often in a tight nodular pattern; there may be perifolliclular mucin as well as pigmentary incontinence.
- Some cases self-cure; some response to immunosuppressive medications, others do not respond whatsoever
- Intrafollicular lymphocytes are predominately CD3+, CD8+ cytotoxic T cells
- Prominent apoptosis of bulbar keratinocytes
41
Pseudopelade
- Novel lymphocytic (predominately CD3+ CD8+ T lymphocytes) isthmus mural folliculitis causing a well-demarcated, visually distinctive and noninflammatory patchy alopecia
- variable hyperpigmentation occurs
- Hair loss typically permanent
- Circulating IgG autoantibodies targeting keratins and tricohyalin
42
What is the the bulge region?
- An outer root sheath protrusion at the level of attachment of the arrector pili muscle
- Source of hair follicle regeneration
43
Degenerative mucinotic mural folliculitis in cats
- unique, presumably immunologic skin disease
- Generalized alopecia, striking thickening of facial skin and varying degrees of lethargy; can cause dramatic thickening and narrowing of the eyelids
- affected skin becomes shiny and waxy and has a rubbery feel
- Skin lesions often begin on head and neck and shoulders
- All DSH or DLH's
- Ensure FIV screening is performed
- Do not respond to immunomodulatory therapy
- Moderate to severe mural and perifollicular inflammation is focused on the isthmus composed of lymphocytes, neutrophils and histiocytes
- Mucin wides the interfollicular cellular spaces , is gray-blue with HE and turquoise with Alcian blue-PAS
staining
- Mucin may also surround hair follicles
- Degeneration of the severely inflamed follicular wall occurs and eventuates to effacement with pyogranulomas
- moderate to severe follicular atrophy
44
Granulomatous mural folliculitis
- Rare, presumed immunological syndrome of multifactorial etiology that affects the dog
- Most associated with an adverse drug reaction to amitrax, cefadroxil, L-thyroxin, and various topicals.
- Some animals regrow hair after offending drug is removed while others do not.
- Alopecia, erythema, scaling, crusting, erosion, exudation
- Severepanfollicular mural inflammation
- Many hair follicles effaced by granulomatous to pyogranulomatous inflammation that extends along follicles to form large linear, or less often, nodular foci
- Hair shafts may remain centrally or be obliterated
- Inflammation includes histiocytes, lymphocytes and neutrophils.
- Multinucleated giants cells may be present and can be numerous
- Follicular inflammation centers on the isthmus
45
How do eosinophilic mucinotic mural folliculitis and follicular mucinosis differ?
- Follicular mucinosis does not have eosinophils and the mucin accumulation is more prominent in the hair follicle
- Eosinophilic mucinotic mural folliculitis has more prominent perifollicular mucin deposition (as well as mural mucin, but not as much) in addition to the presence of eosinophils
46
Th17 cells
- critical for neutrophil effector function
| - This subset believed to protect against extracellular pathogens
47
Th22 cells
- Promote and regulate tissue inflammation and repair
| - Believed to promote epithelial proliferation in the skin
48
What cytokines do Th2 cells produce?
- IL-4
- IL-5
- IL-9
- IL-13
- IL-31
49
What cytokines are known to promote the differentiation or activation of Th2 lymphocytes?
- TSLP
- IL-25
- IL-33
50
Sterile pustular erythroderma of miniature schnauzers
- Rare and severe cutaneous and visceral reaction pattern that is seen exclusively in miniature schnauzers
- Occurs within 48 hours after use of various shampoos
- Numerous cases have been seen with use of "herbal" shampoos however this is not always in the history
- Unknown etiology but suspected to be associated with an adverse drug reaction
- Pyrexia, depression, neutrophilic leukocytosis, heart, liver and lung lesions
- Marked clinical and histologic similarities exist between this disease and sterile neutrophilic dermatoses/Sweet's syndrome
- Erythematous papules and macular erythema which coalesce into erythematous, edematous plaques ; concurrent pustules or vesicles may be present
- Erosion, ulceration and exfoliation
- Lesions markedley painful before clinically evident
- Many affected dogs die
- Epidermis contains extensive broad subcorneal/panepidermal pustules/crusts
- Eosinophilic and neutrophilic dermal inflammation and variable edema; vasculitis and vasculopathic changes may be seen
- Pulmonary interstitial netrophilic infiltrates, myocardial and hepatic necrosis; hepatic lesions suggest terminal DIC
- Can have apoptotic keratinocytes
51
TGF-B
- Immunosuppressive cytokine
- Pronounced inhibitory effect on antigen-specific T-cell proliferation without modulating cytokine production
- Secreted by T reg cells
52
NK cells
- Large granular lymphocytes
- Survey body looking for altered cells (i.e. transformed or infected with viruses, bacteria or parasites)
- Altered cells are subsequently killed by perforin/granzyme or Fas/Fas ligand dependant mechaniams or indirectly via the secretion of cytokines (i.e. IFN-gamma)
- NK cells look for MHC I molecules; if they encounter MHC I molecules (which should be expressed on all nuclear cells), NK cells are INHIBITED; if cells lose MHC I molecules, NK Cells should attack
53
What are the Th17 cytokines?
- IL-17
- IL-21
- IL-22
54
What are the three subsets of lymphocytes noted in the human body?
- T cells
- B cells
- NK cells
55
What is IgD
- Antibody that functions mianly as an antigen receptor on B cells and activates mast cells and basophils to produce antimicrobial factors
56
IgA
- Found in mucosal tissues, saliva, tears, breast milk
| - Prevents colonization by various pathogens
57
IgE
- Binds allergens on mast cells and basophils, trigger histamine release and allergic reactions including anaphylaxis and urticaria
- Can protect against parasitic and helminthic infections
58
IgG
- Provides majority of antibody response that contribute to the immune defense of extracellular pathogens
- Only antibody that is capable of crossing the placenta and protecting the fetus
59
IgM
- Available as either surface-bound on B cells or as secreted form and eliminates microbes in the early stages of humoral immunity before there is sufficient IgM production
60
Name 4 ways in which T cells can be subdivided / classified
1) T cell receptor (alpha beta, gamma delta)
2) Accessory molecules (i.e. CD4 or CD8)
3) Virginity (i.e. naive, memory, effector)
4) Functional role in the immune system (linked to cytokine profile)
61
What is the difference between alpha/beta T cell receptors and gamma/delta T cell receptors?
- Most T cells express alpha beta T cell receptors- typically bind antigenic peptides presented by MHC molecules; immunity provided by alpha/beta T cells include Th1, Th2, Th17 and T reg responses
- A small subset of T cells express gamma/delta T cell receptors; they directly bind to pathogen-derived glycoproteins or nonclassical MHC molecules
- Gamma/delta T cells in men and mice predominately display a tissue-associated repertoire and memory phenotype; act early in immune responses and termed "innate-like effectors"
62
CD4+ Helper T cells
- Critical for helping B cells to produce antibodies by triggering their differentiation into plasma cells in the humoral response
- Heterogenous cell populations with diverse functions depending on environmental requirements that play central roll in humoral or cell-mediated immune responses.
- Effector CD4+ T cells Protect against pathogens by production of Th1 (IFN-gamma), Th2 (IL-4) and Th17 (IL-17) cytokines
- Regulatory CD4+ T cells: capacity to downregulate disproportionate effector responses to (self-) antigen.
63
CD8+ T cells
- Respond to intracellular pathogen (i.e. a virus) by lysing infected cells
64
a) Why cytokines promote the production of Th1 cells ?
b) What transcription factors define Th1 cells?
c) What cytokines do Th1 cells secrete?
a) IL-12, IFN-gamma
b) T-bet (T-box transcription factor)
c) IL-2, TNF-alpha, IFN-gamma
- Th1 cells are the main carriers of cell-mediated immunity
65
a) Why cytokines promote the production of Th2 cells ?
b) What transcription factors define Th2 cells?
c) What cytokines do Th2 cells secrete?
a) IL-4, IL-33, TSLP
b) GATA-3 (zinc-finger transcription factor)
c) IL-4, IL-5, IL-6, IL-13
66
What are the main cytokines influence polarization to a Th1 vs. Th2 response?
IL-12: Th1
| IL-4: Th2
67
a) Why cytokines promote the production of Th17 cells ?
b) What transcription factors define Th17 cells?
c) What cytokines do Th17 cells secrete?
a) IL-6, IL-23, TGF-beta
b) ROR- gamma tau
c) IL-17, IL-21, IL-22
* differentiation into Th17 cells can be inhibited by IFN-gamma and IL-4
68
a) Why cytokines promote the production of T reg cells ?
b) What transcription factors define T reg cells?
c) What cytokines do T reg cells secrete?
a) IL-10, TGF-beta
b) FoxP3
c) IL-10, IL-35, TGF-beta
69
What is the role of Th17 cells?
Promote protection from fungi, protozoa, viruses and a variety of extracellular bacteria
- linked to a list of autoimmune and inflammatory diseases
- May play a role in antitumor immunity
70
What are the major MHC II-dependant antigen presenting cells?
- Dendritic cells: Langerhans cells and Dermal dendritic cells; these are the professional antigen presenting cells
- B cells
- Activated monocytes/macrophages
71
How do the peptide binding grooves of MHC I and MHC 2 molecules differ?
- MHC 1 molecules: present short peptides, 8-12 amino acids in length; have binding pockets to accommodate the charged termini of peptides and thus selectively associated with short peptides
- MHC 2 molecules: binding sites open at both ends; bind peptides with a preferred length of 15-22 amino acids but can bing to longer moities. 10
-
72
What is an allergen?
Antigens that trigger an IgE response
73
How are antigens recognized on B cells vs. T cells?
B-cell receptors consist of antibodies that coat the outside of the B-cell; B-cell receptors recognize the antigen in its native, three dimension form WITHOUT needing to be process. T-cell receptors are situated on the surface of T lymphocytes; T-cell receptors cannot recognize antigens in their native form; they need to be PROCESSED (i.e. broken down to peptides of 8-12 amino acids longs) by an antigen-presenting cell first; phagolyosomes and cathepsin E assists in breaking down these proteins.
74
What is clonal deletion?
When lymphocytes develop in either the bone marrow or thymus and react with host-antigens, they are killed by programmed cell death (i.e. Apoptosis).
75
What is central tolerance?
The process by which self-reacting lymphocytes are destroyed within the bone marrow and thymus.
76
What is peripheral tolerance?
Autoreactive lymphocytes that enter the peripheral circulation are instructed to undergo apoptosis by tolerogenic dendritic cells or become anergic.
77
What is Anergy?
The process by which cells do not receive the appropriate (second) signals when interacting with antigen presenting cells, resulting in lymphocytes not being activated. I.e. does not receive the appropriate co-stimulation.
78
What are the main antigen-presenting cells in the skin?
Langerhans cells (situated in the epidermis) and dermal dendritic cells (situated in the dermis)
79
How are antigens presented to T-cell receptors?
Antigens first need to be PROCESSED (i.e. broken down into smaller peptides and amino acids by phagolysosomes) and then presented on an MHC protein molecule produced inside the antigen-presenting cell. These proteins transport the broken down peptides back to the cell surface where they are presented to adjacent T-cell receptors.
80
MHC Class I molecules
Typically present in all nucleated cells; present endogenous antigen within any nucleated cell (i.e. a piece of self-protein or a virus protein produced within a viral-infected cell)
81
MHC Class II molecules
Typically present only in antigen presenting cells; typically present exogenous antigens
82
What is CD4?
Cell-surface protein present on Helper-T cells; the receptor for MHCII molecules.
83
What is CD8?
Cell-surface protein present on Cytotoxic T-cells; the receptor for MHC I molecules
84
What is CD3?
Part of the T-cell receptor; immunostains for CD 3 can be used to identify T cells
85
What is the difference between immune-mediated and autoimmune disease?
- Autoimmune is when the immune system fails to tolerate self (referred to as immune tolerance) and mounts an immune response to those normal body structures and functions; in autoimmune disease, antibodies or activated lymphocytes develop against normal body constituents and induce the skin leisons
- Immune-mediated, the antigen is foreign to the body; most commonly, the inciting antigens are foreign proteins such as drugs, bacteria, and viruses that stimulate an immunologic reaction that results in host tissue damage.
86
What body sites have immunoglobulins present in normal tissue?
Nasal planum of dogs and cats, footpads of dogs
87
Samples for direct immunofluorescence are usually fixed in what?
```
Michel fixative (okay for 7-14 days; needs to be maintained at a pH of 7.0 - 7.2)
- Samples for immunoperoxidase testing may be formalin fixed
```
88
What is acantholysis?
Breakdown of epidermal intercellular desmosome connections
89
Which antibody subclass may have a significant pathogenic role in the pathomechanism underlying pemphigus foliaceus.
IgG4
90
a) What is the best substrate to use for indirect immunofluorescence for dogs with pemphigus foliaceus?
What is the more reliable substrate for indirect immunofluorescence for canine pemphigus vulgarisms?
a) Neonatal mouse skin
| b) Canine gingival mucosa
91
What are three proposed immunopathogenic pathways that lead to acantholysis?
1) Antibodies may act simply by steric hindrance
2) Antibody binding triggers a number of intracellular signaling events leading ultimately to aberrant phosphorylation of Dsg3 (or other desmosomal proteins) and depleted desmosome formation. Protein kinases are purportedly involved in this process.
3) Intercellular cohesion is dependent on cholinergic mechanisms and the acetylcholine receptor plays an important role in controlling phosphorylation of adhesion molecules. Serum from PV and PF precipitate cholinergic receptors; atropine and other muscarinic acetylcholine antagonists increase Dsg phosphorylation leading to abnormal desmosome formation.
92
What is an LE cell?
Historic test used to screen for SLE; an LE cell is a neutrophil containing an engulfed mononuclear cell nucleus.
93
What is the most specific marker for canine SLE?
Heterogenous nuclear ribonucleoprotein G (HnRNP G)
94
What is Apoptosis?
Form of programmed cell death that results in cell shrinkage, nuclear pyknosis, then karyorrhexis and formation of plasma membrane-bound apoptotic bodies.
95
A direct nikolskiy sign
ability to separate the epidermis from the dermis by application of lateral digital pressure on normal-appearing skin distant from any lesions; characteristic for pemphigus vulgaris
96
A pseudo-Nikolskiy sign
ability to separate the epidermis from the dermis by application of lateral digital pressure to erythematous skin and most commonly presents in SJS or TEN lesions.
97
What breeds are thought to be predisposed to vitiligo?
- Belgian Tervuren
- Doberman pinschers
- Rottweilers
- Collies
- Siamese cats
- Gelderland horses
- Spanish thoroughbreds
- Arabians
98
What breeds of horses has spotted leukotrichia been reported in?
- Shire
- Thoroughbred
- Arabians
99
What melanocyte associated antigens have been thought to be targeted in human VKH?
- Tyrosinase
| - gp100
100
What breeds of dogs are thought to be predisposed to VKH?
- Akitas
- Samoyed
- Siberian Huskies
101
What breeds of dogs are thought to be predisposed to VKH?
- Akitas
- Samoyed
- Siberian Huskies
102
where do cutaneous lesions of VKH most commonly manifest?
- The head with the nasal planum, periocular region and lips most frequently involved
103
What are the common cutaneous lesions seen in VKH?
- leukoderma
- leukotrichia
- erosion
- ulceration
- crust
- alopecia
104
What is a superantigen?
An antigen that can stimulate T cells directly by cross-linking MHC molecules and T-cell receptors at a site away from the peptide bingind cleft resulting in lymphocyte activation, cytokine production and an inflammatory response
105
What are some examples of superantigens?
Exotoxins produced by S. aureus; strains of S. intermedius from dogs with pyoderma also documented to produce enterotoxin A and B
106
What cytokines do Th1 cells predominately secrete?
IL-2, IFN-gamma
107
What cytokines do Th2 cells predominately secrete?
IL-4, IL-5, IL-6, IL-10 and IL-13
108
What cytokine secreted by antigen presenting cells is a potent signal for Th2 development
IL-4
109
What cytokine secreted by antigen-presenting cells is a potent signal for Th1 development?
IL-12
110
Why cytokines do Treg cells primarily secrete?
The immunosuppressive cytokines IL-10 and TGF-beta
111
What is poliosis?
Graying, decreased pigment in the hair.
112
What are 6 round cell tumors of the skin?
Histiocytoma, mast cell tumour, lymphoma, transmissible venereal tumor, plasmacytoma, melanoma
113
What is a fistula?
An abnormal connection between two epithelium lined tissues or vessels that normally do not connect
114
What is a dermoid sinus?
Tubular skin defect caused by incomplete separation of the skin and the neural tube during embryonic development; most commonly found as a heritable congenital defect in Rhodesian ridgebacks.
115
Vacuolar degeneration
Intracellular edema
116
Hydropic degeneration
Vacuolar changes in cells of the stratum basale; a feature of DLE, adverse drug reactions, dermatomyositis, thymoma-associated dermattitis and lichenoid dermatoses.
117
What is a pustule?
Intraepidermal or supepidermal cavity filled with inflammatory cells.
118
What is papillary squirting?
Edema of superficial dermal papillae with exocytosis of leukocytes, dilated vessels, and parakeratotic scaling of overlying epidermis; a feature of seborrheic dermatosis and zinc-responsive dermatosis.
119
What are pautrier microabscesses?
What are pautrier microabscesses?
120
What are munro microabscesses?
Accumulation of neutrophils within or below the stratum corneum, a feature of psoriaform lichenoid dermatosis of springers.
