Things that were highlighted in NAVDF notes Flashcards
What are the components of the extracellular lipid bilayer?
1) Ceramides
2) Free fatty acids
3) Cholesterol
In which layer of the epidermis are tight junctions found?
SG2 only!
Which layer of the epidermis provides a permeability barrier?
SG2, where tight junctions live
What cell is able to BYPASS tight junctions?
Langerhans cells – dendrites can pass, in order to sample superficial AGs
Rate limiting step for collagen synthesis
Prolyl hydroxylase
How does hyperbaric oxygen affect the dermis?
Promotes collagen formation (prolyl hydroxylase)
How does vitamin C affect the dermis?
Promotes collagen formation (prolyl hydroxylase)
What element is needed for lysyl hydroxylase oxidation?
Copper
Signals that induce anagen
Wnt, Shh, KGF, noggin (BMP antagonist)
Signals that inhibit anagen
BMP
Signals that induce catagen
TGF-alpha
EGF
FGF-5
BMP
Signal that promotes hair shaft and IRS differentiation
BMP
(helps keep the epidermis between the follicles WNL)
How does noggin induce anagen?
Acts on Lef-1 transcription factor
Which species’ hair is nonmedullated?
Sphinx, sheep wool, angra goats
First hairs to develop
Sinus hairs
Location of tylotrich hairs on body
Scattered throughout, surrounded by neurovascular tissue
Which hairs have epitrichial sweat glands?
Primary only
Which section of hair follicle is shared in compound hairs?
Infundibulum
Which phase of the hair cycle is the bulb present in?
Anagen
Where does arrector pili muscle attach?
Bulge
Inner root sheath only present during this hair cycle phase
anagen and catagen
Which direction does IRS keratinize?
Outside in (henle first)
Mode of secretion of epitrichial sweat glands
MEROCRINE (not apocrine)
-Secretion via exocytosis
Which species do NOT have epitrichial sweat glands?
Rodents, ferrets
How are epitrichial sweat glands innervated?
NOT directly
Neural control via adrenergic agonists
Humoral control via adrenergic agonists
What medication can downregulate aquaporin 5?
Macrolides (horses treated for Rhodococcus)
What sweat gland change occurs in anhidrosis?
Downregulation of aquaporin 5 (water channel for rapid fluid movement)
Where are epitrichial sweat glands largest on the body?
Glaborous areas
Which part of hair follicle has the entrance for the epitrichial sweat gland?
Infundibulum
What cell surrounds equine sweat glands? #Unique
Myoepithelial cells (all animals), but in a loose basket-weave pattern with a rich surrounding blood supply!!
Gene responsible for midline white markings in horses
KIT mutation
Disease associated with midline white markings in horses
Piebaldism
Gene associated with Waardenburg type 2
MITF
Gene associated with white spotting and blue eyes +/- deafness in dogs
MITF
Mode of inheritance of waardenburg type 2 (White coat/blue eyes)
Autosomal dominant
Other name for waardenburg syndrome type 4 in horses
Lethal white foal syndrome
Gene in lethal white foal syndrome
Endothelin receptor type B (EDNRB)
Mode of inheritance of lethal white foal syndrome (EDNRB)
autosomal co-dominant
Clinical signs lethal white foal syndrome
White hair, blue eyes, deaf, aganglionic megacolon
What happens if a foal is homozygous for EDNRB mutation?
Lethal
(heterozygous for lethal white foal syndrome)
Gene for grey horse phenotype
Syntaxin 17 (STX17)
Mode of inheritance of STX17 in grey horses
autosomal dominant
What happens if melanin is outside of an endosome/unbound?
Cytotoxic
Gene in Gray collie syndrome
AP3 (adaptor protein complex 3)
Which bloodwork finding would you see in Gray Collie Syndrome
Cyclical neutropenia –> ultimately die
Silver cat with large cytoplasmic neutrophil granules and clumped melanin pigment on trichogram. Diagnosis?
Chediak Higashi syndrome
Gene mutation in Chediak Higashi syndrome
LYST/CHS1
Rate limiting step for melanin synthesis
Tyrosinase enzyme
Enzyme needed for eumelanin production
TYRP1, TYRP2, TYR
OCA type 4 in doberman pinschers –> clinical outcome
Make melanoma at a young age
Which gene in white doberman pinschsers makes them develop melanomas?
SLC45A2
Breed with SLC45A2 mutation, white coat, make melanomas
Doberman pinscher
Gene for OCA type 1
Tyrosinase
Gene for OCA type 2
TYRP1 (eumelanin)
Gene associated with cAD in Golden Retrievers
Filaggrin
RAB3C
Gene associated with cAD in GSD
Plakophilin 2
Gene enhancers associated with a risk haplotype
Gene associated with cAD in WHWT
Cytochrome P450 26B1
NAME THAT GENE
Pro-inflammatory molecule on the epidermal differentiation complex (EDC)
-Correlated with severity of cAD and TNFa
-EDC includes filaggrin, loricin, involucrin
S100A8
Environmental influences that INCREASE cAD (5)
1) Urban
2) Regular bathing
3) C-section
4) Household hygeine
5) HDM exposure
Environmental influences that DECREASE cAD (4)
1) Rural
2) Multi-animal household
3) Non-commercial food
4) Skin barrier protective diet
Inflammatory signals released by keratinocytes (6)
1) ICAM-1
2) MHC class II
3) TARC
4) TNFalpha
5) IL-8
How does the microbiome affect the skin barrier? (3)
Healthy bacteria are associated with:
1) Increased ceramides
2) Decreased TEWL
3) Decreased SCORFAD
Mutation in cAD dogs across breeds, geography
TSLP receptor
Lower levels of _______ cells at an early age was associated with a higher risk of cAD at an older age in WHWT
TReg cells
What happens to the diversity of microorganisms on cAD skin?
Decreased diversity
Skewed to Staphylococcus
Biodiversity hypothesis
Modern version of hygiene hypothesis
Loss of macrodiversity in the environment and microdiversity within an individual leads to –>
1) Microbe dysbiosis
2) Immune dysfunction
3) Inflammatory dysresponse, lack of tolerance
4) Clinical symptoms of AD (also arthritis, diabetes, other immune mediated diseases)
How long does complete healing of the tympanic membrane take
21-35d
Thicker after injury
What is the origin of the outer membrane of the tympanic membrane (3-layer membrane)
Ectoderm–> outer ear origin
Center layer = fibrous
Inner layer = pharyngeal pouch origin
What happens to the sebaceous glands in OE canals
Less active
But MORE active/dilated ceruminous (apocrine) glands
What do Staphylococcus have to promote Type 2 inflammation?
Superantigens (endotoxin)
(Forces MHC cl II on APC and TCR on T cells to bind –> activate nonspecific, robust T cell response!)
Which 3 cell signals are implicated in hyperinnervation in cAD?
1) IL-31
2) NGF
3) Artemin (made when AHR is bound to pollutants)
How does allergen immunotherapy work? 4 major mechanisms
1) Desensitization of mast cells, basophils, eosinophils (QUICK): increase inhibitory Fc receptors, increase H2 receptors (block action of histamine)
2) Tolerance: generation of Treg, DCreg, IL10+ ILC (ILCreg), Breg, Tfreg; Reduction of Th2 to Th1 ratio
3) Decrease IgE, increase IgG1, IgG2, IgG4, IgA
4) Decreased # mast cells, basophils, eosinophils in tissue
What cells are involved in a Type 2 response
*Keratinocytes (alarmins, chemokines, IL-1)
*ILC2 (IL-5, IL-13)
*Th2 (IL-4, IL-13; express CTLA, CCR4, CRTH2)
*DC2 (OX40L)
*B cells (respond to IL-4 to make IgE)
*Eosinophils (express H4R, CRTH2 for prostaglandin binding)
What is FoxP3
Treg marker!
Transcription factor
Binds DNA to induce expression of Treg development and functional proteins
How does the Type 2 response affect the skin barrier?
1) Downregulates ceramide synthesis
2) Downregulates Filaggrin expression
3) Downregulates antimicrobial peptide expression
4) Alters skin protein and limit content
T or F: histamine is the most important molecule for induction of itch in atopic dermatitis
FALSE
NONhistaminergic pathway is more important (TSLP, IL4, IL13, IL31)
What type (greek letter) papillomavirus is BPV 1?
DELTA papilloma virus
This means not only does it infect keratinocytes, but ALSO dermal fibroblasts
4 major branches of the skin barrier
1) Physical (disorganized lamellar layers, reduction of CER 1, CER 9, CER; Lipids organized as hexagonal; decreased claudin/occludin of tight junctions, corneodesmosin)
2) Chemical (Decreased antimicrobial peptides; Natural hydration factors, lysozyme, phosphlipase A)
3) Immunological (Treg downregulated, Th2 increased. Hyperactive DC with extra IgE R. Keratinocyte alarmins, chemokines)
4) Microbiological (Dysbiosis; more Staphylococcus. Switch from M restricta to pachydermatis. Bacteria adhere to corneocytes more than normal)
What is the main physical blocker against penetration of external agents in the deeper epidermis?
Tight junctions in SG2
How do urocanic acid and carboxylic pyrrolidone (NMFs) affect skin pH and protease activity?
Decrease pH (more acidic)
Acidic pH INHIBITS protease activation
Outside-Inside-Outside theory
Primary defects in cutaneous barrier in AD → penetration of more allergens, stimulates immune system → exacerbation of skin barrier defect
***
T or F: there is a decrease in ceramides in NONlesional cAD skin?
True
Which TLRs induce production of TSLP by keratinocytes?
TLR3
TLR4
(NOT TLR2, TLR7)
4 phases of wound healing
1) Hemostasis/coagulation
2) Inflammation (neutrophils, then macs)
3) Repair/granulation phase
4) Remodeling/scar formation
What marks the END of the coagulation phase
Fibrin clot
Cells that stores TGF B
Platelets
What type of collagen is present in scar tissue
Collagen 1
What type of collagen is present in granulation tissue
Collagen 3
Which growth factor is overexpressed in proud flesh. Which cell is hyperplastic in proud flesh?
TGF-B1
Mast cell hyperplasia
Which medications are synergistic with HBOT (4)
1) Fluoroquinolones
2) Aminoglycosides
3) Beta-lactams
4) Amphotericin B
Which phase of wound healing would you expect to see exudate (septic or nonseptic)
Inflammatory phase
(neutrophils getting eaten up by macs)
Risk factors for poor wound healing (6)
1) Infection
2) Medications
3) Comorbidities (age, endocrine, liver/kidney, neoplasia, immune-med)
4) Nutrition (need Glu, protein, Mg, Vit A)
5) Location
6) Radiation tx
What is ENDEMIC pemphigus foliaceus?
*Fogo salvagem (Brazil)
*Sand fly salivary antigen LJM11
Also: young, poor women in S Tunisia. High temp, UV radiation, contact with ruminants, infections, genetic susceptibility
What drugs can cause PF in cats?
*Cimetidine
*Doxycycline
*Econazole/Neomycin/Triamcinolone/Amoxicillin
*Itraconazole/lime sulfur
Major autoantigen for canine PF
DSC-1
T or F: Absence of anti-DSC IgG can be used to rule out PF
FALSE.
Many dogs with trunk-dominant PF do not have detectable anti-DSC IgG, even though their major autoantigen is still DSC-1
Feline PF treatments
*Oral glucocorticoids
*Pulse therapy not helpful in cats
*Apoquel (1 mg/kg BID tapered to 0.5mg/kg BID)
+/-
*Cyclosporine
*Chlorambucil
Which layer of haired skin/foot pad has the most DSC1
Stratum granulosum, Stratum spinosum
How does autoantigen IgG lead to blisters in AISBDs?
Fab region binds to autoantigen, which induces C1q component of complement system –> Complement-dependent cytotoxicity –> Blisters
Mechanism of steric hinderance –> acantholysis
Binding of auto-Ab prevents bonding of desmoglein on same cell AND desmosomes between 2 cells
Mechanism of signal transduction –> acantholysis
Auto-Ab affects the signal transduction pathway is affected. Leading to steric hinderance and desmoglein depletion
*Overexpression of c-myc in PV dogs interferes with signaling cascade needed for DSG-3 expression
Autoantigen for BP
*BP180 (Collagen 17)
>
*BP230 (BPAG1e)
Autoantigen for EBA
Type VII collagen
What factors are released by inflammatory cells that lead to blister formation in AISBDs?
*Neutrophil elastase
*MMP-9
*ROS
Degradation of BMZ structures –> results in deep blister