1
Q
K5/K14
A
Stratum basale
2
Q
Epidermal proliferating unit vs. melanocyte proliferating unit?
A
10 basal cells: 1 stem cell
1: 10-20 melanocytes (vs. humans 1:36)
3
Q
K1/K10
A
Terminal differentiation; keratinocytes being to synthesize in stratum spinosum
4
Q
Stratum spinosum
A
Starts to synthesize K1/K10, involucrin, pro-filaggrin and form lamellar bodies
5
Q
Stratum granulosum
A
- KHG: pro-filaggrin, loricin, keratin filaments
- Construction of CE begins (which replaces plasma membrane)
- Desmosomes -> corneodesmosomes
S1: lamellar bodies secrete contents to form the CLE + lipid lamellae , pro-filaggrin turns into filaggrin
S2: tight junctions seal
S3: closest to stratum spinosum
6
Q
KIF assemble and construction of CE is triggered by an increase in what?
A
Calcium
7
Q
Stratum corneum
A
- Organelle activity ceases
- Cell flattens
- Filaggrin bundles KIF
- Corneocytes are formed covered in CE coated with CLE which attaches to intercellular lipid matrix
8
Q
Intercellular lipid matrix
A
Ceramides, free fatty acids, cholesterol
9
Q
Microfilaments
A
Small / actin
10
Q
Microtubules
A
tubulin / large
11
Q
Keratin proteins type 1: 1-8
A
Acidic
12
Q
Keratin proteins type 2: 9-19
A
basic
13
Q
Transglutaminases
A
Enzymes that help create the CE (TG1 outside, TG3 inside)
14
Q
Caspase-14, bleomycin hyrolase
A
Enzyme that processes filaggrin into NMF
15
Q
Natural moisturizing factors
A
Filaggrin is processed into NMF: urocanic acid (UCA) and pyrrolidone carboxylic acid (PCA), also lactic acid, citrate, urea, sugars. UCA + PCA have antimicrobial properties.
16
Q
Involucrin
A
Localizes to cell membrane, first to form (corneocytes to extracellular lipid layer)
17
Q
Loricin
A
Comprises most of CE (especially inner)
18
Q
Envoplakin, periplakin
A
Help connect to the desmosomes
19
Q
SPRs
A
With loricin making up the bulk of the cell
20
Q
Corneocyte lipid envelope
A
w-hydroxyceramides; bonded by TG1
21
Q
Intercellar lipid lamellae
A
Secreted from LB contents to create a water impermeable barrier. Made of ceramides, cholesterol, free fatty acids.
22
Q
Lamellar bodies contents
A
Cholesterol, KLKs, cathepsins, LEKTI, corneodesmosin, AMPs, lipid precursors
23
Q
Desmosomes
A
Desmoglea: dsg/dsc (cadherins)
Outer plaque: Armadillo proteins - plakoglobin, plakophillin
Inner plaque: desmoplakin (+ envoplakin and perkplakin)
24
Q
Corneodesmosomes
A
Desmoglein 1, desmocollin 1, and corneodesmosin (CDSN).
Lower layer they cover the entire cell, at upper layer very few.
25
Kallikreins
Enzyme that cleaves corneodesmosin during desquamation
KLK7: degrades CDSN and dsg1
KLK5: degrades DCSN, dsg1, dsc1
26
Cathepsin
Enzyme that cleaves corneodesmosomes during desquamation
27
Tight junction: location, parts, function
SG2; claudins (primary), occludins, JAMs, ZO proteins. Permeability barrier and prevent entry of foreign antigens. Lamellar bodies secrete into SG1. Langerhans cells extend dendrites beyond TJs.
28
Claudins
Primary transmembrane molecule of the TJ
29
LEKTI
KLK inhibitor (along with cholesterol sulfate) therefore slowly desquamation
30
What does the calcium gradient control?
- Lamellar body secretion
- Transglutaminase activity
- Cleavage of pro-filaggrin -> filaggrin
- Promotes differentiation to corneocytes
31
Hemidesmosome inner plaque
Plectin + BPAG1e (aka BP230)
32
Hemidesmosome outer plaque
Collagen 17 (BPAG2, BP180) + alpha6beta4 integrin + CD151
33
What makes up the lamina lucida?
Laminin 332 (and anchoring filaments)
34
Lamina densa
Collagen 4, nidogen and perlecan
35
What does PAS stain in the BMZ?
Nidogen & perlecan of the lamina densa
36
Sublamina densa
Collagen 7
37
Dermis: components
Fibrous: collagen (strength), elastin (stretch), reticular fibers
ECM: diffuse/ground substance - PG + GAGs (hyaluronan), filamentous - glycoproteins (fibrillins, fibronectins, etc)
Resident cells: fibroblasts, macrophages, melanocytes, dermal dendritic cells, mast cells
Transient cells: neutrophils, eosinophils, lymphocytes, histiocytes, plasma cells
38
Dermis origin
Mesoderm
39
Type 1 collagen
Most abundant in adult skin
40
Type 3 collagen
Fetal skin and in wound healing
41
Type 4 and 5 collagen
Around blood vessels
42
What requires Vitamin C?
Prolyl hydroxylase in collagen synthesis (first and rate-limiting step)
- Hyperbaric oxygen may aid in wound healing by increasing activity of this enzyme
- GCs inhibit prolyl hydroxylase
43
What requires copper?
Lysyl oxide in collagen synthesis (cross-link formation)
44
What requires zinc and copper?
MMP-1 (collagenase) in collagen break-down
45
What synthesizes collagen?
Fibroblasts
46
What stimulates collagen synthesis?
Vitamin C, TGF-b, IL-1, IGF, bleomycin
47
What inhibits collagen synthesis?
GCs, retinoids, vitamin D3, INF-y
48
Prolyl hydroxylase
Rate limiting step for collagen synthesis
49
Masson-Trichrome
Collagen stain (blue/green)
50
Oxytalan fibers
Type of elastic fiber deep in dermis
51
Elaunin
Type of elastic fiber superficial in the dermis
52
What synthesizes elastin?
Fibroblasts
53
What does colchicine do to elastin?
Inhibits synthesis.
54
Verhoeff-van Gieson
Elastin stain
55
Special silver stains
Reticular fibers
56
Hyaluronan
Most important GAG polysaccharide that composes the ground substance.
Aids in wound healing, cellular movement. Highest concentration fetal skin, allows to heal without scarring, very hygroscopic and can expand to a large volume. Produced by fibroblasts.
57
Why do Shar Peis have increased mucin in their skin?
Hyaluronan synthase-2 hyperactivity
58
Alacian blue
Mucin
59
MMP-1
Enzyme produced by fibroblasts that breaks down collagen 1, 2, 3. Crucial for normal tissue remodeling.
60
P-selectin
Rolling: Pre-formed (RAPID!), on platelets and endothelial cells, incited by thrombin and histamine to help initial adhesion of leukocytes to vessel walls.
61
E-selectin
Rolling: Induced by cytokines. On endothelial cells that helps neutrophils and monocytes stick. Induced by TNF-a, IL-1.
62
L-selectin
Rolling: on leukocytes mediating rolling on activated endothelium. Leukocyte homing.
63
ICAM-1
Firm attachment: damaged endothelium releases chemokines (IL-8, others) which increase affinity for integrins (adhesion molecules) allowing for a more firm attachment.
ICAM-1 on endothelium binds LFA-1 on neutrophils and macrophages.
64
VCAM-1
Firm attachment: damaged endothelium releases chemokines (IL-8, others) which increase affinity for integrins (adhesion molecules) allowing for a more firm attachment.
VCAM-1 on endothelium binds VLA-4 on monocytes, eosinophils (more chronic lesions)
65
PECAM-1
Transmigration: guides leukocytes through intercellular junctions, diapedesis
66
Pericytes
cells within blood vessel wall on dermal side, integral for vascular wall and helps regulate capillary flow
67
Lymphatics as compared to blood vessels
Wider, more angular lumen, lack pericytes and blood
68
List a few diseases of lymphatics
Chronic progressive lymphedema, lymphangioma, lymphangiosarcoma
69
Subcutis is of what origin?
Mesenchymal
70
Hair is of what origin?
Ectodermal
71
Hair placode formation
Wnt
72
Dermal papilla maturation and elongation
Shh (sonic hedgehog)
73
Where do hairs develop on the body first?
Face, move downward
74
Homeobox is responsible for what (in embryonic development of the hair)?
Distribution of symmetrical follicles
75
FGF-5
Hair length
76
What signals are required to induce anagen?
Wnt (wingless)
Noggin (BMP antagonist)
Shh (in mature follicles)
77
Lef-1
Transcription factor involved in Wnt signaling pathway. If constantly on -> trichoepitheliomas.
Noggin increases Lef-1.
78
What signals induce catagen?
BMP, EGFr, FGF, vitamin D receptor
79
Essential for development of IRS and hair shaft?
BMP (TGF-b family)
80
EDA
Essential for development of ectodermal tissues (hair, teeth, glands). Downstream mediator of Wnt.
81
Hair shaft
Central medulla, cortex, hair cuticle. Melanin pigment in cortex determines hair color.
82
Anatomy of the hair follicle
Hair shaft
Infundibulum
- skin surface ->SG
Isthmus
- SG -> bulge
- IRS disappears here
Inferior
- bulge -> bulb
Bulb
83
Inner root sheath
- Present bulb to isthmus.
- Absent in telogen follicles.
- Henle (outerside) keratinizes first, Huxley keratinizes at Adamson's fringe.
- Has KHG
- Molds hair shaft
- Moves upwards
84
Outer root sheath
- Contains stem cells
- Goes through trichellimal keratinization at the isthmus
- Continuous with epidermis
- Upper portion has langerhans cells and lower has immune privilege
- Stationary
85
Glassy membrane
Basement membrane derived, surrounds ORS, continuous with BM of dermal papilla. Mineralization happens in toy poodles, beddlington terriers and older dogs.
86
Growth, regression, resting, shedding, hairless
Anagen, catagen, telogen, exogen, ketogen
87
Chinese crested have a defect in which follicular structure?
IRS keratinization defect
88
Hair cycling pattern in most animals vs. rabbits vs. GP
Mosaic vs. synchronized vs. ventral to dorsal
89
Photoperiod is most important for what?
Hair cycling. Followed by temperature.
90
What effect do the following have on hair cycling?
Thyroid hormones
Glucocorticoids
Estrogens
Androgens
Spay
Stimulate
Suppress
Suppress
Suppress (humans), minimal effect animals
Wooly coat
91
What happens when hair follicle immune privilege collapses?
Alopecia areata
92
How does the hair follicle maintain immune privilege?
Reduce MHC 1 & 2, increase CD200, ECM barriers, cytokine production (TGF=b, IL-10)
93
Holocrine glands
Sebaceous glands
94
Merocrine glands
Atrichial / eccrine
Footpads only
95
Apocrine glands
Epitrichial (haired skin)
96
Oil Red O
lipid stain
97
Testosterone dependent gland
Tail gland (supracaudal)
98
Androgen dependent gland
Perianal glands (circumanal or hepatoid)
99
Distribution of melanocytes.
Epidermal (basal layer) and follicular (ORS, hair matrix)
100
Melanocytes express which primary adhesion molecule?
E-cadherin (b/w melanocyte + KC)
101
Fontana-Masson
Melanocytes
102
Melanocyte IHC markers
Vimentin, S-100
103
Chromatophores
Fish, reptiles contain this as pigment which reflect light
104
Discuss the origination and development of melanocytes.
Neural crest:
- Wnt
- BMP
- FGF
Melanoblasts:
- Wnt
- SOX10
- MIFT
Migration:
- ET-3
- SCF-c-KIT
- HGH
- FGF
Proliferation:
- ET-3
- FGF
- HGF
- Wnt
Melanocyte:
- MIFT
- BMP
105
Eumelanin vs. Pheomelanin
- Black brown vs. red-yellow
- Low in cysteine vs. high in cysteine
- High level tyrosinase vs. low level tyrosinase
106
MCR1 is activated by a-MSH to promote ____, and if it is inhibited or mutated, ____.
Eumelanin
Pheomelanin
107
What gene is responsible for determining whether eumelanin or pheomelanin is produced?
MCR1 gene
108
Which gene is responsible for determining lighter or darker eumelanin?
TYRP1
109
What competes with a-MSH for MC1r on melanocytes? What does it promote?
Agouti signaling protein (ASP) inhibits MCR1 -> pheomelanin
110
Pigmentary and non-pigmentary functions of melanocytes.
Pigmentary: cosmetic, UVR, free radical scavenging
Non-pigmentary: secrete IL-8, IL-1a, TNF-a, inhibit KC proliferation, regulate calcium homeostasis
111
Which inhibitor blocks the neural crest cell differentiation into melanocytes that is reduced by UV light?
BMP-4
112
Rate limiting step of melanogenesis AND co-factor?
Tyrosine -> L-Dopa by enzyme tyrosinase with copper as critical co-factor
113
Master transcription factor of melanogenesis
MIFT: induces transcription of tyrosinase, and other things that are needed for melanogenesis
114
What is the primary transcription factor in melanogenesis?
MIFT
115
What are the critical co-factors in melanogenesis?
Copper AND zinc (TRP2 -> TRP1)
116
What is the intermediate step in melanogenesis?
DOPAquinone (split where it either goes to eumelanin or pheomelanin)
117
c-KIT and SCF
Stem cell factor (SF) binds c-KIT receptor on cell surfaces ---> phosphorylation of MIFT activating it's transcription of genes related to melanocyte proliferation, survival, differentiation, melanogenesis.
More transient signaling?
118
What gene abnormality would a ferret with blue eyes and a blaze?
MITF, PAX3, SOX10
119
How does UV light induce melanogenesis?
UV light -> damage to DNA -> induces p53 to lead to POMC being made which breaks into a-MSH which binds MC1r leading to MIFT transcription of tyrosinase
120
What does Wnt3a do in melanogenesis?
Maintains MIFT transcription
121
What does a-MSH do in melanogenesis?
One of the MAIN drivers/stimulators (binds MC1r and induces MIFT transcription).
122
Drivers of melanogenesis?
a-MSH (main).
Other drivers: ACTH, endothelin-1, SF, leukotrienes, PGD, UV-r, NO, histamine
123
Endothelin-1 vs. Endothelin-3
ET1: activates tyrosinase
ET3: melanoblast migration from dermis to basal cells, enteric nerve formation
124
Defects in endothelin pathway lead to what disease?
Waardenberg
Lethal white foal syndrome
125
What is PMEL17?
Holds melanin in melanogenesis.
126
What is dynein vs. kinesin?
Kinesins: antegrade movement of melanosome along dendrite
Dynein: retrograde. movement
127
Myosin-V
anchors actin at dendrite tip for melanosome transfer
128
Cytocrinia
Unique transfer process in which melanocyte ejects melanosome into KC
129
Hair follicle melanocyte vs. epidermal melanocyte
HF: larger, more dendritic, produces larger melanosomes, only present during anagen, proliferation dependent on c-Kit (on melanocyte) and steel factor synthesis (from KCs)
130
What disease may be suspected if you see the following on trichogram:
- Two brooms pushed together
- Trichoptilosis
- Exclamation point
- Onion-like bulb
- Cork-screw hairs
- Comma hairs
- Hair casts
- Macromelanosomes
- All telogen hairs
- Dysplasia of the hair shaft
- Brooms: trichorexxis nodosa
Trichoptilosis: split ends from trauma
- Exclamation point: alopecia areata
- Onion-bulk: Abyssinians
- Cork screw: dermatophytosis
- Comma: dermatophytosis
- Casts: demodex, sebaceous adenitis, follicular disorders
- Macromelanosomes: CDA, BHFD
- All telogen hairs: endocrinopathy
- Hair shaft: follicular dysplasia
LT ACVD
flashcards
Decks in class (16)
# Cards
-
Genodermatosis88
-
Large Animal96
-
Nail terminology22
-
Structure / Function130
-
Cytokines48
-
Infectious disease220
-
Parasitology112
-
Exotics144
-
Immune function116
-
Internal Medicine + Oncology224
-
Nutrition, environmental, trauma113
-
Pharmacology235
-
Dermatohistopathology72
-
Otology134
-
Atopy166
-
Psychoneurodermatology60
