Dermatology Basic Science Flashcards
Desmosomes anchor to what.
Keratins
Desmosomes are consist of what. Which are cytoplasmic and which are transmembrane
Transmembrane: desmocollin1/2/3, desmoglein 1/3
Cytoplasmic: desmoplakin, plakoglobin, plakophilin
What mineral is desmocollin, desmoglein and other cadherins dependent on?
Calcium
What are the 4 types of ways keratinocytes connect to each other?
Desmosomes, adherens, tight junctions, gap junction
Adherins junctions attach to what?
Actin filaments
What do adherens junctions consist of? Which is transmembrane and which is cytoplasmic?
Transmembrane: Classic cadherins (E and P)
Cytoplasmic: alpha catenin, beta catenin
What are tight junctions composed of? And where are they?
Granular Layer. Composed of claudins and occludins. Form tight seal against water loss
What are gap junctions composed of?
connexons. for intercellular ocmmunication.
What keratins are at the basal layer
Keratin 5/14
Increased keratinocyte proliferation is associated with what enzyme? What other factors?
UV, trauma, increased expression of ornithine decarboxylase
Ornithine decarboxylase is inhibited by what 3 things?
corticosteroid, retinoids and vitamin D3
How many days from basal layer to desquamation?
28 days
What keratins are in the stratum spinosum?
Keratin 1 and 10
What causes terminal keratinocyte differentiation in the stratum spinosum
increased intracellular calcium
Cornified cell envelope: Most important lipid? Protein?
Most important lipid is ceramide. Most important protein is loricrin (makes up 80% mass of CE).
Components of keratohyaline granules?
Loricrin, Profillagrin (converted to fillaggrin at the junction of stratum granulosum and stratum corneum), keratin intermediate filaments, involucrin
What enzyme cross links loricrin?
Transglutaminase 1, which is mutated in lamellar ichthyosis. *transglutaminase 3 is targeted in dermatitis herpetiformis
What protein is in both desmosomes and adherens?
Plakoglobin (which is part of the armadillo family)
Desmoglein 1 is affected in what disease states?
Striate PPK, PF, + (PNP, PV, IgA pemphigus) Bullous impetigo, SSSS. (in parenthesis also see in desmoglein 3 mutation)
Desmoglein 4 is affected in what disease states?
Monilethrix (AR), autosomal recessive hypotrichosis
Desmocollin 1 is mutated in what disease states?
IgA pemphigus (SPD type)
Plakoglobin is mutated in what disease states?
Naxos Syndrome
Desmoplakin is mutated what disease states?
Carvajal Syndrome
Beta catenin mutated in?
pilomatricomas seen in myotonic distrophy and Rubenstein-Taybi
Erythrokeratoderma varriabilis mutations in what protein?
Connexin 30.3 and 31
Hidrotic ectodermal dysplasia mutations in what protein?
Connexin 30
Connexin 26 mutations in what diseases?
KID, Bart-Pumphrey, PPK w deafness, Vohwinkel
Keratins
intermediate filaments
Type 1 keratins are low molecular weight keratins. Acidity? Keratin numbers? Chromosome #?
Low-MW Acidic, K9-28, K31-40. Chromosome 17
Type 2 keratins are high molecular weight keratins. Acidity? Keratin numbers? Chromosome #?
High MW. Basic K1-8, K81-86. Chromosome 12
What is the functional unit of a keratin?
Functional unit consist of heterodimers of type 1 and type II filaments that form tetramers and ultimately filaments
Melanocytes are derived from from what cells?
Neural crest cells
Each melanocyte interfaces with how many keratinocytes?
36 (epidermal melanin unit)
Tyrosinase is dependent on what mineral?
Copper
Describe pheomelanin and eumelanin. Melanosome size and colors they make.
Pheomelanin makes yellow/red. Made by round melanosomes. Eumelanin makes black/brown via elliptical melanosomes.
What causes the red hair/fair skin phenotype?
MC1-R loss of function mutation causing increased pheomelanin:eumelanin ratio.
How does skin immediately tan?
Through oxidation of existing melanin
Defects of tyrosinase, packaging of melanosome-specific proteins, lysosome/melanosome trafficking to dendrites cause which diseases?
OCA (oca1 tyrosinase, oca2 p gene, oca3 trp-1). Hermansky-Pudlak (Defects in packaging of melanosome specific proteins). Griscelli + Chediak Higashi are defects in lysosome and melanosome trafficking to dendrites.
Langerhan cell immunostains
CD 207 (langerin, which is the most sensitive and specific), CD1a, S100, CD34 (originate from CD34+ progenitor cells in bone marrow like other monocytes/macrophages), vimentin and actin
Merkel cells are ___. Found in ____.
Merkel cells are slow-adapting mechanoreceptos found in fingertips, lips, oral cavity, hair follicle ORS. Found in stratum basale.
Merkel cell stains for
CK 20+ perinuclear dot, neurofilament, S100, synaptophysin, chromogranin A, VIP, neuron specific enolase and calcitonin gene-related peptide
Lamina Lucida consists of what 3 proteins?
BPAG 2 (collagen 17, BP180), a6b4 integrin, laminin 332 (aka laminin 5, epiligrin)
Lamina Densa consists of what 3 proteins?
Laminin 5 (laminin 332), Collagen 4 (main component), nidogen
Anchoring filaments refers to
bpag2, a6b4 integrin, laminin 332 (aka laminin 5, epiligrin)
Anchoring fibrils refers to
collagen type 7
How does the Basement Membrane Zone function as a permeability barrier?
It has heparan sulfate proteoglycan (negatively charged) in lamina densa, giving a negative charge to the basement membrane.
Collagen composed of what structure?
GLY-X-Y
What two BMZ proteins are park of the plakin family?
BPAg 1 , Plectin
Diseases that affect BPAG1
BP, Paraneoplastic Pemphigus
Diseases that affect BPAG2 N16A extracellular domain?
BP, Pemphigoid gestationis, linear IGA
Diseases that affect BPAG2 Carboxy extracellular domain?
Cicatricial pemphigoid
Diseases that affect a6b4
a6: JEB with pyloric atresia
b4: ocular cicatricial pemphigoid
Diseases that affect laminin 332, laminin 5, epiligrin
Antiepiligrin pemphigoid, JEB
Diseases that affect plectin
EB with muscular dystrophy, EB with pyloric atresia
Diseases that affect collagen 7
dystrophic EB, bullous lupus, EBA
What is the primary collagen in ECM?
collagen 1
What is the collagen 3 found in?
blood vessels, fetal skin, GI tract, new scars, keloids
What enzyme crosslinks collagen?
Lysyl hydroxylase, proline hydroxylase
What accounts for 75% dry weight of the skin? 4%?
Collagen makes up 75%, Elastic Fibers make up 4%
What are elastic fibers made from? What enzyme cross-links the elastic components to each other? What mineral is necessary for these enzyme’s functioning?
Elastic fibers are made from 90% elastin (core) and 10% fibrillin (surrounds elastin). Elastin contains high levels of desmosine and isodesmosine. Lysyl oxidase crosslinks elastin with fibrillin. Copper is necessary for function.
Elaunin fibers run which way. Oxytalan fibers run which way.
Elaunin fibers run horizontally. Oxytalan fibers run perpendicular.
Elastic fibers are in a matrix of glycosaminoglycans which are made from?
Glycosaminoglycans are: hyaluronic acid, chonroitin sulfate, dermatan sulfate and heparan sulfate.
What are lymphatic markers?
D2-40, LYVE-1, Prox1
Itch and pain are innervated by what nerves?
A-delta (larger myelinated) and C-unmyelinated fibers. There are nerves with free nerve endings
Where do Krause end bulbs innervate?
Genitalia, perianal region and vermillion lips. Krazy Krause ens on erotic areas
Where and what do meissener’s corpuscles innervate?
Fast adapting mechanoreceptor of digits; Pressure/light touch. In superficial dermis
Where and what do pacinian corpuscle innervate?
Fast adapting mechanoreceptor of palmoplantar skin, nipples and genital region. Suited for vibration and deeper pressure
Where and what do merkel disksinnervate?
Slow adapting mechanoreceptor of fingertips, lips, and external genitalia. Suited for pressure/touch. Located in the superficial basal epidermis
Where and what do ruffini corpuscle innervate?
Slow adapting mechanoreceptor of fingernails. Deep fat. Sustained pressure
Apocrine glands are under adrenergic or cholinergic control?
adrenergic
Eccrine glands are under adrenergic or cholinergic control?
cholingeric
Eccrine glands are responsible for what function? Sweat is hypertonic/hypotonic?
Thermoregulation. Sweat delivered to the surface is hypotonic. Sweat is secreted as isotonic, but NaCl is reabsored in duct. As the rate of sweating increases, then the solution is more isotonic.
What glans secrete via merocrine, depcapitation secretion, holocine secretion?
Eccrine (merocrine horse looking at mirror), Apocrine (decapitation), Sebaceous glans (holocrine)
Eccrine glands stain with ?
S100, keratin, CEA
Where does apocrine glands empty into?
Empty into follicular infundibulum, above the sebaceous duct. Air above the Sea.
Apocrine glands of the eyelid are called?
Moll’s glands of the eyelids. which empty directly to the surface. ( Ape running through a mall to get eyelashes)
Where does sebaceous glands empty into?
Empty into follicular infundibulum, below the apocrine
What are the components of sebaceous glands?
triglylcerides 50%> wax esters > squalene
Ectopic sebaceous glands on the eyelid tarsal, eyelid margin, lip, areola, prepuce.
eyelid tarsal (meibomian, usual for Kat), eyelid margin (Zeis) , lip (fordyce), areola (montgomery), prepuce (tysons)
How many hairs on the scalp?
100,000
Infundibulum describes the area from what to what?
skin to sebaceous gland opening to the hair follicle
Isthmus describes the area from what to what?
from sebaceous gland to arrector pili muscle
Telogen hairs don’t have what layer of the hair?
Telogen hairs don’t have the inner root sheath
Melanin unit of the hair
1 melanocyte: five keratinocytes
At how many weeks do melanocytes, LCs and merkel cells migrate into the epidermis?
9-12 weeks
What are the durations of the Anagen, Catagen, Telogen?
Anagen (3 years), Catagen (3 weeks), Telogen (3 months)
Complete renewal of the epidermis every how many weeks?
Every 52 weeks
Order of cell influx for wound healing?
Platelets+ Fibrin + Fibronectin–> Neutrophils–> Macrophages
Fibronectin is replaced by
Fibronectin replaced collagen III and then collagen I
UVA and UVB wavelength
UVA (320-400) and UVB (280-320) wavelength
UVA and UVB presence t/o the day
UVA consistently from sunrise to sunset. UVB peaks around noon.
What does UVB, liver and kidney do for vitamin D?
UVB responsible for converting provitamin D3 to previtamin D3. The Liver converts to 25-hydroxyvitamin D3. Kidney convert to 1,25-hydroxyvitamin D3.
Cathelicidins and defensins are ?
Antimicrobial peptides of the innate immune system. (increased in psoriasis and decreased in atopic dermatitis).
Steps of a PCR?
Denaturation, primer annealing/hybridization, primer extension, repeat
Why does RT-PCR reverse transcribe the mRNA into DNA?
Because RNA is fragile.
What is the purpose of Quant-PCR, or Quant-RT-PCR
To measure and compare the number of mRNA transcripts in different types of cells
What is the purpose of a western blot?
To measure the size and amount of protein present in a sample. In this assay, a mixture of proteins is first separated based on molecular weight and/or charge by electrophoresis in a gel matrix, then transferred to a membrane and probed with antibody specific to the protein of interest. The relative amount of protein in different samples may be compared and approximated.
What is the purpose of a ELISA?
High sensitivity and medium specific method for quantifying the amount of a protein. Requires an intact protein. The higher throughput than Western blots, but like Western blots offer only monoplex data, or results of a single protein per assay.
What is the purpose of a Nucleic Acid Assay?
To profile the mRNA expression of thousands o genes in one experiment. Usual patterns of gene expression of two samples are compared to one another (normal vs tumor)
What activation pathway do TLRs use?
All TLRs except for TLR3 use myd88signaling pathway. Myeloid differentiation primary response 88
What is responsible for leukocyte rolling
P selection, e selection
Bakers itch
Acarus mites in flour, hay and dust
Grocers itch
Carpoglyphus passularum (a fruit mite) or Glyciphagus domesticus (a common house mite). Contact usually occurs when handling food with mites in it, such as figs, dates, prunes, grain, cheese, or other dried foods
Isotopic
Rash on top of another rash. ISOTOPIC
What’s wrong with micronized sunscreen
Titanium has more UVB
ZINC HAS MORE UVA AND SLIGHLT MORE UVB
What protein is up regulated in sunburn
P53
