Structure and Function of the Skin

Question 1

_________ are a gene family critical for normal embryologic development; they likely play a very important role in development of skin adenexa, pigment system, and stratified epithelium during embryogenesis.

Answer 1

Homeobox (hox) genes

Question 2

What are the three layers of the ectodermal covering?

Answer 2

1. The basal layer (stratum germinativum)
2. The outer layer (periderm)
3. Then 3 layers forms in between the two layers (stratum intermedium)

Question 3

Dermal development is characterized by an _____ in thickness and number of fibers, a decrease in ground substance, and the transition of ____ cells to _______.

Answer 3

increase
mesenchymal cells to fibroblasts.

Question 4

Fetal skin contains a large percentage of type____ collagen compared with the skin of an adult, which contains a large proportion of type ____collagen.

Answer 4

III
I

Question 5

Embryonal stratum germinativum differentiates into hair germs (primary epithelial germs) that give rise to what three structures?

Answer 5

hair follicles, sebaceous glands, and epitrichial (apocrine) sweat glands.

Question 6

The epidermal placode develops into what three epithelial cylinders?

Answer 6

Innermost = hair shaft
Outermost cylinder = outer root sheath (ORS)
Middle = inner root sheath

Question 7

As the hair peg lengthens, and develops into a hair follicle and hair, list the three bulges that appear?

Answer 7

Lowest (deepest) = develops into the attachment for the arrector pili muscle
Middle = develops into the sebaceous gland
Uppermost = develops into the epitrichial sweat gland

Question 8

Secondary hairs develop on the caudal or cranial side of the primary hair follicle.

Answer 8

caudal

Question 9

What are the six major morphogenic family systems have been recognized to be important

Answer 9

Genes of the Hox cluster
Fibroblast growth factor (FGF)
Transforming growth factor (TGF-B)
Sonic hedgehog (shh)
Wingless or wnt pathway
Neurotrophins

Question 10

What is a marker of early anagen hair follicles and it is important in the protein cross-linking that contributes to the shape and strength of hair?

Answer 10

Transglutaminase

Question 11

The diameter of the hair shaft is determined by the volume of ______, and the length of the hair shaft is determined by both the rate of the hair growth and duration of the anagen.

Answer 11

the hair matrix epithelium

Question 12

The hairs of the cat have been divided into three types based on the gross appearance:

Answer 12

Guard hairs (thickest, straight, evenly tapered to a fine tip).
Awn hairs (thinner, possessing subapical swelling below the hair tip).
Down hairs (thinnest, evenly crimped or undulating.)

***The secondary hairs of the cat are far more numerous than primary***

Question 13

All hair follicles grow in what direction in relation to the epidermis?

Answer 13

obliquely (30-60 degrees)

Question 14

During what phase of the hair cycle do large numbers of keratinocytes in the outer root sheath undergo apoptosis and the epithelial strand regress?

Answer 14

catagen

Question 15

_____ are thought to play a fundamental role in induction of epithelial differentiation. They are the primary target cells that respond to hormones and mediate growth-stimulating signals to the follicular epithelial cells.

Answer 15

Dermal papilla cells (mesenchymal component of hair bulb)

Question 16

Alterations in ____ that control hair follicle structure result in follicular dysplasia.

Answer 16

morphogens

Question 17

What is the normal coat comprised of?

Answer 17

The normal coat is see in the GSD, Welsh Corgi and wild dogs. It is composed of primary hairs (course guard hairs or bristles) and secondary hairs (fine hairs or undercoat).

Question 18

What are the reported ultrastructural changes reported in non-lesional AD skin?

Answer 18

Widening of the intercellular spaces, retention of lamellar bodies in the corneocytes and irregularities and fragmentation of lipid lamellae.

Similar to humans with AD

Question 19

Colonization of staphylococcus sp can result in an increase in ____ and ____ from cutaneous T-cells. This increase in ___ can induce the production of fibronectin, which increases the adherence of staph to keratinocytes.

Answer 19

IL-4/IL-13
IL-4

***Dupulimab binds to the alpha subunit which is shared by IL-13***

Question 20

Colonization by Staph spp. further damages atopic skin as bacteria produce ______ and _____, which additionally decrease ceramides in the SC.

Answer 20

ceramidases and proteases

Question 21

What gene family encodes information critical for normal embryologic development of skin adenexa, pigment system and stratified epithelium during embryogenesis?

Answer 21

Homeobox (Hox) genes
Encode a sequence of 60 amino acids that bind to DNA and regulate transcription (expression of genes into proteins)

Question 22

Embryonic skin consists of a single layer of _____ cells and a dermis containing loosely arranged _____ cells embedded in an interstitial ground substance.

Answer 22

ectodermal
mesenchymal

Question 23

Melanocytes (neutral crest origin) and Langerhans cells (bone marrow origin) become identifiable during what period of embryonic maturation?

Answer 23

ectodermal

Question 24

Dermal development is characterized by an increase in thickness and number of fibers, a decrease in ____ and a transition of mesenchymal cells to _____.

Answer 24

ground substance
fibroblasts

Question 25

Fetal skin contains a large percentage of type ___ collagen compared to the skin of adults which contains a large amount of type ___ collagen.

Answer 25

III I

Question 26

The embryonal stratum germinativum differentiates into hair germs (primary epithelial germs) that give rise to \_\_\_\_, _____ and \_\_\_\_\_.

Answer 26

hair follicles sebaceous glands apocrine glands

Question 27

Hair germs initially consist of an area of crowding or deeply basophilic cells in the basal layer of the epidermis. The areas of crowding becomes buds known as\_\_\_\_\_\_ that protrude into the dermis. Each bud lies a group of mesencymal cells, referred to as _____ from which the dermal papilla is later formed.

Answer 27

epidermal placodes dermal condensate

Question 28

What three epithelial cylinders develop from the dermal placode?

Answer 28

``` innermost = hair shaft middle = IRS outermost = ORS ```

Question 29

As the hair peg lengthens and develops into a hair follicle and hair, three bulges appear? What are the three bulges and what do they develop into?

Answer 29

The lowest (deepest) of the bulges develops into the attachment for the arrector pili muscle; the middle bulge differentiates into the sebaceous glands and the uppermost bulge evolves into the epitrichial sweat gland. These appendages develop on the cranial side of primary hair follicles; secondary hair follicles develop on the caudal side.

Question 30

Where do first hairs appear on the fetus?

Answer 30

vibrissae and tactile or sinus hairs that develop on chin, eyebrows and upper lip as slightly raised dots.

Question 31

At birth, the majority of hair follicles or dogs are ____ ones; ______ develop caudal to the primary hairs during the first 12- 28 weeks of life.

Answer 31

primary secondary follicles

Question 32

\_\_\_\_\_ are substances that control hair follicle development.

Answer 32

morphogens

Question 33

The skin, hair and subcutis of a newborn puppy represent XX% of its body weight, these structures represent approximately XX% of body weight

Answer 33

24 12

Question 34

The pH of normal canine skin is ranges from __ to \_\_.

Answer 34

4.84 - 9.95

Question 35

What enzyme is a marker of early anagen hair follicles, and it is important in the protein cross-linking that contributes to the shape and remarkable physical strength of hairs?

Answer 35

Transglutaminase

Question 36

What are the known growth factors involved in hair follicle induction?

Answer 36

EGF, TGFB1, TGFB2, neurotrophic 3. These growth factors control cellular proliferation and collagenase release from cultured hair follicles.

Question 37

What cell types are involved in the regulation of hair growth, especially during catagen phase?

Answer 37

Interplay between MHC I, chondroitin proteoglycans and activated macrophages.

Question 38

What are intrinsic factors involved in hair cycle?

Answer 38

growth factors, cytokines, dermal papilla, inflammatory cells int he immediate environment

Question 39

The hair cycle and haricot are also affected by hormonal changes. In general, anagen is initiated and advanced by _____ and ____ hormone. Excessive amounts of ____ or ____ inhibit anagen and suppress hair growth rate.

Answer 39

Thyroid, Growth GC, estrogens

Question 40

\_\_\_\_ cells, which are mesenchymal component of the hair bulb, are considered to play a fundamental role in the induction of epithelial differentiation.

Answer 40

Dermal papilla, These cells are morphologically and functionally differentiated from dermal fibroblasts and are thought to be the primary target cells that respond to hormones and mediate growth-stimulating signals to the follicular epithelial cells.

Question 41

What is a 'normal coat'?

Answer 41

Typified by that seen in GSD, Corgi and wild dogs. It is composed of primary hairs (course guard hairs or bristles) and secondary hairs (fine hairs or undercoat).

Question 42

What is a 'short' coat?

Answer 42

The coarse short coat is typified by the Rottweiler and many of the terriers. This type of coat has a strong forth of primary hairs and a much lesser growth of secondary hairs. The fine short coat is exemplified by the boxer, dacshunds, and miniature pinchers. This type of coat has the largest number of hairs per uint area. the secondary hairs are numerous and well developed, and the primary hairs are reduced in size compare dot those of the normal coat.

Question 43

What is the 'long coat'?

Answer 43

The long coat can also be arranged into two subdivisions: the fine long coat and the woolly or course long coat. The fine long coat is found int he cocker spaniel, the Pomeranian and the chow chow. The woolly or course long coat is found in the Poodle, Bedlington terrier and Kerry blue terrier. Secondary hairs make up 70% of the total weight of these coats.

Question 44

Describe the classic 'agouti-type' hair

Answer 44

Ex are the GSD and Norwegian Elkhound The tip is white or light, the heavy body is pigmented brown or black, and the base is a light yellow or red-brown. Pigment cells in the bulb or the hair deposit pigment in or between the cortical and medullary hair cells.

Question 45

The black-brown pigment is \_\_\_\_\_; yellow-red pigment is called \_\_\_\_\_.

Answer 45

eumelanin pheomelanin

Question 46

Activation of melanocortin 1 receptors (MCR1 gene) on melanocytes leads to production of \_\_\_\_\_\_; inhibition or MCR1 results in the production of \_\_\_\_\_.

Answer 46

eumelanin pheomelanin

Question 47

What gene controls the shade of eumelanin?

Answer 47

Tyrosine related protein gene 1 (TYRP-1)

Question 48

The generally recognized gene series involved in the coat color of dogs are called A, B, C, D, E, G, H, I, K, M, P, R, S and T.

Answer 48

1. Agouti (ASIP) 2. brown (TYRP1) 3. C (colored/albino) 4. D (blue dilution, melanophilin (MLPH) 5. extension (MC1R) 6. G (graying) 7. H (Harlequin) 8. I (phaeomelanin dilution) 9. K (black, beta0defensin 103) 10. M (merle, SILV) 11. P (dilute) 12. S (spotting, microphthalmia-associated transcription factor, MITF) 11. T (ticking)

Question 49

What does the 'tabby' coloration consist of?

Answer 49

The underlying pattern is agouti - characterized by hairs with a blueish base and a black tip separated by yellow banding. The tabby genes determine whether the cat has narrow, vertical, gently curving stripes (mackerel), larger patches (blotch) or Abyssinian pattern.

Question 50

How does temperature play a role in 'tipped hair coats'?

Answer 50

Pointed hair coats are characterized by pale-colored hair not he body with darker hairs on the extremities or points. Points drive through a temperature-dependent enzyme that converts melanin precursors into melanin by the process of oxidation. Higher temperatures = lighter hair. Inflammation and hyperemia result in more lightly colored new hair. Expression of this gene is C, tyrosinase gene, TYR

Question 51

What gene determines the multicolored coats in tortoiseshell and piebald spotting patterns?

Answer 51

White gloves gene (KIT)

Question 52

What gene dilutes black to blue (gray), orange to cream, and seal-point ti blue-point (Siamese) AND is inherited as an autosomal recessive trait?

Answer 52

The dilution gene, melanophilin, MLPH

Question 53

What is the difference between Cornish Rex and Devon Rex?

Answer 53

The Cornish Rex lacks primary hairs; The Devon Rex has primary hairs that resemble secondary hairs with absent or stubbled whiskers.

Question 54

What are the boundaries of the areas of distribution of the main cutaneous nerve stems?

Answer 54

Voight lines

Question 55

What lines reflect the course of blood vessels or lymphatics?

Answer 55

Langer lines

Question 56

What lines form the pattern assumed by many different nevoid and acquired skin diseases?

Answer 56

Blashko Lines These lines reflect a mosaic condition deriving either from a single mutated clone of cells originating from a post zygotic mutation or from an X-linked mutation made evident by lyonization.

Question 57

What are the FOUR distinct cell types within the epidermis?

Answer 57

keratinocytes, melanocytes, Langerhan cells, and Merkel cells.

Question 58

What layer of the epidermis consists of cuboidal to columnar cells resting on the basement membrane zone that separates the epidermis from the dermis?

Answer 58

Basal layer, most of these cells are keratinocytes that are constantly reproducing and pushing upward to replenish the epidermal cells above, Cells of the stratum basale contain K5 and K14 keratin filaments.

Question 59

What major cell adhesion molecule provides an anchor for keratin filaments connecting the nuclear envelop to the cell membrane and also anchors adjacent cells together to stabilize the structure of the epidermis?

Answer 59

Desmosomes

Question 60

What are the three major gene families the molecular components of desmosomes belong to?

Answer 60

plakins (desmoplakin) armadillo proteins (plakophilin, plakoglobin) cadherins (desmogleins, desmocollins)

Question 61

What structures are junctional complexes distributed along the inner aspect of basal keratinocytes; their major role is epidermal-dermal adhesion.

Answer 61

hemidesmosomes

Question 62

What structures are a large family of cell surface adhesive receptors. These cell surface glycoproteins are important in cell-cell and cell-matrix interactions, and also act as signal transducers through which extracellular and intracellular compartments can influence and modify each other?

Answer 62

Integrins Each intern consists of a heterodimer of an a and b subunit which are noncovalently associated. In the epidermis, integral expression is confined to the basal layer.

Question 63

Which integrins are most abundant in the epidermis?

Answer 63

a2, a3,b1,a6 and b4

Question 64

a5b1 function?

Answer 64

mediates keratinocyte adhesion to fibronectin

Question 65

a2b1 function?

Answer 65

mediates keratinocyte adhesion to collagens type 1 and type iV and laminin

Question 66

a3b1 function?

Answer 66

receptor for epiligrin and is involved in adhesion to laminin

Question 67

a1b5 function?

Answer 67

mediates keratinocyte adhesion to vitronectin

Question 68

a6b4 function?

Answer 68

mediates keratinocyte adhesion to laminin

Question 69

What layer of the epidermis is composed of daughter cells from the stratum basale?

Answer 69

Stratum Spinosum

Question 70

What are the four major types of adhesive and communicative structures the mediate keratinocyte adhesion?

Answer 70

desmosomes, hemidesmosomes, adherens junctions and focal adhesions,

Question 71

What structures serve primarily as intercellular route of chemical communication?

Answer 71

gap junctions

Question 72

What are the three types of cytoplasmic filaments that make up the keratinocyte cytoskeleton?

Answer 72

cytokeratin actin microtubules (tubulin)

Question 73

\_\_\_\_\_ and _____ are crucial for desmosome and hemidesmosome formation.

Answer 73

calcium and calmodulin

Question 74

What three keratinocyte derived calmodulin-binding proteins participate in a flip-flop regulation of calcium-calmodulin interactions?

Answer 74

caldesmon, desmocalmin and spectrin

Question 75

All epithelia express a keratin pair; which oncists of what structures?

Answer 75

One keratin chain from the acidic subfamily (type 1 keratin, cytokeratins 9-20) and one chain from the neutral-basic subfamily (type II keratins, cytokeratins 1-8).

Question 76

What keratins make up the spinous layer?

Answer 76

K1/K10 AND retain K5/14 synthesized in the basal layer

Question 77

Keratinocytes of the stratum spinosum synthesize what products? These are secreted into the intercellular spaces of the stratum granulosu and are important in the barrier function of the epidermis.

Answer 77

synthesize lamellar granules (keratinosomes, membrane-coating granules, Odland bdies) which contain glycolipids, glycoproteins, phosholipids, free sterols, glucosylceramides and acid hydrolyses.

Question 78

Keratinocytes in stratum spinosum synthesize lamellar granules (Odland bodies) which consist of what substances?

Answer 78

profillagrin, keratin filaments, loracrin

Question 79

Where are keratohyalin granules synthesized?

Answer 79

Keratohyalin granules are synthesized in the stratum granulosum; however, they are not true granules because they lack a membrane and are more accurate described as insoluble aggregates.

Question 80

What are profillagrin degradation productions?

Answer 80

urocanic acid, carboxylic acid, lactic acid; important for normal stratum corneum hydration and also help filter UV radiation.

Question 81

What is a cysteine-rich protein synthesized in the stratum granulosum in association with keratinohyalin granules?

Answer 81

loracrin (synthesized in stratum granulosum) involved in binding keratin filaments together in the corneocyte and anchoring them to the cross-linked envelope.

Question 82

What are the two morphologic forms of keratihyalin granules in the rodent?

Answer 82

The P-F granule - irregularly shaped and contains profillagrin; whereas, the L granule is smaller, rounded and contains loricrin.

Question 83

What are the protein components of the CE?

Answer 83

lorcrin, involucrin, filaggrin, elfin, cystitis A, cornifelin, small proline-rich proteins and "late envelope" proteins

Question 84

\_\_\_\_\_\_ are a superfamily of enzymes that are important in apoptosis, keratinization and hair follicle formation.

Answer 84

Transglutaminases; keratinocytes and epidermal transglutaminase mediate the sequential cross-linking of the cornfield cell envelop precursor proteins. Cheifly expressed in the stratum granulosum and upper stratum spinosum.

Question 85

The most important product of the epidermis is \_\_\_\_; a highly stable disulfide condition-containing fibrous protein.

Answer 85

keratins alpha - keratin = skin/hair beta keratins - feathers/scale

Question 86

What is the function of ornithine decarboxylase?

Answer 86

This enzyme is essential for biosynteisis of polyamides (putrescine, spermidine, and spermine); which encourage epidermal proliferation.

Question 87

What are the four distinct cellular events in the process of cornification?

Answer 87

1. keratinization - synthesis of the principle fibrous proteins of the keratinocytes 2. keratohyaline synthesis - including the histidine-rich protein filaggrin 3. formation of the highly cross-linked insoluble stratum corneum 4. generation of neutral lipid-enriched intercellular domains resulting from the secretion of distinctive lamellar granules.

Question 88

Where are lamellar bodies primarily synthesized?

Answer 88

keratinocytes in the stratum spinosum

Question 89

What are amide-linked fatty acids containing a long-chain amino alcohol (spinchoid base).

Answer 89

ceramides; they are the most important lipid component for lamellar arrangement in the stratum corneum and barrier function.

Question 90

Linoleic acid, an essential fatty acid for dogs and cats, found in which ceramides?

Answer 90

Ceramides 1, 4 and 9.

Question 91

Which ceramides bind to involucrin and other proteins of the CE, forming a scaffold for the binding of tother lipids into intercellular lipid bilayer?

Answer 91

Cermides 1 and 2

Question 92

\_\_\_\_\_\_ play a crucial role plasticizing the horney layer to allow stretching and bending by fluidizing barrier lipids.

Answer 92

ceramides

Question 93

What are transient amplifying cells?

Answer 93

Proliferating keratinocytes that have limited capacity for self renewal & will after a couple of divisions terminally differentiate Both stem cells and amplifying cells lives in basal layer & lower spinous layer Divide rapidly—have an avid uptake but short retention of thymidine

Question 94

What are the three basal cell states?

Answer 94

1. Holoclones: correspond to stem cells Colonies of small, regular cells Give rise to many other colonies A single stem cell from holoclone can give rise to up to 4 million keratinocytes. 2.Meroclones: correspond to the transient amplifying cells Produce colonies, but fewer in number than holoclones Located in the basal and suprabasal layers Provide the bulk of cell divisions needed for stable self-renewal 3. Paraclones: correspond to differentiated, postmitotic cells; Undergo terminal differentiation Yield only very small number of colonies

Question 95

List characteristics of the basal cell layer?

Answer 95

Contains mitotically active, columnar shaped keratinocytes Contain pigmented melanosomes transferred via phagocytosis from melanocytes Attach via keratin filaments (K5 & K14) to basement membrane zone at hemidesmosomes Also express K19 & 15 Attach to other surrounding cells through desmosomes Major function: provided mechanical attachement to underlying basement membrane through hemidesmosomes & integrins

Question 96

Desmosomes

Answer 96

Ca-dependent cell surface modifications that promote adhesion of epidermal cells and resistance to mechanical stress Site where the metabolic barrier of the epidermis occurs

Question 97

Most of the process of terminal differentiation is determined by ______ levels

Answer 97

Low calcium maintains keratinocytes in a high proliferation/low differentiation state High calcium promotes terminal differentiation of keratinocytes

Question 98

\_\_\_\_\_ promotes transition from spinous to granular layer cells

Answer 98

Protein kinase C

Question 99

Recessive X-linked ichthyosis

Answer 99

mutation of steroid sulfatase Results in retention hyperkeratosis

Question 100

Profilaggrin

Answer 100

(F granules) 1st appearing in the granular layer & diffusely distributed w/n cytoplasm Profliaggrin: large Ca binding phosphoprotiein of 10-12 repeating copies of filaggrin protein Release from the keratohyalin granules results in a Ca2+ dependent cleavage (dephosphorylation & proteolysis) into filaggrin monomers Occurs upon entering the transition zone between granular layer & stratum corneum

Question 101

Filaggrin

Answer 101

aggregates with keratin to form macrofilaments A cationic protein, rich in histidine residues Function: an intermediate filament-associated protein, organizing & aggregating keratin into macrofibrils Degraded into free amino acids & molecules including: Urocanic acid & pyrrolidone carboxylic acid Contribute to hydration of stratum corneum & help filter UV radiation

Question 102

Mutation in Transglutaminase 1 gene

Answer 102

lamellar ichthyosis Autosomal recessive condition characterized by large scales and disruption in the uppermost differentiating layers of the epidermis

Question 103

Loricrin abnormalities lead to what two diseases in humans?

Answer 103

Vohwinkel syndrome with ichthyosis progressive symmetric keratodermia

Question 104

Clear Layer contains refractile droplets and a semifluid called what?

Answer 104

eleidin Stratum lucidum, stratum conjunctum Fully keratinized, compact, thin layer of dead cells Anuclear, homogeneous, and hyaline-like Differs histochemically from SC by being rich in protein-bound lipids Best developed in food pads; less developed in nasal planum and absent in all other places

Question 105

What layer of the epidermis is characterized by stacked layers of anucleate, flattened, eosinophilic cornified cells?

Answer 105

Stratum Corneum - Drastic remodeling occurs during the transition from granular cell layer to the stratum corneum Formed by a two-compartment system of lipid-depleted, protein-enriched corneocytes surrounded by a continuous extracellular lipid matrix

Question 106

Primary functions of the extracellular lipid matrix:

Answer 106

Regulation of permeability, desquamation, antimicrobial peptide activity, toxin exclusion, and selective chemical absorption

Question 107

Primary functions of the corneocytes:

Answer 107

Mechanical reinforcement hydration cytokine-mediated initiation of inflammation protection from UV damage

Question 108

The cytoskeleton of all cells of mammals are composed of three filament system:

Answer 108

Microfilaments (6nm) Intermediate filaments (8-10nm) microtubules (25nm)

Question 109

All intermediate filaments contain what 3 structures?

Answer 109

1. Central α helical rod 2. Conserved secondary structure 3. Flanked by distinct amino head & carboxyl terminal end domains

Question 110

Intermediate filaments are subdivided into what 6 groups based on tissue specificity and amino acid sequence?

Answer 110

Acidic type I-------epithelial keratin (9-23) Basic type II-----epithelial keratin (1-8) Type III: vimentin (mesenchymal cells), desmin (muscle), peripherin (peripheral nervous system), & glial fibrillary acidic protein (GFAP) (Glial cells and astrocytes) Type IV: α-internexin (neurofilaments) Type V: lamins (nucleus) Type VI: nestin (stem cells of CNS and skeletal muscle)

Question 111

What are the 3 types of cytoplasmic filament that keratinocyte cytoskeleton consists of?

Answer 111

Actin, microtubules and cytokeratin

Question 112

Largest group of intermediate filaments

Answer 112

Keratins Hallmark of all epithelial cells, including keratinocytes Account for up to 85% of total protein of fully differentiated cells Serve a predominately structural role in the cells

Question 113

Describe Type 1 keratin filaments

Answer 113

Acidic K9-K20

Question 114

Describe Type 2 keratin filaments

Answer 114

Basic or neutral K 1-8

Question 115

Primary keratin structure

Answer 115

Two different chains assemble in pairs to create dimmers Consist of an acidic & a basic keratin subunit Composed of two α-helical chains oriented in a parallel & interwined in a coiled-coil rod formation

Question 116

Describe formation of the cornified cell envelope

Answer 116

As intracellular Ca2+ levels rise in suprabasal cells, envoplakin, periplakin and involucrin are expressed (PIE) and fuse to the plasma membrane via the action of TG1 and 5 (calcium dependent) Lamellar granules fuse to the plasma membrane then get lipid excretion into the intercellular space. TG1 crosslinks ceramide to proteins TG3 crosslinks Loricrin (most abundent) & SPR (small proline rich peptides) - Now PILES)

Question 117

Where are intercellular lipids initially stored?

Answer 117

Intercellular skin lipids are initially stored in the lamellar granules which get extruded into the extracellular space in the upper granular layer during cornification

Question 118

What is the precursor molecule to ceramides?

Answer 118

glucosylceramides (precursor to ceramides, dominant component of the stratum corneum lipids)

Question 119

Where do lipids originate from?

Answer 119

Lipids originate in the Golgi apparatus & first seen in the upper spinous layer (abundant in the granular layer) Lamellar granules fuse with the plasma membrane of keratinocytes & secrete their contents releasing stacks of membranous disks into the intercellular spaces Role in synthesis & storage of cholesterol Vital for normal adhesion & desquamation of cornified cells

Question 120

Abnormal steroid and lipid metabolism

Answer 120

Recessive X-linked ichthyosis – mutation of steroid sulfatase Results in retention hyperkeratosis

Question 121

Phospholipids become _____ cholesterol becomes \_\_\_\_, & spingolipids become \_\_\_\_\_.

Answer 121

Phospholipids become free fatty acids, cholesterol becomes cholesterol esters, & spingolipids become ceramides. \*\*β glucocerebroside, acid sphingomyelinase & phospholipase A are involved in this modification\*\*\*

Question 122

List proteins in the cornfield envelope

Answer 122

1. loricrin 2. involucrin 3. filaggrin 4. elafin 5. cystatin A 6. cornifelin 7. small proline rich proteins 8. "late envelope proteins'

Question 123

Trichohyalin

Answer 123

Significant component of the keratohyalin granules Also part of the granular layer of the epidermis

Question 124

Involucrin

Answer 124

Common component of the cornified envelope Becomes cross-linked to other proteins and is thought to be part of the early component in the assembly of cornified envelope—scaffolding Adjacent to the cell membrane & as the cell membrane becomes replaced, involucrin thought to be the preferred substrate to which external lipids (ceramides) are attached to the surface of the CE

Question 125

Small Proline-rich proteins (SPRs)

Answer 125

Consist of a family of related small proline rich proteins Serve as cross bridging proteins The amount of SPR compared to Loricrin allows for the flexibility, rigidity or the toughness of a composite material (tissue)

Question 126

Envoplakin

Answer 126

Expressed at desmosomal plaques Homologous to desmoplakin Link the CE to desmosomes and keratin filaments attachments for ceramides

Question 127

Periplakin

Answer 127

Expressed along with envoplakin at desmosomal plaques **Serve as attachments for ceramides** Envoplakin & periplakin → heterotetramers. Associate with the plasma membrane in a Ca2+ dependent manner

Question 128

Profilaggrin

Answer 128

Formed initially in the granular layer & initially highly phosphorylated & accumulated in the keratohyaline granules During cornification dephosphorylated & cleaved into filaggrin

Question 129

Filaggrin

Answer 129

Becomes cross-linked to the epidermal CE & coordinates the structure of the cornified cells Aggregates keratin intermediate filaments into tight bundles—this allows for the collapse of the cells Filaggrin half life is 6 hours & degraded mostly into free amino acids High concentration of hydrophilic a.a. is essential for the retention of water & contributes to the osmolarity &flexibility of the cornified layer

Question 130

Three main functions of filaggrin?

Answer 130

1. Alignment of the keratin intermediate filaments 2. Controls cell shape (contracts) 3. Maintenance of epidermal texture

Question 131

Cystatin A

Answer 131

Keratolinin Expressed in the spinous layer Substrate for epidermal TGases & a minor component of the CE Cysteine protease inhibitor - Might be relevant for the bacteriostatic properties of the skin

Question 132

Elafin

Answer 132

SKALP; skin derived anti-leukopeptidase A minor component of CE from normal adult epidermis A potent inhibitor of elastase & proteinase 3 Highly expressed in wounded or psoriatic skin

Question 133

Transglutaminases (TG)

Answer 133

Superfamily of Ca dependent enzymes important for apoptosis, keratinization, and hair follicle formation Present in all stratified epithelia and hair follicles Mainly expressed in the granular to upper spinous layers Catalyze formation lysine bonds between proteins Catalyze the covalent incorporation of biogenic polyamines into proteins

Question 134

Transglutaminase I

Answer 134

Expressed primarily in keratinocytes Membrane bound, processed form accounts for most of the activity in differentiating keratinocytes Catalyzes cross-linking of involucrin at the plasma membrane & cornifin, elafin and the SPR proteins are added subsequently

Question 135

Tranglutaminase 2

Answer 135

Vit A increases activity Important role in would healing – involved in matrix repair & remodeling

Question 136

Transglutaminase 3

Answer 136

cytoplasmic enzyme Initially cross-links loricrin and SPRs together to form small interchain oligomers, which are then permanently affixed to the developing cornified cell envelope via further cross-linking by TGase1

Question 137

Transglutaminase 5

Answer 137

Present in the upper epidermal layers (spinous & granular layers) Induced in the early stages of keratinocyte differentiation Can cross link Loricrin

Question 138

Which enzymes are responsible for desquamation?

Answer 138

Acid phosphatase, Cathepsin-B, Carboxypeptidase, Sterol sulfatase

Question 139

Corneocyte shedding/Desquamation

Answer 139

The final products of differentiation, the squames, finally reach the edge of the epidermis they are mummified remnants composed of cornified envelope surrounded by stacks of lipids packed with keratin macrofilament ---Squames are then shed

Question 140

The corneocytes are held together by \_\_\_\_\_\_\_\_

Answer 140

corneodesmosomes Modified desmosomes structures Located in the upper spinous and granular layers

Question 141

Corneodesmosin

Answer 141

After transport and release from the lamellar bodies, corneodesmosin appears in the extracellular space & become associated with the desmosomal desmogleins & desmocollins

Question 142

Corneodesmosin is cleaved by the stratum corneum ___ and ____ enzymes causing separation of adjacent corneocytes with cell shedding

Answer 142

tryptic and chymotryptic enzymes

Question 143

Saturated FA

Answer 143

contain no carbon-carbon double bonds

Question 144

Unsaturated FA

Answer 144

contain carbon-carbon double bonds

Question 145

Polyunsaturated fatty acids (PUFAs)

Answer 145

Unsaturated fats with two or more double bonds

Question 146

Cats are unique: lack \_\_\_\_\_, have limited ____ activity; unable to synthesize arachidonic acid – must obtain it from the diet

Answer 146

lack Δ-6-desaturase Δ-5-desaturase

Question 147

Mammals are unable to synthesize _____ and \_\_\_\_\_\_

Answer 147

linoleic acid or α-linolenic acid Can make arachidonic acid from linoleic acid and eicosapentaenoic acid from α-linolenic acid

Question 148

Essential fatty acid

Answer 148

a PUFA that cannot by synthesized by animals but is required for normal physiologic function

Question 149

n-3 family

Answer 149

provided by the diet in green leafy veggies Eicosapentaenoic acid can be obtained from marine fish oil

Question 150

n-6 family

Answer 150

derived from veggies and present in seed oils (safflower & sunflower) γ-Linolenic acid (product of linoleic acid) is found in seed oils of borage, evening primrose, & black currant

Question 151

n-9 FAs

Answer 151

(oleic acid) – can ben synthesized de novo from acetyl coenzyme A by liver & tissue microsomes  therefore is non-essential

Question 152

EFA Deficiency

Answer 152

Causes renal & reproductive abnormalities, decreased growth rate, immunologic abnormalities, hypotrichosis, alopecia, scaling skin, weak cutaneous blood vessels and an increases tendency to bruise, decrease wound healing, sebaceous gland hypertrophy accompanied by increased sebum viscosity, and increased transepidermal water loss. Transdermal drug delivery systems use this intercellular lipid portion of the epidermis to allow penetration into the underlying dermis and vasculature

Question 153

Arachidonic acid

Answer 153

most important of all of the EFAs; Fundamental component of cell membranes Skin is unable to convert linoleic acid to AA; lacks Δ-6-DES & Δ-5-DES activity Most AA is present in the phospholipids of the cell membrane Major biologic function: parent to leukotrienes (LTs), prostaglandins (PGs), thromboxanes (TXs), & hydroxyl fatty acids (hydroxyeicosatetraenoic acids (HETEs).

Question 154

What is the rate limiting step in eicosanoid synthesis?

Answer 154

Release of AA from membrane store; Requires liberation by a phospholipase Activated by trauma, thermal injury, ischemia, endotoxin release, antigen-antibody interactions, increased intracellular calcium, cytokine production, or histamine release

Question 155

PGD2

Answer 155

Major site: Mast cells, Langerhans Cells Major biologic activity: neutrophil chemotaxis; induces vasodilation, relaxes smooth muscle, inhibits platelet aggregation, bronchoconstriction

Question 156

PGE2

Answer 156

Major site: Keratinocytes, Fibroblasts & Macrophages Major biologic activity: plasma exudation, stimulates cell proliferation, hyperalgesia, relaxes smooth muscle increases vasodilation

Question 157

PGF2a

Answer 157

Major site: Keratinocytes Major biologic activity: vasoconstriction, bronchoconstriction and smooth muscle contraction, stimulates cell proliferation

Question 158

PGH2

Answer 158

Major biologic activity: precursor to thromboxanes A2 and B2, induction of platelet aggregation and vasoconstriction

Question 159

PGI2

Answer 159

Major site: Vascular Endothelial Cells, Fibroblasts, Macrophages Major biologic activity: inhibits platelet and leukocyte aggregation, induces vasodilation relaxes smooth muscle

Question 160

TXA2

Answer 160

Major site: Platelets, Macrophages Major biologic activity: induces platelet aggregation, vasoconstriction

Question 161

TXB2

Answer 161

Major site: Platelets Major biologic activity: induces vasoconstriction

Question 162

LTB4

Answer 162

Major site: Monocytes, Basophils, Neutrophils, Eosinophils, Mast Cells, Keratinocytes Major biologic activity: induces neutrophil and eos chemotaxis and aggregation/activations, vascular permeability, enhances C3B receptor expression, neutrophil degranulation

Question 163

LTC4

Answer 163

Major site: Mast cells, Keratinocytes Major biologic activity: Plasma exudation, mucus secretion, component of SRS-A, skin vasodilation, increases vascular permeability and bronchoconstriction

Question 164

LTD4

Answer 164

Major site: Mast cells, Keratinocytes Major biologic activity: component of SRS-A, skin vasodilation, mucus secretion increases vascular permeability and bronchoconstriction

Question 165

LTE4

Answer 165

Major site: Mast Cells & Basophils Major biologic activity:component of SRS-A, microvascular vasoconstrictor and bronchoconstriction

Question 166

What are the changes in lipids from the granular to the cornified cell layers?

Answer 166

1. Replacement of phospholipids by ceramides 2. Increase in free sterols 3. Large increase in free fatty acids at the expense of triglycerides and phospholipid Transformation of these lipids provides the outer epidermal layers with a more stable, waxy, and impermeable barrier. Lipids also allow for water-holding in the stratum corneum, cohesion and desquamation of corneocytes, and control of epidermal proliferation and differentiation.

Question 167

What are the two primary sources of lipids in the SC?

Answer 167

corneocyte envelope & intercellular lamellae Lipids on the outer surface of the SC originate from: Cat & Dog: predominately epidermal origin Human: predominately sebaceous origin

Question 168

What makes up the lipid portion of the CCE?

Answer 168

Majority are ceramides, cholesterol, fatty acids & cholesterol esters Intercellular skin lipids are initially stored in the lamellar granules which get extruded into the extracellular space in the upper granular layer during cornification

Question 169

Lamellar granules

Answer 169

Membrane-coating granules, Odland bodies, or keratinosomes Secretory granules (type of lysosome) that deliver precursors of stratum corneum lipids into the intracellular space Contain glycoproteins, glycolipids, phospholipids, free sterols, and a number of acid hydrolases, including lipases, proteases acid phosphatases, and glycosidases

Question 170

Glucosylceramides are the precursors to what?

Answer 170

precursor to ceramides, dominant component of the stratum corneum lipids

Question 171

Lipids originate in the XXX & first seen in the upper spinous layer (abundant in the granular layer)

Answer 171

Golgi apparatus

Question 172

Complex changes in lipid composition occurs after the _______ of the granules by the enzymatic action of acid hydrolases

Answer 172

extrusion of the contents Phospholipids become free fatty acids, cholesterol becomes cholesterol esters, & spingolipids become ceramides. β glucocerebroside, acid sphingomyelinase & phospholipase A are involved in this modification

Question 173

What is the intracellular lipid content?

Answer 173

15-25% free fatty acids 40-50% ceramides 20-25% cholesterol 5-10% cholesterol sulfate

Question 174

The precursors to XXX are glucosylceramides which are located within the lamellar granules

Answer 174

ceramides

Question 175

ceramides

Answer 175

the most important lipid component for lamellar arrangement in the stratum corneum & in barrier function.Plasticize the horny layer to allow stretching & bending by fluidizing barrier lipids (absence results in dissolution of water barrier) Primary carriers of long change fatty acids and linoleic acid Covalently linked to the corneocyte envelope

Question 176

\_\_\_\_ are incorporated into the ceramides

Answer 176

PUFA Linoleic acid specifically

Question 177

Free fatty acids cause an XX pH optimal for certain key enzymes

Answer 177

acidic

Question 178

\_\_\_\_\_ and ____ are activated at an acidic pH & in turn generate ceramides

Answer 178

β-glucocerebrosidase and acidic sphingomyelinase (aSMase) Acidification also regulates stratum corneum integrity/cohesion, thereby restricting desquamation

Question 179

Corneodesmosomes are degraded by _____ & _____ enzymes, which exhibit optimal activity in neutral-basic pH

Answer 179

chymotryptic & tryptic enzymes

Question 180

Lipid envelope

Answer 180

is located exterior to the protein envelope & is covalently attached via ester bonds to the protein envelope via TGase 1. Consists of a monomolecular layer of ω-hydroxy-ceramides which interdigitate with the intercellular lipid lamellae in a Velcro-like fashion.

Question 181

Most cholesterol comes from _______ unchanged

Answer 181

Steroid sulfatase decreases the amount of cholesterol sulfate rather than adding cholesterol to the lipid barrier Increases in cholesterol sulfate leads to an excess of scale (X-linked ichthyosis in humans).

Question 182

Turnover rates for keratinocyte proliferation

Answer 182

Normal dog 22 days Seborrheic Cocker 8 days Horse 17 days Goat 26 days Pig 15 days Human 26-42 days 16-30 from s. basale to s. spinosum 14 days in s. corneum

Question 183

Desmosomes

Answer 183

Transmembrane Protein: Desmosomal cadherins Dsg I, II, III Dsc I, II, II Plaque Protein: Plakoglobin, desmoplakin I, II, IV; desmocalmin; Plakophilin Cytoskeleton Filaments: Cytokeratin Function and Location: Cell-cell adhesion, all keratinocytes

Question 184

Desmosomes

Answer 184

“Spines” of the spinous layer Ca-dependent cell surface modifications that promote adhesion of epidermal cells and resistance to mechanical stress Mechanically hold together the keratinocytes together Physiologic communication between keratinocytes Mediators of intercellular adhesion

Question 185

Desmosomal plaque

Answer 185

Plakoglobin, desmoplakins I & II, keratocalmin, desmoyokin and plakophilin

Question 186

Desmoplakin 1 binds directly to type ___ keratins (K1, 2, 5 & 6)

Answer 186

II

Question 187

Keratocalmin/Desmocalmin

Answer 187

Calmodulin-binding protein Promotes calcium dependent assembly and function of desmosomes

Question 188

Desmogleins 1 and 3

Answer 188

part of the transmembrane portion of the desmosomal plaque Calcium-dependent adhesion molecule (cadherins)

Question 189

Desmocollins

Answer 189

part of the transmembrane portion of the desmosomal plaque Calcium-dependent adhesion molecule (cadherins)

Question 190

Cadherins

Answer 190

transmembrane glycoproteins Mediate cell-cell adhesion in a Ca-dependent manner Major adhesion molecules in desmosomes and adherens junctions

Question 191

\_\_\_\_\_\_\_\_\_ is important as a mediator of adhesion

Answer 191

Ca Exemplified by Darier and Hailey-Hailey disease which exhibit characteristic epidermal dyscohesion Both are caused by mutations in genes that regulate Ca transport

Question 192

Model of hemidesmosome

Answer 192

Keratin intermediate filaments insert into the plate portion (or inner plaque), which consists of bullous pemphigoid anitgen 230 (BP 1) and plectin. The transmembrane component (or outer plaque) consists of bullous pemphigoid anitgen 180 (BP 2) and α6β4 integrin. The extracellular domain of BP 180 has been localized to the extracellular space beneath the hemidesmosome (the lamina lucida) and has been identified as type XVII collagen. The intracellular domain of PB180 is localized in the hemidesmosomal plaque.

Question 193

What are the extracellular components of hemidesmosomes?

Answer 193

**Anchoring filaments** originate at the hemidesmosomes and insert into the lamina densa. The major component of these filaments is laminin 5 which is localized mainly to the lamina densa and the lower lamina lucida and is associated with α6β4 in hemidesmosomes.

Question 194

Plectin attaches intermediate filaments to

Answer 194

1. HDs 2. plasma membranes of basal keratinocytes 3. cross-links other proteins associated with the cytplasmic plaques of HDs

Question 195

Bullous pemphigoid antigen 1 (BP230, BPAG1)

Answer 195

First of two autoantigens in the hemidesmosones of basal keratinocytes detected using circulating autoanitbodies from patients with bullous pemphigoid (BP) Plakin, 230 kDa; non-collagenous protein localized to the cytoplasmic plaque of HDs

Question 196

Bullous pemphigoid antigen 180 (BP 2)

Answer 196

Type II transmembrane collagen (specifically, type XVII collagen) Associated with HD-anchoring filament complexes in basal keratinocytes

Question 197

NC16A domain of BP180

Answer 197

Large, non-collagenous region neat the transmembrane region Binds extracellular N-terminus of α6-integrin Contains the epitopes recognized by BP autoantibodies Target of autoantibodies in a feline, porcine, and equine model of BP

Question 198

α6β4 integrin

Answer 198

Hemidesmosome-associated integrin; receptor for Laminin 5 Large cytoplasmic tail of integrin subunit β4 contains sequences that are required for localization of in HDs The membrane-proximal region of integrin subunit β4 directly associates with plectin, while its distal carboxyl-terminal region binds BPAG1 The proximal extracellular domain of integrin subunit α6 binds the NC16A region of BPAG2 (collagen XVII). Laminins 1 and 5 serve as the preferred ligand for this integrin. Mutation in either α6 or β4 integrin subunits develop Junction Epidermolysis Bullosa associated with pyloric atresia.

Question 199

α5β1

Answer 199

mediates keratinocyte adhesion to fibronectin

Question 200

α2β1

Answer 200

mediates keratinocyte adhesion to collagens type I and IV and laminin

Question 201

α3β1

Answer 201

receptor for epiligrin; involved in adhesion to laminin

Question 202

α1β5

Answer 202

mediates keratinocyte adhesion to vitronectin

Question 203

α6β4

Answer 203

mediates keratinocytes adhesion to laminin

Question 204

β2 integrins

Answer 204

Leukocyte functional antigen-1 (CD11a/CD18) Adhesion molecule on T lymphocytes Essential for most adhesion-dependent lymphocyte function MAC-1, CR3, CD11b/CD18 and CD11c/CD18 (CR4) Found on mononuclear phagocytes, neutrophils, NK cells

Question 205

Adherens junctions

Answer 205

Small punctuate cell-cell attachment points Connect actin filaments to adjacent cells Major players: E and P cadherins

Question 206

E-cadherins

Answer 206

Associated with actin filaments via interactions with catenins, and may regulate the orgainziaiton of adherens junctions and influence epidermal stratification Expressed in keratinocytes of all epidermal layers

Question 207

P-cadherins

Answer 207

expressed only in basal keratinocytes Cytoplasmic domains of the cadherins connects with α- and β-catenin, and plakoglobin (γ-catenin). Catenins connect cadherins to the cytoskeletal network of β-catenin & plakoglobin; α-catenin directly associates with acitn

Question 208

Tight Junctions

Answer 208

An intercellular junction composed of a series of fusions of the junctional membrane, forming a continuous seal Serves as a selective barrier to small molecules and as a total barrier to large molecules Also known as impermeable junction; occluding junction; zonula occludens Most important tight junction proteins in the human epidermis: Occludin, claudins, and zonal occluding proteins Occludin: restricted to the stratum granulosum Zonal occluding protein-1 & claudin-4: found in the suprabasal layers Claudins-1 & -7: found in all epidermal layers

Question 209

Gap junctions

Answer 209

Sites of physiologic communication; while desmosomes/hemidesmosomes are sites of mechanical coupling More abundant in more differentiated keratinocytes Consist of 2 connexons from adjacent cell membranes

Question 210

Connexins

Answer 210

Intracellular gatekeepers Transmembrane proteins Connexons on adjoining cells associate to form gap junctions Different connexin based on layer of epidermis Basal: Connexin 43 Spinous: Connexin 26 Cornified cells: Connexons 31 and 31.1 These changes relate to intracellular ionic signaling (specifically calcium) Connexin-26 is one of the most highly upregulated genes in human psoriatic plaques Missense mutations of connexin-26 result in 5 distinct ichthyosis-like skin disorders

Question 211

Skin-associated lymphoid tissue

Answer 211

Langerhans’ cells, keratinocytes, epidermotrophic T lymphocytes, & draining peripheral lymph nodes

Question 212

List 5 immunologic role of keratinocytes

Answer 212

Produce IL-1 Produce various cytokines (IL-3, protaglandins, leukotrienes, interferon) Are phagocytic Can express antigens associated with immune response gene in a variety of lymphocyte-mediated skin diseases (presumably as a result of interferon-γ secretion by activated lymphocytes)

Question 213

Immunologic activity of unperturbed skin

Answer 213

produce only a few mediators Cytokines: IL-1, IL-7 & transforming growth factor-β (TGF-β) Contain large quantities of pre-formed & biologically active IL-1α and immature IL-1β immediate initiator of inflammatory and repair processes after epidermal injury

Question 214

IL-7

Answer 214

important lymphocyte growth factor

Question 215

TGF-β

Answer 215

growth-regulating effects on keratinocytes Modulates inflammatory/immune response Important for Langerhans’ cell development

Question 216

Antimicrobial peptides

Answer 216

an important evolutionary conserved innate host defense mechanism in many organisms Keratinocytes produce cathelicidins (IL-37) and β-defensins MOA may relate to membrane insertion and pore formation

Question 217

β-defensins

Answer 217

Cysteine-rich cationic low-molecular-weight antimicrobial peptides Essential part of cutaneous innate immunity Attract dendritic cells and memory T cells via CC cehmokine receptor 6 (CCR6)

Question 218

Cathelicidins:

Answer 218

cationic peptides with a structurally variable antimicrobial domain at the C-terminus In mammals, pigs & cattle – a variety of cathelicidin genes exists Pronounced antibacterial, antifungal, and antiviral activities Attracts mast cells and neutrophils Secreted into human sweat Down regulated in atopic dermatitis

Question 219

Psoriasin (S100A7)

Answer 219

secreted predominately by keratinocytes plays a major role in killing E. coli

Question 220

Keratinocytes synthesize and release complement components ___ and factor \_\_\_.

Answer 220

C3 and factor B

Question 221

Eicosanoids

Answer 221

an ensemble of lipid mediators regulating inflammatory and immunologic reactions Can produce and release the cylcooxygenase product prostaglandin E2, (both pro-inflammatory and immunosuppressive proteins) When acting on dendritic cells, promotes the development of IL-4 dominated type 2 T cell responses

Question 222

Things that stimulate keratinocyte growth

Answer 222

1) EGF 2) Transforming growth factor α 3) KGF 4) IL-1 α 5) IL-6 (increasing UV light) 6) β-FGF

Question 223

Difference between neoplastic and regular keratinocytes

Answer 223

1) Neoplastic cell cycle shorter 2) Neoplastic cells have whorls 3) Anisocytosis 4) Lacks cells surface antigens 5) Growth faster without Cholera toxin and EGF

Question 224

Integrins

Answer 224

Large family of cell surface adhesive receptors (surface glycoproteins) Important in cell-cell and cell-matrix interactions Facilitate association of matrix molecules and basal keratinocytes Act as a link for collagen, laminin, fibronectin, thrombospondin, and vitronectin to the cytoskeleton of keratinocytes Vital for communication

Question 225

β1 integrins

Answer 225

found on the lateral surfaces of keratinocytes Downregulated during differentiation, thought to be important for extracellular matrix attachment

Question 226

β4 integrins

Answer 226

found associated with hemidesmosomes; mediates station adhesion

Question 227

During wound healing, ____ integrins are redistributed to promote keratinocyte migration on matrix molecules like fibronectin.

Answer 227

B1 integrins Integrins α5β1 and ανβ1 are also involved with wound healing

Question 228

Difference between Epidermal growth factor (EGF) and TGF

Answer 228

EGF is not produced by keratinocytes; TGF is produced by keratinocytes Both bind to the same tyrosine kinase receptor in the basal cell and suprabasal cell layers to stimulate proliferation Over-expression leads to hyperplasia, hyperkeratosis, formation of spontaneous papillomas and hyper proliferative disorders

Question 229

Keratinocyte-derived growth factor (KGF)

Answer 229

dermal transcripts with receptors on keratinocytes member of the fibroblast growth factor family Potent mitogen for keratinocytes Ectopic expression will lead to epidermal thickening

Question 230

Transforming growth factor β (TGF-β)

Answer 230

causes a decrease in DNA synthesis and mitosis of keratinocytes, promotes differentiation TGF-β1 and TGF-β2 are expressed in the upper epidermal layers; upregulated by TGF-β as well as other agents that promote differentiation (ie Ca) Important role in homeostatic regulation of the epidermis Other growth factors produced by keratinocytes include Basic fibroblast growth factor (influence on the proliferation of melanocytes) & platelet-derived growth factor (functions in the dermis)

Question 231

Vitamin D3 effects on proliferation and differentiation?

Answer 231

Causes a decrease in keratinocyte proliferation Causes an increase in keratinocyte differentiation

Question 232

Terminal Epidermal Differentiation Processes that are Calcium-Dependent

Answer 232

Intercellular structure formation -- Desmosome assembly & function, Gap junction assembly & function Protein Expression -- Involucrin, Keratins 1, 2e, 9, & 10, Loricrin, Profilaggrin, Small proline-rich peptides, Transglutaminase Release of keratohyaline granule contents -- Release of loricrin & profilaggrin Enzyme function -- Cleave of profilaggrin to filaggrin, Transglutaminase activity

Question 233

Optimal water concentration of SC

Answer 233

20-35% Must be at least 10% to look & feel normal

Question 234

Atopy and filaggrin defect in humans

Answer 234

``` Atopic dermatitis (eczema) in humans affects ~20% population Two independent loss-of-function genetic variants in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis ```

Question 235

Origin of melanocytes?

Answer 235

Neural Crest

Question 236

Location of melanocytes?

Answer 236

Basal layer of the epidermis outer root sheath and hair matrix of hair follicles ducts of sebaceous and sweat glands perivascularly in the superficial dermis Eye, ear, and CNS

Question 237

There are no histochemical stains the cane performed on routinely process skin biopsy specimens that exclusively stain melanin. What stains rely oj the ability o melanin to reduce silver from a silver solution.

Answer 237

Do not stain readily with hematoxylin eosin and actually show up clear Argentaffin stains rely on the ability of melanin to reduce silver from a silver solution. Examples of argentaffin stains include Fontana Masson and GMS. Argyrophil are similar stains but use an external suaver reducer to produce elemental silver (Grimelous stain). These agents also stain neurosecretory granules and formalin pigment.

Question 238

IHC of Melanocytes?

Answer 238

Positive for vimentin and S-100 protein

Question 239

Melanocytes produce what cytokines in response to inflammation?

Answer 239

Secrete IL-8, IL-1α, TNFα, MCF in response to inflammation

Question 240

Functions of melanocytes:

Answer 240

cosmetic entity: protective coloration (camouflage and mimicry), social communication (sexual attraction) barrier against ionizing radiation: protection against UV light scavenger of cytotoxic radicals and intermediates: esp. during rapid proliferation and differentiation of the hair follicle additional roles include: restrain keratinocyte proliferation, calcium homeostasis secrete IL-8, IL-1α, TNFα, MCF in response to inflammation

Question 241

Pigmentation: Steps (4 steps)

Answer 241

The synthesis and distribution of melanin in the epidermis, involves several steps: Transcription of proteins required for melanogenesis Melanosome biogenesis Transport of melanosomes to the tips of melanocyte dendrites Transfer of melanosomes to keratinocytes

Question 242

Constitutive pigment

Answer 242

the pigmentation that is genetically determined in the absence of stimulatory influences

Question 243

Facultative pigment

Answer 243

the pigmentation which occurs with various stimuli (ex UV light, inflammation, hormones)

Question 244

Normal human skin colors and pigments (4)

Answer 244

Red: Dermis by oxygenated hemoglobin Yellow: Epidermis by exogenously produced carontenoids Brown: Endogenously produced melanin Blue: Dermis by unoxygenated hemoglobin in venules

Question 245

What is the rate limiting step in melanogenesis?

Answer 245

Tyrosinase is the rate limiting enzyme in the melanin pathway Melanogensis place exclusively within melanocytes and on the specialized organelle, the melanosome

Question 246

Where are the majority of melanocytes present?

Answer 246

Largest number of melanocytes is present in the skin and hair Present in the epidermal basal layer Approx 1 melanocyte per 10-20 basal keratinocytes in dogs

Question 247

Nevi and melanomas

Answer 247

mislocation of melanocytes in the dermis. Constant need for synthesis and transfer of melanosomes from melanocytes to keratinocytes to maintain continuous pigmentation

Question 248

Where is the only site of pigment production for the hair shaft? How are these different that epidermal melanocytes?

Answer 248

Hair bulb: only site of pigment production for the hair shaft Located in the proximal hair bulb during anagen phase Differ from epidermal melanocytes by being larger, more dendritic, with more extensive Golgi and RER, and by producing larger melanosomes.

Question 249

Melanocytes proliferate, migrate, & undergo maturation during \_\_\_\_\_

Answer 249

early to mid-anlagen Depends on c-Kit expression by melanocytes and SF synthesis by keratinocytes Melanogenesis & melanin transfer to keratinocytes occur throughout anagen phase Melanocytes apoptose during late catagen Melanogenically active melanocytes are restricted to the upper hair matrix of the anagen hair follicle, below the pre-cortical keratinocyte population, correlating with the anagen transfer of melanin predominately to the hair shaft cortex, less to the medulla, & only rarely to the hair cuticle

Question 250

Melanocytes determine hair color by the amount of ______ transferred as well as by the ____ of eumelanin (black-brown) to pheomelanin (red-yellow)

Answer 250

melanin ratio

Question 251

Define Graying

Answer 251

the gradual decline in the melanogenically active melanocytes in the hair bulb (determined by age and genetics); there is also a component of ineffective melanosome transfer

Question 252

Where do ocular melanocytes reside? What is their main function?

Answer 252

Reside in the cochlea; important for hearing Reside as intermediate cells of the stria vascularis A loss of otic melanocytes leads to deafness. Help in the maintenance of the endolymph through the regulation of potassium transport

Question 253

Endolymphatic fluid of the cochlea maintain high concentrations of positively charged \_\_\_\_\_\_.

Answer 253

high concentrations of positively charged potassium In the absence of cochlear melanocytes, the endolymphatic potential is low, leading to deafness.

Question 254

Congenital Hereditary Sensorineural Deafness - what are the genes involved in cats and dogs?

Answer 254

Usually seen in dog and cat breeds with white pigmentation Dogs carrying the **piebald** or **merle genes** & cats carrying the **white gene**, the hair cell loss is secondary to degeneration of the cochlear blood supply studies demonstrate an absence of strial melanocytes In the Dalmatian, postnatal auditory function development has been shown to proceed normally up until 3 wks at which point the strial degeneration produces rapid loss of hair cell function In general, loss of melanocytes at any age --- deafness

Question 255

Waardenburg syndrome type 2

Answer 255

deaf due to lack of melanocytes within the inner ear (like the Dalmatian) \*\*\*However there is a preservation of hearing in albinos, which indicates that melanin production within otherwise viable melanocytes are not essential for hearing. BUT albinos are more susceptible than the normal population to hearing loss from noise and/or exposure to toxic agents, therefore melanin provides some protective effect.

Question 256

Where are cephalic melanocytes located?

Answer 256

Dispersed throughout the meninges; particularly dense in the leptomeninges above the pons and medulla oblongata. Function as scavengers for toxic cations and ROS

Question 257

Melanocytogenesis

Answer 257

1. Precursor cell (melanoblasts) development and migration from the neural crest to peripheral sites 2. Differentiation of melanoblasts into melanocytes 3. Survival and proliferation of melanocytes 4. Synthesis of melanosomes and melanin

Question 258

How do melanoblasts development and migration from the neural crest to peripheral sites

Answer 258

Derived from neuroectoderm; from the dorsal portions of the closing neural tube. Migrate along a dorsolateral path between the mesodermal and ectodermal layer. Final destinations include: hair follicles, skin, inner ear cochlea, choroids, ciliary body, and iris Defects in melanocyte migration typically appear most prominently on the ventral surface as ‘white spotting’, as this is the greatest distance (watershed zone) form the dorsum

Question 259

Factors that influence the development and migration of melanoblasts

Answer 259

Wnt ET3 (endothelin-3) BMPs (bone morphogentic proteins) steel factor (SF; stem cell factor SCF, c-Kit ligand) Hepatocyte growth factor (HGC)/scatter factor

Question 260

Wnt glycoproteins play an important role in melanogenesis via what ways?

Answer 260

Expressed in the dorsal neural tube during neural crest cell migration Directs the maturation of pluripotent neural crest cells into melanoblasts Bind and activate Frizzled, a transmembrane heptahelical G protein-linked receptor for Wnt Induce the accumulation of β-catenin Regulation of microphthalmia-associated transcription factor (Mitf) transcription

Question 261

Mift (microphthalmia transcription factor) is the primary regulator of melanogenesis. Mift induces the transcription of what 4 factors to allow melanogenesis to occur?

Answer 261

1. tyrosinase 2. tyrosinase-related protein-1 (TRP-1) 3. 3,4 dihydrozyphenylalanin (DOPA) 4. chrome tautomerase (TRP-2)

Question 262

Bone Morphogenetic Proteins: (BMPs):

Answer 262

Belong to the transforming growth factor-β family Suppresses neural crest cell differentiation into melanoblasts: • Wnt antagonists • There is a decrease in BMP expression in the dorsal neural tube at the time of melanoblast migration

Question 263

Steel Factor

Answer 263

Early melanoblast development requires the presence of the cytokine SF (mast/SCF, c-Kit ligand) and its tyrosine kinase transmembrane receptor c-Kit

Question 264

Stem Cell Factor

Answer 264

crucial role in permitting melanoblast survival and promoting proliferation, both initially in the dorsolateral migration pathway and later from the dermal mesenchyme to colonize the follicles and epidermis

Question 265

Regulation of microphthalmia-associated transcription factor (Mitf) transcription by ____ Signaling

Answer 265

Wnt Signalling When Wnt is not bound to Frizzled is inactive Wnt binding activates Frizzled leading to GSK3β (enzyme glycogen synthase kinase 3β) dissociation from β-catenin, which then translocates to the nucleus where it binds with specific transcription factors (Tr factor to initiate Mitf transcription).

Question 266

What is c-Kit?

Answer 266

a tyrosine kinase receptor involved in melanoblast expansion, survival and migration Expressed by epidermal keratinocytes; as soon as c-Kit is expressed on melanoblasts, these cells begin their migration to their final destination

Question 267

Endothelins: (ETs)

Answer 267

Involved in the late steps of melanoblast migration from the dermis to the basal layer of the epidermis. ET1, ET2, ET3 ET3: Synthesized by ectodermal cells EdnrB receptor interacts with ET3; important during melanoblast migration along the dorso-lateral pathway; proper expression is required for survival, proliferation, and/or migration of melanoblasts and normal formation of **enteric nerves**. Defects in ET3 or EdnrB (Waardenburg Syndrome 4) results in prominent melanocytes loss

Question 268

What cells synthesize ET3?

Answer 268

Synthesized by ectodermal cells - interact with endothelia receptor B on melanoblasts

Question 269

EdnrB receptor

Answer 269

interacts with ET3; important during melanoblast migration along the dorso-lateral pathway; proper expression is required for survival, proliferation, and/or migration of melanoblasts and normal formation of enteric nerves. Defects in ET3 or EdnrB result in prominent melanocytes loss

Question 270

Hepatocyte Growth Factor: (HGF/Scatter Factor)

Answer 270

Involved in the late steps of melanocyte migration from the dermis into the epidermis Ligand for the transmembrane tyrosine kinase receptor Met. Also regulates cadherin expression in melanocytes (down regulates E-cadherin)

Question 271

The cytoplasmic domains for cadherins in melanocytes bind to what structure?

Answer 271

In melanocytes, their cytoplasmic domains bind to β-catenin

Question 272

E-cadherins where before entry into the epidermis?

Answer 272

induced in melanoblasts before their entry into the epidermis; later when the melanoblasts migrate into the hair follicle, expression is muted, and the cells begin to express P-cadherin Role in suppressing melanocytes proliferation in the epidermis Cadherin expression by melanocytes matches the cadherin expression of surrounding cells

Question 273

Melanosome

Answer 273

unique membrane-bound organelle in which melanin biosynthesis takes place; thought to represent a modified lysosome as it contains enzymes and other proteins - Proteins found in both lysosomes and melanosomes: liposomal-associated membrane protines (LAMPs), acid phosphatase - Like a lysosome, melanosome can endocytose receptors that are targeted for degradation

Question 274

Where are the genes located for proper melanosome function?

Answer 274

located on the pink-eye dilution and mottled loci

Question 275

What are the two TYPES of melanosomes?

Answer 275

Can be divided into eumelanosomes and pheomelanosomes, Eumelanosomes: large (0.9 x 0.3 μm), elliptical in shape, contain a highly structured fibrillar glycoprotein required for eumelanin synthesis. Pheomelanosomes: smaller (0.7 μm in diameter), spherical in shape, their glycoprotein is loose and disorganized

Question 276

What are the four stages of melanosome maturation?

Answer 276

Stage I melanosomes: (premelanosomes) develop from endoplasmic reticulum; have an amorphous matrix and display internal vesicles that form as a result of membrane invagination; already contain glycoprotein Pmel17 (gp100) but requires further processing to become a component of the final fibrillar matrix Stage II melanosomes: Eumelanosomes at this stage have organized structured fibrillar matrix, but no active melanin synthesis. They contain tyrosinase In pheomelanosomes, melanin synthesis already takes place Stage III melanosomes: deposition of melanin on the fibrillar matrix is detected within eumelanosomes Stage IV melanosomes: fully melanized and their internal matrix is masked by melanin deposits

Question 277

Stage I melanosomes

Answer 277

(premelanosomes) develop from endoplasmic reticulum; have an amorphous matrix and display internal vesicles that form as a result of membrane invagination; already contain glycoprotein Pmel17 (gp100) but requires further processing to become a component of the final fibrillar matrix

Question 278

Stage II melanosomes

Answer 278

Eumelanosomes at this stage have organized structured fibrillar matrix, but no active melanin synthesis. They contain tyrosinase In pheomelanosomes, melanin synthesis already takes place

Question 279

Stage III melanosomes

Answer 279

deposition of melanin on the fibrillar matrix is detected within eumelanosomes

Question 280

Stage IV melanosomes

Answer 280

fully melanized and their internal matrix is masked by melanin deposits

Question 281

Where are melanogenic proteins produced in the cell?

Answer 281

In general: structural proteins involved in melanogenesis are thought to originate from the RER and enzymatic proteins are through to originate from the Golgi.

Question 282

What process is required for proper association of tyrosinoase with melanosomes and its activity?

Answer 282

\*\*\*\*\*Glycosylation steps are required for proper association of tyrosinase with melanosomes as well as for its activity - Mature tyrosinenase is folded in the ER, the trafficked/sorted in the Gogli apparatus & then into endosomes & finally melanosomes

Question 283

Tyrosinase mutations

Answer 283

- Found in Oculocutaneous albinism type I - Complete inability to synthesize melanin in skin, hair and eyes - Melanocytes are present

Question 284

TRP-2

Answer 284

\*\*\*\*also known as DOPAchrome tautomerase Synthesized in the ER; undergoes several maturation steps in the Golgi and trans-Gogli network Eventually localizes in the melanosome & spans its membrane W/n the melanosome, it complexes with tyrosinase and TRP-1 \*\*\*During melanin synthesis, TRP-2 converts DOPAchrome to the carboxylated derivative DHICA Requires zinc for proper function

Question 285

Protein Kinase C-β

Answer 285

involved in regulating tyrosinase activity Phosphorlyates serine residues on the cytoplasmic domains of tyrosinase, thus activating it In melanocytes, activated PKC-β is associated with melanosomes

Question 286

Pmel17

Answer 286

Glycoprotein that plays a critical role in fibril matrix formation within eumelanosomes Transcription is induced by α-MSH through Mitf Synthesized in the ER, glycosylated and cleaved then transported to stage I melanosomes to form a fibrillar structure that is the backbone of eumelanosome matrix, contributes to melanosome ellipsoid shape, and promotes melanin polymerization

Question 287

MART-1/Melan A

Answer 287

membrane-associated protein present in stage I and II melanosomes Forms a complex with Pmel17; affects the expression, stability, trafficking, and processing of Pmel17 within the melanosomes

Question 288

P Protein

Answer 288

(pink-eyed dilution); a transmembrane protein responsible for maintaining acidic environment within the melanosomes

Question 289

SLC24A5

Answer 289

melanosome-associated cation exchanger; mutations in slc24α5 in zebrafish lead to hypopigmentation

Question 290

Lysosomal-Associated Membrane Proteins

Answer 290

linked to melanosome membranes and/or matrix; thought to protect melanosomal integrity by acting as scavengers of free radicals that are produced during melanin biosynthesis

Question 291

Microphthalmia-Associated Transcription Factor

Answer 291

\*\*\*Regulatory Protein\*\*\* Mitf Termed the master gene for melanocyte survival - Key factor regulating the transcription of the major melanogenic proteins (tyrosinase, TRP-1, TRP-2, PKC-β, MART-1)

Question 292

Mitf Role in Melanocyte Proliferation and Survival

Answer 292

Promotes melanocyte survival by upregulating the expression of a major anti-apoptotic protein, BCL2 - It is frequently overexpressed or amplified in melanomas \*\*Mutations in MITF are found in Waardenburg syndrome type 2

Question 293

Melanocortin 1 Receptor

Answer 293

Comprise a family of 5 related receptors; each with 7 transmembrane domains that belong to the G-protein coupled receptor superfamily MC3R and MC4R: found in the CNS, absent in melanocytes MC2R: expressed in adrenal cortex MC5R: expressed in peripheral adipocytes

Question 294

MC1R

Answer 294

expressed in a number of cells, including endothelial cells, fibroblasts, keratinocytes; but HIGHEST expression is found in melanocytes ACTH &α-MSH activate MC1R which leads to G protein-dependent activation of adenylate cyclase increased intracellular cAMP level, induced Mitf transcription and upregulating the level of melanogenic proteins (tyrosinase)

Question 295

Polymorphisms with MC1R

Answer 295

largely responsible for different skin/hair color among humans Agouti gene encodes an antagonist for MC1R

Question 296

\_\_\_\_\_ gene encodes an antagonist for MC1R

Answer 296

Agouti

Question 297

α-MSH is an antagonist for which cytokine?

Answer 297

IL-1

Question 298

What is the Raper-Mason pathway?

Answer 298

pathway for the biosynthesis of melanin. The bifunctional enzyme, tyrosinase (A) converts tyrosine and dopa to dopaquinone. Tyrosinase is assumed to be the sole enzyme associated with this pathway and the rest of the reactions (B) are presumed to be of nonenzymatic origin \*\*inhibition of this reaction blocks melanin synthesis

Question 299

Melanosome Transfer

Answer 299

The melanosome is transferred from the origin in melanocyte perikaryon to the tips of the dendrites Takes place on microtubules, arranged parallel to the long axis of the dendrite

Question 300

Describe the melanosome exocytosis pathway

Answer 300

involves fusion of the melansomal membrane with the melanocyte plasma membrane, melanosome release into the intercellular space, and phagocytosis by surrounding keratinocytes.

Question 301

Melanosome Cytophagocytosis

Answer 301

indicating the phagocytosis of a live cell or a portion of it; the keratinocyte cytophagocytose the tip of a melanocyte dendrite, which then fuses with lysosomes inside the keratinocyte, which is transported to a supranuclear location where the phagolysosome membranes break up, releasing the melanosomes.

Question 302

Melanosome Fusion of plasma membranes

Answer 302

Fusion of keratinocyte and melanocyte plasma membranes creates a space through which melanosomes are transferred from the melanocyte to the keratinocyte. There is evidence of filopodia (slender, filiform, pointed cytoplasmic projections at the tip of melanocyte dendrites) that adhere and fuse with keratinocyte plasma membranes.

Question 303

What is protease-activated receptor-2 (PAR-2)?

Answer 303

* Controls melanosome ingestion and phagocytosis by keratinocytes * Exerts a regulatory role in skin pigmentation * UV induced activity and expression * Inhibition of PAR-2 willprevents UVB-induced tanning

Question 304

Melanosomes are degraded by what enzymes?

Answer 304

Undergo degradation by lysosomal acid hydrolase enzymes (released from keratinocytes) and are extruded into the stratum corneum Melanin is discarded; amino acids, lipids, and carbohydrates may be reabsorbed below the cornified layer and reutilized in epidermal metabolism

Question 305

List melanogenic inhibitors

Answer 305

Sphingolipids: a class of membrane-associated lipids that act as signal transducers; decrease melanocgenesis (in part by enhancing Mitf degradation) BMP-4: downregulates tyrosinase expression TNFa IL-1 IL-6

Question 306

What is the function of melanin?

Answer 306

Provide protection against UV-induced DNA damage by absorbing & scattering UV radiation (280 – 400 nm) - Radiation is converted into heat (less toxic form of energy)

Question 307

What is the tanning response? immediate tanning? Delayed tanning?

Answer 307

UV irradiation induces tanning: facultative skin color; Increase above baseline or constitutive skin pigmentation that provides protection against future UV irradiation Occurs within 5 to 10 minutes of exposure and fades within minutes to days Represent melansomal relocation from the perikaryon to the melanocyte dendrites Occurs within 3 to 4 days after exposure (both UVB (280-340) & UVA (320-400)) Increase in epidermal melanocytes, melanocyte dendricity & melanosome transfer to keratinocytes with greater melanization of individual melanosomes Total amount of epidermal melanin in increased

Question 308

What are the direct effects of UV Irradiation?

Answer 308

Triggers several biologic reactions though interaction with cellular chromophores that absorb photons Most UVA effects - results of oxidative damage mediated through UVA absorption by cellular chromophores like melanin precursors that act as photosensitizers UVB irradiation - directly absorbed by cellular DNA, leading to the formation of DNA lesions (mainly cyclobutane dimmers and pyrimidine pyrimidone photoproducts) p53 protein is activated; plasma membrane lipids release DAG which then activates PKC-β to stimulate melanogenesis by activating tyrosinase

Question 309

How does the Maltese dilution effect coat color in cats?

Answer 309

Maltese dilution: non-uniform distribution of very large, irregularly sized and shaped melanin granules. an autosomal recessive trait of cats that **dilutes black cats to blue, and orange cats to cream**

Question 310

Describe the Horses Coat Color

Answer 310

Dominant W allele: horse will lack pigment from birth but have blue or brown eyes C allele: causes pigment dilution G allele: horses are fully colored at birth but subsequently acquire increasing number of white hairs with age; skin and eyes remain pigmented Ex: Lippizaner, Camarque

Question 311

Leukoderma in horses

Answer 311

Common in horses May be localized or multifocal; temporary or permanent Often seen as a complication of onchocerciasis, dourine, herpes coital examthema, lupus erythematosus, pressure sores, ear papillomas, ventral midline dermatitis, regressing viral papillomatosis, or freezing and burns (chemical, thermal, radiation) Reported to follow contact with phenols and rubber (many rubbers contain \*\*\*monobenzyl ether of hydroquinone\*\*\* which inhibits melanogenesis)

Question 312

\_\_\_\_\_ may cause hyperpigmentation in dogs, attributed to iron deposition. Change in humans may be seen with parenteral/topical application of silver, gold, or mercury.

Answer 312

Minocycline

Question 313

Color dilution and cerebellar degeneration in Rhodesian Ridgebacks

Answer 313

Age: Birth Breed: Rhodesian Ridgebacks Cause: Autosomal recessive Clinical Signs: Pups born with dilute color in coat, neurologic abnormalities by 2 weeks of age. Coat color is bluish. Pups are ataxic, difficulty crawling and nursing – open eyes late Diagnosis: Purkinje cell degeneration and cutaneous abnormalities typical of color dilution alopecia

Question 314

What is piebaldism?

Answer 314

Genetically determined white spotting. Dominant trait. Melanocytes are absent or incompletely differentiated in affected sites.

Question 315

Graying

Answer 315

Age: Mature dogs Breed:German Shepherds, Irish setters, Labrador retrievers, Goldens more likely to develop gray muzzles and chin at younger age Cause: Thought to result from reduction in melanocyte replication through senescence. Appears to be age and genetically related since certain breeds are more prone Clinical Signs: Graying of hair

Question 316

Tyrosinase Deficiency

Answer 316

Breed: Chow chows. Cause: Deficiency of tyrosinase. Clinical Signs: Normal bluish/black tongue turns pink. Portions of hair shafts turn white. Buccal mucosa may rapidly depigment. Diagnosis: Confirm with skin biopsy Histopath: Tyrosine added to histo prep. Incubated. Melanin measured after tissue staining. Tx: No effective tx, however, melanin reappears in 2-4 months spontaneously.

Question 317

Chromatophore

Answer 317

Pigment-containing and light-reflecting cells found in amphibians, fish, reptiles, crustaceans, and cephalopods Largely responsible for generating skin and eye colour in cold-blooded animals Generated in the neural crest during embryonic development Grouped into subclasses based on their colour (more properly "hue") under white light: • xanthophores (yellow) • erythrophores (red) • iridophores (reflective / iridescent) • leucophores (white) • melanophores (black/brown) • cyanophores (blue

Question 318

Cyanophores

Answer 318

**A cell in the skin of frogs**, chameleons, etc, in which pigment is concentrated or dispersed, causing the animal to change color.

Question 319

Merkel Cell - What are the markers and stains? Function?

Answer 319

Markers and Stains: Cytokeratin-20 Functions: 1) Slow Adapting Mechanoreceptor innervated with type I 2) Control sweat production, hair follicle and blood flow 3) Keratinocyte proliferation

Question 320

Cutaneous vasculature function

Answer 320

Skin metabolism Temperature regulation Defense system against invaders: Leukocyte trafficking Wound healing Angiogenesis Nutritional supply of the skin – for epidermis, sweat glands, sebaceous glands, hair

Question 321

Vasculature arrangement in dog model

Answer 321

3 intercommunicating plexuses of arteries and veins (humans only have 2) 1. Deep plexus 2. Middle plexus 3. Superficial plexus

Question 322

Deep plexus

Answer 322

Found at the interface of the dermis and subcutis Branches from this plexus descend into the subcutis and ascend to supply the lower portions of the hair follicles and the epitrichial sweat glands, feed the middle plexus

Question 323

Middle plexus

Answer 323

Lies at the level of the sebaceous glands gives off branches to the arrector pili muscles Ascending and descending braches supply the middle portions of the hair follicles and the sebaceous glands Ascending branches to feed the superficial plexus

Question 324

Superficial plexus

Answer 324

Just below the basement membrane Contains capillary loops that supply the epidermis and upper portion of the hair follicles

Question 325

Arterioles

Answer 325

Consist of endothelial cells surrounded by basement membrane & two layers of smooth muscle cells Function: as part of the resistance vessels in skin

Question 326

Arterial and venous capillaries

Answer 326

Lack surrounding smooth muscle cells

Question 327

Postcapillary venules

Answer 327

The majority of the superficial dermal vessels Most physiologically reactive segment of the microcirculation Site where inflammatory cells migrate from the vascular space into tissues Site where endothelial cells develop gaps that result in increase vascular permeability during inflammation Immue complexes are typically deposited here

Question 328

Blood vessel endothelial cells are characterized by?

Answer 328

1. Ultrastructurally by a peripheral basement membrane and intracytoplasmic Weibel-Palade bodies (rod-shaped tubular structures enveloped in a continuous single membrane) 2. Storage for Factor VIII, P-selectin, histamine 3. By their possession of factor VIII (vonWillebrand) antigen, plasminogen activators, & prostaglandins 4. By CD31 (platelet endothelial cell adhesion molecule [PECAM]) 5. By being phagocytic (esp in the presence of carbon, mycobacteria or fibrin)

Question 329

Blood vessel endothelial cells key function?

Answer 329

key regulators of leukocyte trafficking

Question 330

Selectins are upregulated on what structures during inflammation?

Answer 330

(E- and P-selectin) and members of the immunoglobulin superfamily (ICAM-1, vascular cell adhesion molecule-1 [VCAM-1]) are upregulated on endothelial cells with inflammatory stimulation

Question 331

What two inflammatory cytokines induce E-selectin

Answer 331

induced by IL-1 and TNFα

Question 332

P-selectin

Answer 332

Stored in Weibel Palade bodies Specific for leukocyte recruitment to the skin Mediate rolling, adhesion, and transmigration of leukocytes from the blood stream

Question 333

ICAM-1/ICAM-2

Answer 333

expressed on skin microvessel endothelial cells ICAM-1 is upregulated by IL-1, TNFα, and IFNγ Both serve as the binding site to leukocyte LFA-1 General adhesion molecules of lymphocytes

Question 334

VCAM-1 (Vascular cell adhesion molecule)

Answer 334

Not normally present on endothelial cells General adhesion molecule for lymphocytes Induced by TNFα or LPS

Question 335

Glomus: Hoyer-Grosser’s organ

Answer 335

* A special arteriovenous shunt located within the deep dermis * Consist of an arterial segment (Sucquet-Hoyer canal) and a venous segment * Rich cholinergic nerve supply

Question 336

Pericytes

Answer 336

* Aligned parallel to blood vessels on the dermal side * Vary from fusiform to clublike in appearance * Contractile cells, containing actin-like and myosin-like filaments * Important in regulating capillary flow * Larger # of pericytes surround the endothelial cells in post capillary venules * Pericytes and endothelial cells make numerous contacts over their entire surface

Question 337

Function of pericytes?

Answer 337

1. Important in regulating capillary blood flow 2. Essential for microvessel stability 3. Participate in the control of angiogenesis 4. Major contractile cells responsible for producing the endothelial cel gaps in the postcapillary venular segment where the events of inflammation occur 5. Endothelial cell gaps develop both, at the interendothelial cell junction and through the cell itself 6. Gap formation is associated with agents such as histamine, bradykinin

Question 338

Veil cells

Answer 338

* Surround all dermal microvessels, entirely external to blood vessel walls * Flat, adventitial, fibroblast-like cells * Stain for factor XIIIa - component of the dermal dendrocyte system * Negative for 1 or B cell markers and CD1a negative * Demarcates the vessel from the surrounding dermis * Perivascular mast cells are usually present in the space between the vascular wall and the surrounding veil cells

Question 339

Innervation of the cutaneous blood vessels

Answer 339

Under dual vasomotor control Separate nervous signals for vasoconstriction and vasodilatation Under normothermic conditions, skin blood flow averages approximately 5% of cardiac output

Question 340

Reflex vasoconstriction (in response to cold and baroreflexes) is mediated through what fibers?

Answer 340

adrenergic sympathetic fibers distributed widely over most of the skin (epinephrine/norepinephrine)

Question 341

In most of the skin vasodilatation occurring during heat exposure depends on _____ signals that cause blood vessels to dilate = active vasodilatation

Answer 341

sympathetic nervous signals o Occurs in almost all skin outside the acral regions o Vasodilatation occurs near the onset of sweating & therefore is not sensible to small temperature changes o The neurotransmitter is unknown however, there is evidence that active vasodilatation is mediated by release of acetylcholine.

Question 342

Sympathetic nervous system receptors

Answer 342

β-receptors: relax smooth muscle cells causing vasodilation α-receptors: constrict smooth muscle cells causing vasoconstriction Mediators of smooth muscle tone: Catecholamines: activate both α & β receptor; Because α receptors predominate, vasoconstriction occurs Vasodilators: Histamine Bradykinin Kallikrein Carbon dioxide Lactate NO Substance P Skin temperature affects heat loss responses also through direct actions on the effectors themselves

Question 343

Specialized organelles of endothelial cells

Answer 343

Weibel-Palade bodies (WPB) Fenestrae Caveloar system

Question 344

Weibel-Palade bodies (WPB):

Answer 344

Elongated, membrane-bound organelles that display longitudinal striations Distributed randomly throughout the cytoplasm in vascular endothelial cells Contain von Willebrand factor (vWF, factor VIII-related antigen), P-selectin (CD62P), lysosomal-membrane-associated glycoprotein 3 (LAMP-3 or CD63), 1,3-fucosyltransferase VI, and IL-8

Question 345

Endothelial junctions

Answer 345

Neighboring endothelial cells connect to each other by forming interdigitating protrusions connected by junctions Vary depending on the site of the vascular tree -- allow for varying degrees of permeability for proteins and cells Intercellular tight (occluding) junctions: Adherens junctions Gap junctions Complexus adherens or syndesmos

Question 346

Intercellular tight (occluding) junctions

Answer 346

Consist of continuous belt-like meshwork of six anastomosing junctional strands, which prevent the transport of macromolecules Virtually absent in postcapillary venules

Question 347

What are gap junction proteins?

Answer 347

connexins

Question 348

Molecular markers of endothelial cells

Answer 348

vWF, CD31 (PECAM-1),ICAM-2,CD141 (thrombomodulin)

Question 349

vWF

Answer 349

most widely used marker, which may be detected in WPB or within Golgi apparatus or endoplasmic reticulum; also found in megakaryocytes and platelets

Question 350

CD31 (PECAM-1)

Answer 350

found on endothelium, platelets & circulating leukocytes Nearly all endothelium secretes and binds CD143 (angiotensin-converting enzyme) to the cell surface Most endothelial cells express anticoagulant protein CD141 (thrombomodulin)

Question 351

ICAM-2

Answer 351

May be the single best marker for endothelium mainly as it is not generally found on other cell types

Question 352

Endothelial Role in Leukocyte trafficking

Answer 352

Initial tethering, rolling, and firm adhesion Initial tethering: mediated by selectins L-selectin (CD62L), E-selectin (CD62E), and P-selectin (CD62P) P-selectin: endothelial cells L-selectin: leukocytes E-selectin: expressed by endothelial cells; induced by TNF-α or IL-1β Adhesion of leukocytes to endothelium is mediated by leukocyte integrins β2 integrins (CD18): LFA-1 & Mac-1; induced by PAF -- Bind to ICAM-1 Emigration/Diapedesis

Question 353

Lymph vessel location

Answer 353

o Lie in the superficial dermis and surround the adnexae, usually not seen above the middle dermis o Arise from capillary networks ; drain into a subcutaneous lymphatic plexus

Question 354

Lymph vessel distinguishing features from capillaries

Answer 354

Have wider and more angular lumina; have flatter and more attenuated endothelial cells Have no pericytes Contain little to no blood in normal situations

Question 355

Lymph vessel function

Answer 355

o Regulate pressure of the interstitial fluid by resorption of fluid released from vessels o Clear the tissues of cells, proteins, lipids, bacteria, and degraded substances including materials that have penetrated the skin o Link the skin and regional lymph nodes o Lymph flow within the skin depends on movements of the tissue caused by arterial pulsations, muscle contractions and body movement; backflow is prevented by bicuspid-like valves within the vessels

Question 356

Intermediate filaments

Answer 356

Intermediate filaments connect the nuclear membrane to hemidesmosomes on the keratinocytes membrane. These filaments are responsible for maintaining the integrity and structure of basal epidermal cells. Composition: Keratin-5 + Keratin-14

Question 357

Inner plaque components

Answer 357

plectin + BPAG1-e

Question 358

Outer plaque components

Answer 358

Integrin alpha-6/beta-4 + cytoplasmic domain (aminal terminus) of collagen XVII (BPAG2, BP180).

Question 359

Anchoring filaments

Answer 359

Anchoring filaments connect hemidesmosomes to anchoring fibrils throughout the lamina lucida. The lamina lucida is thought to be a fixation artefact and probably does not exist in vivo. Composition: intact and shed extracellular domain (carboxyl terminus) of collagen XVII (BPAG2, BP180).

Question 360

What are focal contacts?

Answer 360

Focal contacts are inter-hemidesmosomal adhesion structures that are mostly functional during wound healing in which epidermal migration occurs. Composition (main components): integrins alpha-2/beta-1, alpha-3/beta-1, alpha- 5/beta-1; laminin isoforms (3A32, 3A11); collagen XXIII; nidogens, fibulins.

Question 361

In the skin, integrin alpha-6/beta-4 connects intermediate filaments, via hemidesmosomes, to what structure?

Answer 361

laminin-5 (Lm3A32)

Question 362

Both alpha-2/beta-1, alpha-3/beta-1 and alpha-5/beta-1 integrins are present at non-hemidesmosomal focal contacts during _______ migration. In this case, they will link the laminin-5 (Lm3A32)/-6(Lm3A11) complex to the actin microfilament network.

Answer 362

basal keratinocyte migration

Question 363

Large deletions in ____ have also been found to underlie JEB in Charolais calves and in Churra sheep.

Answer 363

ITGB4

Question 364

Epidermal stratum germinativum differentiates into hair germs (primary epitheial germs) that give rise to what three structures?

Answer 364

hair follicles, sebaceous glands and epitrichial glands

Question 365

Hair germs initially consist of an area of crowding of deeply basophilic cells in the basal layer of the epidermis. Subsequently, the areas of crowding become buds known what structure that protrudes into the dermis?

Answer 365

epidermal placodes

Question 366

Beneath each epidermal placode lies a group of mesenchymal cells, referred to as what structures, from which the dermal hair papilla is later formed?

Answer 366

dermal condensate

Question 367

The epidermal placode develops into three epithelial cylinders. The innermost cylinder forms the hair shft. The outermost cylinder forms what structure?

Answer 367

Outer root shealth

Question 368

As the hair peg lengthens and develops into a hair follicle and hair, three buges appear. The lowest (deepest) of the bulges develops into the attachement for what structure?

Answer 368

arrector pili muscle

Question 369

As the hair peg lengthens and develops into a hair follicle and hair, three buges appear. The middle buldge develops into the attachement for what structure?

Answer 369

sebaceous glands

Question 370

As the hair peg lengthens and develops into a hair follicle and hair, three bulges appear. The uppermost bulge develops into the attachment for what structure?

Answer 370

epitrichial sweat glands \*\*\* All these structures develop on the cranial side of the prinary hair follicle\*\*\* (secondary hairs develop on the caudal side)

Question 371

The skin is an active site for ______ metabolism.

Answer 371

fatty acid

Question 372

Signals controlling hair follicle induction, development, regression and reactivation have not been identified. however, what growth factors or their receptors have been localized to hair follciles and surrounding mesenchyme?

Answer 372

EGF, TGFb, TGFb2, neutotrophin 3

Question 373

An interplay between class 1 major histocompatibility complex (MHC) expression and what two other factors are involved in the regulation of hair growth, especially during the catagen phase?

Answer 373

chondroitin proteoglycans and activated macrophages

Question 374

The hair follicle is a source and target of \_\_\_\_\_\_, neutropharmacologic manipulations alter hair cycling.

Answer 374

neurotrophins

Question 375

The trophic effects of cutaneous nerve on follicular growth are exerted via regulation of what four factors?

Answer 375

vascular tone neuropeptides stimulation of receptors on follicular keratinocytes dermal papilla fibroblasts modulation of macrophages and mast cells

Question 376

Hair growth responds premoninantly to \_\_\_\_; and to a lesser extent\_\_\_\_\_.

Answer 376

photoperiod ambient temperature \*\* sinus hairs are not subjected to seasonal shedding\*\*

Question 377

The hair cycle and haircoat are also affected by hormonal changes. in general anagen is initated and advanced by thyroid hormone and growth hormone. Conversely, excessive amounts of ____ or ____ inhibit anagen and suppress hair growth rate.

Answer 377

Estrogens and glucocorticoids

Question 378

The molecular components of the desmosome belong to what three major gene families?

Answer 378

plakins (desmoplakin), armadillo proteins (plakoglobin and plakophilin) and demosomal cadherens (desmoglein and desmocollin)

Question 379

Linkage of the keratin intermediate filament (cytokeratin) network to the hemidesmosome and the basal keratinocyte plasma membrane involves several components including what 4 structures?

Answer 379

plaque proteins, bullous pemphigoid antigen 1 (BPAG1, BP230) and plectin, the transmembrane proteins a6b4 integrin and BPAGII (collagen XVII) and laminin 332A (laminin 5)

Question 380

Release of profilagggrin from keratohyalin granules is followed by its _____ dependent cleavage into filaggrin monomers that function to aggregate, pack and align keratin filaments.

Answer 380

Calcium-dependent

Question 381

Keratohyalin granules are composed of what products?

Answer 381

profillagrin, keratin filaments and loricin

Question 382

What ultrastructural feature characterizes granular cells at the cell margins?

Answer 382

clustered lamellar granules

Question 383

In rodents, what two morphologic forms of keratohyalin granules occur?

Answer 383

P-F granule is irregularly shaped and contains profilaggrin, whereas the L-granule is smaller, rounded and contains loricrin.

Question 384

What layer is a fully keratinized, compact, thin layer of dead cells? This layer is anuclear, homogeneous and hyaline like, it contains regratile droplets and a semifluid substance called \_\_\_\_\_.

Answer 384

stratum lucidum eleidin

Question 385

How does the stratum lucidum differ from the stratum corneum histochemically?

Answer 385

Differs from the stratum corneum by being rich in protein bound lipids. The stratum lucidum is best developed in the foot pads and less developed in the nasal planum - absent from all other layers of the skin. AKA stratum conjuctum

Question 386

The termically differentiated corneocyte has a highly apecialized structure that forms under its plasma membrane, \_\_\_\_\_\_\_\_\_\_.

Answer 386

the cornified envelope (CE) The CE develops under the plasma membrane of stratified epidermal cells, cells of the inner root sheath and medulla of the hair follicle and the cuticle of the claw.

Question 387

Why is the corneocyte not contain a true cell membrane - what component is it missing?

Answer 387

CE contains no phopholipids

Question 388

CE formation is associated with increased activity of what enzyme (calcium dependent) that catalyze cross-linking of soluable and particulate protein precursors into large insoluable polymers.

Answer 388

Transglutaminase

Question 389

What are the known physiologic systems that regulate that are important to carry out the biologically processes of the skin (differentiation, immune response, proliferation, inflammation)?

Answer 389

1. Protein Kinase C/Phospholipase C Second messenger system 2. Receptor-linked Tyrosinekinase system 3. Calcium/calmodulin second messenger system 4. cAMP dependent protein kinase system

Question 390

There appears to be a host of hormones and enzymes that can induce and increase the acivity of what enzyme during epidermal proliferation?

Answer 390

**Ornithine decarboxylase** - this enzyme is essential for biosynthesis of polyamines (putrescine, spermidine and spermine - known to be important for normal keratinization.

Question 391

What are the four distinct cellular events in the process of cornification?

Answer 391

1. keratinization (synthesis of the principal fibrous proteins of the keratinocyte) 2. keratohyalin synthesis (incuding the histidine rich protein filaggrin) 3. formation of the highly cross-linked insoluable stratum corneum cornified cell envelope (including the structural protein involucrin) 4. Generation of neutral lipid enriched intercellular domains, resulting from the secretion of distincitive cellular lamellar granules.

Question 392

Lamellar granules are synthesized primarily where?

Answer 392

lamellar granules are primarily synthesized in the stratum spinosum and displaced to the apex of the periphery of the cell as it reaches the stratum granulosum. They fuse with the plasma membrane and secrete their contents (phospoholipid, ceramides, FFA, hydrolytic enzymes and sterols).

Question 393

What labeling technique has been shown that the turnover (cell renewal) time fot he viable epidermis of the dog is approximately 22 days?

Answer 393

Tritated thymidine Clipping = 15 days Cocker spaniels = 7 days

Question 394

The use of what technique provides useful model for in vitro studies of epidermal kinetics, pathogenesis of various dermatological disease and cutaneous effected of arios pharmacologic agents?

Answer 394

cultured canine keratinocytes \*\*\*express antigens associated with PV, PF, and deposit laminin V and type IV collagen\*\*\*

Question 395

Synthesis of epidermal lamellar bodies is synthesized where in the epidermis?

Answer 395

Stratum spinosum

Question 396

List the contents in lamellar vesicles?

Answer 396

1. polar lipids 2. glucosylcermadies 3. sphingomyelin 4. free sterols 5. phospholipids 6. hydrolytic enzymes

Question 397

In response to increase in what the concentration in the stratum granulosum, will cause the lamellar bodies to fuse with the plasma membrane and secrete their contents into the intercellular spaces?

Answer 397

calcium

Question 398

Ceramides are _____ linked fatty acids containing long-chan amino ______ (sphingoid base)

Answer 398

amide-linked alcohol

Question 399

\_\_\_\_\_\_\_ are the most important lipid component for lamellar arrangement in the stratum corneum and in barrier function.

Answer 399

Ceramides

Question 400

\_\_\_\_\_ are importnat because they are incorporated into the ceramides.

Answer 400

PUFAs

Question 401

Linoleic acid, an essential fatty acid for dogs and cats, in found in cermamides ____ , ___ and \_\_\_.

Answer 401

Ceramides 1, 4, 9

Question 402

Which two ceramides bind to involucrin and other proteins of the CE, forming a scaffold for the binding of other lipids into an intercellular lipid bilayer located parallel to the corneocytes in the stratum corneum?

Answer 402

ceramides 1 and 2

Question 403

PUFAs have important roles in the skin as precursors of \_\_\_\_\_.

Answer 403

Eicosanoids

Question 404

PUFA fatty acids are liberated from phopholipids by ____ and are subsequently metabolized by ____ and ____ enzymes into prostagladines and leukotrienes.

Answer 404

PLA2 Cyclooxygenase, lipoxygenase

Question 405

Skin surface lipids can be studied qualitatively by various extraction methods or quantitatively using \_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 405

the lipometer or sebumeter.

Question 406

Melanocytes, the second type of cell found in the ___ layer of the epidermis, are also found in the outer root shealth and hair matric of the hair folluicles, in the ducts of sebaceous and sweat glands and to a lesser extent in the superficial dermis.

Answer 406

basal layer of the epidermis

Question 407

Melanocytes are derived from where? and mirgrate inot the epidermis in early fetal life.

Answer 407

neural crest They are also found int he eyes (retinal pigment epithelium), cochlea (stria vascularis) and meniges.

Question 408

Melanocytes have long cytoplasmic extensions (dendrites) that weave among keratinocytes and trasnfer pigment containing ______ to the keratinocytes.

Answer 408

melanosomes \*\*\* In general - there is 1 melanocyte per 10 to 20 keratinocytes in the basal cell layer of the canine skin = epidermal melanin unit\*\*\*

Question 409

Although melanin absorbs light over a broad spectrum, including UVA and UVB, it is not partiularly efficient absorber of \_\_\_\_.

Answer 409

UVL

Question 410

What is the different between UVA and UVB light?

Answer 410

Two types of UV light are proven to contribute to the risk for skin cancer: Ultraviolet A (UVA) has a longer wavelength, and is associated with skin aging. **Ultraviolet B (UVB) has a shorter wavelength and is associated with skin burning**.

Question 411

Skin color is also influenced by ____ found in epidermal cells; red from oxygenated hemoglobin and blue from unoxygenated blood.

Answer 411

yellow carotenoids

Question 412

Pheomelanins differ from eumelanins by containing a high proportion of \_\_\_\_.

Answer 412

sulfur

Question 413

Despite different properties of the different melanins, they all arise from a common metabolic pathway in which _____ is the key intermediate.

Answer 413

dopaquinone

Question 414

Melanin synthesis takes place exclusively within the ____ and ont he specialized organelle, the \_\_\_\_\_\_.

Answer 414

melanocyte melanosome

Question 415

The specific enzyme, \_\_\_\_, catalyzes conersion of tyrosine to dopa.

Answer 415

Tyrosinase \*\*\* rate limiting enzyme in the melanin othway. It is a CU containing enzyme found exclusively in melanocytes, and is thus a good epcific marker for these cells\*\*\*

Question 416

What are the catalytic activities of tyrosinase?

Answer 416

The most critical is its tyrosine hydrozylase activity - converting tyrosine to dopa It is also able to use dopa or 5,6-dihyroxyindole (DHI) as substrates for oxiudase activities. \*\*\*mutations in the **tyrosine structural gene** are responsible for several types of albinism\*\*

Question 417

Once dopa is formed, it can spontaneosly auto-oxidize into ____ without tyrosinase (although its slower) and continue through the melanin pathway to dopachrome, 5,6-dihydroyindole-2-carboxylic acid, DHI and indole-5,6-quinone.

Answer 417

dopaquinone

Question 418

Classifications of Melanin: Eumelanin

Answer 418

Dark brown-black alkali-insoluable no sulfur content Polymer of 5,6-dihydroxyindole and 5,6-dihydroxyindole - carboxylic acid Ellipsoidal (melanosome shape) Lamellae or fillaments (melanosome structure)

Question 419

Classifications of melanin: Pheomelanin

Answer 419

Yellow-reddish brown alkali-soluable high sulfur content Polymers of benzothiazine units derived from cyteinyldopa Spherical (melanosome shape) Microvesicles/microgranules (melanosome structure)

Question 420

What enzymes converts dopachrome to DHICA and what metal is required for reaction?

Answer 420

TYRP2 - requires presence of zinc

Question 421

The determination to produce eumelanins or pheomelanins is predominatly under ____ control.

Answer 421

genetic

Question 422

If sulfhydryl groups are present, _____ is produced. It has been proposed that the "switching' of melanin synthesis is mainly controlled by the levels of \_\_\_\_\_\_, with high levels producing eumelanins and low levels producing pheomelanins.

Answer 422

pheomelanins tyrosinase

Question 423

Melanosomes originate from the \_\_\_\_\_, where the tyrosinase enzyme is formed.

Answer 423

golgi apparatus

Question 424

Transfer of melanin involes the endoytosis of the dendrite tips of the incorporated stage ___ melanosomes by the adjacent keratinocytes.

Answer 424

IV melanosomes

Question 425

Melanocytes eject melanosomes into keratinocytes by a unique biological transfer process called \_\_\_\_\_.

Answer 425

cytocrinia

Question 426

Steps in melanogenesis

Answer 426

1. Melanoblast migration from neutral crest 2. Melanoblast differentiation into melanochtes in skin 3. Melanosome gene activation 5. Synthesis of tyrosinease and melanogenic proteins 6. Posttranslational processivng and glycosylation of tyosinases and transport 7. fusion of vesicles to form. lanosomes 8. Control of activity of tyrosinase and tyrosine-related proteins 9. Melanin biosynthesis 10. Melanosome transfer to keratinocyte 11. Melanosome degradation 12. Melanin removal with loss of cornified cells

Question 427

A pivitol transcription factor in expression and differentiation of many enzymes involved in melanin synthesis is \_\_\_\_\_\_\_\_.

Answer 427

microphthalmia transcription factor (MITF)

Question 428

One major determinant of melanogensis is the \_\_\_\_\_, a G-protein coupled receptor that regulates pigment phenotype.

Answer 428

melanocortin 1 receptor (MC1R)

Question 429

Agonists of MCR1 include _______ and \_\_\_\_\_\_.

Answer 429

alpha-melanocte-stimulating hormone (MSH) and corticotropin.

Question 430

\_\_\_\_\_ gene encodes an antagonist of MCR1.

Answer 430

Agouti

Question 431

What is a tyrosinase kinase receptor involved in melanobast expansion, survival, and mirgration. Mutations in this have been identified in piebaldism and have leads to progression of lemanocytes toward metastatic melanoma phenotypes.

Answer 431

c-Kit

Question 432

Melanocytes secrete what cytokine?

Answer 432

IL-8

Question 433

What is a neutoimmunomodulatory and antiinflammatory peptide that is synthesized and released by keratinocytes, Langerhan cells, fibroblasts, endothelial cells, and melanocytes themselves?

Answer 433

a-MSH a-MSH can modulated keratinocyte proliferation and differentiation, as well as endothelial cell and fibroblast cytokine and collagenase production. It also downregulates the production of proinflammatory cytokines and accessory molecules on antigen-presenting cells. It is an antagonist of IL-1.

Question 434

Folliculr melanocytes undergo cyclic modifaction in coordination with the hair cycle. Melanocytes are located where in the air follicle during anagen? Melanocytes undergo apoptosis during late \_\_\_\_\_.

Answer 434

proximal hair bulb catagen

Question 435

Argentaffin stain

Answer 435

This stain relies on the abiity of melanin to reduce silver fron a cilver solution. ex. Fontana Masson and Gomori methaniamine silver These agents also stain neurosecretory granules and formalin pigment

Question 436

Argyrophil stains

Answer 436

Similar to argentaffin stains but use an external silver reducer to produce elemantal silver. example of argyrophil stain is Grimelius stain. Argyophil stains also stain nerves, reticulum and elastic fibers.

Question 437

Postassium permanganate can be used to ____ melanocytes to faciliate the study of internal organelles.

Answer 437

bleach

Question 438

Merkel cell

Answer 438

Dendritic epidermal clear cells confined to the basal cell layer, or just below, and ocur predominatly in the tylotrich pads and hair follicle epithelium. These specialized cells function as SLOW-ADAPTING TYPE 1 mechanorecptors. Merkel cells contain a large cytoplasiic vauole that displaced the cell nucleus dorsally and are usually parallel to the skin surface. Merkel cells may have other functions such as influencing cutaneous blood flow and sweat production (releasing. vasoactive intestinal peptide, coordinaing kerainotcyte proliferation and maintaining/stimulating stem cell population in hair follicle.

Question 439

What are the IHC markers for merkle cells?

Answer 439

K8, K18,K19 and K20.

Question 440

THe BMZ can be divided into the following 4 components:

Answer 440

1. the basal cell plasma membrane 2. the lamina lucida 3. the lamina densa 4. sublamina densa area (lamin fibroreticularis) The first three componnets appear to be primarily of the epidermal origin. The epidermal basement membrane is composed of a wide variety of glycoproteins and other macromolecues.

Question 441

What are the insoluable fibers of the dermis?

Answer 441

collagen and elastin

Question 442

What are the major soluable macromolecules of the dermis?

Answer 442

proteoglycans and hyaluronan

Question 443

What accounts for most of the tensile strength and elasticity of the skin; it is involved in regulation of cell growth, proliferation, adhesion, migration, and differentiation, and it modulates wound healing and the structure and function of the epidermis?

Answer 443

dermis

Question 444

Why is the dermis of scrotal skin unique?

Answer 444

It contains numerous smooth muscle bundles

Question 445

Most of the dermal extracellylar matrix (fibers and ground substance) is synthesized by what cell?

Answer 445

fibroblasts; which respod to a variety of stimuli such as growth factos elaborated by keraintocytes, infammatory cells and fibroblasts themselves.

Question 446

What three collagen types predominate in the dermis?

Answer 446

Collagens I, II and V

Question 447

Dermal fibers consist of what three structures?

Answer 447

Formed by fibroblasts and are collagenous, reticular and elastic

Question 448

What fibers have GREAT tensile strength and are the largest and most numerous fibers. They are thick bands composed of multiple protein fibrils and are differentially **stained by Masson Trichome.**

Answer 448

Collagenous fibers

Question 449

What two 'unusual' amino acids are measured in urine as indices of collagen turnover?

Answer 449

hydroxylysine and 4-hydroxyproline

Question 450

What fibers are fine, branching structures that closely approximate collagen with age. They can be detected best with s**pecial silver stains?**

Answer 450

Reticulin

Question 451

What fibers are composed of single fine branches that possess great elasticity and accound for about 4% of the dermal extracellular matrix? T**hey are well visualized by Verhoeff and van Gieson elastin stains.**

Answer 451

Elastic fibers

Question 452

The two components of elastic fibers are amorphous elastin, which contains what two unique cross-linked amino acids along microfibrils which contain ____ and \_\_\_\_\_?

Answer 452

desmosine and isodesmosine = where all the strength comes from \*\*fibrillin and type IV collagen\*\*

Question 453

What collagen type predominates the dermis? Describe it.

Answer 453

Type I collagen (87%), Type III and Type V predominate Type I is it is triple helix structure composed of three polypeptide a chains coiled around each other much like a rope. This confirmation five the molecule a rodlike shape. Each a chain is composed of approximately 1000 aa with GLYCINE accounting for 1/3 - aa are arranged in repeated triplets.

Question 454

The remarkable strenth of elastic fibers is dervied from the unusual cross-linking of desmosine and isodesmosine. What is the precurser to elastin?

Answer 454

tropoelastin

Question 455

Collagen III are composed of how many alpha chains?

Answer 455

composed of three identical a chains with high content of hydroxyproline and glycine that form broad collagen fibers in the dermis and also in the gastrointestinal/vascular connective tissues and fetal skin.

Question 456

Type V collagen

Answer 456

forms large fibrils and is found in the dermis in association with type I and III collagen

Question 457

Type VI Collagen

Answer 457

form triple helical microfibrils arranged in a network to stabilize the large type I collagen molecules in the dermis.

Question 458

Collagen III and collagen V are also concentrated around what structure?

Answer 458

blood vessels

Question 459

Type IV collagen (lamina densa) and type V (lamina lucida) collagen are found in \_\_\_\_\_, and type VII collagen is found in the ______ of the BMZ.

Answer 459

BMZ anchoring fibrils

Question 460

What two collgen types are considered *fibril-associated collagens with interrupted triple helices (FACITS)*?

Answer 460

XII and XIV

Question 461

What factors will cause collagen abnormalities?

Answer 461

Genetic defects, vit C deficiency, iron, copper and from B-aminoproprionitril poisoning.

Question 462

Collagen synthesis is stimulated by what factors?

Answer 462

ascorbic acid, TGFb, IL-1, IGF1 (somatomedin C), IGF-2, superoxide generating systems and bleomycin.

Question 463

Collagen synthesis is inhibited by what factors?

Answer 463

GC, retinoids, vit D, parathormone, prostaglandin E2, IFNy, D-penicilliamine and minoxidil.

Question 464

Collagenases are members of the _____ gene family

Answer 464

MMP

Question 465

What is a major source of collagenase under normal conidtions of remodeling?

Answer 465

Dermal fibroblasts Under certain conditions, keratincytes, neutrophils, eosinopihils and macrophages can release a variety of proteolytic enzymes and collagenases.

Question 466

The superficial dermis contains fine, loosely arranged collagen fibers that are irregularly distributed and a network of fine elastin fibers. The deep dermis contains what arrangement of collagen and elastin?

Answer 466

The deep dermis containsthick densely arranged collagen fibers that tend to parallel the skin surface, and elastin fibers that are thicker and less numerous than in the superficial dermis.

Question 467

Elastic fibers have extensive cross-linkages owing to the presence of desmosine and isodemosine, which form colvaent cross-links resistant to \_\_\_\_\_\_.

Answer 467

degradation

Question 468

In the superficial dermis, elastic fibers known as ______ fibers are organized in an arcade like arrangment. From these fibers, still thinner eslatic fibers called _____ fibers ascend almost vertically to terminate at the dermoepidermal juinction and anchor to the basement membrane.

Answer 468

elaunin oxytalan

Question 469

The _____ present in neutrophils and eosinophils are the most potent, and they readily degrade elastic fibers in disease states.

Answer 469

elastases (serine proteases)

Question 470

What is the affected protein in Ehlers Danlos syndrome?

Answer 470

alpha chains of types I, III or V collgen; procollagen-lysine; lysyl hydroxylase; procollagen N peptidase; tenascin x; xylosylprotein 4-b-galactosyl-transferase

Question 471

What is the affected proteins in Cutis laxa syndrome?

Answer 471

elastin, ATP-dependent copper transporter; fibulin 4; fibulin 5

Question 472

What is the affected protein in EB?

Answer 472

a1 chains of types VII and XVII collagen

Question 473

The ground substance is a viscoelastic gel-sol of fibroblast origin composed of \_\_\_\_\_that usually linked in vivo to \_\_\_\_\_\_.

Answer 473

GAGs proteoglycans

Question 474

The major proteoglycans and GAGs include ____ and \_\_\_\_\_.

Answer 474

hyaluronate and heparin in the epidermis synthesized by keratinocytes heparin sulfate and chondroitin 6 sulfate in the BM

Question 475

What are fibronectins?

Answer 475

glycoproteins capable of muliple interactions with cell surfaces and other matrix components. They are produced by keratinocytes, fibroblasts, endothelial cells and histiocytes. Moderate cell to cell interactions and cell adhesions to the substrate, and they modulate microvascular integrity, vascular permeability, basement membrane assembly, and wound healing. Present in lamina Lucida and lamina dense of BMZ

Question 476

large glycoprotein that is prominently expressed at epithelial-mesenchymal interfaces. It plays a significant role in epithelial morphogenesis and proliferation and wound healing?

Answer 476

Tenasin

Question 477

Mucin

Answer 477

In shar peis, large amounts of mucin (mainly HA) are found throughout the dermis, which could be confused with mucinosis in other breeds. Shar Peis have a high level of serum HA than dogs of thother breeds, and i**ncreased HA Synthase 2 mRNA transcription** by dermal fibroblasts from Shar-Pei dogs.

Question 478

The hair follicle is divided into what three parts?

Answer 478

medulla, cortex and cuticle Medulla - the innermost region of the hair, is composed of longitudinal rows of cuboidal cells. The cells are solid near the hair root, the rest of the hair shaft contains air and glycogen vacuoles. Cortex - the middle layer, consists of completely cornified spindle shaped cells whose long axis is paraellel to the hair shaft. These cells contain the pigment that give hair its color. This part also contributes most to the mechanical propers of the hair fibers. The cuticle is the outermost region of the hair, and consists of flat, cornified, ancuclear cells arranged like 'slate on a roof'

Question 479

Compare secondary hairs and primary hairs

Answer 479

Secondary hairs have a narrower medulla and a more prominent cuticle than primary hairs, and lanugo hairs have NO medulla.

Question 480

Cats and dogs have a _______ follicle arrangment.

Answer 480

compound hair follicle In general, the cluster consists of 2 to 5 large primary hairs surrounded by groups of smaller secondary hairs. one of the primary hairs is the largest (central primary hair) and the remaining primary hairs are smaller (lateral primary hairs. Each primary hair has a sebaceus and apocrine gland and an arrector pili muslce. Secondary hairs may be accompanied only by a sebaceous gland. The primary hairs generally emerge indenpendently through seperate pores; the secondary hairs emerge through a common pore.

Question 481

List the FIVE major components of the hair follicle

Answer 481

1. dermal hair papilla 2. hair matrix 3. hair itself 4. inner root sheath 5. outer root sheath

Question 482

The pluripotent cells of the ____ give rise to the hair and the inner root sheath. The outer root sheath represents a downward extension of the \_\_\_\_\_\_\_.

Answer 482

hair matrix epidermis

Question 483

The anagen hair follicle is divided into these three anatomic segments:

Answer 483

1. the infundibulum (aka pilosebaceous region - the upper portion which consists of the segment from the entrance of the sebaceous duct (_where trichelemmal keratinization begins_) to the skin surface. 2. isthmus (the middle portions, which consists of the segment between the entrace of the sebaceous duct and the attachment of the arrector pili muslce. This is where the trichohyaline granule containing cellular portion of the inner root sheath begins. 3. The ingerior segement (the lowest portion, which extends from the attachemnt of the arrector pili muscle to the dermal papilla).

Question 484

Where does the trichohyaline granule containing cellular portion of the inner root sheath begins?

Answer 484

isthmus

Question 485

What constitutes that permanent portion of the hair follicle/ what segement is transitory?

Answer 485

The infundibulum and isthmus make up the permanent portion of the hair follicle. The inferior segment is transitory. \*\*\*dogs have no anatomic structure analogous to the human hair follicular buldge\*\* Studies in dogs suggest that the stem cells are distributed through the follucular infundibulum and isthmus rather than being concentrated in the bulsge area, as they are through to be in humans.

Question 486

The inner root sheath is composed of what three concentric layers?

Answer 486

(going from in to out) 1. inner root sheath cuticle - a flattened single layer of overlaping cells that point towards the hair bulb and interblock the the hair cuticle) 2. the Huxley layer ( one to three nucleared cells thick) 3. Henle layer (a single layer of non-nucleated cells **These layers contain eosinophiic cytoplasmic granules called 'trichohyalin granules'**

Question 487

Describe trichohyalin granules

Answer 487

Eosinophilic cytoplasmic granules Trichohyalin is a major protein component of these granules, which are morphologic **hallmarks of the IRS** and medually cells of the hair follicle. Trichohyalin functions as a keratin-assocaited protein that promotes the lateral alignment and aggregation of parallel buncles of intermediate filaments in inner root sheath cells. Expression of trichohyalin is closely associated with expression of filaggrin - the major keratohyalin granule protein.

Question 488

What is the prime function of the IRS?

Answer 488

The prime function of the IRS is to mold the hair within it, which it accomplishes by hardening in advance of the hair. \*\* The telogen hair folliucle contains no inner root sheath nor inferior segment\*\*

Question 489

The amino acid **\_\_\_\_\_\_** occurs in high concentrations in the hair and trichohyalin granules AND has been used as a marker for hair follicle differentiation.

Answer 489

**citrulline**

Question 490

Describe the outer root sheath

Answer 490

The outer root sheath is thickest near the epidermis and granually decreases in thickness toward the hair bulb. In its lower portion (from the isthmus otf the hair follicle downward), the ORS is covered by the inner root sheath. It does not undergo keratinixation , its cell shave a clear, vacuolated cytoplasm (glycogen). The the middle portion of the hair follicle (isthmus), the ORS is no longer covered by the inner root sheath, and it undergoes trichilemmal keratinization

Question 491

The the middle portion of the hair follicle (isthmus), the ORS is no longer covered by the inner root sheath, and it undergoes \_\_\_\_\_\_\_\_\_\_.

Answer 491

trichilemmal keratinization

Question 492

What is the innermost layer of the outer root sheath?

Answer 492

The innermost cell layer of the ORS is a speacial single-cell layer, located just outside the Henle layer, whse pattern of cell idffereniation and keratinization is ultrastructually and immunohistochemically different from that of the min layer of the outer sheath. The cells are disctinctly flattened and lack lamellar bodies.

Question 493

What are the the two prominent structures that surround the outer root sheath?

Answer 493

1. BMZ ('glassy membrane") 2. fibrous root sheath. \*\*perifollicular mineralization of the BMZ has been described in health toy poodles and Bedlington terriers\*\*\*

Question 494

The dermal hair papilla is continous with the ____ and is covered by a thin continuation of the \_\_\_\_.

Answer 494

dermal connective tissue, basement membrane

Question 495

The inner root sheath and hair grow from a layer of plump _____ that cover the papilla.

Answer 495

plump nucleated epithelial cells. These cells reguarly show mitosis and are called the **hair matrix**.

Question 496

The morphology of the dermal papilla changes through the hair growth cycle, being ____ in volume in mature anagen and ____ in volume during telogen.

Answer 496

maximal, minimal This is nostly a result of changes in the amount of extracellular matrix within the papilla. In the anagen hair follucle, dermal papilla volume is proportional to the volume of the hair. Just below the dermal papuilla is a fibroelastic cusion called **Aaro-perkins corpuscle.**

Question 497

What structure is just below the dermal papilla is a fibroelastic cushion?

Answer 497

Aaro-perkins corpuscle.

Question 498

What structure represents multiple corrugations of the inner root sheath that project into the pilar canal immediately below the sebaceous duct opening?

Answer 498

Follicular folds \*\* Believed to be artifact of fixation and processing, becuase they are not seen in unprocessed sections\*\*

Question 499

What are two specilized types of tactile hairs that are found in mammalian skin?

Answer 499

Sinus hairs and tylotrich hairs. Sinus hairs (vibrissae, whiskers) are found on the muzzle, lip, eyelid, face and throat and on the palmar aspect of the carpus of cats. Sinus hairs are characterized by an endothelium-lined blood sinus interposed between the external root sheath of the follucle and outer connective tissue capsule.

Question 500

Describe the structure of sinus hairs?

Answer 500

They are characterized by an endothelium-lined blood sinus interposed between the external root sheath of the follucle and an out connective tissue capsule. The sinus is divded into a superior non-trabecular ring sinus and an inferior cavernous sinus. A cusion like thickening of mesenchyme (sinus pad) projects into the annular sinus. The cavernous sinuses are covered by traeculae containing many nerve fibers. *Pancinian corpuscles* are situated close ot the sinus hair follicles. Sinus hairs are thought to functions as **slow-adapting mechanoreceptors**.

Question 501

What are Tylotrich hairs?

Answer 501

These hairs are scattered among ordinary body hairs, The hair follicles are larger than surrounding follicles and contain a single stout hair and an annular complex of neurovascular tissue that surround the follicle at the level of the sebaceous glands. Tyrlotrich hairs are thought to function as rapid-adapting mechanoreceptors. Each tylotrich follicle is associated with a tylotrich pad. Tylotrich pads are composed of a thickened and distinctive epidermis underlaid by a convex are of fine connective tissue that is highly vascularized and well innervated. Unmyelinated nerve dibers end as flat plaques in assoacited with merkel cells, which serve as **slow-adapting touch receptors.**

Question 502

What is the histologic appearance of the anagen hair follicle?

Answer 502

characterized by a well-developed spindle-shaped dermal papilla capped by the hair matrix to form the follicular bulb. Hair matrix cells are often heavily melanized and show mitotic activity. The anagen hair follicle extends into the deep dermis and subcutis. Anagen has been divided into seven stages of growth.

Question 503

What is the histologic appearance of the catagen hair follicle?

Answer 503

It is characterized by retraction toward the surface; a thickened, irregular, undulating BMZ; an increased number of apoptotic keratinocytes, a thickened BMZ between the hair matrix and the dermal papulla; a smaller bulb and an ovoid or round dermal papilla. The catagen follucle epithelium is shortened in length and reduced in volume - shrinks from the position of the har bulb to just below the entry of the sebaceous duct - the volume reduction largely accompanied with apoptosis. The TGFb pathway is involed in the induction of catagen, and caspases play essential roles in the execution of apoptosis.

Question 504

What is the best morphologic feature of the catagen hair follicle?

Answer 504

Partial replacement of the inner root sheath by trichelemmal keratinization. Additionally, melanogensis ceases, the proximal hair shaft is depigmented, the mitotic activity stops.

Question 505

As the follicular epithelium is lost, the adventitial collagen and neurovasuclar network of the follicle condenses along the ract of the previous anagen follicle. This specialized adventitial struction the \_\_\_\_\_, is probably requed to prescisely direct the downward growth of the new follicular epithelium as the follicle reenters anagen.

Answer 505

follicular stile

Question 506

What is the histologic appearance of the telogen hair follicle?

Answer 506

The telogen hair follicle is reduced to about one third of the former length and is characterized by the small dermal papilla that is separated from the matrix cells, no hair bulb, lack of melanin and mitotic activity, and absence of the inner root sheath and presence of a club hair.

Question 507

Hair follicles show four morphologic patterns of keratinization

Answer 507

1. infundibular (like epidermis - basketweave with keratohyaline granules) 2. trichilemmal (a serrated, more closely packed eosinophilic keratin with scant or no keratohyaline granules) 3. hair matrix or trichogenic - characterized by retention of nuclear outlines (ghost cells) 4. inner root sheath and hair shaft medullary (compact and opaque keratin with blue-gray to eosinophilic color and red trichohyaline granules, as in the Henle and Huxley layers.

Question 508

A hair plucked in anagn shows a larger expanded root that is moist and glistening, often pigmented and ____ at the end. A hair pluacked in telogen showes a ____ with little or no pigement.

Answer 508

square tapered club root

Question 509

What cells are present in the hair follicles outer root sheath and have been shown to migrate to the epidermis within 72 hours following ultraviolet radiation.

Answer 509

Langerhan cells; the hair follicle serves as a reservoir to repopulate the epidermis with Langerhan cells. This follicular reservois paradigm is also seen following thermal injury and in vitiligo, in which follicular keratinocytes and melanocytes replenish epidermal cell population.

Question 510

What type of gland are simple or branched alveolar glands distirbued througout all haired skin in all mammals except whales and porpoises.

Answer 510

Sebaceous (holocrine) glands; these glands usually open through a duct inot the pulary canal in the infundibulum. Sebaceous glands are largest and most numeous near mucocutnaeous junctions, in the interdigital spaces, on the dorsal neck and rumo, the chin, and on the dorsal tail (supracaudal glad). ## Footnote **Sebaceous glands are NOT found in the food pad and nasal planum.**

Question 511

Sebaceous gland lobules are bordered by a BMZ on which ther sit a single layer of deeply basophilic basal cells called?

Answer 511

Reserve cells; these cells become progessively more lipidized and eventually disintegrate to form sebum toward the center of the lobule. The increase in lipid content can be detected by **Oil Red** staining.

Question 512

Sebaceous glands express at least two different receptors involed in the uptake of circulating lipids; what are these two receptors?

Answer 512

FATP4 (fatty acid transporter 4) and LDL (low-density lipoprotein) receptor. \*\*\*Sebaceous ducts are lined by squamous epithelium

Question 513

Enzyme histochenical studies have indicated that all mammalian sebaceous glands contain what three enzymes?

Answer 513

succinate acid dehydrogenase, cytochrome oxidase and a few esterases.

Question 514

Describe epitrichial (apocrine) glands?

Answer 514

Epitrichial sweat glads are generally coiled and saccular or tubular and are distributed throughout all haired skin. T**hey are not present in foodpads or nasal planum.** These glands are located below the sebaceous glands, and they usually open through a duct into the pilary canal in the infundibulum, above the sebaceous duct opening. Epitrichial glands tend to be larger in areas where there are less hair follicles. They are largest and most numerous near mucocutaneous junctions, interdigital spaces and over the dorsal aspect of the neck. In general, epitrichial glands do not appear to be innervated. Enzyme shitochemical studies have demonstrated alkaline phosphatase and acid phophatase in epitrichial sweat gland secreotry epithelium. IHC has shown acini and ducts are positive for cytokeratin and S-100 protein.

Question 515

Atrichial (merocrine) sweat glads are found on in \_\_\_\_\_\_.

Answer 515

footpads These glands are small and tightly coiled and they are located in the deep dermis and subcutis of the footpads. Secroty coils consist of a single layer of cuboidal ro columnar epithlial cells and as ingle layer of fusiform myoepithelial cells. Enzyme histochemical studies have demonstrated cytochrome oxidase, succinate and other dehydrogenases, phophorylases and alkaline phosphatase. These glands are richly supplied with **cholinesterase-positive nerves**.

Question 516

Normal dogs with intact pelage have a critical temperature of? If coat is shaved off, it increases to?

Answer 516

14C (57F) 23C (77F)

Question 517

Describe the circumanal gland

Answer 517

these glands are present at birth and develop from ducts that originate from the inner and outer perianal side of the extneral root sheath of hair follicles. These glands are also found in the skin of the prepuce and dorsal/ventral aspects of the tail. ## Footnote **These glands are positive for cytokeratin.**

Question 518

Tail gland

Answer 518

aka supracaudal gland, preen gland is an oval shaped area located on the dorsal surface of the tail over the fifth to seventh coccygeal vertebrae, about 5cm distal to the anus. This gland is consistently present in most dogs histologically; visible in only 5%. Histologically, the canine tail gland is composed predominately of **hepatoid cells** that are identical to those in the hepatoid circumanal glands - dependent on testosterone to form the topographic-ethnologic unit. The tail gland of the cat consists of numeous large sebaceous glands that run the entire length of the dorsal surface of the tail. Excess accumulation of glandular secretion in the area is called 'stud tail'

Question 519

Describe arrector pili muscles

Answer 519

These muscles are of msenchymal origin and consist of smooth muslce with intracellular and extracellular vacuoles. They are present in all haired skin and are largest on the dorsal neck and rump. Arrector pili muscles originate in the superficial dermis and insert approximately perpendicular on the primary hair follicles. These muslces receive **cholinergic innervation** and contact in response to **epinephrine and norepeinephrine**, producing piloerection. Arrector pili mucles probably function int he termoregulation and in the emptying of sebaceous glands. They are also important in providing socail signals.

Question 520

Cutaneous blood vessles are generally arranged in three intercommunicating plexuses of arteries and veins. Identify and describe these three plexuses?

Answer 520

_deep plexus_ - is found at the interface of the dermis and subvutous. Branches from this plexus descend into the subcutis and ascend to supple the lower portiosn of the hair follicles and epitrichial sweat glands. The ascending vessels continue upward to feed the _middle plexus_, whih lies at the level of the sebaceous glands. The middle plexus give off branches to the affector pili muscles, ascending and descending brances that supply the middle portions of the hair follicles and sebaceous glands, and ascending branches to feed the _superficial plexus._ _Capillary loops_ immediately below the epidermis emanate from the superficial plexus and supply the epidermis and upper portion of the hair folicles.

Question 521

The majority of superficial dermal vessels are \_\_\_\_\_\_, which are the most physiologically reactive sements of the microcirculation and also the site where inflammatory cells migrate from the vascular space into tissues and endothelial cells develop gaps the result in increased vascular permeability.

Answer 521

postcapillary venules

Question 522

Blood vessels endothelial cells are mesenchymal in origin and are characterized by what 4 factors?

Answer 522

1. Ultrastucturally by a peripheral basement membrane and intracytoplasmic **Weibel-Palade bodies** (rod-shaped tubular structures enveloped in a continuous single membrnae) 2. By their possession of factor VIII (von willebrane) antigen, plasminogen activators, and protaglandins. 3. by CD31 (platelet endothelial cell adhesion molecule 4. by being phagocytic; Endothelial cells are strateically located between intravascular and tissue compartments and serve as key regulators of leukocyte trafficking.

Question 523

Angiogensis is controlled in part by what three factors?

Answer 523

mast cells (histamine), macrophages (TNFa) and TGFB

Question 524

Pericytes

Answer 524

vary from fusiform to clublike in appeance, are aligned parallel to blood vessels on their **dermal side**. They are contractile cells containing actin-like and myosin-like filaments, and they are important in regulating capillary flow.

Question 525

Veil cells

Answer 525

are flat, adventitial, fibroblast-like cells that surround *all* dermal microvessels. Although their exact function and nature are undetermined, the fact that they stain for factor **XIIIa indicated that they are component of the dermal dendrocyte system.** Unlike pericytes, which are an integral component of the vascular wall and enmeshed in the mural basement membrane material, veil cells are entirely external to the wall. The weil cell dermarcates the vessel from the durround dermis. Perivascular mast cells are usually present in the space between the vascular wall and surround veil cells.

Question 526

\_\_\_\_\_\_ is an excellent noninvasive technique for meauring cutaneous microcirculation. The technique can be aplied to monitor inflammation caused by various drugs, chemicals and allergens related to blood flow.

Answer 526

Laser doppler flowmetry

Question 527

Where do cutaneous lymphatics arise from?

Answer 527

Lymphatics arise from capillary networks that lie in the superficial dermis and surround the adnexa. Vessels arising from these networks drain into a subcutanous lymphatic plexus. Lymph vessels are not usually seen **above the middle dermis** in route in histologic preparation of normal skin.

Question 528

What is the function of lymphatics in the skin?

Answer 528

Lymphatics control the movement of interstitial tissue fluid. The supply, permeation, and removal of tissue fluid are important for proper skin function. Lymphatics are the drains that take away the debris and excess matter that results from daily wear and tear. They are essential channels for the return of protein and cells from the tissues to the blood stream.

Question 529

How are lymph vessels distinguished from blood vessels?

Answer 529

1. possessing wider and more angular lumina 2. having a flatter and more attentuated endothelial cells 3. having no pericytes 4. containing no blood

Question 530

The subcutis is about 90% _____ by weight?

Answer 530

triglyceride

Question 531

What are the functions of the subcutis?

Answer 531

1. energy reserve 2. thermogenesis and insulation 3. protective padding and support 4. maintaining surfaec contours 5. steroid reservois and as the site of steroid metabolism and estrogen production.

Question 532

Basal cell keratinocytes express which keratins?

Answer 532

K1, K5, K6 and K14

Question 533

CERs are sphingoid consisting of sphingoid bases that are amide-linked to what?

Answer 533

fatty acids

Question 534

In the stratum spinosum CERs are synthesized by the de novo pathway and then converted to _____ and \_\_\_\_\_. These are then packed into lamellar granules.

Answer 534

glucosylceramides and sphingomyelin synthase

Question 535

the SG-SC boundaries, glucosylceramides and sphingomyelins are converted back to CERs by _______ and ______ respectively.

Answer 535

B-glucocerebrosidase and sphingomyelinase respectively.

Question 536

Ceramides in the SC initially are formed as fee extractable CERs. But some are subsequently degraded to protein bound CERs. The free-extractable and protein-bound CERs are cleaved to generates ________ by spingosine kinase. It is though that S1p has anti-inflammatory activity. S1p is irreversibly digested to degradation products by S1p lyase (SGPL1

Answer 536

sphingosine-1-phosphate

Question 537

the amount of the anti-inflammatory product S1p in the skin and plasma is decreased in dogs with CAD and this change is probably associated with up-regulation of ____ gene transcription.

Answer 537

SGPL1

Question 538

In response to \_\_\_\_\_\_, the keratohyalin granules are degranulated, their content is released to the cytoplasm and profilaggrin is broken down into filaggrin molecules at the SC-SG boundary

Answer 538

Increased intracellular calcium concentration

Question 539

What is the major role of filaggrin monomers?

Answer 539

* The major role of FLG monomers in the SC is in the aggregation of keratin intermediate filaments into tight bundles, thereby leading to collapse of the cells, which then have a flattened appearance and providing mechanical strength to the cells. * It is also though that pyrrolidone carboxylic a and urocanic acids, the degraded products of FLG monomers act as natural moisturizing factors in the upper SC. * FLG appears to play a role in providing mechanical strength to corneocytes and hampering percutaneous entry of foreign materials through the SC. * It is debatable whether the FLG degradation products (NFF) provide water holding capacity to the SC, and this needs further investigation.

Question 540

In the stratum spinosum layer, kertinocytes begin to express K1/K10; characterisitic of terminal differentiation. K5 and K14 are still present in the cytoplasm. Additionally, dogs also express which other keratins?

Answer 540

K4, K15,K16

Question 541

At the interface of the granular and cornified layers. the lamellar granules fuse with what structure at the apical surface of the cell and secrete lipid laden disks into the intercellular space?

Answer 541

plasma membrane

Question 542

What is the key component of the corneocyte cornified cell envelope?

Answer 542

loricrin

Question 543

what are the three types of filaments that form the cytoskeleton of all epithelial cells?

Answer 543

microfilaments, microtubules and intermediate filaments

Question 544

Keratin intermediate filaments

Answer 544

Comprised of keratin proteins assembled in precise fashion. The keratin proteins have a tripartite structure, compsied of a central alpha-helical rod domain, an amino-termal head and a carboxy-termal tail. The epidermal keratin termal domains exhibit structural motids known as "glucin loops" which are also seen in loricrin and corneodesmosin and are suggested to mediate intermolecular adheson by acting like velcro.

Question 545

Describe KIF assembly

Answer 545

keratins are though to self-asseble into filaments. The assembly starts with type I and type II keratin molecules spontaneously forming coiled-coil heterodimers. The heterodimers align in antiparallel and staggered pattern to form ouble coiled-coil tetramers. The tetramers are the building blocks of the kIP and assemble end to end to form protofilaments (2-3 nm diameter) and laterally into protofibrils (two protofilements) and then finally into intermediate filaments (4 protofibrils). This process relies on lateral interactions between the staggered coiled-coils as well as head-to-head interactions between the same keratin proteins, and keratins are cross-liked by interchain disulfide bonds.

Question 546

What are the associated proteins that contribute to the organization of the KIFs?

Answer 546

Filaggrin plays an important role in promoting the keratin bundling. Filaggrin is a histadine rich protein. Profilaggrin, the precursor molecule for filaggrin and primary component of keratohyalin granuesl, consists of multiple filagggrin untis (4 in dogs). Between N and C termal domains.

Question 547

How are natural moisturizing factors produced?

Answer 547

Profillagrin is cleaved into filaggrin at the transiion from the granular to cornified layers, and filaggrin binds the KIFs, facilitating the flattening of the cornified cells. Fillagrin is ultimately degraded to a mixture of hygroscopic molecules, such as amino acids, urocaniic acid, pyrrolidone carboxylic acid, lactic acid, cirtrate and sugars. These procuts of filaggrin degradation are categorized as the natural moisturizing factors = contibute to hydration, pH and barrier function, urocanic acid plays a role in photoprotetion. The protease caspase-14 is required for filaggrin degradation.

Question 548

Where does the CE start and what enzyme is required?

Answer 548

The formation of CE starts inside of the granular keratinocyte cell membrnae and involved transglutaminases, which are a family of calcium dependent enzymes that catalyze the formation of N (epsolon) - gamma glutyl-lysine isopeptide bonds. Increases in extracellyklar calcium levels in the suprabasal layers leads to increased intracelllar calcium levels which, in turn, increases the TG activity. The isopeptide bonds are highly resistant to most common proteolytic enzymes, contributing to the strucutal strength of the stratum corneum.

Question 549

As the CE formation begins, where are envoplakin, periplakin and involucrin localized?

Answer 549

Envoplakin and periplakin are expressed at the desmosomal plauqes, and involucrin, a highly soluable glutamin-rich protein, locailzied to the cell membrane. Involucrin forms a scaffold for the attachement of other components fo CE. TG1 and TG3 catalyze the formation of isopeptide bonds between lysine and glutamine residues cross-linking involucin to most other CE proteins. Involucrin glytamyl residues and other cornified envelope proteins covalently bind to omega-hydroxycermides. In the finished CE structure, involucrin is localized to the outer protion of the CE scaffold and connects the corneocytes to the extracellular lipid layer.

Question 550

After locicrin is released from keratohyalin granules, where does it accumulate?

Answer 550

Loricrin, a cystein rich highly flexible protein WITH glycine loops (velcro), is the MAJOR structural component of the CE. It comprises over 70% of its mass, and is gound primarily in the inner portions of the CE. After being released from keratohyalin granules, Loricrin accumulates at the desmosomes. TG3 cross-links loricrin and small proline rich peptides together, and TH1 cross-links those oligmers ot the developing CE. Multiple other proteins including filaggrin, cystatin A, cornifelin, SPRs, elafin, S100 proteins, late envelope proteins, demoplakin, and keratins, are also crosslinked to the developing scaffold to become part of the final CE.

Question 551

What are the remaining internal structures of the keratinocyte once the CE firmation progresses and the organelles of the keratinocyte are degraded?

Answer 551

The KIFs are covalently linked to several CE proteins, including lorcrin, envoplakin and involucrin, through lysine residues on teh head domain of type II kerain chains. The CE eventually replaces the plasma membrnae. The mature corneocyte is flattened cells. KIF+Fillagrin (inside cell) Loricrin (inside)/Involucrin (outside)

Question 552

Where do lamellar bodies originate from?

Answer 552

In the upper spinous and granular layers, lamellar granules (aka lamellar bodies) appear from within the Golgi apparatus. These granules contain phopholipids, glucosylceramides, sphinogmyelin and cholesterol. Numerous enzymes and their inhibitors are also released from the lamellar bodies. These inlcude lipid enzymes and their inhibitors are also released from lamellar bodies which incude lipid hydrolases (b-glucocerebrosidase, acidic sphinomyelinase and secretory PLAs, and serine and cystein proteeases, kallikrins and cathepsins) Lamellar garanules also contain cornedesmosin, steroid sulfatase and AMPs such as B-defensin 2 and cathelicidin LL-37.

Question 553

Trafficking of lamellar granules from the trans-golgi network to the plasma membrane is facilitated by what complex?

Answer 553

CHEVI (C-homologues in Endosome-Vesicle Interaction Complex)

Question 554

What complex drives the fusion of the vesicle membrane with the plasma membrane?

Answer 554

THe CHEVI complex is through to interact with the SNARE protein complex which drives the fusion of the two membranes.

Question 555

What is the primary signal for inducing lamellar granule secretion?

Answer 555

The increase in extracellular calcium concentration in the granular layer appers to be the primary signal for inducing lamellar granule secretion. The secreted lipds are arranged into intercellular lamellae parallel to the cell sugace and metabolzied by the secreted enzymes from polar to nonpolar products. Glucosylceramides are converted into cermides (b-glucocerebrosidase) Spingomyelin is converted into ceramides (acidic spingomyelinase) Phospholipids are converted into FFA and glycorol (phoholipases). The free fatty acids contributed to the acidication of the SC which is important for functioning of many enzymes. Glycerol is hygroscopic and helps to keep the SC hydrated.

Question 556

What are the major lipid classes in the SC?

Answer 556

ceramides, free fatty acids and cholesterol

Question 557

Ceramides are categoized into how many different structural groups?

Answer 557

11; cermides are amide-linked fatty acids attached to spingoid bases, which are long-chain amino alcohols. Ceramides are categozied into structural groups based on the shpingoid base and the types of attached fatty acids. The shingoid bases include phytoshingosine (P), singosine (S), 6 0 hydroxylspingosine (H), and dihydrospinogsine (D), a-hydroxy fatty acids (A) and nonhydroxy fatty acids (N). The stuctural group yields a ceramide group name such as EOS representing a shingosine base with an attached esterified -omega-hydroxy fatty acids.

Question 558

What are the three omega-hydroxyceramides that are unique to the stratum corneum and carry very long chain amide-linked fatty acids?

Answer 558

EOS (ceramide 1) EOH (cermide 2) EOP (cermide 9)

Question 559

CLE (corneocyte lipid envelope)

Answer 559

The omega cermaides are covalently bonded to involucrin primarily as well as envoplakin and periplakin in the CE and interdigitate with the intercellular lipid lamellae. This layer of omega-hydroxycermides bonded to the CE is called the CLE (corneocyte lipid envelope). The CLE forms a key linkin the stratum corneum barrier, and malformations in the CLE result in ichthyosis. The omega-hydroxyceramides are known to play an important role in epidermal barrier function.

Question 560

What is the key rate limiting enzyme in free fatty acid synthesis pathways?

Answer 560

acetyl-CoA carboxylase and fatty acid synthase

Question 561

What is the role of fatty acids in the epidermis?

Answer 561

Fatty acids are long carbon chains with methyl group at one end. ,the epidermis contains free fatty acids as well as fatty acids bound to triglyceridesm phospholipids, glycosylceramides and cermides. Epidermal free fatty acids range in chain length from C12 to C24 The epidermis synthesizes saturated and monounsaturated FA but not omega-6 polyunsaturated essential fatty acids (EFAs) such as linoleic acid and alpha-lineoleni acid, which must be supplied by diet. Linoleic acid is contained in phopholipids glycosylcermides, ceramide 1, ceramide 4 and cermide 9.

Question 562

Cholesterol is synthesized from ____ in the lower epidermis in a pathway in which ____ reductase is the rate limiting enzyme.

Answer 562

acetate hydroxymethylglutaryl CoA (HMG CoA) reducatse is the rate limiting enzyme. Some cholesterol is incorporated into the lamellar granules and secreted to the granule-cornified layer interface uncahgned. Some of the cholesterol is fulgurylated to cholesterol sulfate.

Question 563

Cholesterol sulfate plays a role in inhibiting ____ proteases involed in desqumation.

Answer 563

serine

Question 564

Desmosomes are composed of mulitple proteins and are divided into several regions based upon their electron micrographi appearance. Those three regions are?

Answer 564

the desmoglea - extracellular portion between adhered keratinocytes outer dense plaque - within keratinocyte PM (bordering the membrane) inner dense plaque - within keratinocyte PM (intertwined with KF)

Question 565

The molecular components of desmosomes fall into what three major gene families and consist of multiple proteins?

Answer 565

Cadherins: transmembrane molecules that form a Ca-dependent adhesive interface between neighboring keratinocytes. Their extracellular portions comprise the desmoglea (desmogelin, desmocollin) Armadillo protein damily: at the desmosomes, these proteins bind to the cytoplasmic protions of the cadherins. - Plakoglobin - binds to desmoplakin and cadherins - Plakophilin - binds to cadherin complexes to strength the plaque Plakin protein family - Desmoplakin - binds KIFs to plakoglobin - Envoplakin and periplakin

Question 566

What are corneodesmosomes?

Answer 566

At the transition from the granular to the cornidied layer, the morphology of the desmosomes changes as they are integrated into the CE. The cornified layer, these sites of keratinocyte cohesion are known as corneodesmosomes, and they play a key role in SC barrier function.

Question 567

What are the three moelcular components of corneodesmosomes?

Answer 567

desmoglein1, desmocollin1 and corneodesmosin (CDSN)

Question 568

What is the function of CDSN?

Answer 568

It is a glycoprotein with high serine and glycine content particularly at its termal regions. Like keratins and loricrin, CDSN forms strutural motids called 'glycine loops' which mediated reversible and adjustable intermoelcular adhesion by acting like Velcro. CDSN is synthesized by granular keratinocytes and secreted from lamellar granules into the itnercellular space starting in the second layer of the SG. CDSN binds ot the desmoglea shortly before the transformation of desmosomes to corneodesmosomes.

Question 569

What are tight junctions?

Answer 569

aka zonulae occludens, are cell to cell contacts that leave virtually no intercellular space betwen neighbnoring cells. Tight junctions provide a semipermeable size and ion specific 'gste' barrier that regulates the diffusion of ions and solutes through the interceullular spaces in simple and stratified epithelia = paracellular pathway Tight junctions also perform a 'fence function' to maintain cell polarity, demarcating the apical and basolateral cell membrane regions, by restricting the diffusion of apical and basolateral cell membrane molecules within the cell membrane.

Question 570

Epidermal tight junctions are composed of what two families of tranmembrane molecules?

Answer 570

Claudins and occludins (and intracellular zonula occludens (ZO) proteins) Claudins 1, 4, and 7 are expressed in the epidermis.

Question 571

What are junctional adhesion molecules (JAMs)

Answer 571

JAMS are an IgG-like family of transmembrane receptors that interact with proteins of the tight junctions and adherens junction to regular barrier function, cell migration and cell proliferation.

Question 572

Many of the components of moelcules of tight juntions are present in the non-cornified epidermal layers, but functional tight juntions are located ONLY in what layer?

Answer 572

Stratum Granulosum In the stratum corneum, tight junction-related structures surround corneodesmosomes at the lateral esges of corneocytes preventing the acces of proteases involved in cornodesmosome degradation.

Question 573

What are adherens junctions?

Answer 573

These are found on the lateral and apical membranes of basal cells and on the entire cell surface of suprabasal cells. Adherens junctions are cadhein-based junctions that libnk the actin cytoskeleton to the plasma membrane. Transmembrane cadherins, E-cedherin, form the physical linkages between E-cadherin molecules on adjacent cells. They initiatio and maintain cell-cell adhesion, regulate the organization of the actin cytoskeleton, and establish a hub for cell signaling and regulatation of gene transcription. Adherens junctions are also involved in regulating keratinocyte proliferation and differentiation and play a role in wound healing.

Question 574

What are adheren junctions composed of?

Answer 574

AJ are composed of a cadherin-catenin complex. The cytoplasmic tail of E-cadherin binds to the cytoplasmic catenins, B-catenin and p120 catenin. B-catenin binds a-catenin, and a-catenin link the F-actin cytoskeleton to the junction There appears to be a dynamic relationship between adherens junctions and the intracellular actin cytoskeleton. The extracellular cadherin domains bind a cahderin on the opposing cell surface in calcium dependent manner.

Question 575

What enzymes are involved in desquamation?

Answer 575

The enzymes include kallireins (serine proteases), and cathepsins (cystein proteases). KLKs are synthesizes as proenzymes and activated by themselves or other proteases in a complex ph-dependent proteolytic network. As ph decreases, inhibitors are less effective. KLK 1,5,6,7 and 14 are involved in the degradation of corneodesmosomes. Multiple enzyme inhibitor regulate this enzymatic degradation, including the KLK inhibitor - LEKTI (lymphepithelial Kazal-type-related inhibtor), SPINK6, elafin, serpins adn cholesterol sulfate.

Question 576

What is the cysteine protease inhibitor is localized on cornodesmosomes following secretion by lamellar granules and inhibits cathepsin V (cleaves corneodesmosomes)

Answer 576

Cystatin M/E

Question 577

What is the role of Ca gradient in keratinocyte differentiation?

Answer 577

Calcium ions and their concentration in the epidermis play essemtial roles in regulating keratinocyte differentiation, skin barrier formation and pearmability homeostasis. Ca concentrations are low in the basal and spinous layers with progressively increasing levels towards the stratum granuloms (stored in ER) and decreasing levels again in the stratum corneum Tight junctions and the stratum corneum are both through to the crucial to generate and maintain gradeitn by preventing Ca diffusion from the SG to SC. Ca regulate the transcription of all genes encoding keratinocyte differentiatrion-specific proteins, adn the gradient relects the relative concentration of Ca required for state specific protein expression in each layer.

Question 578

The high level of Ca in teh SG regulates which important processes for cornification?

Answer 578

The high levels of calcium in the granulaer layers regulates lamellar granule secretion, TG activity and the cleavage of profillagrin to filaggrin.

Question 579

Where is the intracellular calcium stored to maintain gradient?

Answer 579

Calcium is stored in the endoplasmic reticulum. Keraintocytes express several types of calcium channels which permit Ca influx into keratinocytes from extracellular sources. In the granular layer, the calcium-sensing receptor, a subfamily of G protein coupled receptors in the keratiocyte plasma membrane, senses the rise in extracellular Ca and activates the intraceullar signals that lead to the release of Ca from intraceullar ER stores and stimulates Ca infux through calcium channles. The results is an increase in extraceullar Ca which promotes differentiation fro granulate keratinocytes to corneocytes.

Question 580

In the non-cornified epidermal layers, what cells procide a barrier to water loss from the interior?

Answer 580

tight junctions

Question 581

The plasma membrane of basal keratinocytes provides localization and organizational cues largely due to what structures?

Answer 581

Integrins

Question 582

B4 binds to collagen XVII (BP180 or BPAG2) via fibronectin domains ___ and \_\_\_. It also binds to plectin and BPAG1 (BP230) via fibronectin domains __ and \_\_.

Answer 582

Fibronectin domains III and IV Fibroectin domains I and II

Question 583

Laminin 332 is one of the major epidermal laminins. It is Initially synthesized, assebled and secreted by kerainocytes in precursor form and processed by what extracellular enzyme?

Answer 583

Tolloid

Question 584

Laminin 511

Answer 584

Produced by dermal microvascular endothelial cells Abundant in the interfollicular epidermis and dermal blood cells Contains multiple globular chains that bind to nidogen (collagen IV)

Question 585

Laminin 311

Answer 585

Consists of a3, B1 and y1 chains Regulate cellular functions with laminin 332 Share binding domain in a3 chain

Question 586

What are the two isoforms of nidogen?

Answer 586

Two isoforms: Nidogen -1: binds perlecan and collagen IV Nidogen-2: binds collagen IV and I and perlecan, NOT filbulin

Question 587

Fibulin

Answer 587

Able to bridge carious BMZ molecules (fibronectin, collagen IV, perlecan, and nidogen 1) Thought to stabilzie moelcular organization of extracellular membrane structures

Question 588

Where are retinal pigments cells derived from?

Answer 588

Optic cup of the forebrain

Question 589

What keratins are expressed throughout all layers and in hyper proliferative disorders?

Answer 589

K6/K16

Question 590

What are the keratins of the ‘upper spinous layer’?

Answer 590

K2/K11

Question 591

Which fatty acids are keratolytic and fungistatic?

Answer 591

caprylic, propionic and undecylenic acid

Question 592

What two anti-inflammatory compounds can be synthesized from linoleum acid and linolenic acid?

Answer 592

DGLA and EPA \*\*DGLA is the elongation product of [γ-linolenic acid](https://en.wikipedia.org/wiki/Gamma-linolenic_acid). Elongases add additional carbon molecules to existing chain.

Question 593

Delta-desaturase deficiency in atopic humans cannot convert DGLA, linoleic and linolenic acid into what substance?

Answer 593

Is there is a delta-6-deficiency - Linoleic, linolenic and DGLA accumulate locally, it cannot be metabolized into arachidonic acid. DGLA completes with AA for cyclooxygense and lipoixygenase enzymes. This competitive inhibition it thought to be the mechanism of anti-inflammatory action of fatty acid therapy -which generally involves the modification of leukotriene and prostaglandin synthesis.

Question 594

What are the effects of prostaglandins on the skin?

Answer 594

Alteration of vascular permeability Potentiation of vasoactive substance such as histamine Modulation of lymphocyte function Potentiation of pain and pruritus \*\*Prostaglandins and Leukotrienes potentiate each other

Question 595

What are the effects of Leukotriene on the skin?

Answer 595

Alter vascular permeability Activate neutrophils Modify lymphocyte function Cause potent neutrophil and eosinophil chemotaxis

Question 596

y-Linoleic acid is found in relatively high concentrations in primrose, borage and black current oils. It is elongated TO DGLA, which directs completes with AA as a substrate for cyclooxyrgenase and 15-lipoxygenase. The result of DGLA metabolism is the formation of what two products?

Answer 596

Prostaglandin E and 15-hydroxy-8,11,13-ETA \*\*\*EPA is supplied by using old water marine oils and competes as a substrate for cyclooxygenase and lipoxygenase.

Question 597

EPA can also be supplied by the conversion of a-linoLENic acid into EPA and what other fatty acid?

Answer 597

DHA An excellent source if linoLENic acid is chia sed and flaxseed

Question 598

Metabolism of EPA by lipoxygenase enzymes results in the formation of what two products?

Answer 598

LTB5 and 15-hydroxyEPA. These two products are thought to inhibit LTB4 - which is a potent pro-inflammatory mediator.

Question 599

THe mechanism of how EFAs function I controlling pruritus includes inhibition of _____ and metabolism o metabolic byproducts of ____ metabolism

Answer 599

AA Fatty Acid

Question 600

List hormones 5 hormones that stimulate hair cycle List 6 hormones that inhibit hair cycle

Answer 600

Stimulators: Thyroid homrone Corticotropin Melatonin Androgens Growth Hormone Inhibitors: Cortisol Estrogen CRH Corticotripin Prolactin Parathyroid-related hormone

Question 601

List 10 Growth Factors that stimulate hair cycle

Answer 601

FGF-7 HGF Insulin-like growth factor Sonic Hedge Hog Keratinocyte growth Factor Wnt B-catenin TGF-a Nerve growth factor GDNF

Question 602

List 9 Growth Factors that inhibit hair cycle

Answer 602

Epidermal Growth Factor FGF2 FGF5 Brain-derived neurotrophin Neutrotropin 3 Neurotropin 4 TGFa TGFb1 TGFb2

Question 603

Which cytokine stimulates hair cycle?

Answer 603

Substance P

Question 604

Which cytokines inhibits hair cycle?

Answer 604

IL-1 and IL-6

Question 605

Do retinoids and calcitriols stimulate or inhibit hair cycle?

Answer 605

Inhibit! Acivin, Noggin, Folistatin, Cyclosporine, Monoxidil and Finasteride stimulate

Question 606

What are the 3 trophic effects of cutaneous nerves on follicular growth?

Answer 606

Regulate Vascular Tone Neuropeptide stimulating of receptors on follicular keratinocytes and dermal papilla modulating of macrophages and mast cell activity

Question 607

What cells of the hair bulb consists of mesenchymal cells and is considered to play a fundamental role in epithelial differentiation?

Answer 607

Dermal papilla cells These are then PRIMARY target cells of the hair follicle that respond to hormones and mediate growth-stimulating signals to the follicular epithelial cells.

Question 608

White cats with blue eyes often have what abnormality?

Answer 608

Cochlear degeneration and deafness

Question 609

What gene in cats results with the gradual replacement of eumelanin with pheomelanin seen in Norweigain Forest Cats?

Answer 609

Amber gene

Question 610

What gene controls the acromelanism enzyme that converts melanin precursors into melanin by a process of oxidation?

Answer 610

C, tyrosinase gene, TYR

Question 611

Tuxedo cats white spotting is controlled by what gene?

Answer 611

white gloves gene (KIT)

Question 612

Hemidesmosomes and ____ are located on the basal surface of basal cells and mediate adhesion to the underlying extracellular matrix whereas desmosomes and ______ mediate adhesion between keratinocytes in all epidermal layers.

Answer 612

focal adhesions adherens junctions

Question 613

P-Cadherin is present in which layer of the epidermis?

Answer 613

Basal

Question 614

What are the transmembrane proteins for focal adhering versus adherent junctions?

Answer 614

Focal adherens - B1 integrins Adherens junctions - P and E Cadherins

Question 615

What are the plaque proteins associated with focal adhesions versus adherens junctions?

Answer 615

focal adhesions - Talin, Vinculin, a-actinin, paxillin and zykin adherens junctions - plakoglobin-a and b-catenin; alpha- actin; vinculin

Question 616

Profilaggrin is cleaved by several enzymes when it is converted to the functional fillagrin protein. The profilaggrin linker domain is cleaved by \_\_\_\_\_\_. Fillagrin is further degraded into natural moisturizing factors by what enzyme?

Answer 616

kallikrein-related [_peptidase_](https://www.sciencedirect.com/topics/medicine-and-dentistry/peptidase) 5KLK5 Caspase 14

Question 617

What locations does the CE develop beneath the plasma membrane?

Answer 617

stratified epidermal cells cells of the inner root sheath medulla of the hair follicle cuticle of the claw

Question 618

What protein binds ceramides covalently to create the backbone for the attachment of intracellular lipids?

Answer 618

Involucrin

Question 619

Transglutaminases are chiefly expressed in what layers of the epidermis?

Answer 619

Stratum granulosum Stratum spinosum (upper)

Question 620

Ceramides 1 and 2 bind to what protein in the CE, forming a scaffold for the binding of other lipids into an intercellular lipid bilayer parallel to corneocytes in the SC?

Answer 620

Involucrin

Question 621

Where are melanocytes found in the hair follicle?

Answer 621

Outer root sheath

Question 622

What are the 3 catalytic activities of tyrosinase?

Answer 622

Converting tyrosine to Dopa (rate limiting step) Can use Dopa or 5,6-dihydroxyindole asa substrates for oxidase activities.

Question 623

Once Dopa is formed, it can spontaneously autooxidize to _______ without tyrosinase (although at a slower rate) and continue through the melanin pathway to dopa chrome, 5,6 dihydroxyindole-2-carbxylic acid, DHI and indole-5,6-quinone

Answer 623

dopaquinone

Question 624

What are three agonists of MC1R?

Answer 624

a-MSH Corticotropin Agouti gene (antagonist)

Question 625

What is the major determinant of melanogenesis that regulates pigment phenotype?

Answer 625

melanocortin-1-receptor

Question 626

Loss of what receptors expression is associated with progression of melanocytes toward metastatic melanoma phenotypes?

Answer 626

c-kit - a tyrosine kinase receptor involved in melanoblast expansion, survival and migration. \*\*mutations are involved in piebaldism

Question 627

What is a neuroimmunomodulatory and anti-inflammatory peptide that is synthesized and released by keratinocytes, Langerhan cells, fibroblasts, endothelial cells and melanocytes?

Answer 627

a-MSH

Question 628

In dogs, dermal dendrocytes are positive for what markers?

Answer 628

CD1, Factor XIIIa, MCH II and Thy-1 positive (CD90)

Question 629

Mast cells are present where in the dermis and near what structures?

Answer 629

Mast cells are most abundant around superficial derma blood vessel and appendages. Toludine blue and acid orcein Giemsa will help more easily recognize these cells.

Question 630

The inner root sheath keratinizing and disintegrates when it reaches what layer of the hair follicle?

Answer 630

Isthmus

Question 631

Atrichial sweating from the footpads of cats and dogs can be provoked by what stimuli? and less by what other stimuli?

Answer 631

Cholinergic Adrenergic \*\*Atropine blocks glandular responses to these agents

Question 632

What muslces receive **cholinergic innervation** and contact in response to **epinephrine and norepeinephrine**, producing piloerection.

Answer 632

Arrector pili muscles

Question 633

The\_\_\_\_\_\_\_\_\_ are a gene family critical for normal embryologic development; they likely play a very important role in development of skin adenexa, pigment system, and stratified epithelium during embryogenesis.

Answer 633

Homeobox (hox) genes

Question 634

The arterioles consist of endothelial cells surrounded by two layers of smooth muscle cells, whereas arterial and venous capillaries lack what layer?

Answer 634

smooth muscle cells

Question 635

Selectins and members of the \_\_\_\_\_\_\_\_(ICAM1; vascular cell adhesion molecule, VCAM1) are upregualted on endothelial cels following inflammatory stimulation and mediate rolling, adhesion and transmigration of leukocytes from the blood stream.

Answer 635

immunoglobulin SUPERFAMILY

Question 636

Angiogenesis is controlled by what 3 things?

Answer 636

mast cells (histamine), TNFa and TGFb

Question 637

What is a signalling protein that promotes the growth of new blood vessels. It is part of the mechanism that restores the blood supply to cells and tissues when they are deprived of oxygenated blood due to compromised blood circulation.

Answer 637

What is **Vascular endothelial growth factor** (VEGF)

Question 638

Arteriovenous anastomoses are normal connection between arteries and veins that allow arterial blood to enter the venous circulation without passing through what?

Answer 638

capillaries Most common over extremities (legs and ears) A “glomus" is a shunt in the deep dermis - the partial segment is called “sucquet-hoyer canal” from the arteriole. Glomus cells are generally considered modified smooth muscle cells.

Question 639

The motor innervation of skin is attributable to sympathetic fibers of the _____ nervous system.

Answer 639

autonomic

Question 640

What do the somatic sensory system mediate?

Answer 640

touch, head, cold, pressure, vibration proprioception, pain and pruritus

Question 641

What to the nerves of the autonomic motor system control?

Answer 641

They control cutaneous vascular resistance, pilomotor responses, regulate the secretory activities of glands.

Question 642

Although the cutaneous nerve trunks are considered somatic sensory nerves, they carry what types of fibers?

Answer 642

myelinated post-ganglionic sympathetic fibers

Question 643

What are hairless, knob-like innervated structure that are precent in the haired skin of cats and dogs.

Answer 643

tylotrich pads