14 - Skin Barrier Flashcards
The tough outer protective layer of an animal or plant that demarcates the body from the external environment
Integument
Cell-cell adhesive junction that seals the intercellular space and controls paracellular molecular movement
Occlusive junction
The occlusive junction of invertebrates is called a _____, and that of vertebrates is called a _____
Septate junction
Tight junction
Fourteen-sided polyhedron composed of eight hexagons and six squares
Proposed as the best shape for packing equal-sized cells together to fill the space using the minimal surface area of each cell
Kelvin’s tetrakaidecahedron
The loss of water that passes from inside to outside a body through the epidermis
Basically in proportion to the level of barrier damage or formation
Transepidermal water loss
Compartmentalizes the cell from the external environment in unicellular organisms
Lipid bilayer membrane
Because the lipid bilayer membrane is highly fragile, most unicellular organisms have an additional barrier structure outside of the cell membrane (ie, _____) that functions as a type of armor
Cell wall
The cell membrane of unicellular organisms corresponds to the _____ in multicellular organisms
Epidermis
The stratum granulosum consists of at least _____ layers of flattened granular cells
Three
SG1, SG2, SG3
Tight junctions seal the intercellular spaces in the _____ layer
SG2
The stratum corneum consists of dead cornified cells (corneocytes) and functions as an _____ interface barrier
Air-liquid
Under the stratum corneum, cells area immersed in a water environment. The extracellular water environment of the epidermis is divided into two parts by the tight junction barrier, which is a _____ interface barrier
Liquid-liquid
Epidermal cells proliferate only in the _____, differentiate with detachment from the basement membrane, move upward, become flattened at the _____, form a tight junction at the _____, lose the tight junction at _____, terminally differentiate into corneocytes, and detach from the top of the cornified layer as squamous scales
Basal layer
Stratum granulosum
SG2 layer
SG1 layer
The stratum corneum in humans is approximately _____ micrometers thick and contains about _____ layers of cornified cells
10-20
10-25
Diseases affecting cornified envelope formation (gene and protein affected)
- Vohwinkel syndrome with ichthyosis (LOR - loricrin)
2. ARCI 1 (TGM1 - transglutaminase 1)
Diseases affecting cholesterol biosynthesis (gene and protein affected)
- CHILD syndrome (NSDHL - NAD(P)H steroid dehydrogenase-like protein)
- MCCPD (MSMO1 - methylsterol monooxygenase 1)
Diseases affecting acylceramide biosynthesis (gene and protein affected)
- ISQMR (ELOVL4 - elongation of very-long-chain fatty acid-like 4)
- ARCI5 (CYP4F22 - cytochrome P450 4F22)
- ARCI9 (CERS3 - ceramide synthetase 3)
- Chanarin-Dorfman syndrome (ABHD5 - ABHD5/CGI58)
- ARCI10 (PNPLA1 - patatin-like phospholipase domain containing 1)
- ARCI2 (ALOX12B - arachidonate 12-lipoxygenase type 12R)
- ARIC3 (ALOXE3 - arachidonate lipoxygenase 3)
Diseases affecting lipid transport (gene and protein affected)
- ARCI4A (ABCA12 - ATP-binding cassette A12)
2. ARCI4B/Harlequin ichthyosis (ABCA12 - ATP-binding cassette A12)
Diseases affecting desquamation (gene and protein affected)
- ARCI11 (ST14 - maltriptase)
2. Netherton syndrome (SPINK5 - LEKTI)
Diseases affecting desmosomes and corneodesmosomes (gene and protein affected)
- Peeling skin syndrome 1 (CDSN - corneodesmosin)
2. SAM syndrome (DSG1 - desmoglein 1)
Diseases filaggrin metabolism (gene and protein affected)
- Ichthyosis vulgaris (FLG - filagrrin)
2. ARCI12 (CASP14 - caspase 14)
Diseases affecting tight junctions (gene and protein affected)
- Neonatal ichthyosis sclerosing cholangitis syndrome (CLDN1 - claudin-1)
Basic diffusion barrier on the body surface of both monocellular organisms and multicellular organisms
Lipid bilayer cell membrane
Y/N: Both monocellular organisms and multicellular organisms are equipped with additional outer barriers
Yes
Corneocytes are terminally differentiated dead keratinocytes that adhere to one another via proteinaceous cell-cell adhesion complexes called _____ and the adhesive force of intercellular lipid lamellae
Corneodesmosomes
Y/N: The basket-weave structure of the stratum corneum is an artifact of the processing of specimens
Yes
Basic structure of the stratum corneum: protein-based bricks (_____) and lipid-based mortar (_____)
Corneocytes
Intercellular lipid lamellae
The surface of the corneocytes is coated with a thin layer of ceramide (_____)
Lipid envelope
During cornification, a _____ consisting of a 10-nm-thick layer of highly cross-linked insoluble proteins is formed beneath the plasma membrane, and the lipid bilayer of plasma membrane is replaced by a 5-nm-thick layer of acylceramides, which is called _____
Cornified cell envelope
Corneocyte lipid envelope
_____ expressed in granular layer cells associated with the inner surface of the plasma membrane in a calcium-dependent manner and are cross-linked to one another by _____
Envoplakin, periplakin, and involucrin
Transglutaminase 1
Before the scaffold covers the inner surface of the plasma membrane, _____ are produced from the Golgi complex and become fused to the plasma membrane
Lamellar bodies
The limiting membrane of lamellar bodies is rich in _____ composed of omega-hydroxylated ultra-long-chan fatty acids
Acylceramides
The fusion of the _____ with the plasma membrane gradually increases the amount of acylceramides within the lipid bilayer of the plasma membrane
Limiting membrane
The acylceramides eventually replace the plasma membrane, which is called the _____
Corneocyte lipid envelope
On the inner surface of the scaffold, loricrin molecules are translocated from the cytosol and covalently cross-linked onto the scaffold to build the
Cornified cell envelope
Insoluble protein that may contribute to the water resistance of the cornified cell envelope
Eventually becomes the major component of the cornified cell envelope
Loricrin
Keratinocytes of the stratum granulosum develop a specific system of _____ that allow secretion of intercorneocyte lipid lamellae
Lamellar bodies
Produced from the Golgi complex and stored within the cytoplasm in SG3 cells as intracellular vesicles
Lamellar bodies
ABCA12 functions in cellular lipid trafficking on the limiting membrane of lamellar bodies, in which severe defects cause
Harlequin ichthyosis
After extrusion of the lamellar bodies into the extracellular spaces, the (polar/nonpolar) lipids are enzymatically converted into (polar/nonpolar) products
Polar
Nonpolar
_____ are hydrolyzed to generate ceramides, and ____ are converted into free fatty acids
Glycosphingolipids
Phospholipids
Very dense structure packed into the interstices of corneocytes, thus forming a water-impermeable barrier
Stratified lipid bilayer
Major classes of lipids in the stratum corneum
Cholesterol
Free fatty acids
Ceramides
Y/N: Basal-layer keratinocytes are not capable of resorbing cholesterol from the circulation
No - capable
Y/N: Epidermal keratinocytes actively biosynthesize cholesterol and free fatty acids
Yes
The majority of the cholesterol in the epidermis is synthesized in situ from
Acetyl coenzyme A
The rate-limiting step in cholesterol biosynthesis is catalyzed by
Hydroxymethylglutaryl CoA reductase
The cholesterol biosynthesis pathway in the epidermis is also important for the production of vitamin
D
The metabolic intermediate of cholesterol biosynthesis, _____, is converted to previtamin D in a photolytic reaction by UVB radiation; this is followed by thermal isomerization to form vitamin D3
7-dehydrocholesterol
Free fatty acid synthesis originates from _____, produced from acetyl-CoA via acetyl-CoA carboxylase
Malonyl-CoA
Fatty acids unable to be produced by the human body
Essential fatty acids
Consist of long-chain amino alcohols, called sphingoid bases, linked to a fatty acid via an amide bond
Ceramides
Whereas ceramides are a minor lipid component in the mammalian body (
10
30-40
Major cell-cell adhesion structure in the granular, spinous, and basal layers
Desmosomes
Secreted by lamellar bodies int the extracellular spaces surrounding the SG1 cells
Corneodesmosin
Corneodesmosis is integrated into the desmosomes, resulting i the formation of
Corneodesmosomes
Specific cell adhesion structures between corneocytes
Corneodesmosomes
The outermost corneocytes are detached, one by one, from the top layer of the stratum corneum; this process is called
Desquamation
The major proteases involved in the degradation of corneodesmosomes are
Serine proteases belonging to the kallikrein group
Kallikreins _____ are known to exist in the stratum corneum
5, 7, and 14
The protease activity of the activated kallikreins is thought to be inhibited by the direct binding of
Lymphoepithelial Kazal-type-related inhibitor
The inhibition of kallikreins by LEKTI (promote/prevent) premature desquamation
Prevent
The (lower/higher) pH of the intercellular spaces in the outer layers of the stratum corneum is thought to facilitate the dissociation of kallikreins from LEKTI and the kaiilkrein-dependent degradation of corneodesmosomes
Lower
Congenital defects of _____ induce congenital ichthyosis, probably caused by insufficiency activation of kallikrein proteases
Maltriptase
Congenital defects of _____ induce Netherton syndrome, probably caused by the enhanced degradation of corneodesmosomes by kallikreins
LEKTI
Major protein of the stratum corneum
Filaggrin
In humans, filaggrin is expressed only in
Cornified stratified epithelia
Expressed in the stratum granulosum and forms intracellular aggregates known as keratohyalin granules
Profilaggrin
Water-soluble small molecules permeate into the _____ layers of the statum corneum where protein structure is proteolytically degraded
Upper
In the _____ layers of the stratum corneum, filaggrin degraded into natural moisturizing factors
Middle
In the _____ layers of the stratum corneum, filaggrin monomers bundle keratin filaments
Lower
Y/N: Most patients with severe barrier defects, such as those with Netherton syndrome, have multiple allergies
Yes
Y/N: Most patients who have mutations in the filaggrin gene basically develop ichthyosis vulgaris, and only some of these patients develop allergic disease
Yes
Major pathway by which external molecules can penetrate the stratum corneum
Paracellular route
After passing through the stratum corneum, small molecules such as haptens can easily permeate the dermis, probably through the
Transcellular pathway
In simple epithelia, the tight junctions are located at the
Apical-most part of the apical junctional complex
The cell membrane is divided into two parts at the _____ - the apical cell membrane and basolateral cell membrane
Tight junctions
Tight junctions consist of tight junction strands, which are mainly composed of
Four-transmembrane proteins of claudins
The flattened variation of Kelvin’s tetrakaidecahedron is seen in the
Stratum corneum
Stratum granulosum
The physical properties of the skin surface itself prevents bacterial growth, that is, a (low/high) carbohydrate and water content and a weakly (basic/acidic) pH
Low
Acidic
pH of skin
5.6-6.4
The weak acidic pH of the skin is due to various substances, such as _____ from sebaceous glands or derived from phospholipid hydrolysis in the stratum corneum, _____ secreted from eccrine glands, _____ mostly derived from the degradation products of filaggrin, and metabolites produced by microorganisms
Free fatty acids
Lactic acid
Urocanic acid
Evolutionary ancient innate immune effectors produced by almost all plants and animals
Also act as “alarmins” to alert host cells to react to injuries and microbial invasions
Antimicrobial proteins
Two major antimicrobial proteins of the skin
Cathelicidins
Beta-defensins
Keratinocytes in the (hair follicle/interfollicular epidermis) constitutively produce cathelicidins and beta-defensis at a higher level than the keratinocytes of the (hair follicle/interfollicular epidermis)
Hair follicle
Interfollicular epidermis
The microenvironment of the (hair follicle/interfollicular epidermis) facilitates bacterial colonization much more readily than that of the (hair follicle/interfollicular epidermis)
Hair follicle
Interfollicular epidermis
Dominant commensal bacterium of the skin microbiota
Staphylococcus epidermidis
Defensins and cathelicidins are usually (anionic/cationic) and interact with the bacterial membrane surface through electrostatic interactions
Cationic
Some _____ form pores in the bacterial membrane to disrupt membrane integrity and promote bacterial lysis
Defensins
Bind to bacterial membranes and promote membrane insertion and disruption
Cathelicidins
Y/N: The chemotactic activities of different types of antimicrobial proteins are distinct from one another, and each recruits different types of cells
Yes
Y/N: Full-term newborn babies have a well-developed and functional skin barrier at birth
Yes
Infant skin has a (thinner/thicker) stratum corneum with (low/high) levels of natural moisturizing factors and (lesser/greater) transepidermal water loss compared with adult skin
Thinner
Low
Greater
Transepidermal water loss in healthy full-term newborns at birth is (lower/equal to/greater) than that of adult skin
Equal to or lower
Formation of the fetal biofilm vernix caseosa during the
Third trimester
Protects the epidermis from amniotic fluid and facilitates formation of the stratum corneum beneath it
Vernix caseosa
Vernix (retension/removal) after birth has been reported to result in greater skin hydration and a lower skin surface pH at 24 hours after birth
Retention
Babies born before _____ weeks of gestation lack the covering of the vernix
28
Babies delivered at _____ weeks of gestation have only a few layers of stratum corneum
25
Babies delivered before _____ weeks of gestation lack the stratum corneum
24
Y/N: The transepidermal water loss of extremely preterm infants is significantly higher than that of full-term infants even at 1 month after delivery
Yes
Preterm newborn/full-term newborn/infant/ adult:
NMFs high in the vernix caseosa
Full-term newborn
Preterm newborn/full-term newborn/infant/ adult:
NMFs low in the stratum corneum
Infant
Preterm newborn/full-term newborn/infant/ adult:
NMFs high in the stratum corneum
Adult
Preterm newborn/full-term newborn/infant/ adult:
High surface pH
Full-term newborn
Preterm newborn/full-term newborn/infant/ adult:
Low surface pH
Infant
Adult
Preterm newborn/full-term newborn/infant/ adult:
High sebum
Infant
Preterm newborn/full-term newborn/infant/ adult:
Low sebum
Adult
Preterm newborn/full-term newborn/infant/ adult:
High stratum corneum water content
Infant
Preterm newborn/full-term newborn/infant/ adult:
Low stratum corneum water content
Adult
Preterm newborn/full-term newborn/infant/ adult:
Low dermal collagen fiber density
Infant
Preterm newborn/full-term newborn/infant/ adult:
High dermal collagen fiber density
Adult
Preterm newborn/full-term newborn/infant/ adult:
High rate of water absorption
Infant
Preterm newborn/full-term newborn/infant/ adult:
Low rate of water absorption
Adult
Preterm newborn/full-term newborn/infant/ adult:
Very high to high TEWL
Preterm newborn
Preterm newborn/full-term newborn/infant/ adult:
Low TEWL
Full-term newborn
Adult
Preterm newborn/full-term newborn/infant/ adult:
High TEWL
Infant
Barriers against UV stresses at the stratum corneum:
_____ at the air-skin interface
Absorption by _____
Diffraction via _____
Reflection
Trans-urocanic acid
Keratin filaments
In the viable cell layer of the epidermis, _____ is the major factor that absorbs UV irradiation
Melanin
In humans, cooling is mainly achieved by the
Evaporation of water secreted from eccrine sweat glands
Human skin has the (lowest/highest) reported density of eccrine sweat glands among all mammals
Highest
When the body temperature (lowers/rises), skin surface blood vessels are dilated, and the skin appears red
Rises
In (cold/hot) air, the skin turns pale because blood vessels contract to decrease blood flow
Cold
Mechanism by which the core body temperature is maintained under conditions of extreme cold or heat in homothermic animals
Vascular concurrent heat exchange