Structure and function of the skin Flashcards
The primary keratinocyte intercellular junction is the:
Desmosome
Desmosomes connect to keratinocytes by anchoring onto:
Keratin
Desmosomes consist of ______ which are cytoplasmic, and ____ which are transmembrane
- Desmoplakin, plakophilin, plakoglobin.
- Desmocollin 1/2/3, and desmoglein 1/3
Desmocollin, desmoglein and other cadherins are dependant on _____ to function
Calcium
Adherence junctions function to_____ by anchoring/attaching to ______
- mediate tight intercellular binding
- Actin filaments
Tight junctions are made up of ______. They function to________
- claudins and occludins
- form tight seal against water loss in granular layer
Gap Junctions function is _______. They are composed of _______.
- intercellular communication
- Connexons which are made of 6 connexins
Which keratins are produced in stratum basale
5+14
Cellular proliferation in the stratum basale is stimulated by:
trauma, UV radiation (increased ornithine decarboxylase expression is associated with proliferative states)
Ornithine decarboxylase is inhibited by:
Retinoids, corticosteroids, Vitamin D3
What percentage of cells in the basal level are stem cells?
10%
Transit time from basal layer to SC is? And from SC to desquamation?
14 days, and another 14 days
Function of stratum corneum is:
mechanical barrier
Structure of stratum corneum:
protein rich corneocytes with no nuclei (bricks) and lipid matrix (mortar)
______ are the intermediate filaments that comprise the primary cytoskeleton of the epidermis
Keratins
Type I Keratins have _____ molecular weight
- are (acidic/basic)
- K#______
- chromosome #______
- Low molecular weight
- acidic
- K9-28, K31-40 (hair keratins)
- chromosome 17
Type II Keratins have _____ molecular weight
- are (acidic/basic)
- K#______
- chromosome #______
- high molecular weight
- basic
- K1-8, K81-86 (hair keratins)
- chromosome 12
Functional unit of keratin:
heterodimers of type I and type II filaments that form tetramers and ultimately filaments
Keratin is anchored to plasma membrane by:
desmosomes
Keratinocytes produce which IL’s and what other molecule?
IL-1,6,8,10,12 and TNF alpha
Melanocytes are derived from ______
neural crest
Activation of what molecule is required for melanocyte development/migration?
C-kit
Piebaldism occurs as a result of____
loss of C-kit–>impaired melanocyte migration and proliferation
Mutations of C-kit are associated with____
acral and mucosal melanoma
Each melanocyte interfaces with ___ keratinocytes?
36
- Melanin is produced in _____ from its precursor _____.
- this process involves a copper dependent enzyme _____
- melanosomes, tyrosine
- Tyrosinase
Pheomelanin color:
Eumelanin color:
- red/yellow
- black/brown
Difference in skin color is due to differences in:
- melanosomes
- in darker individuals are larger and have more melanin
- Melanosomes are more stable and are transferred individually in dark skin (light skin are smaller, lighter, and less stable
Melanin production is stimulated by _____ and _____ on _____ on melanocytes
- melanocyte-stimulating hormone (MSH)
- ACTH
- on MC1-R
MC1-R loss of function mutations—->_____ and phenotype of ____
- increased pheomelanin:eumelanin ratio
Reason that darker skin types are “protected” more from the sun?
- Melanin absorbs UV and protects against UV induced mutations
- Immediate tanning is due to_____
- delayed tanning is due to____
- oxidation of existing melanin
- new melanin synthesis
Oculocutaneous albinism is due to:
defects in enzymes required to convert tyrosinase to melanin
Defects in packaging of melanosome-specific proteins leads to which syndrome?
Hermansky-Pudlak (Hermansky Pudlak Hates Packaging melanosome proteins)
Defects in lysosome and melanosome trafficking to dendrites leads to ___ syndromes (2 different syndromes)
- Griscelli
- Chediak-Higashi syndrome
Griscelli and Chediak-Higashki are not good traffickers along the dendrite highway
Major antigen presenting cell of the skin is the ____
langerhan cell
Describe the form of a langerhan cell:
- reniform (kidney shaped) nuclei
- tennis racket shaped Birbeck granules seen on EM
Positive immunostains for Langerhan cells:
- CD207 (Langerin), CD1a, S100, CD34, Vimentin,
Actin
Layer of skin where langerhan cells do work:
Stratum spinosum “L”
What do langerhan cells do after encountering and processing an antigen in the stratum spinosum?
- migrate to lymph nodes and activate T-cells
What down-regulates langerhan cells?
- UV exposure
Merkel cells are (slow/fast?) adapting mechanoreceptors and are found in _____ parts of body, and ____ layer of skin. They communicate with ____.
- slow adapting mechanoreceptors
- fingertips, lips, oral cavity, hair follicles
- stratum basale
- communicate with neurons
______ marker/pattern is sensitive and specific for merkel cells?
- Merkel cells are also positive for_____
- CK20+ in perinuclear dot pattern
- also positive for neurofilaments, S100, synaptophysin, chromogranin A, vasoactive intestinal peptide, neuron-specific enolase, and calcitonin gene-related peptide
Semipermeable barrier between epidermis and dermis that also serves to adhere basal keratinocytes to underlying dermis is the ______
basement membrane zone
Basement membrane zone:
- Describe the connection between basal keratinocyte and hemidesmosome.
- intracellular keratin filaments K5 and K14 attach to hemidesmosomal plaques (plectin and BPAG1) on basal plasma membrane.
- hemidesmosomal plaque proteins bind to intracellular portions of the anchoring filaments (BPAG2 and alpha 6 Beta 4 integrin)
- see diagram in book (pg 6)
Basement membrane zone:
- the extracellular portion of anchoring filaments (BPAG2, alpha 6 beta 4 integrin, and laminin 332) that extende from hemidesmosome down to lamina densa is the _____
- lamina lucida
- see diagram in book (pg 6)
____ is the weakest portion of basement membrane zone.
- this is the zone of separation in which two disorders?
- lamina lucida
- salt-split skion and suction blisters
Basement membrane zone:
- anchoring filaments in lamina densa attach to _____ which results in attachment between basal keratinocyte and lamina densa.
- Type IV collagen
- see diagram in book (pg 6)
Basement membrane zone:
- Describe structure of sublamina densa
- loops of type VII collagen arise from underside of lamina densa, extend down into dermis, hook around dermal type I and IIIO collagen fibers, then loop back up to reattach to lamina densa
- this firmly anchors lamina densa to papillary dermis
Basement membrane zone functions to adhere basal keratinocytes to underlying dermis, AND as a permeability barrier mainly due to _____
- negatively charged heparan sulfate proteoglycan in the lamina densa
Dermis is derived from _____ and divided into what layers?
- dermis derived from mesoderm
- superficial papillary, and deep reticular dermis
- Fibroblasts are located in which layer of skin?
- what are the two general functions of fibroblasts?
- fibroblasts are located in the dermis
- fibroblasts create extracellular matrix and are involved in wound healing.
Glomus cells are specialized_____ cells that are derived from ______.
- smooth muscle cells
- Sucquet-Hoyer canals
- “suck it Hoyer! i got these smooth glumus cells”
Sucquet-Hoyer Canals (help to form glomus) allow for shunting of blood from _____ to _____, and are found mainly in which parts of body?
- From arterioles to venules (bypassing capillaries)
- palms/soles (this is why glomus tumor favor acral sites)
- “Suck it Hoyer! i got these smooth glomus cells in the palm of my hand”
Overproduction of glomus cells leads to ____, which most commonly occurs in which part of body?
- glomus tumor
- palms and soles (because glomus cells are mostly found in palms and soles)
Function of dermal dentritic cells:
- highly phagocytic cells
Extracellular matrix function:
- provides structure and support to the dermis; essential for water retention and for signal transduction
Extracellular matrix is composed of:
- collagen
- elastin
- fibrillins
- fibulins
- integrins
- laminins
- glycoproteins
- proteoglycans
Describe the structure of collagen
- triple helices formed by amino acid chains where every third residue is glycine-X-Y, with X and Y most likely being proline and hydroxyproline/hydroxylysine respectively.
- “C” for Collagen is third letter in alphabet, every THIRD residue is glyCine
____ accounts for 75% of dry weight of the skin and is #1 component of the dermis
- Collagen
Primary collagen of the extracellular matrix is____
- Type I
____ and _____ catalyze crosslinking of collagen
- Lysyl hydroxylase
- Proline hydroxylase
Crosslinking of collagen depends on _____, deficiency leads to _____
- Vitamin C
- Scurvy
Defects in collagen and/or collagen cross-linking results in most forms of _____
- Ehlers Danlos syndrome (see page 7 for specifics)
- Ehlers Danlos cant cross-link collagen
____ degrades collagen
- matrix malloproteinases
____ increases collagen
- Retinoids
____ and ____ decrease collagen
- corticosteroids
- UV
Terminal keratinocyte differentiation is secondary to increased ____ in supra;basal epidermis
- intracellular calcium
Odland bodies (lamellar granules) are produced in which layer of skin, and primarily contain _____
- Spinous layer
- ceramides
____ are specialized lysosomes that dishcarge ceramides in stratum corneum
- odland bodies/lamellar granlues
_____ help to form the cornified cell envelope
- ceramides
Two diseases that are secondary to decreased lamellar granules (odland bodies) are :
- Flegels disease
- Harlequin ichthyosis
- Flegel and Harlequin are odd guys
stratum granulosum has prominent basophilic keratohylaine granules which contain____
- profilaggrin, loricrin, and involucrin
Cornified cell envelope production takes place primarily in which layer of skin
- granular
number one component of cornified cell envelope is _____
Loricrin
Cross linking of proteins and lipid of cornified cell envelope occurs via_____
transglutaminase I
- this is the “glue” for the cornified cell envelope
elastic fibers of skin are made up of 90% ____ and 10% ____
- 90% elastin (core)
- 10% fibrillin (surrounds elastin)
- desmosine and isodesmosine are found in high levels in ______
- elastin
desmosine and isodesmosine, which are found in high levels in Elastin, crosslink with fibrillin via ____
- lysyl oxidase
lysyl oxidase, which helps in the crosslinking of elastin, requires ____ for function
- copper
fibrillin 1 mutation of elastic tissue=
Marfans
fibrillin 2 mutation of elastic tissue=
Congenital contractural arachnodactyly
- 2 C’s- congenital contractural
Fibulin 5 defect of elastic tissueleads to _____
Cutis laxa
- cutis laxa is a liar who fibbed 5 times!
ABCC6 mutation in elastic tissue leads to ____
pseudoxanthoma elasticum (fragmentation and calcification of elastic fibers
- psuedoxanthoma elsasticum….ABC news
Elaunin fibers in elastic tissue run ____ in reticular dermis and oxytalan fibers run ____ to DEJ in papillary dermis
- horizontal/parallel in reticular dermis
- vertical/perpendicular in papillary dermis
- mnemonic: “stand (vertical) up-high (high in dermis) with OXYgen (oxytalan)
Fibers in elastic tissue are set in a matrix of ____ and ____ which retain large quantities of _____. This is called ______
- proteoglycans and glycosaminoglycans
- retain large quantities of water (up to 1000x’s their volume!)
- ground substance
Most important glycosaminoglycan is _____
- hyaluronic acid ( in addition to chondroitin sulfate, dermatan sulfate, and heparan sulfate)
Two vascular plexuses of skin are_____ and _____
- superficial (vessels of reticular dermis
- deep (vessels of follicles and glands)
primary mediator of vasculogenesis in skin is _____
- VEGF
Name the four lymphatic vessel markers
- Prox1
- Podoplanin
- LYVE-1
- VEGFR-3
Free nerve endings of skin sense ____ and ____
- Itch and pain
Krause end bulb are specialized nerve receptors located where?
- genitalia, perianal region, vermillion lips
- Krazy Krause ends on erotic areas
Meissner’s corpuscle are ____ (fast/slow) adapting nerve receptors, they are _____ (deep/superficial) they are located on the _____ and are suited for which type of sensation?
- fast
- superficial
- on the digits
- pressure/LIGHT touch
- meiSSner= Speed, Superficial
Merkel nerve endings are located ____ (superficial/deep), concentrated in which regions of body, are ____ (fast/slow) adapting, and best suited for ____
- superficial (basal layer of epidermis)
- concentrated in fingertips, lips, external genitalia
- slow adapting
- suited for pressure/touch
Ruffini corpuscle nerve endings are located____ (deep/superficial). concentrated around _____, are ____ (fast/slow adapting) suited for _____
- deep, in the fat (deep in the rough- golf)
- concentrated around fingernails
- slow adapting
- sustained pressure (he hits into the rough when hes under sustained pressure, and is slow to get out)
Pacinian corpuscel nerve endings are mechanoreceptors located ____ (superficial/deep) are located ______, are ____ (fast/slow) adapting and suited for ____.
- deeP
- Palmoplantar skin, niPPles, genital region
- fast adapting
- vibration and deeper pressure
Vascular smooth muscle, apocrine glands, and arrector pili contraction are under ____ (adrenergic or cholinergic) control
- Adrenergic
- vAscular, AApocrine, AArrector pili
Eccrine glands are under ___ ( adrenergic or cholinergic) control
- Cholinergic
- eCCrine, CCCholinergic
Eccrine glands function to :
- thermoregulate and excrete waste
Eccrine glands are found on all skin surfaces except ____
external auditory canal, lips, glans penis, clitoris, and labia minora
Highest concentration of eccrine glands are on ____
palms and soles
Eccrine glands are innervated by ____ which synapse with ____ acetylcholine receptors on the glands
- postganglionic sympathetic fibers
- muscarinic (this is why botox decreases sweat . by inhibiting Acetylcholinesterase)
sweat is (hyper or hypotonic) on skin surface
- hypotonic (NaCl gets reabsorbed)
Eccrine glands stain for ____
- S100, Keratin, CEA
Apocrine glands are located ____
- Anogenital region, Axillae, external Auidotry canal, Areola of nipple, eyelid margin
- remember the A’s of Apocrine glands
Secretory products of apocrine glands are released through process of ______, and include ___
- decapitation secretion
- cholesterol, triglycerides, squalene, fatty acids
- decapitate the smelly stuff
____ is pigmented mixture of lipids and proteins secreted by apocrine glands responsible for yellow-brown color of chromhidrosis
- Lipofuscin
- Lipofuscin makes your t shirts yeLLow
Ectopic or modified apocrine glands include :
- these empty directly to ___
- mammary glands, ceruminous glands of external auditory canal, and Moll’s gland of the eyelids
- surface of skin
Sebaceous glands are found primarily on:
- scalp, face, upper anterior trunk
Sebaceous glands are NOT found on the:
- palms/soles
Sebacous glands are normally associated with a ____
- hair follicle
Sebaceous gland maturation is signaled by _____
- pubertal androgen production
Which type of secretion do sebaceous glands secrete?
- Holocrine secretion
Sebum contains mostly ____ in addition to_____ and ____
- Triglycerides (50%)
- wax esters
- squalene
Name the ectopic sebaceous glands and their location
- Meibomian glands- eyelid
- Fordyce spots- vermillion lip
- montgomery tubercles- areola/nipples- on the titties
- Tysons glands- labia minora/prepuce
- Zeis glands- eyelid margin
