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MSK > Cell Biology of Skin > Flashcards

Cell Biology of Skin Flashcards

1
Q

The […] is the avascular outermost layer of the skin; it is nourished by the richly perfused, underlying […]

A

epidermis

dermis

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2
Q

What are the functions of the skin (6)?

A
  • Physical barrier (physical, chemical, and biologic agents in the external environment (i.e., mechanical barrier, permeability barrier, ultraviolet barrier)
  • Immune function (provides immunologic information obtained during antigen processing to the appropriate effector cells in the lymphatic tissue)
  • Homeostasis (regulating body temperature and water loss)
  • Sensory (external environment to the nervous system)
  • Endocrine (secreting hormones, cytokines, and growth factors and converting precursor molecules into hormonally active molecules (vitamin D3))
  • Exocrine (secretion of sweat, sebaceous, and apocrine glands)
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3
Q

What are the shapes of the cells in the skin?

A

Stratified squamous epithelium

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4
Q

What cell type makes up the 4 layers of the skin?

A

Keratinocytes

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5
Q

Label each layer of the skin.

A
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6
Q

Stratum Corneum

  • Are the cells nucleated?
  • What do they contain?
A

Stratum Corneum: non-nucleated dead cells filled with keratin

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7
Q

Stratum Lucidum

  • This layer of skin is only found where?
  • Are the cells here nucleated?
  • Do they contain granules?
A

Stratum Lucidum: found only in palmar and plantar skin; no nuclei or granules

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8
Q

Stratum Granulosum

  • Are nuclei present?
  • What substance is present in the granules in this layer?
  • What protein is found in cells in this layer?
A

Stratum Granulosum: most superficial layer in which nuclei are present; contains keratohyalin granules, bundles of keratin

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9
Q

Stratum Spinosum

  • Cells in this layer are […] active
  • Does this layer contain desmosomes?
A

Stratum Spinosum: also mitotically active; keratinocytes connected to each other by desmosomes

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10
Q

Stratum Basale

  • What types of cells are found in this layer?
A

Stratum Basale: mitotically active cells that attach directly to basement membrane by hemidesmosomes. Contains stem cells.

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11
Q

What are the main cells found in the epidermis?

A
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12
Q

Keratinocytes, melanocytes and merkel cells are specialized skin cells and structures formed from […] months of gestation and are of […] origin.

A

3-6

Ectodermal

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13
Q
  • What is a merkel cell?
  • Where are they found in the human body?
  • What special molecules do they produce?
A
  • Cells that relay touch-related information such as texture and pressure to the brain
  • Present in human skin at varying levels according to body site; highest density on the fingertips and lips/face
  • Produce certain hormones and are sometimes referred to as neuroendocrine cells, although the reasons they produce certain hormones is unknown
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14
Q

How often does the outermost layer of the skin shed?

A

Every 24 hours

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15
Q

It normally takes about […] (time) for a cell to migrate from the stratum basale to the stratum granulosum and another […] (time) to cross the stratum corneum.

c

A

2 weeks

2 weeks

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16
Q

Keratinocytes and melanocytes are present in the skin in a […] to […] ratio.

A

10 : 1

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17
Q

What is shown in this image?

A

Stem cell keratinocytes that are present in the stratum basale drive skin renewal. These stems cells an either divide to produce more stem cells or they can differentiate into keratinocytes.

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18
Q

Melanocytes are derived from […] cells and are found in the […] of the epidermis. Their primary function is to produce […].

A

neural crest

stratum basale

melanin pigment

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19
Q

How is stratification of the epidermis promoted?

A

Via asymmetric division of epidermal progenitor cells

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20
Q

What signaling pathway is important for skin development and maintenance?

A

Wnt

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21
Q

Melanin production is stimulated by what 4 things?

A
  1. Sun exposure
  2. MSH (Melanocyte Stimulating Hormone)
  3. Estrogen
  4. Progesterone
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22
Q

What is the relationship between melanocyte stimulating hormone (MSH) and adrenocortiotropic hormone (ACTH)?

A

MSH and ACTH share the same precursor, POMC (pro-opiomelanocortin). Patients with conditions caused by excess ACTH due to higher levels of POMC (example, Cushing’s disease) often also have skin hyperpigmentation due to the concurrent overproduction of MSH.

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23
Q

What is the function of melanin?

A

Melanin absorbs radiant energy from the sun to protect the skin from UV radiation

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24
Q

How is melanin stored?

A

Melanin accumulates in organelles called melanosomes, which are then phagocytosed by neighboring keratinocytes for melanin storage

25
Q

What drives differences in pigmentation between individuals?

A
  • Pigmentation differences among individuals are driven by differences in the amount and distribution of melanin produced by each individual.
  • The number of melanocytes is essentially the same between the sexes and different races
26
Q

What is the role of Myc expression in the keratinocyte lifecycle?

A

Myc induces cell mitosis in the basal layer and also suppression of integrin expression. This suppression of integrin expression induces exit from the basal layer compartment and terminal differentiation into a keratinocyte. Suppression of integrin also activates apoptosis (downregulate Bcl-2 and upregulate caspase 8)

27
Q

What is shown in this image in the stratum spinosum?

A

The increasing size of the keratinocytes from the basale to the spinosum demonstrates that the cells are becoming apoptotic as they move up from the basale to the surface of the skin.

28
Q

The dermis is composed of a […] that imparts […] to the skin. Dermis is derived from […].

A

dense connective tissue

mechanical support, strength, and thickness

mesoderm

29
Q

How is the skin on the palms of the hands and the soles of the feet different from elsewhere in the body?

A

These areas are subject to the most abrasion, are hairless, and have a much thicker epidermal layer than skin in any other location

30
Q

Terminal differentiation of the epidermal cells, which begins with the cell divisions in the stratum basale, is considered a specialized form of apoptosis. Why is this different from normal apoptosis?

A

Cells in the stratum granulosum exhibit typical apoptotic nuclear morphology, including fragmentation of their DNA. However, the cellular fragmentation associated with normal apoptosis does not occur; instead, the cells become filled with filaments of the intracellular protein keratin and are later sloughed from the skin surface

31
Q

Where in the layers of the skin is melanin found?

A

Stratum Basale - basal cells also contain various amounts of melanin in their cytoplasm that is transferred from neighboring melanocytes interspersed in this layer.

32
Q

Describe the cell junctions that are present in the stratum basale.

A

Basal cells exhibit extensive cell junctions; they are connected to each other and to keratinocytes by desmosomes and to the underlying basal lamina by hemidesmosomes.

33
Q

Describe:

  • The shape of keratinocytes in the stratum spinosum
  • The cell to cell junctions of the stratum spinosum
A
  • Keratinocytes in this layer are larger than those of the stratum basale. They exhibit numerous cytoplasmic processes or spines, which gives this layer its name.
  • The processes are attached to similar processes of adjacent cells by desmosomes
34
Q

Describe the granules present in keratinocytes of the stratum granulosum.

A

Keratinocytes in this layer contain numerous keratohyalin granules, which contain cystine-rich and histidine-rich proteins. These proteins are the precursors for which are the precursors of the protein filaggrin, (keratin filament aggregating protein), which aggregates the keratin filaments present within the cornified cells of the stratum corneum.

35
Q

Stratum Corneum

  • Describe the cells in this section of the skin
  • Are these cells more or less differentiated than cells in deeper layers?
A
  • Flattened, dry, anucleate cells without cytoplasmic organelles that are filled almost entirely with keratin filaments
  • The cells in the stratum corneum are the most differentiated cells in the skin
36
Q
  • What is the water barrier?
  • Where is it located?
A
  • The thick plasma membrane of cells in the stratum corneum is coated from the outside, in the deeper portion of this layer, with an extracellular layer of lipids that form the major constituent of the water barrier in the epidermis
  • Between stratum granulosum and stratum corneum
37
Q

What are the 2 essential functions of keratinocytes once they leave the stratum basale?

A
  • Produce keratin - the major heteropolymeric structural proteins of the epidermis
  • Participate in the formation of the epidermal water barrier
38
Q

Why does the stratum basale stain highly basophilic?

A

The cytoplasm of immature keratinocytes appears basophilic in histologic sections because of the large number of free ribosomes, most of which are engaged in the synthesis of keratins, which will later be assembled into keratin filaments.

39
Q

Keratin is a type of […] filament.

A

Intermediate

40
Q

Describe the process of keratinization that occurs when cells leave the stratum granulosum and enter the stratum corneum.

A

As the number of granules increases, their contents are released into the keratinocyte cytoplasm. Filaggrin and trichohyalin promote aggregation of keratin filaments, thus initiating the conversion of granular cells into cornified cells. This process occurs in 2 to 6 hours, the time it takes for the cells to leave the stratum granulosum and enter the stratum corneum. The keratin fibril formed in this process is called soft keratin in contrast to the hard keratin of hair and nails.

41
Q

Describe the process of desquamitization of the stratum corneum.

A

Cells are regularly exfoliated or desquamated from the surface of the stratum corneum. The continuous exfoliation of surface keratinocytes is a regulated proteolytic process that involves degradation of the cells’ desmosomes.

42
Q

What is KLK (kallikrein-related serine peptidases)?

A

KLKs (serine peptidases) are enzymes that cause cleavage of desmosomes in a pH-dependent manner. They are involved in desquamation.

43
Q

What is LEKTI (lymphoepithelial Kazal-type inhibitor)?

A

A physiologic serine protease inhibitor that interacts with KLKs in neutral pH and prevents desmosomal cleavage. However, as pH decreases in more superficial portions of the stratum corneum as described, LEKTI progressively releases KLKs at the lower pH, thus allowing KLKs to degrade the desmosomes and cause keratinocyte release.

44
Q

Netherton Syndrome

  • What gene is mutated?
  • What process does this affect?
  • How does the disease present?
A
  • Pathogenic mutations in the gene called serine protease inhibitor Kazal-type 5 (SPINK5), which encodes LEKTI
  • Deficient or dysfunctional LEKTI means that the person is unable to inhibit KLKs so they will have increased desquamatization, or increased shedding of the their stratum corneum
  • Characterized by decreased skin barrier function, generalized redness of the skin (erythroderma), and scaling
45
Q

Water Barrier

  • What is its function?
  • What 2 factors contribute to its formation?
A
  • Essential for mammalian “dry” epithelia and is responsible for maintaining body homeostasis.
  • (1) deposition of insoluble proteins on the inner surface of keratinocyte plasma membrane and (2) a lipid layer that is attached to the outer surface of keratinocyte plasma membrane
46
Q
  • What is a lamellar body?
  • Where are they made?
  • What is their relationship to the water barrier?
A
  • They are tubular or ovoid-shaped membrane-bound organelles that are unique to mammalian epidermis. They contain probarrier lipids (glycosphingolipids, phospholipids, ceramides), enzymes (acidic sphingomyelinase, and secretory phospholipase A2) and proteases
  • Golgi apparatus
  • Contents are secreted by exocytosis into the intercellular spaces between the stratum granulosum and stratum corneum –> organization of these intercellular lipid lamellae is responsible for the formation of the epidermal water barrier
47
Q

What are the 2 envelopes of the water barrier?

A
  • Cell envelope
    • 15-nm-thick
    • Insoluble proteins deposited on the inner surface of the plasma membrane that contribute to the strong mechanical properties of the barrier
    • Formed by cross-linking small proline-rich (SPR) proteins and larger structural proteins
  • Lipid envelope
    • 5-nm-thick
    • Lipids attached to the cell surface by ester bonds
    • Major lipid components are ceramides, cholesterol, and free fatty acids
    • Most important component is the monomolecular layer of acylglucosylceramide, which provides a “Teflon-like” coating on the cell surface.
    • Barrier is constantly maintained by keratinocytes entering the process of terminal differentiation
48
Q

Epidermal cell replacement is maintained by what 3 processes?

A
  • Division of basal cells in the stratum basale
  • Differentiation and programmed cell death as the cells move upwards to stratum corneum
  • Cell loss by exfoliation from the skin surface
49
Q

Melanocytes are derived from […] cells

A

Neural crest

50
Q

Can we regenerate melanocytes?

A

Yes - a pool of undifferentiated melanocyte stem cells resides in the area of the hair follicle called the follicular bulge. Melanocytes maintain the capacity to replicate throughout their life, although at a much slower rate than keratinocytes.

51
Q

What gene regulates the differentiation of melanocyte stem cells?

A

Differentiation of the melanocyte stem cell is regulated by the expression of the Pax3 gene

52
Q

What junctional attachments do melanocytes have with neighboring cells?

A

No desmosomal attachments with neighboring keratinocytes. However, melanocytes that reside close to the basal lamina have structures that resemble hemidesmosomes and focal adhesions.

53
Q
  • Describe (general) the pathway of melanin production.
  • Where does this reaction occur?
A
  • Melanin is produced by the oxidation of tyrosine to DOPA by tyrosinase and the subsequent transformation of DOPA into melanin
  • These reactions initially occur in membrane-bounded, lysosome-related organelles called premelanosomes, which are derived from the Golgi apparatus
54
Q
  • What is MSH?
  • What does it do?
  • Where is it produced?
  • What does it bind to?
  • What does binding to receptor cause?
A
  • Melanocyte-stimulating hormone
  • Regulates melanin synthesis
  • Produced by the anterior lobe of the pituitary gland
  • Binds to the melanocortin 1 receptor (MC1R) on melanocytes and (GPCR)
  • Increases the activity of tyrosinase, thus stimulating synthesis of melanin
55
Q

Describe the process of melanin transfer from melanocyte to keratinocyte.

A

Developing melanosomes and their melanin contents are transferred to neighboring keratinocytes by pigment donation. This process, which involves the phagocytosis of the tips of the melanocyte processes by keratinocytes, is a type of cytocrine secretion because a small amount of cytoplasm surrounding the melanosome is also phagocytosed.

56
Q
  • What are the 2 subtypes of melanin?
  • What is each responsible for?
  • Activation of the MC1R receptor promotes formation of which type of melanin?
A
  • Pheomelanin - not UV protective, imbues skin and hair and iris with yellow and red color
  • Eumelanin - brown pigment, imbues skin with black and brown color and protects against UVB radiation by absorbing and dissipating the rays and their cancerous DNA cross-linking effects
  • Eumelanin
57
Q

People with red hair have mutations in what gene?

A

MC1R

58
Q

In lighter skins, melanin is degraded […] than in darker skins

A

Faster

59
Q

Describe the 3 stages of the follicular cycle:

  • Anagen
  • Catagen
  • Telogen
A

A period of growth (anagen) in which a new hair develops is followed by a brief period in which growth stops (catagen). Catagen is followed by a long rest period (telogen) in which the follicle atrophies, and the hair is eventually lost.

MSK (38 decks)

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