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ACVD Exam > Cornification > Flashcards

Cornification Flashcards

1
Q

What is cornification?

A

The process by which keratinocytes undergo terminal differentiation
- Nucleus and cytoplasmic organelles are hydrolyzed
- Marked reduction of cytosolic water
- Flattened shape

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2
Q

What is the cornified envelope?

A

Proteinaceous wrapper over a dense core of keratin

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3
Q

What is the cornecyte lipid envelope?

A

Overlying monolayer of ceramides

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4
Q

What is filaggrin degraded into?

A

Natural moiusturizing factor
Free amino acids (glutamine, arginine, histidine)
Urocanic acid - UV protection
Pyrrolidonecaroboxylic acid (moisturizing factor)
Lactic acid, citrate, urea

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5
Q

What enzyme breaks down filaggrin?

A

Caspase 14
Calpain 1
Bleomycin hydrolase

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6
Q

What keratins are in the stratum basale?

A

K5 and K15 (humans and dogs)
K1 and 6 in dogs

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7
Q

What is the epidermal proliferative unit?

A

10 basal cells: 1 stem cell surrounded by rapidly proliferating transit amplifying cells

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8
Q

What makes up the “spines” of the stratum spinosum

A

Desmosomes

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9
Q

What keratins are expressed in the stratum spinosum

A

K1 and 10
K4 and K15/16

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10
Q

What proteins do the cells of the spinous layer produce

A

Involucrin and fillagrin
+ form lamellar bodies (lamellar granules, membrane-coated granules, Odland bodies, keratinosomes) which contain lipids, proteins and enzymes

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11
Q

What layers is the stratum granulosum split into?

A

SG1
SG2 - tight junctions seal intracellular spaces
SG3

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12
Q

At what layer do tight junctions seal intracellular spaces?

A

Stratum granulosum SG2

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13
Q

Where in the epidermis would you find keratohyalin granules?

A

Stratum granulosum

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14
Q

What are keratohyalin granules

A

These basophilic granules are accumulations of the synthesized proteins, primarily profilaggrin, loricrin and keratin filaments, needed for the construction of the stratum corneum.

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15
Q

What is fillagrin?

A

protein involved in the aggregation of keratin

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16
Q

What is loricrin

A

key component of the corneocyte cornified envelope

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17
Q

What change triggers the assembly of the keratin intermediate filaments and construction of the cornified envelope?

A

Increased intracellular calcium

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18
Q

Where do the keratin intermediate filaments and cornified envelop develop in the epidermis?

A

Stratum granulosum

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19
Q

Where do epidermal lamellar bodies secrete their contents?

A

Extracellular spaces at SG1 and the apical surfaces of SG2 cells

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20
Q

What does the cornfield cell envelope replace

A

Plasma membrane

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21
Q

What happens to the keratinocyte as it transitions from the stratum granulosum to the stratum corneum

A

1) Organelle activities cease
2) Cell Flattens with keratin intermediate filament bundling
3) Degradation of nucleus and organelles

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22
Q

What are corneocytes

A

Dead, flattened, terminally differentiated keratinocytes that have lost all nuclei and organelles

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23
Q

What makes up the CLE?

A

ceramides
free fatty acids
cholesterol

24
Q

What are corneocytes

A

flattened, keratin-filled cells, lacking organelles and plasma membranes, that are coated with an insoluble proteinaceous layer known as the cornified cell envelope (CE).

25
Q

What makes up the tripartite structure of keratin proteins?

A

α-helical rod domain
an amino-terminal head
a carboxy-terminal tail

26
Q

What are features of Type 1 keratins?

A

acidic
smaller than type II
include K9-19 in the epidermis

27
Q

What are features of Type 2 keratins?

A

basic
larger than type I
include K9-19

28
Q

How many filaggrin monomers are present in dogs

A

4

29
Q

Where does enzymatic cleavage of profilaggrin into filaggrin occur?

A

Transition of granular to cornified layer

30
Q

What enzymes cleave filaggrin?

A

Caspase-14
Bleomycin hydrolase

31
Q

What are the products of filaggrin degradation

A

Natural moisturizing factors: Most importantly urocanic acid (photoprotection, hydration, antimicrobial) and pyrrolidone carboxylic acid (hydration, antimicrobial)

32
Q

Name components of the cornified cell envelope

A

Involucrin
Loricrin
Envoplakin
Periplakin
Small proline-rich peptides
Keratins
Filaggrin

33
Q

What is necessary for transglutimase activity

A

Increase intracellular calcium

34
Q

Where is TG1 located

A

Membrane

35
Q

Where is TG3 located

A

Cytoplasm

36
Q

Which protein is the major structural component of the CE

A

Loricrin (70% of mass) - cystine-rich highly flexible protein with glycine loops and is a fundamental promoter of terminal differentiation

37
Q

What is the function of TG3

A

Crosslinking of loricrin and SPRs

38
Q

What is the function of TG1?

A

Cross link oligomers to the developing CW

39
Q

What is the corneocyte lipid envelope?

A

Hydrophobic intercellular ω-hydroxyceramides lipids that fill the spaces between the corneocytes

40
Q

What are the major lipid classes of the stratum corneum extracellular lipid layer?

A

ceramides (50%)
free fatty acids (15%)
cholesterol (25%

41
Q

What are ceramides?

A

amide-linked fatty acids attached to long chain amino alcohols called sphingoid bases

42
Q

What are the contents of Lamellar bodies?

A

lipid precursors, including glucosylceramides, sphingomyelin, phospholipids, and cholesterol sulfate,

enzymes: β-glucocerebrosidase, acidic sphingomyelinase, phospholipase A2, and steroid sulfatase, respectively

43
Q

From what is cholesterol synthesized?

A

Acetate - from lower epidermis

44
Q

Which enzyme metabolizes cholesterol suphate to cholesterol?

A

Steroid sulphatase (contained within LBs)

NB some cholesterol is incorporated into LBs unchanged

45
Q

What is the role of cholesterol sulfate?

A

Inhibits serine proteases (kallikreins) involved in desquamation

46
Q

Which enzymes control desquamation?

A

Kallikreins (serine proteases)
Cathepsins (cysteine proteases)

47
Q

What are desmosomes?

A

Specialized keratinocyte junctions that link KIFs to sites of intercellular adhesion, tethering adjacent cells and providing structural strength for the epidermis

48
Q

What are the three genre families of desmosomes?

A

Cadherins – These are transmembrane molecules that form a calcium-dependent adhesive interface between neighboring keratinocytes. Their extracellular portions comprise the desmoglea.
➢ Desmogleins
➢ Desmocollins
❖ Armadillo protein family – At the desmosomes, these proteins bind to the cytoplasmic portions of the cadherins.
➢ Plakoglobin – binds to desmoplakin and cadherins
➢ Plakophilin – binds to cadherin complexes to strengthen the plaque
❖ Plakin protein family
➢ Desmoplakin – binds KIFs to plakoglobin
➢ Envoplakin and periplakin

49
Q

What molecules are contained within corneodesmosomes?

A

desmoglein 1
desmocollin 1
corneodesmosin (CDSN)

50
Q

Which molecules contain corneodesmosin?

A

Keratins
Loricrin
Corneodemsosomes

CDSN forms structural motifs called “glycine loops” which have been suggested to mediate reversible and adjustable intermolecular adhesion by acting like Velcro.

51
Q

Where are tight junctions located

A

SG2

52
Q

What are tight junctions made up of?

A

claudins
occludins
junctional adhesion molecules (JAMs)
zonula occludens (ZO) proteins.

53
Q

What are Caudins?

A

Primary transmebrane molecules that function as a zip lock to seal the intercellular barrier, and claudins 1, 4, and 7 are expressed in the epidermis.

54
Q

What is desquamation?

A

process by which corneocytes are shed from the epidermal surface

55
Q

Which enzymes mediate desquamation?

A

Promoters:
kallikreins (KLK, a family of serine proteases)
cathepsins (cysteine proteases)

Inhibitors:
KLK inhibitors LEKTI (lymphoepithelial Kazal-type-related inhibitor, encoded by SPINK5 gene)
cholesterol sulfate

56
Q

At what layer is the concentration of Ca2+ highest in the epidermis

A

Stratum granulosum (low in basal and spinous layers and decreases again in stratum corneum)

57
Q

What processes are controlled by high intracellular calcium?

A

lamellar body secretion
transglutaminase activity
cleavage of profilaggrin to filaggrin

ACVD Exam (21 decks)

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