Bafl Exam 3: Biology Of Keratinocytes

Front 1

Origin of keratinocytes?

Back 1

Ectoderm

Front 2

Where are the stem cells for keratinocytes found?

Back 2

interfollicular basal layer, bulge region of hair follicles

Front 3

How many days does it take for a keratinocyte to moved from the basal layer to the stratum corneum? Through the stratum corneum?

Back 3

14 days

14 days

Front 4

Do all keratinocytes in the basal layer migrate to the top?

Back 4

NO- some cells are stem cells and remain in the basal layer (this was a Merz question)

Front 5

What signal is neccesary to maintain the proliferative state of the basal layer stem cells?

Back 5

p63

suppresses cell cycle inhibitors

Front 6

What promoted terminal differentiation of basal deratinocytes and spinous layer development?

Back 6

notch

Front 7

Which ion is necessary for keratinocyte differentiation?

Back 7

CALCIUM

Front 8

Acidic vs basic keratins (both epithelial and hair).

type and which chromosome?

Back 8

Acidic: K9- K28 (epithelial), K 31-K 40 (hair), chromosome 17 (17 year olds drop acid, small dog (K9) drinking acid), low molecular weight

Basic: K1-K8, K 71-80 (epithelial bookends!), K 81-86, chromosome 12

Front 9

Location and associated disease?

K1, K 10

Back 9

suprabasalar layer, NO PALM

EHK, epidermolytic icthyosis

Front 10

Location and associated disease?

K1, K9

Back 10

palmoplantar suprabasal layer

vorner epidermolytic PPK

Front 11

Location and associated disease?

K2e, K10

Back 11

Granular layer

Icthyosis bullosa of Siemens (Sie - 2ie)

Front 12

Location and associated disease?

K3, K12

Back 12

Cornea

Meesmann corneal dystrophy

Front 13

Location and associated disease?

K4, K13

Back 13

non keratinizing stratified squamous epithelium

white sponge nevus

Front 14

Location and associated disease?

K5, K14

Back 14

Basal layer

EBS multiple types, dowling degos, naegeli franschetti jadassohn, dermatopathia pigmentosa reticularis

Front 15

Location and associated disease?

K6a, K16

Back 15

ORS, hyperproliferative states, UVR, wound healing

Pachyonychia congenita 1 (Jadassohn–Lewandowsky syndrome)- oral leukokeratosis

Front 16

Location and associated disease?

K6b, K17

Back 16

nail bed

Pachyonychia congenita 2 (Jackson Lawler syndrome)- EICs, prenatal teeth, steatocystoma

Front 17

Location and associated disease?

K8, K18

Back 17

simple endothelium

IBD, cryptogenic cirrhosis

Front 18

K20

Back 18

Merkel cells

Front 19

Location and associated disease?

K 75

Back 19

hair medulla, PFB

Front 20

Location and associated disease?

K81, 83, 86

Back 20

hair cortex, monolethrix

Front 21

Location and associated disease?

K74

Back 21

hair IRS, wooly hair

Front 22

4 types of cells in the basal layer?

Back 22

melanocytes, keratinocytes, merkel cells, langerhans cells

Front 23

What keratins do basal keratinocytes make/express?

Back 23

K5/14

Front 24

What keratins are made in the stratum spinosum?

Back 24

Produce 1/10

express, but don't produce 5/14 (this is made in the basal layer)

Front 25

In what layer do lamellar granules start to form?

Back 25

stratum spinosum

Front 26

What is contained within the lamellar granules (odland bodies)? Decreased numbers of lamellar granules are associated with what?

Back 26

Lamellar granules - ceramide, FFA, cholesterol (these start to form in the stratum spinosum, in the upper granulosum, enzymes degrade lamella granules to release their contents --> cornified lipid envelop formation)

decreased number of LG in Flege's disease, Harlequin icthyosis

Front 27

Normal number, but structurally abnormal lamellar granules seen in what disease?

Back 27

congenital ichthyosiform erythroderma

Front 28

What keratins are expressed in the stratum granulosum?

Back 28

Express K1/10 (made in stratum spinosum) --> K2/11

Front 29

Keratohyaline granules start forming in what layer?

Back 29

Stratum granulosum

Front 30

what is in the keratohyaline granules?

Back 30

F granules- contain profilaggrin

L granules- contain loricrin

Front 31

Which component of the cornified envelop is decrease in psoriasis?

Back 31

decreased loricrin, increased involucrin

Front 32

What common condition has decreased profillagrin?

Back 32

ichthyosis vulgaris

Front 33

This filaggrin degradation produce blocks UV and forms NMF?

Back 33

urocanic acid

Front 34

Where is the cornified envelope formed?

Back 34

Initiated in the upper spinosum, completed in the SC

Contains LIP

Loricrin (80%)

Involucrin

Profillagrin (cleaves to fillagrin)

Front 35

What are the 5 components of the desmosome junction?

Back 35

1. Desmoglein (transmembrane, Ca2+ dependent cadherin)

2. Desmocollin (transmembrane, Ca2+ dependent cadherin)

3. Desmoplakin DP (link btw cadherin and keratin)

4. Plakoglobin PG (link btw cadherin and keratin)

5. Plakophilin PKP (link btw cadherin and keratin)

Front 36

What are the cadherins?

Back 36

Desmolgein

Desmocollin

Front 37

Which member of the plakin family is found in both desmosomes and adherens junctions?

Back 37

Plakoglobin

Front 38

Associated disease?

Desmocollin 1?

Back 38

Desmocollin 1 (transmembrane cadherin)

subcorneal pustular dermatosis

Front 39

Components of adherens junctions?

Back 39

aka zona adherens

classic cadherins (E, P, N)

plakoglobin

alpha catenin

beta catenin

Front 40

Associated disease?

Desmoglein 1

Back 40

Desmoglein 1- Pemphigus foliaceous, bullous impetigo, SSSS, striate PPK

Front 41

Associated disease?

Desmoglein 3

Back 41

Desmoglein 3- pemphigus vulgaris

Front 42

Associated disease?

Desmoplakin

Back 42

striate PPK, carvajal syndrome, wooly hair syndrome

Front 43

What are the cutaneous effects of EGFR inhibitors?

Back 43

PRIDE!!!

papulopustules/paronychia, regulatory abnormalities of hair growth, itching, dryness, EGFRi

Front 44

What therapies are best used to manage EGFR inhibitor side effects?

Back 44

ORAL TETRACYCLINES

remember, examples of EGFR inhibitors include gefitinib, erlotinib, afatinib, and icotinib for lung cancer, and cetuximab for colon cancer.

Front 45

Which antimicrobial proteins are expressed constitutively in keratinocytes? Stimulated?

Back 45

Constitutive expression: B definsins, leukocytes protease inhibitors

Stimulated: HBD2, LL37, TLR, STAT3

**remember, AD has decreased expression of LL37 and HBD2

** psoriasis has increased expression of LL37 and HBD2

This is why there are so many more infections in AD!!!!

Front 46

Inheritance patterns of EBS?

Back 46

All are AD except EBS with muscular dystrophy

Front 47

Defect in EBS?

Back 47

K5/14

Front 48

Presentation of Dowling Degos disease? Mutation?

Back 48

AD mutation in keratin 5

Black/brown macules in reticular distrubution in axillae, neck, inframmary, can be a/w perianal SCC

Front 49

Presentation of bullous congenital ichthyosiform erythroderma? Mutation?

Back 49

EHK- BCIE

AD mutation in K1, 10

newborn- widespread bulla, erythroderma

infant to adult- corrugated hyperkeratosis prominent in flexures, malodorous, macerated intertriginous regions

Front 50

Ichthyosis bullosa of Siemens presentation? Mutation?

Back 50

AD mutation in K2e, 10

similar to EHK, but with milder blistering

fragile blisters early in life (Mauserung phenomenon- superficial molting in neonates)

Front 51

Diffuse PPK presentations of Unna-Thost and Vorner? Mutation?

Back 51

Unna- Thost (U --> non epidermolytic), AD mutation in K1 (one, UNO thost), hyperkeratosis over pressure areas

Vorner (epidermolytic), AD mutation in K9 >K1 (9ER, vornER), hyperkeratosis over pressure areas

Front 52

Pachyonychia congenita 1 vs 2?

Back 52

PC1 (Jadassohn Lewandowsky)- defect in K6a/16, oral leukokeratosis (ONE tongue)

PC2 (Jackson Lawler)- defect in K6b, 17, natal teeth (TWO teeth), steatocystoma multiplex, velus hair cysts

Front 53

mutation?

Back 53

Monilethrix, AD mutation in K81/86 (hHb1/6)

Hair findings- short, fragile, dry, lusterless, breaking internodal

Cutaneous/other- KP, brittle nails, tooth abnormalities, cataracts, MR

Front 54

White sponge nevus of Cannon has a mutation in what?

Back 54

AD mutation in K4/13

white fissured, spongy plaques on oral mucosa, esophagus, vagina, rectum

Front 55

Which keratin pair is expressed in a hyperproliferative epidermis?

1/10

3/12

5/14

6/16

8/18

Back 55

6/16

Front 56

Type I (acidic) hair keratins?

Type II (basic) hair keratins?

Back 56

I: 31-40

II: 81-86

Front 57

Just read this...

Back 57

Keratinocyte adhesion:

Desmosomal cadherins- desmosomes

Classic cadherins- adherens junctions

Catenins- desmosomes and adherens

Claudins- tight junctions

Connexins- gap junctions

Front 58

All of the following pertain to odland bodies except:

a. contain squalene

b. are found intracellularly in the upper level of keratinocytes

c. discharge their contents into the extracellular space at the junction of the granular and cornified layers

d. establish a barrier to water loss

e. mediate stratum corneum adhesion in conjunction with filaggrin

Back 58

odland bodies (lamellar granules) do NOT contain squalene

Front 59

Odland bodies:

a. contain keratins

b. are found intracellularly in the basal cell layer

c. are exclusively intracellular

d. crosslink with K5/14

e. are secretory granules with features of lysosomes

Back 59

Odland bodies (lamellar granules) are secretory granules with features of lysosomes

Front 60

What is the major lipid barrier of the skin?

Back 60

ceramide

Front 61

What is the major component of the cornified envelop which surrounds corneocytes?

Back 61

loricrin (80%)

Front 62

What component of the stratum corneum blocks UV light?

Back 62

urocanic acid

Front 63

At what estimated gestational age are all layers of the keratinized epidermis identifiable?

8w

12w

16w

20w

24w

Back 63

24 weeks!!

mature epidermis complete with interfollicular keratinization

Front 64

Epidermal stratification occurs at what EGA?

4w

8w

12w

16w

20w

Back 64

8 weeks, remember p63 is responsible for this!!!

Front 65

Once a keratinocyte leaves the basal layer, how long until it is shed?

Back 65

28 days (14 days to get to the corneum, 14 days to get through)

Front 66

T/F, not all basal cells have the potential to divide

Back 66

TRUE