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Structure and function by Ana > Structure and function by Ana > Flashcards

Structure and function by Ana Flashcards

1
Q

Explain waste bin hypothesis of CLE formation?

A

More than 190 proteins bound in CE (proteomics research)
Some proteins are needed for the function of CLE, but others can be used as a “sink” to remove them and to stabilize them from cell matrix/ cytoskeletal collapse

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2
Q

4 essential components of SC during cornification (different in Split 2017 notes and 2019)

A
  1. corneocytes
  2. Intercellular lipids
  3. Adhesion complexes
  4. enzyme/enzyme inhibitor network
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3
Q

Function of ceramides

A

-elasticity and barrier function
-free fatty acids from ceramides contribute to skin surface acidification
-free sphingoid bases have antimicrobial activity
-involved in cell-signaling events: proliferation, differentiation, apoptosis® must be compartmentalized

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4
Q

Function of fatty acids in SC?

A

-contribute to barrier function
-help to organize the lamellae of the LE
-contribute to generation of an acid skin surface pH (due to action of secretory phospholipase-A2)

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5
Q

Most common fatty acids in SC in humans

A

Palmitic acid
Stearic acid
Oleic acid
Behenic acid
Lignoceric acid

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6
Q

Synonyms for Lamellar bodies?

A

lamellar granules
Odland bodies, keratinosomes,
membrane-coating granules

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7
Q

What do the Lamellar bodies contain?

A

lipid, cholesterol, enzymes like (lipid hydrolyses) : beta-glucocerebrosidase, acidic sphingomyelinase, secretory phospholipase A2, acidic/neutral lipases; cell adhesion protein (corneodesmosin) , serine protease (KLK7,8) protease inhibitors (LEKTI, LEKTI-2), AMP (beta-defensin) , corneodesmosin
-each molecule is in an isolated aggregate

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8
Q

What is the function of ABCA12 ?

A

transporter essential for delivery of glucosylceramides in Lamellar bodies to the intercellular space

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9
Q

Mutation in ABCA12 causes ?

A

Harlequin ichthyosis (human)
Italian Chianina cattle

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10
Q

Role of calcium in desquamation?

A

Ca enters in the cell (voltage gated Ca channels) due to influx of sodium that causes membrane depolarization
-ca influx initiates cornification at SG-SC interface
-promotes TGM activity and CE protein functions
-it activates ca dependant proteases and indipentant also to cleave profillagrin into fillagrin

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11
Q

Deletion of caspase 14 in mice results in?

A

-altered SC hydration
-Increased TEWL
-increased sensitivity to UVB

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12
Q

what is desquamation?

A

regulated process of shedding corneocytes from the skin surface
-proteases breakdown the corneodesmosomes
- mediate this process: serine, cysteine, aspartic proteases

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13
Q

How does elevated pH affect SC and desquamation?

A

elevated pH increases enzyme activity , increases corneodesmosome degradation and accelerates desquamation

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14
Q

What is a) LEKTI
b) where is it produced and stored
c)what does it do ?

A

a) lymphoepithelial Kazal-type 5 inhibitor
b)produced in SG and delivered by Lamellar bodies to SG-SC interface
c)inhibits KLK 5,7,14 (kallikrein) which is involved in desquamation

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15
Q

What is cystatin A ?

A

-inhibitor of desquamation
-produced in apocrine glands and secreted in sweat
-inhibits epidermal enzymes and barrier disrupting enzymes produce by bacteria or HDM
-incorporated in CLE

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16
Q

GENERAL SYMPTOMS OF ICHTHYOSES

A

-scaling, with or without hyperkeratosis, dry skin, variable erythroderma

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17
Q

WHAT ARE THE 2 BASIC FORMS OF ICHTHYOSES

A
  1. Non-syndromic (affects only the skin)
  2. Syndromic (affects the skin and other organs)
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18
Q

NON-SYNDROMIC VARIANTS IN HUMANS

A
  1. Common ichthyoses
  2. Autosomal recessive congenital ichthyoses (ARCI)
  3. Keratinopathic ichthyoses (epidermolytic)
    Other forms
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19
Q

WHAT ARE CORNEOCYTES

A

=tough, insoluble, dead cells that form structural layers (20-50+) of s.corneum
-critical for support of intercellular lipids
-physically resist skin injury
-form via programmed cell death from viable keratinocytes in outer stratum granulosum (SG1)

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20
Q

WHAT HAPPENS WHEN KERATINOCYTES BECOME CORNEOCYTES

A

-lose water and cell volume (50-80%)
-become dry discs with faceted margins (about 1 mm thick and 30-40 mm in diameter)
-complete collapse and compaction of keratin intermediate filament network by filaggrin (filament aggregating protein)

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21
Q

ICHTHTYOSES IN ANIMALS THAT AFFECT CORNEOCYTE FORMATION

A
  1. TGM-1 in JRT (resembles lamellar ichthyosis in humans)
  2. KRT 10 in Norfolk Terrier (Epidermolytic hyperkeratosis)
  3. KRT16 in Dogue de Bordeaux (footpad hyperkeratosis)
  4. FAM83G in Kromfohrländer and Irish terrier (hereditary footpad hyperkeratosis, resembles human palmar plantar non-epidermolytic keratoderma)
  5. ADAMTS17 in a miniature Bull terrier (primary lens luxation+ abnormal footpad hyperkeratosis)
  6. FAM83H in Cavalier King Charles Spaniels (congenital keratoconjunctivitis sicca and ichthyosiform dermatosis)
  7. SUV39H2 in Labrador retrievers (nasal parakeratosis)
  8. SUV39H2 in Greyhounds (similar to Labradors)
    9.MKLN1 in Bull terriers (lethal acrodermatitis)
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22
Q

WHAT DO INTERCELLULAR LIPIDS DO IN STRATUM CORNEUM

A

-they are non-polar lipids that seal layers of corneocytes
-form major permeability barrier of the skin to water and environmental molecules

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23
Q

HOW DOES THE LIPID ENVELOPE FORM

A

-lipid stacks unfurl on the cell surface and fuse to form a continuous layer of organized lipids (stacked in lipid lamellae)
-coats the corneocyte surface
-this multi-layered (stacked) structure of lipid envelope is important for function; altered by changing the lipid composition

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24
Q

WHAT IS TREATMENT STRATEGY “BLOCK AND REPLACE” IN HEREDITARY DISOREDRS OF LIPID METABOLISM

A

-first we block the pathway affected to limit toxic metabolites
-then, replace the lipid missing after the defect in the pathway

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25
Q

ICHTHYOSES IN ANIMALS AFFECTING INTERCELLULAR LIPIDS

A
  1. ABCA12 in Italian Chianina cattle (severe hyperkeratosis and fissuring)
  2. PNPLA1 in Golden retrievers
  3. FATP4 (SLC27A4) in Great Danes (thickened, folded and wrinkled skin)
  4. NIPAL4 in American Bulldogs (generalized brown scale, erythroderma, 2nd infections, variable pruritus)
  5. NIPAL4 in American Bully dog
  6. NSDHL in Labrador retriever (similar to CHILD’s syndrome in people)
  7. NSDHL in a cat (resembles human ILVEN disease)
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26
Q

WHAT IS CHILD’S SYNDROME?

A

-acronym for congenital hemidysplasia with ichthyosiform erythroderma and limb defects

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27
Q

WHAT ARE CORNEODESMOSOMES

A

=main, structural, cell adhesion junctions between corneocytes
-formed through modification of stratum granulosum desmosomes

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28
Q

WHAT DOES CORNEODESMOSIN DO

A

-binds extracellular cadherins (desmoglein-1, desmocolin-1) of desmosomes
-exhibits homo-oligomerization
-stabilizes desmosomes and increases their flexibility and elasticity through glycine-loop properties

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29
Q

WHAT DO TIGHT JUNCTIONS DO

A

-form continuous, zipper-like, strings of cell-cell junctions that seal the periphery of keratinocytes in stratum granulosum closely together
-form a selective, paracellular permeability barrier to electrolyte and solute movement in the upper dermis
-they create “internal skin barrier” below the stratum corneum ®help limit water loss
-contain claudins
-contribute to keratinocyte polarization (fence function) and for spatial coordination of corneodesmosome breakdown during desquamation

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30
Q

NAME SEVERAL EXAMPLES OF BIOCHEMICAL CHANGES IN STRATUM CORNEUM THAT SHOWS IMPACT HOW ENZYME NETWORK MANAGES DESQUAMATION

A

-cholesterol sulphate is processed to free cholesterol (by steroid sulphatase)
-phospholipids are broken down to free fatty acids (by phospholipases)
-ceramides are broken down ceramidase, sphingosine kinase and S1P lyase
-profilaggrin is processed to filaggrin and then to free amino acids (natural moisturizing factors)

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31
Q

WHAT ARE THE CONSEQUENCES OF ENZYME ACTIVITY IN STRATUM CORNEUM

A

-pH, calcium ion concentration and moisture drop
-free amino acids increase
-conditions additionally favor towards activation of proteases involved in desquamation + inactivation of their inhibitors

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32
Q

NAME PROTEASE INHIBITORS

A

-lymphoepithelial Kazal-type related inhibitor -1, 2 and 3
-cystatin M/E

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33
Q

ICHTHYOSES IN ANIMALS AFFECTING ENZYMES OR ENZYME INHIBITORS

A
  1. ST14 (suppressor of tumorigenicity 14 gene, matriptase) in Akhal-Teke horses (Naked foal syndrome)-mild ichthyosis and marked alopecia, death
    ASPRV1 (aspartic peptidase, retroviral-like 1, skin aspartic protease) in GSD
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34
Q

HOW LONG DOES CORNIFICATION, MATURITION AND DESQUAMATION LASTS IN DOGS, HUMANS, MICE

A

-dogs 20-25 days
-humans 40-56 days
-mice 8-10 days

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35
Q

WHAT IS EPIDERMIS

A

-stratified epithelium generated by stem cells and their progeny in the deep basal layer (SB) that terminally differentiate into distinct morphological layers of epidermis (SB, SS, SG, SC)

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36
Q

WHAT HAPPENS DURING EPIDERMAL STRATIFICATION

A

-stem cells randomly divide and give rise to transiently amplifying cells that proliferate to form the epidermis
-transiently amplifying cells withdraw from the cell cycle, migrate off the basal layer and terminally differentiate to form upper epidermal layers
-usually regular stacks of corneocytes (trunk, face)
-irregular and overlapping stacks of corneocytes (footpad)

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37
Q

WHAT IS STRATUM CORNEUM

A

-is composed of thin, tightly packed corneocytes that are interconnected by modified desmosomes (corneodesmosomes) and are sealed together by an intercellular lipid-enriched matrix (brick and mortar)

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38
Q

WHAT IS S. CORNEUM CONTENT

A

-70 % protein
-15 % lipid and cholesterol
-15% water
-varies by species , body location

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39
Q

WHAT ARE THE PARTS OD STRATUM CORENUM

A

-stratum compactum (deep layer where main permeability barrier function it thought to occur, before the desquamation begins)
-stratum disjunctum (superficial layer, cell layers start to separate, basket weave pattern)

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40
Q

WHICH TGM ARE INVOLVED IN CORNIFICATION OF THE EPIDERMIS AND HF

A

-TGM 1,3, 5

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41
Q

DETAILS ABOUT INVOLUCRIN

A

-alpha helical morphology
-key CE protein because it is deposited early along the inner surface of the plasma membrane
-TGM1 cross-links involucrin to other structural proteins to help to form CE scaffold
-major anchor for ceramides (via TGM1 and TGM5 activity) and replacement of plasma membrane

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42
Q

DETAILS ABOUT LORICRIN

A

-expressed in SG
-stored in keratohyalin granules
-major structural protein of the CE
-compromises 70-80% of the CE total mass
-insoluble at physiologic conditions
-it has non-organised structure with discrete domains and may contain flexible glycine loop domains®contributes to SC elasticity
-main reinforcement protein®deposited on involucrin, cystatin-A, elafin, desmosomal proteins
-cross-links mostly to itself and lesser to small proline-rich proteins
-binds keratin intermediate filaments and filaggrin®another link between CE and cytoskeleton (besides corneodesmosomes)

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43
Q

WHICH ARE 6 MEMBERS OF S100 FUSED-TYPE PROTEINS

A
  1. Filaggrin
  2. Filaggrin-2
  3. Hornerin
  4. Repetin
  5. Cornulin
    Trichohyalin and trichohyalin-like protein 1
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44
Q

NAME DISEASES CONNECETD TO FILAGGRIN MUTATIONS

A

1.ICHTHYOSIS VULGARIS in people- loss of fuction mutation in filaggrin gene
-hyperkeratosis, diminished keratohyalin granules, dry scaly skin, elevated skin surface pH
2. FLAKY TAIL MICE –lack functional filaggrin monomers
-have phenotypic characteristics with ichthyosis vulgaris
3. ATOPIC DERMATITIS –people, loss-of-function mutation
4. ASTHMA –people, loss-of-function mutation

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45
Q

GIVE GENERAL INFORMATIONS ABOUT FREE FATTY ACIDS IN SC

A

-compromise 10-15% by weight of SC lipids
-composition is unique to serum or sebum and even to viable epidermis
-they are thought to be synthetized in epidermis
-essential fatty acids are limited and contribute to fatty acid side chains of some ceramides
-contribute to barrier function
-help to organize the lamellae of the LE
-contribute to generation of an acid skin surface pH (due to action of secretory phospholipase-A2)

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46
Q

IN HUMANS, SC FATTY ACIDS ARE MADE OF WICH ACIDS

A
  1. Palmitic acid (PaSOBeLi)
  2. Stearic acid
  3. Oleic acid
  4. Behenic acid
    5.Lignoceric acid
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47
Q

WHAT IS TEWL

A

an insensible water loss
-normal movement of water through SC into the atmosphere
-readings is in grams per square meter per hour

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48
Q

TEWL IS AFFECTED BY (Videmont, 2011)

A
  1. Breed
  2. Age
  3. Anatomical site
    4.Hair clipping
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49
Q

WHICH ARE 2 MAJOR PROTEIN-BOUND CERAMIDES FOUND IN CANINE AND HUMAN SC (Nishifuji, 2013)

A

-CER[EOS] (sphingosine+ esterified w-hydroxy fatty acid) and CER[EOH] (6-hydroxy sphingosine+ esterified w-hydroxy fatty acid) - human
- CER[EOS] and CER[EOP] (phytospingosine+ esterified w-hydroxy fatty acid) - canine

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50
Q

IN HOW MANY HUMAN PATIENTS MUTATIONS IN FLG GENE HAVE BEEN ESTABLISHED IN AD (Honzke, 2015)?

A

-10-50% of AD patients have mutations in FLG gene
-BUT! Filaggrin expression is downregulated in all AD patients irrespective of FLG status due to downstream effect of Th2 cytokines IL-4 IL-13

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51
Q
A
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51
Q

ARE FILAGGRIN MUTATIONS CONNECED TO BACTERIAL INFECTIONS OF THE SKIN AND WHY (Honzke, 2015)

A

-yes, increased bacterial infections
-lower level of filaggrin breakdown products (normally inhibit bacterial growth)
- reduced levels of AMP further enhance the risk of skin infections

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52
Q

WHAT ARE THE 2 PHYSICAL BARRIERS IN MAMALIAN EPIDERMIS ( Yokouchi, 2018)

A
  1. SC
  2. Tight junctions
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53
Q

IN MULTILAYERED (STRATIFIED) EPITHELIA WHERE ARE TJs LOCATED (Yokouchi, 2018)

A

-between keratinocytes at the 2nd layer of SG (flattened Kelvin’s tetrakaidecahedron cells)

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54
Q

What is the difference between tight junctions and gap junctions?

A

Tight junctions-prevent molecules
from passing through intercellular space
Gap junctions- allow communication
between intercellular space

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55
Q

WHAT ARE TJ AND HOW DOES THE STRUCTURE OF TJ LOOKS LIKE (Yokouchi, 2018)

A

specific cell-cell junctions sealing the intercellular space between endothelial or epithelial cells
-the cell membrane is divided into: APICAL and BASOLATERAL MEMBRANE at the TJs
-TJs consists of TJ STRANDS which are mainly comprised of four-transmembrane claudin proteins on the plasma membrane
-claudins are located in a line and are laterally associated with each other to form TJ strands
-TJ strands on opposing plasma membranes of adjacent cells are associated with each other to form paired TJ strands
-paired TJ strands form a zip lock between plasma membrane of adjacent cells, thereby forming a barrier against molecular movement through the paracellular pathway

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56
Q

NAME MAJOR MOLECULAR COMPONENTS OF TJs

A
  1. claudin
  2. Occludin
  3. JAM-A transmembrane proteins
  4. Tricellulin
    5.Angulins

1.ZO-1
2. ZO-2 intracellular scaffold proteins
3. ZO-3

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57
Q

WHAT ARE THE 3 ELEMENTS OF THE SKIN BARRIER (Yokouchi, 2018)

A
  1. SC-an air-liquid interface barrier
  2. TJ- as a liquid-liquid interface barrier
  3. LC-as a frontline player of the immune barrier
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58
Q

HOW MANY KERATINOCYTES DO HUMAN LOOSE IN 24 HOURS (Yokouchi, 2018)

A

-40 000 000

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59
Q

IN WITCH DISEASES ARE TJs AFFECTED (YOKOUCHI, 2018)

A
  1. Neonatal ichthyosis-sclerosing cholangitis syndrome (NISCH) (loss of claudin-1)
  2. Skin infections (S. aureus, HIV)
  3. AD
    4.UV radiation
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60
Q

HOW DOES UV RADIATION AFFECTS THE SKIN and TJs (Yokouchi, 2018)

A

-inflammation
-local or systemic immunosuppression
-DNA damage + production of oxidized lipids and the release of immune-modulating cytokines (prostaglandin E2, IL-4, IL-10)
-negative impact on TJ-unknown if is direct effect or indirectly through inflammation-fragmented claudin-1, claudin-4 and occludin

61
Q

WHICH ARE THE MAIN PROETASES INVOLVED IN CORNEODESMOSOME DEGRADATION

A

-kallikrein-related peptidases (KLK)
-KLKs are stored in LG, until they are secreted at the apical side of the SG
-after secretion, KLK undergo proteolytic maturation and target corneodesmosomes by cleaving the structural proteins, corneodesmosin, Dg-1, Dc-1

62
Q

WHO IS THE MAJOR ENDOGENOUS KLK INHIBITOR (Ishida-Yamamoto, 2018)

A

-Lymphoepithelial KAZAL-type related inhibitor (LEKTI)
-stored in LG
-after secretion, LEKTI is proteolyzed into several inhibitory fragments, which bind to KLKs and inhibit their proteolytic activities
+CATHEPSIN V and inhibitor CYSTATIN M /E is also involved in corneodesmosome degradation

63
Q

WHAY DO WE HAVE BASKET WEAVE AFFEARANCE ON HISTOLOGY (Ishida-Yamamoto, 2018)

A

-only corneodesmosomes at the edge of flattened cells remain undigested because they are resistant to proteolytic degradation

64
Q

BASED ON HISTOLOGIC FINDINGS ICHTHYOSES CAN BE DIVIDED (HOFFMAN, 2016)

A
  1. Epidermolytic
  2. Non-epidermolytic forms
65
Q

WHAT DOES EPIDERMOLYTIC ICHTYHOSIS MEAN

A

-vacuolization and lysis of keratinocytes
-hypergranulosis and hyperkeratosis within SS, SG

66
Q

WHAT DOES NON-EPIDERMOLYTIC ICHTYHYOSES MEAN

A

-marked, lamellar, orthokeratotic hyperkeratosis and mild acanthosis

67
Q

WHAT ARE RETENTION ICHTHYOSES (Guagure, 2009)

A

-absence of desquamation

68
Q

WHAT ARE CORNEODESMOSOMES

A

-are cell adhesion junctions of the SC
-during transition of SG to the SC -desmosomes are structurally and molecularly modified into corneodesmosomes
-extracellularly, Dg-1 and Dc-1 in SG is converted to electron dense plaque through incorporation of CORNEODESMOSIN
-corneodesmosin is expressed in upper SS and SG, secreted extracellularly from LB during cornification where it binds to cadherins and itself
-intracellularly, cytoplasmic plaque of the desmosome (containing keratin linker proteins desmoplakin, plakoglobin, plakophilin) is morphologically integrated into newly forming cornified cell envelope
-periplakin binds internal plaque of desmosome and recruits envoplakin-they localize to the cornified envelope along the inner cell membrane surface

69
Q

WHAT DOES CORNEODESMOSIN DO

A

-stabilizes the desmosome
-promote cell adhesion
-increases flexibility and elasticity through glycine loop properties
-has ability to reform, reversibly after disruption

70
Q

WHERE IS CORNEODESMOSIN EXPRESSED

A
  1. Superficial epidermis
  2. Follicular internal root sheath
  3. Hair shaft medulla
  4. Cornifying portions of the upper GI tract
71
Q

WHAT ARE THE FUNCTIONS OF TJ

A

1.cell adhesion
2.regulation of tissue proliferation and differentiation
3. vesicle transport
4. interactions with cell signaling pathways

72
Q

WHAT ARE GAP JUNCTIONS

A

=specialized transmembrane structures that create channels between cells with selective permeability
-formed by :
1. CONNEXINS PROTEINS
2. PANNEXIN PROTEINS
-6 connexin proteins form half of a channel in the plasma membrane in one cell = a CONNEXON which meets up with the connexon of another cell to create an intracellular channel -connection the cytosol of 2 cells

73
Q

WHAT IS THE FUNCTION OF GAP JUNCTIONS

A

=Rapid communication between cells or large group of cells ®coordinate function through selective transfer of small molecules/second messengers, ions
-transmit Ca2+ , Na+, K+,ATP, glutamate…
-molecules less than 1 kDa
-exact function is not described ®important for normal barrier function

74
Q

WHAT KERATINS ARE EXPRESSED FROM BASAL TO SC (Homberg, 2014)

A

-basal keratinocytes: K5/K14 (organized in loose bundles that extends from hemidesmosomes and desmosomes through cytoplasm of basal keratinocytes)
-suprabasal keratinocytes: K1/10 (flattening of cells, reorganization of tightly bundled keratins)
+at sites of mechanical strain, palm and soles: K2e,K9
+epidermal injury+ HF, nail: K6, K16, K17
-epidermal stem cells (bulge of HF) :K15
-vibrissae bulge: K5/K15/K17/K19 (loose keratin bundles) and K5/K17 (tight bundles)
-neurosensory Merkel cells: K8/K18/K19/K20

75
Q

WHAT IS ACTUALLY THE PURPOUSE OF HEMIDESMOSOMES (Homberg, 2014)

A

-act as mechanosensors and transduce signaling process
-sites where IF cytoskeleton reacts on mechanical forces

76
Q

HOW ARE TYPE III IF DESMIN AND VIMENTIN CONNECTED WITH SKIN BLISTERING (Homberg, 2014)

A

-desmin and vimentin are required for the interaction with plectin

77
Q

WHAT HAPPENS TO HEMIDESMOSOMES WHEN THERE ARE NO KERATINS (Homberg, 2014)

A

-absence of keratins induces relocalization of plectin away from hemidesmosomes into more diffuse cytoplasmic distribution in keratinocytes

78
Q

NAME INTERCELLULAR JUNCTION COMPLEXES (Zimmer, 2020)

A

-TJ
-gap junctions
-adherens junction
-desmosomes

78
Q

MUTATION IN KERATIN GENES RESULT IN DISORDERS AFFECTING WICH ORGANS (Homberg, 2014):

A

-skin and hair
-liver and intestine

79
Q

WHAT IS THE PREDOMINANT BACTERIA ON HEALTHY CANINE SKIN (Bradley, 2016)?

A

-species: Porphyromonas, Staphylococcus, Streptococcus, Propionibacterium, Corynebacterium
-genera belonging to families Neisseriaceae and Moraxellaceae

79
Q

IS MICROFLORA DIFFERENT IN ORAL CAVITY IN HEALTHY AND DOGS WITH AD ? and NAME THEM(Bradley, 2016)

A

-no it’s the same
- Porphyromonas, Conchiformibius, Fusobacterium and unclassified Moraxellaceae, Flavobacterium, and unclassified Prevotellaceae species

79
Q

WHAT IS THE DIFFERENCE BETWEEN HEALTY AND AD DOGS IN MICROBIOME ANALYSIS (Bradley, 2016)

A

-same taxa are present in healthy and atopic dogs, BUT dogs with flares of AD have increased abundance of Staphylococcus species in all skin sites and decreased microbial diversity (Shannon Diversity Index)

80
Q

DID SHANNON DIVERSITY INDEX CHANGED WHEN AD DOG WERE TRETAED WITH ANTIBIOTICS AND HOW? WHAT DOES IT TELL US ? (Bradley, 2016)

A

-SDI increased during treatment of dogs with ATB (1 and 2 visit) and approached mean of the control, healthy group
-antimicrobial therapy restores diversity of the skin microbiome in cAD, But effects may dissipate when treatment is withdrawn and bacterial dermatitis reoccur

81
Q

HOW IS SHANNON DIVERSITY INDEX CORRELATED WITH SEVERITY OF LESIONS (Bradley, 2016)

A

-SDI in inversely correlated with erythema, alopecia and lichenification and total lesion scoring
-it suggests that decreased microbial diversity is associated with lesion severity

82
Q

HOW ARE AD FLARES CORRELATED WITH SKIN BARRIER DYSFUNCTION (pH, TEWL, hydration) (Bradley 2016) ?

A

-with AD flares, alpha diversity decreases and is correlated with disease severity, TEWL( positive) and pH (negatively)
-skin moisture did not correlate with lesion scores and diversity

83
Q

WHICH 2 SPECIES DOMINATE DURING AD FLARES IN DOGS AND IN HUMANS (Bradley, 2016)

A

-Staphylococcus and Corynebacterium in both

84
Q

WHICH METHOD IS USED FOR PERFORMING SKIN MICROBIOME RESEARCH (Kong, 2016)

A

-16 S ribosomal RNA (rRNA) gene amplicon sequencing

85
Q

WHAT IS ALPHA DIVERSITY (metagenomics wiki)

A

-variation of microbes in a single sample

86
Q

WHAT IS A SHANNON DIVERSITY INDEX (metagenomics wiki)

A

-combines richness and diversity
-it measures both the number of species and the inequality between species abundances
-a large value is given by the presence of many species with well-balanced abundances. Values can range from one (in case of a single dominant species) to the total number of all species (in case of all species having equal abundance).

87
Q

WHAT IS A BETA DIVERSITY (metagenomics wiki)

A

-variation of microbial communities between samples

88
Q

WHAT ARE THE PRIMARY BACETRIAL PHILA ON CATS (Older, 2019)

A

-Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes

89
Q

WHAT FUNGAL MYCOBIOTA IS FOUND IN HUMANS, DOGS AND CATS ( Older, 2019)

A

-humans: Malassezia spp.
-cat& dogs: Dothideomycetes ( Cladoporium spp., Alternaria spp., Epicoccum spp.)

90
Q

CAT BREEDS WITH INCEASED RISK FOR CUTANEOUS INFECTION (Older, 2019)

A

-Persian cats for dermatophytosis
-Devon Rex for Malassezia dermatitis

91
Q

HOW DOES CAT BREED, HAIR LENGTH and LIFESTYLE (IN/OUTDOOR) AFFECT MICROBIOTA (Older, 2019)

A

-Devon Rex has lowest diversity
-Bengal cars have highest
-hair length did not have any significance on microbiota
-significant difference between out and indoor cars was seen only in oral cavity (no skin)

92
Q

WHICH BACETRIAL TAXA WERE FOUND IN CATS STUDY OF OLDER, 2019

A

-Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria

93
Q

HOW DID BREED and HAIR LENGTH AFFECT FUNGAL MICROBIOTA (Older, 2019)

A

-alpha diversity was significant between cat breeds
-sphinx and Bengal cast have the highest diversity
-breeds with short (DSH) and very short hair (Cornish rex, devon rex, Sphinx) have more diverse communities than ones with long hair

94
Q

WHAT WERE THE MOST ABUNDANT FUNGAL GENERA (Older, 2019)

A

-Cladosporium spp. And Malassezia spp.

95
Q

DIFFERENCE BETWEEN BACTERIA IN SKIN IN INDOOR AND OUTDOOR CATS (Older, 2019)

A

-no difference-but numbers of different taxa were the same !

96
Q

WHAT 2 FUNGAL TAXA WERE FOUND ON SKIN FROM OUTDOOR CATS AND NOT IN INDOOR CATS (EXCEPT ORAL CAVITY) (Older, 2019)

A

Ustilaginomycetes and Ustilaginales

97
Q

WHAT WERE 2 MOST PREVALENT MALASSEZIA SPECIAS FOUND IN CATS IN STUDY OF OLDER, 2019

A

-M. restricta and M. globosa
+ Devon Rex has highest abundance

98
Q

DID SEX OR AGE AFFECT MICROBIOTA (Older, 2019)

A

-yes, females have more diverse fungal communities in oral cavity and the skin
-older cats (7+ years) had more diverse bacterial and fungal communities on skin when compared to adult cats

99
Q

WHAT ARE 3 MAIN HYPOTHESES ABOUT VITILIGO ETHIOPATHOGENESIS (Tham, 2019)

A
  1. neural
  2. chemical (oxidative) -injure melanocytes and induces novel autoantigens or expose cryptical cellular antigens (activate immune response against melanocytes)
  3. autoimmune (antibodies against melanocytes + innate immune system: NK and inflammatory DC , CD8 +
100
Q

WHICH PROPOSED MECHANISM ARE INVOLVED IN DEVELOPMENT AND PROGRESSION OF VITILIGO (Tham, 2019)

A
  1. genetic susceptibility
  2. mechanical stress
  3. Koebnerization (trauma induced lesions)
  4. Psychological stress
  5. Reduced melanocytes antioxidant defenses
  6. Microbial dysbiosis
    Aberrant melanocytes-keratinocyte intercellular communication
101
Q

WHICH BREEDS ARE PREDISPOSED FOR VITILIGO DOGS (Tham, 2019)

A
  1. Rottweiler
  2. Collies
  3. Doberman pinscher
  4. Belgian Turvuerens
  5. Labrador retriever
  6. GSD
  7. English sheepdog
  8. Beauceron Shepherd dogs
    -mean age: 24-26 months
    -no sex predisposition
102
Q

WHICH BREEDS ARE PREDISPOSED FOR VITILIGO CATS (Tham, 2019)

A
  1. Siamese
  2. European mixed
    -mean age: 21 months
    -2 females , 1 male
103
Q

WHICH BREEDS ARE PREDISPOSED FOR VITILIGO HORSES (Tham, 2019)

A
  1. Gelderland’s
  2. Spanish thoroughbreds
  3. Arabians (Arabian fading syndrome or “pinky Arab”)
  4. Belgians
    -females are overrepresented
    -median is 48 months
104
Q

HOW IS VITILIGO CLASSIFIED IN HUMAN MEDICINE ( Tham, 2019)

A
  1. Segmental
  2. Non-segmental variants - with 3 major subsets:
    a. Generalized
    b. Acrofacial
    c. Universal
    d. Mixed
    Unclassified (focal and mucosal vitiligo)
104
Q
A
105
Q

IN DOGS, WERE DO MACULAR DEPIGMENTATION IS USUALLY SEEN ( Tham, 2019)

A

-face
Most common-gingiva and lips
-progressed: eyelids, eyelashes, nasal planum, oral cavity ( hard palate and buccal mucosa), pinnae and muzzle
+ footpads, scrotum, nails/claws, paws/limbs, neck/trunk/rump

-generalized depigmentation in only 2 dogs
+ RARE follicular vitiligo ( 7 Labrador puppies had leukotrichia without leukoderma)

106
Q

HUMAN VITILIGO HAS BEEN ASSOCIATED WITH WHAT AUTOIMMUNE DISEASES and drug(Tham, 2019)

A
  1. SLE
  2. Autoimmune thyroid disease
  3. Addison disease
  4. VKH
    +sunitinib (tyrosine kinase inhibitor)
107
Q

ARE THERE SOME REPORT OF SYSTEMIC DISEASES FOR DOGS AND VITILIGO (Tham, 2019)

A

1.DM
2. Adissons
3. toceranib phosphate

108
Q

WHERE DO LESIONS IN CATS APPEAR WITH VITILIGO (Tham, 2019)

A
  1. Nasal planum
  2. Periocular area
  3. Footpads
109
Q

WHERE DO LESIONS APPEAR IN HORSES WITH VITILIGO (Tham, 2019)

A
  1. Head/face
    + or leukotrichia and leukoderma on the body without affecting the head
110
Q

WHAT IS THAMS OPINION ON ACQUIRED IDIOPATHIC LEUKOTRICHIA OR SPOTTED LEUKOTRICHIA AND WHAT BREED ARE AFFECTED (Tham, 2019)

A

1.thoroughbread
2. Shire
3. Arabians
-multifocal, well-circumscribed, small circular areas of near complete leukotrichia on normal skin
-neck , trunk, rump
-variant of vitiligo in horses?

111
Q

TREATMENT OF VITILIGO IN HUMANS ( Tham, 2019)

A
  1. First line therapy -NB-UVB radiation
  2. systemic GCs
  3. non-responding areas-surgical grafting
  4. extensive and refractory vitiligo- hydroquinone monobenzyl ether or 4-methoxyphenol
    + segmented (2-3 % affected) -topical GC and calcineurin inhibitors + localized NB-UVB
112
Q

WHICH TREATMENT OPTIONS HAVE SHOWN IMPROVEMENT IN DOGS (Tham, 2019)

A
  1. psoralens with ultraviolet light
  2. ammoidin (xanthotoxin) and solar exposure
  3. L-phenylalanine (a tyrosine precursor) 6 months
    ±vitamin and mineral supplementation with diet change
    ±ACTH injections
    ±change in environment
    + spontaneous remission in Belgian Tervueren, litter of Labradors
    + after drug administration stopped Bernese mounting dog (toceranib phosphate)
113
Q

WHICH TREATMENT OPTIONS HAVE SHOWN IMPROVEMENT IN HORSES (Tham, 2019)

A
  1. Oral nutritional supplements (A, D, B12, E)
    ± with chelated copper ( relapsed when stopped)
  2. Carrots for 1 year (4-5kg/animal/day)

+ show horses and localized : 0,1% betamethasone or 0,05% Clobetasol
Tacrolimus ( BID for 6 months)
- treatment will stop the progression but doesn’t guarantee partial or full repigmentation

114
Q
A
115
Q

HOW IS AUTOIMMUNITY OF VITILIGO DRIVEN IN HUMANS AND WHAT DRUGS ARE BEING USED TO STOP IT (Tham, 2019)

A

-driven by IFN-g-CXCL10 cytokine signaling pathway
-involves activation of JAK 1 and 2 -ruxolitinib

116
Q

WHAT ARE THE SYMPTOMS OF VKH IN HUMANS (Tham , 2019)

A

-bilat granulomatous posterior or panuveitis with retinal detachment
-disk edema and vitritis
-tinnitus
-hearing loss
-vertigo
-meningitis
-poliosis
-vitiligo

117
Q

WHAT IS THE ETIOPATHOGENESIS OF VKH DISEASE IN HUMANS ( Tham, 2019)

A

-autoimmune disease that targets the melanocytes or melanocyte-associated antigens (tyrosinase and gp100)
-increased susceptibility in certain human leukocyte antigens (HLA)
-70% of lesional cells were T cells
-choroidal infiltrate is composed predominantly of helper T cells
-tyrosinase peptide antigens are target as well
-cell-mediated immunity

-antiretinal antibodies (ARA) could be 1st or 2nd

118
Q

WHAT COULD BE THE TRIGGER FACTORS IN HUMANS AND HOW DO THEY EXPLAIN THEIR INVOLVEMENT ( Tham, 2019)

A

-viral infections-Epstein-Barr and cytomegalovirus
-due to similarities between viral antigens and proteins form pigmented cells - the molecular mimicry theory
WHAT HAS BEEN PROVEN FOR ETIOPATHOGENESIS OF VKH-LIKE IN DOGS (Tham, 2019)
-has autoimmune basis
-DLA-DQA1*00201 has occurred in higher incidence in American Akitas
-injection of peptides derived from tyrosinase-related protein into rats and Akitas-caused clinical signs
-ARA were detected

119
Q

NAME BREEDS PREDISPOSED FOR VKH-LIKE (Tham, 2019)

A

-Akitas
-Samoyed
-Siberian Huskies
-mean 3 years
-males are affected nearly twice often than females

120
Q

IN WHICH LOCATIONS DOES VKH-LIKE OCCUR (Tham, 2019)

A

-85% developed oftalmic clinical signs first (6 months needed to develop other)
-8% developed cutaneous signs first (6 months needed to develop other)
-9% had both systems involved

120
Q

WHAT ARE THE CINICAL SIGNS OF OCULAR VKH-LIKE IN DOGS(Tham, 2019)

A

-blindness or poor/decreased vision
-uveitis
-conjunctivitis

121
Q
A
121
Q

WHAT ARE THE CINICAL SIGNS OF CUTANEOUS VKH-LIKE IN DOGS(Tham, 2019)

A

-leukoderma and /or leukotrichia
-erosions-ulcerations
-alopecia
-crust
-erythema
+ swelling of the nose, hyperkeratosis of footpads, onychomadesis (antigen epitope spreading?)
-bilat and symmetrical (iris heterochromia – only on brown iris!, blue was unaffected)

-face and head- 86% nasal planum
-periorbital skin/eyelids74%
-lips 65%
+ additional mouth/oral cavity (palate), footpads, genitalia (all were males!!!)

122
Q

WHAT SYSTEMIC SIGNS WERE REPORTED WITH VKH-LIKE IN DOGS (Tham, 2019)

A

-lethargy
-left head tilt with change in behavior
-lethargy and cranial nerve II deficit
-dysacusis
-left head tilt and reduced appetite
-transient pica and depression

123
Q

WHAT ARE TREATMENT OPTIONS FOR VKH-LIKE IN DOGS

A

-ciclosporin
-azathioprine
-methotrexate
-chlorambucil
-mycophenolate
-cyclophosphamide
-GC

+ topical GC and cycloplegic agents (to reduce synechiae)
+spontaneous remission has never been recorded
-time to clinical remission- 2 weeks to 10 months

123
Q

WHAT IS A PIGMENTARY SINAPSE (Linder, Split)

A

=melanosome transfer at dendrites of melanocytes to keratinocytes

124
Q

NAME FACTORS NEEDED FOR SURVIVAL, EXPANSION AND DIFFERENTATION OF MELANOBLASTS INTO MELANOCYTES (Linder, Split)

A
  1. KIT (gene encoding for receptor tyrosine kinase, CD117, )
  2. EDNRB (endothelin receptor type B)
  3. FGF
  4. WNT (Wingless)
  5. P-cadherin
  6. E-cadherin
125
Q
A
126
Q

NAME DISORDERS OF MELANOBLAST MIGRATION – NEUROCRESTOPATHIES (Linder, Split)

A
  1. Piebaldism
  2. Waardenburg syndrome
  3. Tietz syndrome
127
Q

NAME POSSIBLE SOURCES OF MELANOCYTES (Linder, Split)

A
  1. Dermal neural crest stem cells-like cells
  2. Schwann cell precursors (stem cells)
128
Q

WHAT ARE THE KEY FEACTURES OF MELANOSOMES (Linder, Split)

A

-melanin production and storage
-lysosome-related organelles -dense granules of platelets, type II pneumocytes lamellar bodies,
-eumelanosomes (hold black-brown eumelanin) and pheomelanosomes (hold red-yellow pheomelanin)

129
Q

DISORDERS OF MELANOSOME TRANSFER ( Linder, Split)

A
  1. Griscelli syndrome
  2. Lavender foal syndrome
  3. Diluted coat colour
  4. Colour dilution alopecia
129
Q

NAME AMINOACIDS THAT CAN CAUSE DECERASED MELANIN SYTHESIS ( Linder, Split)

A
  1. Phenylalanine
  2. Tyrosine
    + copper deficiency
130
Q

NAME DISORDERS OF MELANOSOME FORMATION AND CARGO SORTING (Linder, Split)

A
  1. Hermansky-Pudlak syndrome
  2. Grey Collie syndrome
  3. Chediak-Higashi syndrome
  4. Merle coat phenotype
  5. Equine multiple congenital ocular anomalies
  6. Rat-tail syndrome
131
Q

NAME DISORDERS OF MELANIN SYNTHESIS (Linder, Split)

A

Oculo-cutaneous albinism

132
Q

NAME FUNCTIONS OF CORNEODESMOSOME (Linder, Split)

A

-stabilizes the desmosome
-promotes cell adhesion
-increases flexibility and elasticity

133
Q

ON WHAT IS FORMATION OF TIGHT JUNCTIONS DEPENDENT ON (Linder, Split):

A
  1. E- cadherin
  2. Calcium concentrations
134
Q

WHAT ARE THE FUNCTIONS OF GAP JUNCTIONS (Linder, Split):

A

-rapid communication between cells or large group of cells
-selective transfer of small molecules/ 2nd messengers and ions
-transmit Ca2+, Na+, K+, ATP, glutamate

135
Q

WHAT ARE THE FUNCTIONS OF FREE FATTY ACIDS (Linder, Split)

A

-contribute to fatty acid side chains of some ceramides
-contribute to barrier function
-help to organize lamellae of the LE
-contribute to generation of acid skin surface pH (secretory phospholipase A2)

136
Q
A
136
Q

WHAT MOLECULES ARE BEEING TRANSPORTED BY LAMELLAR BODIES (Linder, Split)

A
  1. Lipids
  2. Lipid related enzymes
  3. Cell adhesion proteins (corneodesisin)
  4. Serine protease (KLK7, KLK8)
  5. Protease inhibitors (LEKTI, LEKTI-2)
  6. AMP (beta defensins)
137
Q

HOW pH ALTERS DESQUAMATION ( Linder, Split)

A

-acidic pH slows desquamation, and higher pH promotes desquamation

138
Q

WHAT IS THE pH OF HUMAN AND DOG SKIN (Linder, Split)

A

-human adult pH 5.4-5.9
-human newborn pH 6.5

-dog: pH 7.2-8.5
Ears, feet pH 6.7-7.1
+skin pigmentation is linked with more acidic skin through melanosome properties and melanosome breakdown

139
Q

WHAT ARE EXOGENOUS SOURCES OF SC ACIDIFICATION

A

1.pilo-sebaceous
2.apocrine
3. eccrine gland sources
+ microbial metabolism (conversion of sebaceous triglycerides to free fatty acids or by direct production of microbial factors)
- free fatty acids, lactic acid, amino acids

140
Q

WHAT ARE MAJOR ENDOGENOUS EPIDERMAL SOURCES FOR MAINTAINIG ACID MANTLE (Linder, Split)

A

-production of free fatty acids by sPLA2 action on phospholipids
-activity of type-1, sodium-proton exchanger (NHE1) located in outer granular layer
-breakdown of ceramides in SC to free fatty acids and sphingoid bases
-natural moisturizing factors (partially)
+skin pigmentation is linked with more acidic skin through melanosome properties and melanosome breakdown

141
Q

COMPOSITION OF EPIDERMIS!!!!

A

Keratinocytes 85-95%
Melanocytes 5 %
Langerhans cells 3-8%
Merkel cells 2%
Lymphocytes: in humans, mice, alpaca, ovine and bovine
in D,C and horses: no lymphocytes

142
Q
A

Structure and function by Ana (4 decks)

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