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190 Cards in this Set

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What are the 2 main components of the Lamina Lucida?
1) Hemidesmosome Complex
2) Anchoring Filaments
What are the 4 components of the hemidesmosome complex?
1) BPAg1
2) BPAg2
3) Plectin
4) a6b4 Integrins
Is BPAg1 intracellular, extracellular or a transmembrane protein?
BPAg1 is an Intracellular protein
What is the molecular weight of BPAg1?
230kD
Is BPAg1 part of the Plakin or Plectin family?
BPAg1 is in the Plakin family
What function does BPAg1 serve as part of the hemidesmosome?
Attaches intermediate filaments to the hemidesmosome plaque
Is BPAg2 intracellular, extracellular or a transmembrane protein?
BPAg2 is a transmembrane protein
What is the molecular weight of BPAg2 ?
180kD
What 3 proteins does BPAg2 interact with intracellularly?
1) BPI
2) b4 Integrin
3) Plectin
What 2 proteins does the NC-16 domain of BPAg2 interact with extracellularly?
1) a6 Integrin
2) Laminin 5
What 2 components of the hemidesmosomal complex are part of the Plakin family?
1) BPAg1
2) Plectin
What is the function of Plectin in the hemidesmosomal complex?
Plectin links intermediate filaments to the plasma membrane
What is the function of a6b4 integrin in the hemidesmosomal complex?
a6b4 integrin, links the intermediate filaments to the extracellular matrix
Name the 4 different anchoring filaments
1) Laminin 5
2) Uncein
3) Fibronectin
4) Nidogen (aka Entactin)
What does Laminin 5 do?
Binds to a6b4 integrin
What does Nidogen (aka Entactin) do?
Binds Laminin 1
What are the 2 main components of the Lamina Densa?
1) Type 4 Collagen
2) Heparin sulfate proteoglycan
What are the 2 types of anchoring proteins found in the Sublamina Densa?
1) Anchoring fibrils
2) Acnhoring plaques
What is the main anchoring fibril?
Collagen 7
What are the 2 main anchoring plaques?
1) Collagen 4
2) Laminin 5
What 2 growth factors stimulate Melanocytes?
1) Beta-FGF
2) TGF-Alpha
What 3 factors inhibit Melanocytes?
1) IL-1
2) IL-6
3) TGF-Beta
Tyrosine is converted to what in the synthesis of melanin?
Tyrosine➜DOPA➜DOPA quinine ➜melanin
What enzyme catalyzes the conversion of Tyrosine to Melanin?
Tyrosinase
In dark skinned people, are melanosomes larger or smaller?
Dark skinned people have larger melanosomes
Do dark skinned people have more, less or the same number of melanosomes as white people?
Dark skinned people have more melanosomes
Do the melanosomes in dark skinned people have more, less or the same amount of melanin as white people?
Dark skinned people have more melanin in each melanosome
Do you find free nerve endings in the epidermis, sub epidermis or dermis?
Free nerve endings are found subepidermally
What type of fibers are free nerve endings made from?
Free nerve endings are made of Penicillate fibers
Where do you find free nerve endings on the body?
Hair-bearing skin
What 4 sensations do free nerve endings provide on hair-bearing skin?
1) Touch
2) Pain
3) Temperture
4) Itch
What sensation do free nerve endings provide on non-hairy ridged areas of the skin?
Fine touch discrimination
Where are papillary nerve endings found?
At the follicular orifice
Where sensation are papillary nerve endings particularly sensitive to?
Cold
Where do you find Meissner's Corpuscles?
In the dermal papilla of digital skin
What 2 sensations do Meissner's Corpuscles detect?
1) Touch
2) Light Pressure
Where do you find Pacinian Corpuscles?
Deep in the dermis or SQ fat in weight-bearing areas of the body
What type of sensation do Pacinian Corpuscles detect?
Vibration
What is the Pacinian Corpuscle?
Mechanoreceptor
What are Krase End-Bulbs?
Mucocutaeous end-organs
What 5 areas on the body can you find Krase End-Bulbs?
1) Glans Penis
2) Prepuce
3) Clitoris
4) Labia Minora
5) Vermillion border of the lip
What are Langerhans cells and where do they originate from?
Antigen Presenting cells
Originate from precursors in the bone marrow
What 3 places can you find Langerhans cells?
1) Epithelial tissue
2) Lymph Nodes
3) Suprabasilar Layer of the Skin
What impairs Langerhans Cells?
UVR
To what cell do Langerhans cells present antigens to?
T-cells with MCH II
What are Glomus cells, and what do they do?
Vascular smooth muscles that shunt from A➜V to bypass capillaries
Where can you find Glomus cells on the body?
Hands & Feet
What are Glomus cells derived from?
Suquet-Hoyer canals
What are Merkel cells?
Mechanoreceptor
What layer of the skin can you find Merkel cells?
Basal Layer
What are Merkel cells?
Mechanoreceptors that have connections with neurons
What stain do you use for Merkel cells?
CK 20
What is the normal transit time of keratinocytes from basal layer to the stratum corneum?
14 days
What is the normal time for keratinocytes to be shed from the stratum corneum?
14 days
Which 2 keratins are upregulated in Psoriasis?
1) K6
2) K16
Which 2 keratins are downregulated in Psoriasis?
1) K1
2) K10
Which 2 keratins are made in the Stratum Spinosum?
1) K1
2) K10
Which 2 keratins are produced in the Granular Layer?
1) K2 (K1➜K2)
2) K11 (K10➜K11)
Which 3 keratins are produced in the Basal Layer?
1) K5
2) K14
3) K19
Which diseases are associated with Gap Junction mutation in connexin-26?
1) Vohwinkel's Syndrome
2) Keratitis-Ichthyosis-Deafness Syndrome (KID)
3) PPK with deafness
Which disease is associated with Gap Junction mutation in connexin 30.3 and 31?
Erythrokeratoderma Variabilis
What disease is associated with Gap Junction mutation in connexin-30?
Clouston's Syndrome (Hidrotic Ectodermal Dysplasia)
Lamellar Granules or Odland Bodies are found where?
First apparent in the upper spinous layer, but primary site of action is the granular layer
Diseases Associated with Lamellar Granules or Odland Bodies
1) Flegel's
2) Harlequin Fetus
3) X-linked Icthyosis
In the granular layer, filaggrin is catabolized to what?
Urocanic Acid
Urocanic Acid serves what function?
Provides UV Protection
What are the proteins of the Cornified Envelope?
Filaggrin, Loricrin and Involucrin
What is the #1 Protein of the Cornified Envelope (CE)?
Loricrin (75% of CE's Mass)
What disease is associated with Transglutaminase 1?
Lamellar Icthyosis
What disease is associated with Transglutaminase 3?
Dermatitis Herpetiformis
What are the 4 stages of wound healing?
1) Inflammatory Stage
2) Epithelialization
3) Granulation
4) Wound Contraction
Which cell is required for wound healing?
Macrophages
-provide debridement and secretion
If the basal layer is lost, what 3 proteins act as a provisional matrix in wound healing?
1) Collagen 5
2) Fibrin
3) Fibronectin
What is the sequence of granulation tissue formation?
Fibronectin ➔ Collagen 3 ➔Collagen 1
When does granulation tissue start to form after injury?
4 days
Which 2 cells are the first to respond to tissue injury?
1) Neutrophils (greater in number)
2) Monocytes
What proteoglycan deposit helps to increase wound strength?
Hyaluronan
What is scar strength at 1 week?
5%
What is scar strength at 3 weeks?
20%
What is scar strength at 1 year?
80%
Where do you find Lanugo hair?
Fine hair found on the fetus
What defines Vellus Hair?
Hair less than 1cm in length
What defines Indeterminate Hair?
Hair that is 1cm long
What defines Terminal Hair?
Hair longer than 1cm
What are the layers of the hair follicle, from outside->inside?
ORS->IRS->Henle's layer->Huxley's layer-> Cuticle -> Cortex -> Medulla
What is the Critical line of Auber?
-The widest diameter of the hair bulb
-Most mitotic activity is below this line
Hair styling breaks what bonds?
Disulfide bonds
What is the time cycle and % of Anagen hair on the scalp?
2-6 years
85% of all hairs
What is the time cycle and % of Catagen hair on the scalp?
2-3 weeks
1% of all hairs
What is the time cycle and % of Telogen hair on the scalp?
2-3 months
14% of all hairs
Eumelanin is found in what color hair?
Black hair
Pheomelanin is found in what color hair?
Red or Blond Hair
Red hair corresponds to what mutation of what receptor?
Loss of function mutation of Melanocortin-1 Receptor (MC1R)
Shifts from Eumelanin to Pheomelanin
What type of stimulation do Eccrine Glands need?
Cholinergic Stimulation
What 2 stains are positive in Eccrine Glands?
S-100 and CEA
What type of secretion do Sebaceous Glands exhibit?
Holocrine secretion
What type of secretion do Apocrine Glands exhibit?
Decapitation Secretion
Where are Apocrine Glands found?
1) Axilla
2) Anogenital areas
3) External Auditory canal = Ceruminous
4) Eyelids = Moll's Glands
5) Breast = Mammary Glands
What causes the odor in Apocrine Glands?
C6-C11 Acids
What is the function of the BMZ?
Supportive structure to anchor the epidermis to the dermis
How does the BMZ anchor the epidermis to the dermis?
Anchoring occurs through the cytoskeleton in keratinocytes, that bind to Laminin 5 in the Lamina Lucida
What does Laminin 5 bind to?
Laminin 5 in the Lamina Lucida binds to Type 7 Collagen in the Lamina Densa
What is the function of Hemidesmosomes?
Hemidesmosomes are the anchoring complex that attach basal cells of the epidermis to the basement membrane
They link the keratin cytoskeleton of basal cells to Laminin 5 which is in the Lamina Lucida
What are the 3 portions of Hemidesmosomes?
1) Cytoplasmic Portion
-Attachment Plaque
2) Transmembrane Portion
-BP antigen 2 (180kD)
-Integrin
3) Extracellular Portion (in the Lamina Lucida)
-Anchoring filaments
-Subbasal dense plate
What makes up the cytoplasmic portion of the hemidesmosome?
They cytoplasmic portion is the attachment plaque. The attachment plaque= BPAg1 and Plectin
-K5 and K14 are bound to the plaque by Desmocalmin and Desmoplakin
-Intracellular portion of BPAg2 (180kD) and Collagen 17 are also present
What are the components of the transmembrane portion of the hemidesmosome?
1) BPAg2
2) a6b4 integrin (interacts with Laminin 5 to form anchoring filaments)
What makes up the extracellular portion of the hemidesmosome?
-Integrins and BPAg2 cross the membrane (transmembrane portion) and attach to the sub basal plate
-Anchoring filaments made from a6b4 integrin & Laminin 5, extend from the sub basal plate into the lamina densa,
What is the weakest layer of the BMZ?
Lamina Lucida
What is the Lamina Lucida?
-Electron-Lucent zone
-Made of Laminin 1, Nidogen (Entactin) and Fibronectin
-Anchoring filaments (Laminin 5 & a6b4 integrin) cross the lamina lucida
-One side connects to the attachment plaque of the plasma membrane of the basal k-cyte
-The other side connects to the sub basal dense plate
What are the components of the Lamina Densa?
1) Type 4 Collagen
2) Entactin (Nidogen): binds laminin, collagen 4, perlecan, and fibulins
3) Fibulins
What are Fibulins?
Calcium-Binding Extracellular matrix proteins
What do Fibulins do?
Function to support the structural network of different basement membranes by joining other supramolecular structures, elastic fibers, and aggregates
-found in basement membranes and vessel walls
What disease is associated with a mutation in Fibulin-1?
Marfan's Syndrome
What is the Sublamina Densa composed of?
Type 7 collagen
-Contains network of anchoring fibrils
What do anchoring fibrils attach to?
Anchoring fibrils originate in the Lamina Densa, dip down into the dermis, and attach to an anchoring plaque or loop back to reinsert into the Lamina Densa
How long does it take for complete renewal of the epidermis?
26-28 days total
What interleukin do Langerhans cells produce?
IL-1
Describe the components of the Desmosome
・Connects K-cytes together, structure consists of:
・A desmosomal plaque on the inside of the cell membrane
・Transmembrane glycoproteins
・Central plate that crosses the intercellular space between 2 keratinocytes
What are the 7 components of the Desmosomal plaque?
1) 6 polypeptides
2) Plakoglobin
3) Desmoplakin 1
4) Desmoplakin 2
5) Keratocalmin
6) Desmoyokin
7) Band 6 Protein
What do adhesion molecules do?
・Cell-to-cell adhesion, interaction between cells, cell signaling, inflammation, migration of cells, wound healing, embryogenesis
Name the 4 families of adhesion molecules
1) Cadherins
2) Integrins
3) Selectins
4) Immunoglobin supergenes
What are tight junctions and what do they do?
Composed of proteins called Claudins
・Regulates epidermal barrier permeability
・Mutation in Claudin-1 linked to rare icthyosis
What are gap junctions and what do they do?
・Allow for communication between cells
・Made of connexins
What are Lamellar Bodies (aka Odland bodies)?
Secretory Organelles (Lysosomes) found inside keratinocytes in the stratum spinosum.
What is the purpose of Lamellar bodies (Odland bodies)?
Ceramide helps with barrier function and adhesion
What are Keratohyaline granules?
・Blue granules that contain Profilaggrin, and Loricrin
Where is Filaggrin cleaved from Proilaggrin?
At transformation from granular to horny layer
What function do Keratohyaline granules serve?
Involved in formation of cornified cell envelope
-rich in sulfur
What is the Cornified cell envelope (CCE)?
An extremely durable protein-lipid polymer
-assembled on the interior of the keratinocyte
-eventually resides on the exterior of the corneocyte
What does the CCE do?
Provides a mechanical and chemical barrier
-Calcium-dependant transglutaminases create an insoluble shield
Where does the dermis originate from?
Mesodermal origin
What is the major protein of the Dermis and what makes it?
Collagen is the major protein of the Dermis
Fibroblasts make collagen
Which type of collagen is common in adult skin?
collagen type 1
Which type of collagen is common in fetal skin?
Collagen type 3
What are the components of the Dermis?
1) Ground substance
2) Subpapillary vascular plexus
3) Deeper vascular plexus (around hair follicles and eccrine sweat glands)
4) Fibroblasts, Macrophages, and Mast cells
Which type of nerve fibers are in the dermis?
Unmyelinated nerve fibers (C-type)
-Detect temperature, pain and itch
-located in the papillary dermis and basal layer
-Encapsulated nerve endings detect touch and pressure
What are Cadherins?
Calcium-dependant cell-cell adhesion molecules
What are integrins and what do they do?
Integrate intracellular cytoskeleton with extracellular matrix
-2 sub-units: α and β
What do Lamellar (Odland) bodies secrete and where?
Store & secrete ceramide into the extracellular matrix (inter-cellular space)
What are the 2 characteristics of Type 1 Keratins?
1) Smaller
2) Acidic
What chromosome is associated with Type 1 Keratins?
Chromosome 17
Which keratins are type 1 keratins?
K9-20
What are the 2 characteristics of Type 2 Keratins?
1) Larger
2) Basic
What chromosome is associated with Type 2 Keratins?
Chromosome 12
Which keratins are type 2 keratins?
K1-8
What is the structure of collagen?
Glycine-X-Y structure
Which 2 amino acids are important for Elastin?
1) Isodesmosine
2) Desmosine
Which amino acid is important for Vimentin?
1) Citrullin
Which 2 amino acids are important for Collagen?
1) Hydroxylysine
2) Hydroxyproline
Name the 4 most important intermediate filaments (aka tonofilaments)
1) Keratins
2) Vimentin
3) Desmin
4) Neurofilaments
What cell is the first responder to release mediators like ADP in tissue injury?
Platelets
How soon does re-epithelialization begin after injury?
Starts within hours
Which 2 enzymes help during re-epithelialization?
1) Integrin receptors guide the path
2) Collagenase assists
What cell type is most important for wound contraction?
Myofibroblasts (contain actin)
At how many weeks into gestation do the first hair follicles form?
9 weeks gestation
Where do the first hair follicles form?
On the face
Which part of the follicle maintains the integrity of the hair?
Cuticle
What part of the follicle contains the bulk of the keratins?
Cortex
During which hair cycle are pluripotent matrix keratinocytes most active?
Anagen
During which hair cycle does thinning and loss of pigment of the hair occur?
Catagen
At which hair cycle stage do the matrix cells terminally differentiate?
Catagen
During which hair cycle is club-shaped hair shed?
Telogen
At which hair cycle stage is the IRS absent?
Telogen
Melanin is formed only during this hair cycle stage
Anagen
When do sebaceous glands enlarge?
After puberty
Which 2 areas do you not find sebaceous glands?
1) Palms
2) Soles
Name the 3 areas with unique sebaceous glands
1) Montgomery's Areolar Tubercles
2) Fordyce Spots
3) Meibomian Eyelid glands
Why are Montgomery's areolar tubercles unique sebaceous glands?
・No hair associated
・Free standing glands
Where do you find sebaceous glands?
Everywhere, usually associated with hair follicles.
EXCEPT: PALMS & SOLES
Where do you find Fordyce spots?
Free sebaceous glands on the vermillion
What are Meibomian glands?
Modified sebaceous glands on the eyelids
What is the #1 component of sebum?
Glycerides
-followed by wax esters and squalene
What are epidermal lipids composed of?
Mostly glycerides, followed by cholesterol.
-NO wax esters or squalene
Name the 5 areas where you can find Apocrine Glands.
1) Axilla
2) Anogenital
3) External Auditory Canal (ceruminous)
4) Eyelids (Moll's)
5) Breast (Mammary)
What type of secretion do you see with ceruminous glands in the external auditory canal?
Decapitation (Apocrine)
What are Moll's glands in the eyelid?
Apocrine glands
What type of secretion do you see in the Mammary glands?
Decapitation (Apocrine)
What are the 3 main components of the BMZ?
1) Lamina Lucida
2) Lamina Densa
3) Sub-lamina Densa
Which of the anchoring filaments is dumbbell shaped?
Nidogen (entactin)
What do anchoring filaments bind?
Laminin 1
Where do we get vitamin D2 & D3 from?
Diet
On the skin, what acts on 7-dehydrocholesterol to form Vitamin D3?
UVB
Skin-derived vitamin D3 binds to what to be transported to the liver?
Vitamin D transport-protein
In the liver vitamin D3 is hydroxylated at what position to produce calcidiol?
25' position
Where is calcidiol transported to?
Kidney
In the kidney, calcidiol is acted on by what to produce calcitriol (1,25-dihydroxycholecalciferol)?
1-hydroxylase
Name the 4 main Cadherins.
1) Desmocollin
2) Desmoglein
3) E Cadherin
4) P Cadherin
"DEP is Cad"
D esmoglein and Desmocollin
E cadherin
P cadherin
What 4 cells make up the epidermis?
1) Keratinocytes 80%
2) Melanocytes (base layer)
3) Langerhans cells (suprabasal 2-8%)
4) Merkel cells (basal layer)
This cell can release, respond to and produce TNF-alpha.
Langerhans cells