Structure and function of the skin Flashcards
The primary keratinocyte intercellular junction is the:
Desmosome
Desmosomes connect to keratinocytes by anchoring onto:
Keratin
Desmosomes consist of ______ which are cytoplasmic, and ____ which are transmembrane
- Desmoplakin, plakophilin, plakoglobin.
- Desmocollin 1/2/3, and desmoglein 1/3
Desmocollin, desmoglein and other cadherins are dependant on _____ to function
Calcium
Adherence junctions function to_____ by anchoring/attaching to ______
- mediate tight intercellular binding
- Actin filaments
Tight junctions are made up of ______. They function to________
- claudins and occludins
- form tight seal against water loss in granular layer
Gap Junctions function is _______. They are composed of _______.
- intercellular communication
- Connexons which are made of 6 connexins
Which keratins are produced in stratum basale
5+14
Cellular proliferation in the stratum basale is stimulated by:
trauma, UV radiation (increased ornithine decarboxylase expression is associated with proliferative states)
Ornithine decarboxylase is inhibited by:
Retinoids, corticosteroids, Vitamin D3
What percentage of cells in the basal level are stem cells?
10%
Transit time from basal layer to SC is? And from SC to desquamation?
14 days, and another 14 days
Function of stratum corneum is:
mechanical barrier
Structure of stratum corneum:
protein rich corneocytes with no nuclei (bricks) and lipid matrix (mortar)
______ are the intermediate filaments that comprise the primary cytoskeleton of the epidermis
Keratins
Type I Keratins have _____ molecular weight
- are (acidic/basic)
- K#______
- chromosome #______
- Low molecular weight
- acidic
- K9-28, K31-40 (hair keratins)
- chromosome 17
Type II Keratins have _____ molecular weight
- are (acidic/basic)
- K#______
- chromosome #______
- high molecular weight
- basic
- K1-8, K81-86 (hair keratins)
- chromosome 12
Functional unit of keratin:
heterodimers of type I and type II filaments that form tetramers and ultimately filaments
Keratin is anchored to plasma membrane by:
desmosomes
Keratinocytes produce which IL’s and what other molecule?
IL-1,6,8,10,12 and TNF alpha
Melanocytes are derived from ______
neural crest
Activation of what molecule is required for melanocyte development/migration?
C-kit
Piebaldism occurs as a result of____
loss of C-kit–>impaired melanocyte migration and proliferation
Mutations of C-kit are associated with____
acral and mucosal melanoma
Each melanocyte interfaces with ___ keratinocytes?
36
- Melanin is produced in _____ from its precursor _____.
- this process involves a copper dependent enzyme _____
- melanosomes, tyrosine
- Tyrosinase
Pheomelanin color:
Eumelanin color:
- red/yellow
- black/brown
Difference in skin color is due to differences in:
- melanosomes
- in darker individuals are larger and have more melanin
- Melanosomes are more stable and are transferred individually in dark skin (light skin are smaller, lighter, and less stable
Melanin production is stimulated by _____ and _____ on _____ on melanocytes
- melanocyte-stimulating hormone (MSH)
- ACTH
- on MC1-R
MC1-R loss of function mutations—->_____ and phenotype of ____
- increased pheomelanin:eumelanin ratio
Reason that darker skin types are “protected” more from the sun?
- Melanin absorbs UV and protects against UV induced mutations
- Immediate tanning is due to_____
- delayed tanning is due to____
- oxidation of existing melanin
- new melanin synthesis
Oculocutaneous albinism is due to:
defects in enzymes required to convert tyrosinase to melanin
Defects in packaging of melanosome-specific proteins leads to which syndrome?
Hermansky-Pudlak (Hermansky Pudlak Hates Packaging melanosome proteins)
Defects in lysosome and melanosome trafficking to dendrites leads to ___ syndromes (2 different syndromes)
- Griscelli
- Chediak-Higashi syndrome
Griscelli and Chediak-Higashki are not good traffickers along the dendrite highway
Major antigen presenting cell of the skin is the ____
langerhan cell
Describe the form of a langerhan cell:
- reniform (kidney shaped) nuclei
- tennis racket shaped Birbeck granules seen on EM
Positive immunostains for Langerhan cells:
- CD207 (Langerin), CD1a, S100, CD34, Vimentin,
Actin
Layer of skin where langerhan cells do work:
Stratum spinosum “L”
What do langerhan cells do after encountering and processing an antigen in the stratum spinosum?
- migrate to lymph nodes and activate T-cells
What down-regulates langerhan cells?
- UV exposure
Merkel cells are (slow/fast?) adapting mechanoreceptors and are found in _____ parts of body, and ____ layer of skin. They communicate with ____.
- slow adapting mechanoreceptors
- fingertips, lips, oral cavity, hair follicles
- stratum basale
- communicate with neurons
______ marker/pattern is sensitive and specific for merkel cells?
- Merkel cells are also positive for_____
- CK20+ in perinuclear dot pattern
- also positive for neurofilaments, S100, synaptophysin, chromogranin A, vasoactive intestinal peptide, neuron-specific enolase, and calcitonin gene-related peptide
Semipermeable barrier between epidermis and dermis that also serves to adhere basal keratinocytes to underlying dermis is the ______
basement membrane zone
Basement membrane zone:
- Describe the connection between basal keratinocyte and hemidesmosome.
- intracellular keratin filaments K5 and K14 attach to hemidesmosomal plaques (plectin and BPAG1) on basal plasma membrane.
- hemidesmosomal plaque proteins bind to intracellular portions of the anchoring filaments (BPAG2 and alpha 6 Beta 4 integrin)
- see diagram in book (pg 6)
Basement membrane zone:
- the extracellular portion of anchoring filaments (BPAG2, alpha 6 beta 4 integrin, and laminin 332) that extende from hemidesmosome down to lamina densa is the _____
- lamina lucida
- see diagram in book (pg 6)