Block III: Skin video 2 Flashcards
What enzyme is involved in the water-proofing mechanism step1? and what other proteins does it crosslink to
This involves transglutaminase-1 enzyme that crosslinks small proline rich (SPR) proteins as well as structural proteins such as cystatin, desmoplakin, elafin, envoplakin, filaggrin, involucrin, loricrin,
keratin and other proteins to make the membranes impermeable to water
What protein is the major structural protein in water proofing?
Loricrin is the major structural protein coating the membrane surface as part of this cornification
of the envelope, accounting for 80% of the protein mass.
What happens in step 2 of waterproofing mechanism?
The contents of the membrane coating granules are
exocytosed into the extracellular space- These granules contain sphingolipids (ceramides –
acylglucosylceramide), cholesterol, and fatty acids which form a water impermeable intercellular barrier
What transmembrane protein is required for impermeable water barrier?
ABCA12 lipid transporter protein (blocks water, not lipids) in membrane of lamellar granule
What breaksdown desmosomes? (desquamation)
Kallikrein-related serine peptidases
(KLK5, KLK7, KLK14)
What binds to KLKs?
At neutral pH as found in lower levels of stratum corneum, lymphoepithelial Kazal-type inhibitor
(LEKTI) binds to the KLKs and prevents this
cleavage
By what are KLKs activated?
by cleavage by mesotrypsin and LEKTI inhibition is
lost as pH drops into the surface. activated KLKs cleave desmosomes
Where are melanocytes present and with what do they interact?
Are small clear cells among the keratinocytes in the
stratum basale.
Interact with adjacent keratinocytes to form
epidermal-melanin unit
Where are melanocytes derived from?
neural crest cells
What are the functions of melanocytes?
responsible for the synthesis of melanin granules.
Nodesmosomes are present (bc they are not part of the epidermis)
identify
High magnification micrographs of epidermis with melanocytes in the
stratum basale layer
identify
What intially sinthesized the melanin granule?
Initially synthesized as a premelanosome
granule from the golgi containing tyrosinase
What does tyrosinase do on tyrosine?
gives LDOPA (dihydroxyphenylalanine) which is
modified for the formation of pheomelanin
(reddish pigment) or eumelanin (blueblack
pigment)
is tyrosine activity lost?
lost in mature granule
where is melanocyte?
embedded in keratinocyte
identify
High magnification micrograph of epidermis melanin granules in
The keratinocytes in the stratum basale layer; protects from UV
By what does skin color depend?
- size of melanin granules
- differences in melanin granules packing
- degree of melanization of granules
- degree to which granules are broken down
identify
Melanin granules in cell in stratum spinosum; clustered
WHat mutations are present in albinism?
inherited abnormalities of melanin synthesis and are typically characterized by a congenital reduction or absence of melanin pigment.
Albinism results from defective production of melanin from tyrosine through a complex
pathway of metabolic reactions
What are the main types of albinism?
oculocutaneous albinism (OCA) and ocular
albinism (OA). The first involves both the skin and eyes while the 2nd only involves the eyes
What gene is necessary to maintain the presence of melanocyte stem cells?
Bcl2 (anti apoptotic factor); melanocytes are lost by apoptosis if this gene is lost or mutated
what can deplete melanocytes?
age; skin cancer increases with age bc there is no more protection; gray hair lightening of skin color
are there desmosomes in langerhans cell?
No desmosomal connections to other cells
What are birbek’s granules?
present in langerhans cell cytoplasm and he,p in sequestion and processing of viruses. high [C-type lectin receptor] (langerin)
How is the nucleus of langehans cell?
folded or indented
identify
langerhans cell birbek’s granules
identify
EM of Langerhans cell with its characteristic indented nucleus
and immunostained section showing distribution of Langerhans cells in
the epidermis
Explain some fucntions of langehans cell?
- antigen-presenting cell similar to dendritic cells and macrophages; operate immunologically as surveillance in epidermis for foreing antigens or pathigens (viruses)
- determine appropriate adaptive immune reponse (tolerance or edema) to foreign things though interactions with keratinocytes.
- stable and capable of slow turnover and renewal
What happens when langerhans cell enocunters dangerous situation?
such as a wound in the skin, pathological bacteria or viruses, they become activated and can migrate
to nearby lymph nodes and instruct T lymphocytes
to mount an effective immunological response.
In particular, when encountering dangerous viruses they may initiate a potent cytotoxic T-cell (CD 8 T-cell)
response against cells containing the virus
Explain correlation of langehans cell to HIV
newer evidence suggests the cells may capture the virus and prevent infection by its
sequestration within the Birbeck granules
Note that Langerhan’s cells as found in the vaginal stratified squamous epithelium may be an entirely different story since these cells appear to be more similar to other dendritic antigen-presenting cells and may transmit the virus to the T-lymphocytes resulting in their death
Where are merkel cells located and derived?
located in the stratum basale & are connected to other cells by desmosomes. Thus probably
derive from keratinocytes
By what are merkel cells characterized and what do their free nerve endings form?
- presence of dense-cored neurosecretory
granules in cytoplasm - Possess intimate contact with expanded terminals of free nerveendings to form Merkel’s
corpuscle
identify
EM of Merkel’s cell showing neurosecretory granules
in the cytoplasm and an adjacent peripheral nerve terminal
What are the functions of merkel cells?
- Are thought to be form of afferent sensory cell
- Are thought to be involved in two-point sensory
discrimination
What neoplasms of skin are keratonocyte derived?
- Basal Cell Carcinoma - the most common
malignant neoplasm in Caucasians. Slow growing
- rarely metastasizes - Squamous Cell Carcinoma - greater tendency to
metastasize to regional lymph nodes
identify
phograph of skin with malignant melanoma
What neoplasms of skin are melanocyte derived?
- Malignant Melanoma - very aggressive tumor
with strong tendency to metastasize
What neoplasms of skin are langerhans derived?
- Histocytosis X (Langerhans cell histiocytosis),
immunological diseases characterized by an
abnormal increase and accumulation of
Langerhans cells, which may form tumors affecting
various parts of the body, including the bones,
lungs, skull, and other areas and organs.
What neoplasms of skin are merkel cell derived?
- Merkel Cell Cancer. Relatively rare but highly
invasive.
identify
Micrograph showing malignant
melanoma lesion in skin
WHat are the layers of the dermis?
papillary layer
reticular layer
what does the papillary layer consists of?
immediately under epidermis. Consists of loose CT. Smaller diameter collagen fibers & elastic fibers. Numerous capillaries, small blood vessels, and nerves
what does the reticular layer consists of?
dense irregular CT. Thicker larger diameter collagen
fibers and elastic fibers
What is the function of the layers of the dermis?
strength. Papillary & reticular layer have numerous elastic fibers. With age these tend to fragment, giving rise to wrinkles
identify
Micrographs showing the dermis at low and higher magnification with papillary layer
with loose CT and reticular layer with dense irregular CT
identify
Micrograph showing
dermis with papillary (PL) and
reticular layers (RL) and elastic
fibers
how is hypodermins called and its function?
(subcutaneous fascia or superficial fascia), it is important in providing a flexible attachment of
skin to underlying tissues
what does hypodermis consists of, its function ans what glands can we find here?
- Consists of loose CT which frequently contains white adipose tissue (panniculus adiposus) which serves as energy store and for thermal insulation
- The basal portions of hairs & eccrine sweat glands are frequently present in the hypodermis
identify
Low magnification micrograph of skin showing the epidermis, dermis and hypodermis
