intro to derma Flashcards
How does the skin arise?
joining of the epidermis (from ectoderm) and dermis(from mesoderm) touching thinner surface of epidermis *diagram
What is the mesoderm important for?
induces differentiation of structures in epidermis e.g. hair follicle
how does the skin develop by week 4?
epidermis is formed: single basal layer of cuboid cells
In week 5?
a secondary layer of squamous, non-keratinisng cuboidal cells (periderm) developed
What does the periderm generate?
White, waxy, protective substance == Vernix caseosa
What does vernix caseosa do?
protects doetus from aminotic fluid during gestation and protects from bacteria at birth
from week 11 of skin develop?
basal layer of cuboidal cells STRATUM germinativum proliferates and forms multilayered intermediate zone
By week 20 what happens?
4 more superficial strata: Spinosum (spinous) Granulosum(granular) Lucidium(clear; found on palms and soles) Corneum (horny) - most super
between weeks 10-17?
epidermal ridges develop , protrude into dermis beneath. gaps = dermal papillae where neurovascular supply develops
weeks 9-13?
hair follicles aka pilosebaceous unit ( inc. hair foll, errector pili muscle, sebaceous gland) in stratum germinativum and appearance of lanugo hair (fine)
What are melanocytes?
pigment cells - give skin and hair colour
how are melanocytes developed?
melanoblasts (precursor cells) arise from neural crest. they migrate dorsally between week 6-8 to developing epidermis (& dermis) and hair follicles. by weeks 12-13 most at their destination and differentiate into melanocytes
how are differentiated melanocytes replenished?
subset of melanoblasts form melanocyte stem cells in hair follicle bulge
Regulation of melanocytes?
Melanocortin 1 receptor (MC1R), a G protein-coupled receptor regulates quantity and quality of melanins produced.
What is MC1R controlled by?
agonists: alpha melanocyte-stimulating hormone (alphaMSH) and adrenocorticotropic hormone (ACTH) and antagonist, Agouti signalling protein (ASP)
What does activation of MCR lead to?
agonist activates -> melanogenic cascade (pigment production) -> synthesis of eumelanin
what does ASP do?
reverses effects of agonists and elicits production of pheomelanin(pale pigment)
What upregulates the expression of the MC1R gene
ACTH
what happens to melanocytes when exposed to uv?
increased expression of MITF & downstream melanogenic proteins, inc Pmel 17, MART-1, TYR, TRP1 & DCT
also increases PAR2 in keratinocytes which increases uptake and distribution of melanosomes (pigment packages) by keratinocytes
what allows melanocytes to distribute melanosomes?
the fact that is a dendritic cell
Structure of the skin ( overview)
epidermis basement membrane (dermal-epidermal junction) dermis: -connective tissue subcutaneous fat
What is the epidermis made of?
looks like a brick wall:
keratinocytes
How are cells divided in the basal layer?
Progressive differentiation:
- stratum spinosum
- stratum granulosum
- stratum lucidum (palms and soles only)
- stratum corneum ( no nuclei or organelles)
How long to surface?
cells progress from basal layer to surface in approx 30 days
When is cell progression accelerated?
in skin diseases such as psoriasis
What is in the cytoskeleton of keratinocytes and sizes?
filamentous cytoskeleton:
actin containing microfilaments (7nm)
tubulin - containing microfilaments (20-25nm)
intermediate filaments (7-10nm)
What are the 5 roles of keratin?
structural properties cell signalling stress response apoptosis wound healing
What are desmosomes?
Major adhesion complexes in epidermis
What are the functions of desmosomes?
anchors keratin intermediate filaments to cell membrane and bridges adjacent keratinocytes
allows cells to withstand trauma
What are gap junctions?
Clusters of intercellular channels (connexons)
What do gap junctions do and why are they important?
directly forms connections between cytoplasm of adjacent keratinocytes
essential for cell synchronisation, cell differentiation, cell growth, and metabolic coordination
what are adherens junctions?
transmembrane structures which engage with actin skeleton
What are tight junctions?**
barrier integrity and cell polarity
What are melanocytes?
dendritic cells that distribute melanin pigment in melanosomes to keratinocytes
what are Langerhans cells?
dendritic cells that are antigen-presenting
What are Merkel cells?
mechanosensory receptors
What are the roles of the basement membrane?
Cell adhesion and cell migration
What is the basement membrane also known as ?
dermal-epidermal junction
What proteins are present in the basement membrane?
collagens (IV, VII), laminin and integrins
What does the dermis do?
supports extracellular matrix - provides resistance
What is the papillary dermis?
superficial, vascular, loose areolar tissue
What is the reticular dermis?
deep, dense connective tissue -> forms bulk of dermis
Describe the protein make up of the dermis
80-85% is collagen: mainly type I and III, 2-4% elastic fibres: fibrillin, elastin
What is the function of glycoproteins
facilitate cell adhesion and cell motility :
e.g. fibulin, integrins and fibronectin
Where/what is the ground substance?
glycosaminoglycan and proteoglycan ( maintain hydration) between dermal collagen and elastic tissue
What cells are present in the ground substance?
fibroblasts - main primary cells mast cells neutrophils histiocytes lymphocytes dermal dendritic cells
Describe the blood supply of the skin
deep and superficial vascular plexus which doesn’t cross into epidermis
sensory innervation of skin ?
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autonomic innervation
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describe the distribution of nerves
1 million afferent nerve fibres, branching network often accompanies blood vessels
forms mesh of interlacing nerves in the superficial dermis
distribution varies by body site (face, extremities and genitalia)
What are corpuscular nerves?
(afferent nerves) encapsulated receptors (dermis e.g. Pacinian, Meissner)
What are free nerves?
afferent nerves
non-encapsulated receptors (epidermis e.g. Merkel cells)
What is Meissner’s corpuscle?
- encapsulated, unmyelinated, mechanoreceptors
for light touch and slow vibration
senses low-frequency stimulation at level of dermal papilla
Where is the Meissner’s corpuscle most concentrated?
thick hairless skin (finger pads and lips)
What is the Ruffini corpuscle?
aka bulbous corpuscle
slow-acting mechanoreceptor
sensitive to skin stretch
deeper in dermis
What shape is the ruffini corpuscle?
spindle
Where is the ruffini corpuscle most dense?
highest density around finger nails - monitors slipage of of objects
What is the Pacinian corpuscle?
encapsulated and ovoid
rapidly adapting - phasic mechanoreceptor
for deep pressure and vibration - detects surface texture
dermal papillae of hands and feet
What are Merkel cells/ discs?
Oval shaped Non-encapsulated mechanoreceptors that sense light, sustained touch/pressure
they are a type of modified epidermal cells
WHere are Merkel cells found?
They are in the startum basale, directly above basement membrane
most dense in fingertips but also found in palms, soles, oral and genital muscosa
Describe the distribution of bacteria on the skin and what affects this?
~ 1 million bac per cm squared
predominantly actinobacteria
affected by environment
What is the role of bacteria on skin?
immune modulation and epithelial health
What are the functions of the skin?
immunological barrier physical barrier thermoregulation sensation metabolic features aesthetic appearance
How does the skin act as an immune barrier?
through Langerhans cells
-responds against the microbial threat and contribute to immune tolerance.
a dense network is formed for potential invaders to interact.*
Describe the function of Langerhans cells
specialised to sense the environment, they initiate an immune response.
How do Langerhans cells prevent autoimmune response?
by causing the production of t regulatory cells