Brief description Of Skin and All functions of skins

1. FUNCTION OF SKIN
MODERATOR: DR PUNEET BHARGAW SIR
PRESENTER: DR TEJARAM

2. • Skin is the largest organ in the body.
• In a 70-kg individual - weighs over 5 kg
• surface area - approx - 1.7m2
INTRODUCTION

3. LAYERS OF SKIN:-
Epidermis
Dermis
Sub cutis (Hypodermis)

4. EPIDERMIS
Epidermal layer composed of various type of cells-
• 1.Keratinocytes (>90%)
• 2.Dendritic cells (langerhans cells, melanocytes)
• 3.neuroendocrine cells (merkel cells)
• 4.unmyelinated axons

5. • DERMIS-
1. Endothelial cells and vasculature
2. Neural cells and nervous system
3. Lymphatic system
4. Fibroblasts
5. Dendritic & non dendritic monocyte/macrophages
6. Mast cells
• Sub cutis - separated from body by panniculus carnosus, a vestigial striated
muscle.
DERMIS and SUBCUTANEOUS TISSUE

6. • Can be described under following headings:
1. BARRIER FUNCTION –A) PERMIABILITY BARRIER
B) CHEMICAL BARRIER
C) BARRIER TO UV RADIATION
D) MECHANICAL BARRIER
2. THERMOREGULATION
3. SENSORY FUNCTION
4. IMMUNOLOGICAL FUNCTION
5. ENDOCRINAL FUNCTION
6. SOCIAL AND SEXUAL COMMUNICATION AND COSMETICS

7. Barrier function

9. • CORNIFIED ENVELOP –
- Formed by terminal differentiation in the epidermis
- Acellular and anuclear structure
- Core consist of keratin surrounded by highly crosslinked networks of
protein mainly loricrin .
- This core surrounded by lipid rich in ceramides that are also crosslink
- Crosslinking is mainly due to transglutaminase enzyme

10. • CORNIFIED ENVELOPES-

11. • Small lamellated, membrane coated granules in cytoplasm of granular layer.
• These are numerous in upper part of spinous layer & discharge lipids in
intercellular space.
• play an important roles in barrier function and intercellular cohesion within the
stratum corneum.
Odland bodies

12. 1.Terminally differentiated epidermal keratinocytes (KCs)
2. The acidic ( normal Ph =4.5 to 6.5), hydrolipidic nature of the skin, as a result of
sweat, sebum, lipids.
3.Antimicrobial peptides (AMPs)
4. The skin microbiome , which prevent other undesirable bacteria from developing.
The physical and biochemical skin barrier results from the combination
of :

13. • Forms the first line of defence.
• depends on both the cornified material of the
keratinocytes and the intercellular material, particularly
lipids.
• A two compartment model of stratum corneum as a
barrier is currently accepted,
- in which protein –rich cells, the corneocyte, are
embedded within a continuous lipid rich matrix.

14. • filaggrin, the protein component of the keratohyalin granule.
• Filaggrin is responsible for keratin filament aggregation, and is
subsequently broken down into individual hygroscopic amino acids
that form the basis of the natural moisturizing factor within
corneocytes.
• Dermal–epidermal junction components contribute to cell migration
(for example during wound healing) as well as epithelial–
mesenchymal signalling events

15. • Dermal components consists of a supporting matrix in which
polysaccharides and proteins are enmeshed to a network that
provides resilience to the skin and has a remarkable capacity for
retaining water.
• Collagen is the major extracellular matrix protein, comprising80–85%
of the dry weight of the dermis

16. • The main interstitial collagens are types I and III, whereas the principal basement
membrane collagen is type IV
• elastic fibres accounts for 2–4% of the extracellular matrix in the dermis
• It consist of 2 component: Elastin
Elastin‐associated microfibrils
• These together give skin its elasticity and resilience.
• The dermis also contains a number of non‐collagenous glycoproteins, including
fibronectins, fibulins and integrins which facilitate cell adhesion and cell motility.

17. • Dermal Ground substance is made up of glycosaminoglycan/proteoglycan
macromolecules.
• provide a vital role by maintaining hydration, mostly due to the high
water‐binding capacity of hyaluronic acid.

18. • An intact stratum corneum prevents invasion of the skin by normal
skin flora or pathogenic microorganisms.
• However, both minor injury to the skin, as well as skin diseases, can
provide portals of entry to microorganisms, particularly streptococci
or staphylococci
• AMPs are a diverse group of peptides that are present on epithelial
surfaces, such as the epidermis and its appendages, as a first line of
immune defence by many living things
ANTIMICROBIAL PEPTIDE AS A CHEMICAL
BARRIER:-

19. • AMPs directly kill a broad spectrum of microbes, including Gram-
positive and Gram-negative bacteria, fungi and certain viruses.
• In addition, these peptides interact with the host itself, targeting
events that complement their role as naturally occurring antibiotics

20. • AMPs can be divided on the basis of their
1)Structures,
2)Ability to interact with bacterial membrane
Two major families-
A) Defensins
B) Cathelicidins

21. Defensins
• broadly dispersed family of gene-encoded antibiotics that are
subdivided into the
1) α-defensins
2) β-defensins
Human neutrophils express a number of distinct defensins, six α-
defensins having been identified .

22. • α-defensins 1, 2, 3 and 4 ( human neutrophil peptides (HNPs) 1–4).
• The other two α-defensins, known as human defensins 5 and 6 (HD-5 and HD-6),
are abundantly expressed in Paneth’s cells of the small intestinal crypts and in
epithelial cells of the female urogenital tract .

23. • Four types of β-defensins have been identified.
• human β-defensins (HBDs) 1–4
• β-defensins have a broad spectrum of antimicrobial activity and act
indirectly, being chemotactic for immature dendritic and memory T
cells , promoting histamine release and prostaglandin D2 production
in mast cells

24. Cathelicidins
• The human cathelicidin LL-37/hCAP18 was cloned from cDNA isolated
from human bone marrow as FALL-39
• The mature AMP is referred to as LL-37 because it begins with two
leucine residues and is 37 amino acids long.
• The bactericidal activity of human cathelicidin peptide requires
proteolytic activation from its precursor by enzymes including
neutrophil elastase and proteinase .
• LL-37 has a broad spectrum of antimicrobial activity and is a
chemoattractant for various inflammatory cell types.

25. • As with the defensins, LL-37 has the potential to participate in the
innate immune response both by killing bacteria and by recruiting a
cellular immune response.
• Other proteins with antibacterial activity in the skin include
adrenomedullin , cystatin and secretory protease inhibitor.
Impaired production of AMPs has been observed in the epidermis in
atopic dermatitis .
After injury, the skin responds rapidly with increased production of
AMPs from the epidermis and recruited neutrophils .

26. ULTRAVIOLET RADIATION
• The sun’s radiation is made up of infrared, visible and ultraviolet (UV) light and it
is the UV rays that affect the skin.
• The shorter wavelength UVB rays penetrate the epidermis and are the cause of
sunburn and, in the long term, contribute to premature ageing of the skin and the
pathogenesis of skin cancer.
• UVA rays penetrate the skin more deeply and are considered to have an
important role in chronic sun damage, particularly skin ageing but also skin
cancer development.

27. • The skin has two barriers to UV radiation:
a) Melanin barrier in the epidermis; and a
b) Protein barrier, concentrated in the stratum corneum.
• Both function by absorbing radiation, thereby minimizing absorption by DNA and
other cellular constituents .
• In the long term, there is thickening of the epidermis in response to chronic sun
exposure.
• Absorption of radiation by epidermal lipids may contribute to protection from UV
radiation .

28. Skin has an important role in immunological host defence, particularly
involving those cells residing in (keratinocytes, Langerhans’ cells) or
passing through (T lymphocytes) the epidermis .
LANGERHAN’S CELL –
-Dendritic cell , dopa negative ,ATPase positive
-Derived from bone marrow
-Distributed in the basal ,spinous ,granular cell layers
IMMUNOLOGICAL FUNCTION:-

29. • Pale staining ,have convoluted nuclei .
• Contain rod or racquet –shaped granules (birbeck granules )
• Play important role in immune mechanism –
- Antigen presentation
- Stimulation of T- cell
- Phagocyotosis
-Immunohistochemical marker – CD1a, S-100 , CD207 POSITIVE

30. T lymphocytes are able to recognize antigen only when it has been
presented by specialized cells, termed antigen-presenting cells (APCs)
or accessory cells .
The T cell recognizes the antigen in association with products of the
major histocompatibility complex (MHC) gene region of the APC.

31. In helper T cell (Th cell) activation, the antigen moiety is usually presented in the
context of MHC class II molecules, whereas most cytotoxic T cells recognize the
antigen in association with MHC class I molecules.
the predominant APC populations in the MHC class II-dependent antigen-
presenting pathway are mononuclear phagocytes , Langerhans’ cells , B cells and
lymphoid dendritic cells .
T-cell activation is preceded by interaction of surface molecules, including T-cell
antigen receptor (TCR) occupancy by the antigen–MHC complex.

32. • In human skin, most T cells are found in the dermis, usually grouped around
postcapillary venules and the appendages.
• Langerhans’ cells involved in antigen presentation in damaged epidermis
undergo phenotypic and functional changes prior to leaving the epidermis,
entering the dermal lymphatics and migrating to the paracortical areas of the
draining lymph nodes.
• At this stage, they present the antigen–MHC complex on their surface to the TCR
on either CD4/CD8− or CD4−/CD8 resting T cells, and elicit an antigen-specific T-
cell response .

33. SKIN ASSOCIATE LYMPHOID TISSUE
- SALT provides defined sites for antigen presentation within peripheral
organs ,
- All lymphocytes in SALT are t lymphocyte
- The T cells in SALT are antigen experienced memory T cells

34. • EVIDENCE IN FAVOR OF THE EXISTANCE OF SALT
1) The cutaneous microenvirment is capable on it own accepting
,processing , presenting nominal antigen
2) Peripheral lymph node are able to accept immunologic singal
derived from skin
3) Subset of T lymphocyte display affinity for skin

36. Microflora of skin
• Skin microflora are microorganism that are resident on our skin .
• Mostly bacterial species but fungi , viruses , mites can present .
- Microflora are two type
a) Resident microorganism
b) Transient bacteria

37. • A) Resident bacteria – mostly found in upper part of epidermis and
around hair follicle
- Staphylococcus
- Micrococcus
- Cornybacterium
- Dermabacter
- Malasezzia

38. • B) Transient bacteria – they can be only isolated and cultured from
skin sample from time to time .
-Gram positive –clotrsidia in perianal area
-Gram negative – Acinetobacter
* Gram negative bacteria are not consider part of the normal skin
microbiota , as the low humidity and high osmotic pressure of the skin
are unfavourble for their growth .

39. • Skin sites can be grouped into three types
1) Dry body area – forearms ,legs ,feet
-Mainly coagulase negative streptococci epidermidis , s. hominis
2) Moist body site ( intertriginous area )
-Corynebacterium
3) Sebaceous sites
- Cutibacteria , demodex folliculorum , malasezzia

40. Functions of microflora
• A strain of s. epidermidis produces antibiotics like compound called
bacteriocins .
• Commensales deplete nutrients and produce toxic metabiolites thus
preventing adherence of harmful bacteria to skin cells
• They enhance the immune response to pathogenic bacteria via
interferons , other cytokines and phagocytosis .
• Lipotechoic acid in cell wall of gram positive bacteria stimulate mast
cells to release cathelicidine (antimicrobial peptides )

41. THERMOREGULATION
• Vasodilatation or vasoconstriction of the blood vessels in the deep or superficial
plexuses helps regulate heat loss.
• Eccrine sweat glands are found at all skin sites and are present in densities of
100–600/cm2; they play a major role in heat control.
• Secretions from apocrine sweat glands contribute to body odour (pheromones).
• Skin lubrication and waterproofing is provided by sebum secreted from
sebaceous glands.

42. By blood vessels
• abundance of blood vessels found in the dermis, If the body must cool down, the
body vasodilates these blood vessels.
1. Radiation: The now enlarged peripheral vessels of the skin allow for greater
amounts of blood to flow near the surface of the skin. This allows for our body
to release a lot of body heat through radiation.
2. Convection :if a fluid such as circulating air or water in a pool comes into
contact with the skin, this will allow for heat loss through the process of
convection.

43. • The higher the amount of our body surface exposed to this (usually) circulating
air (e.g. as little clothing as possible), the higher the speed of the circulating air
(e.g. it’s really windy), and the smaller the distance between the skin surface and
the blood vessels, the greater the loss of heat.

44. 3. Conduction: the direct heat transfer of heat from a hotter surface, to a colder
surface touching that hotter surface.
4. Perspiration:The body also thermoregulates via the process of sweating

45. By sweat glands:
• Sympathetic nerve terminals cluster mainly around the secretory coil
of the sweat gland, but a few projections extend to the sweat duct.
• Acetylcholine is the primary neurotransmitter released from
cholinergic sudomotor nerves
• It binds to muscarinic receptors on the eccrine sweat gland, although
sweating can also occur via exogenous administration of α‐ or
β‐adrenergic agonists.
• Released acetylcholine is rapidly hydrolysed by acetylcholinesterase

46. • There is also presence of glomus cells which plays an important role in
thermoregulation.
• Special vascular structure located with in reticular dermis
• Formation occurs in pads, nail beds of fingers & toes, volar aspect of hand & feet,
ears, center of face.
• Glomus concerned with temperature regulation by special arterio-venous shunt ,
that directly connects arteriole to a venule.

47. SENSORY AND AUTONOMIC FUNCTIONS
• The sensory nervous system detects
1. The sensations of touch,
2. Vibration,
3. Pressure,
4. Change in temperature (warmth and cold),
5. Pain (including heat pain) and
6. Itch

48. Autonomic function
• In the skin, autonomic nerve fibers almost completely derive from sympathetic
(cholinergic)
• Autonomic nerve fibers constitute only a minority of cutaneous nerve fibers and
are restricted to the dermis, innervating blood vessels, arteriovenous
anastomoses, lymphatic vessels, erector pili muscles, eccrine glands, apocrine
glands, and hair follicles
• The cutaneous autonomic nervous system plays a crucial part in regulating sweat
gland function, vasomotricity, skin blood flow and thereby body temperature
homeostasis.

49. • Sensory ending in skin 1) free nerve ending
2) corpuscular receptors
1) Free nerve ending –
-Present in papillary dermis
- Have a schwann cell sheath and a basal lamina
Sensory function

50. • A) penicillated nerve ending – Hair bearing skin in the subepidermal
location .
-Unmylinated branches
- Rapidly adapting receptors
- Perceive the sensation of touch ,temp., pain and itch ,somewhat
discrimination .
- Free nerve ending present in non hairy skin have a more precise
distribution and projection individually and vertically into a dermal
Papilla without overlapping distribution .

51. • 2) Papillary nerve ending –
-Present at the follicular orifice
-Inervating deeper parts of the hair follicle
- Receptive to cold sensation
3)Free nerve ending of hair follicle –
-Associate with hair follicle run parallel to it and encircle it
- Fibres arise from myelinated axons of the deep dermal plexus .

52. Corpuscular receptors
• Either encapsulated with a small core – present in dermis
- Or noncapsulated –present in epidermis
- Site –Palms , soles, mucocutaneous junction
1) Pacinian corpuscle –
-Deeper dermis and subcutaneous tissue
-present at the tips of fingers and toes
-Mechnoreceptors responding to vibratatory stimuli

53. • 2) GOLGI –MAZZONI CORPUSCLE –
-Subcutaenous tissue
-present on finger tip
3) KRAUSE END BULB –
-Encapsulated swelling of myelinated fibre situated in the superficial
layers of the dermis .

54. 4) Meissner ‘s corpulse –
- Mechanoreceptor
- Dermal papiilae of digital skin
5) Ruffini corpulse –
-Nerve terminals present in human digits .
-Myelinated afferent fibre , endings are directly related to collegen
fibrils .
6) Mucocutanous end organs

55. The sensory fibers can be grouped by conduction velocity into three broad
categories:
1. myelinated Aβ and Ad
2. unmyelinated C subtypes.
Nociceptors and temperature receptors are primarily of the Ad and C subtype.

56. Aβ fibers :mechanoreceptors which feels pressure, stretch, or hair movement;
further subdivided by the adaptation characteristics of the fibers:
• Slowly adapting type I (SAI) fibers innervate Merkel cell-neural complexes
• Slowly adapting type II (SAII) fibers are thought to innervate Ruffini corpuscles
• rapidly adapting (RA) fibers innervate Meissner and Pacinian corpuscles.

57. • Glabrous skin has two main types of superficial mechanoreceptor:
1. a rapidly adapting receptor, the Meissner’s corpuscle;
2. a slowly adapting receptor, the Merkel’s receptor.
• Subcutaneous tissue and the deeper dermis beneath both hairy and glabrous skin
contain two types of mechanoreceptors:
1. Pacinian corpuscle, a rapidly adapting receptor;
2. Ruffini’s corpuscle, a slowly adapting receptor

58. • Sensory fibers transmit sensory signals (temperature and pH changes, chemicals,
inflammatory mediators, pressure) via dorsal root ganglia and the spinal cord to
specific areas of the CNS, resulting in the perception of burning, pain, itching, or
touch.
• In addition, when stimulated, peripheral nerve endings induce neighboring
afferent nerve fibers in the dermis and epidermis to release neuropeptides, a
process known as “axon reflex”

60. Endocrinal function
• Synthesis of vitamin D3 via conversion of 7 dehydrocholesterol under the
influence of UVB radiation.
• It is produced in innermost layer of the skin : stratum basal and stratum
spinosum.
• The UVB light blocking function of melanin leads to a requirement of greater UV
light exposure in dark skin individual .

62. Effect of calcitriol on cutaneous biology
• 1) Effect on keratinocytes –
- Stimulation of in vitro keratinocytes proliferation at low
concentrations
- Inhibition at higher concentration
-Therapeutic effects of topical vitamin D occurs via
1) Genomic mechanism – Inhibition of keratinocyte proliferation
2) Non genomic mechanism – induce proliferation

63. 2) Immunomodulatory effect

64. • 3) Effects on keratinocytes apoptosis
-Calcitriols causes stimulation of ceramides synthesis by inducing the
mg 2+ dependent sphingomyelinase .
- In return ceramides enhance pro –differentiating effect on
keratinocytes by feedback loop.
- Increase apoptosis of keratinocytes

65. • 4) Effect as an antioxidents –
- Antioxidant in keratinocytes in vitro
-photoprotection against UVB

67. THANK YOU