Dermatology Summary: Skin Functions, Immune System, and Phenomena

The Function of the Skin

Issues

1-191) The function of the skin

• Largest organ in the body (4kg; 1.8-2m2) - 15-20% body weight
• Primary role = barrier à prevent entry of noxious chemicals and infectious organisms + prevent exit of water and chemicals - Barrier to mechanical, physical, and chemical agents:

Mechanical Barrier Properties

• Mechanical:
  • Elastic possibilities of the skin - dense collagen w/ elastic fibers
  • Constant proliferation (cellular turnover)
  • Connection between dermis and epidermis

Physical Barrier Properties

• Physical:
  • Prevention against UV radiation
  • Prevention against cold and heat (controls heat and water loss)
  • Antimicrobial peptides

Chemical Barrier Properties

• Chemical:
  • Thin lipid coat (sebum + epidermal lipids) + acid skin (pH = 4.2-5.6)
  • Presence of keratin - resistant to acids
  • Regeneration of lipids - about 1 hour (skin is still more sensitive to external agents)

Additional Skin Functions

• Protection of body liquids and internal organs
• Antimicrobial protection
  • Natural flora - constant microorganisms on the skin; rich in areas w/ high density of sebaceous glands and scalp
  • Newborns: decreased
  • Children: similar to adults
  • Sex: more in males
  • High humidity: increased
  • Season: increased in the summer
  • Shower: temporarily decreases; increases after 1-2 hours
• Thermoregulation: evaporation through dilation and constriction of blood vessels in the skin
• Acts as a sensory organ (pain, temperature, vibration, touch)
• Food reserve in the form of subcutaneous fat
• Resorption
  • Horny layer is the most important - when it's lost the barrier doesn't work
  • Higher when epidermis is thicker and in skin folds
  • Depends on the condition of the skin, physical and chemical characteristics of the substances, vehicle, and concentration of the substance
• Excretion: metabolic waste, sweat, and sebum
• Vitamin D synthesis (keratinocytes)
• Melanin synthesis
• Immunological processes
• Cosmetic aspects
• Manifestation of feelings
• When confronted w/ insults from the outside, it usually adapts easily and returns to a normal state; but sometimes it fails to do so and a skin disorder appears

Skin as an Immunological Organ

2) Skin as an immunological organ SIS => Skin Immune System consists of:

Cellular Components of Skin Immune System

1. Cellular components: A. Keratinocytes B. Langerhans cells C. T-Lymphocytes D. Dermal dendritic cells E. T-cytotoxic (Tc) cells F. T-regulatory (Tregs) cells G. Natural Killer Cells H. Killer Cells I. Mast cells- that either cause Adaptive or Innate immune response, leading to many skin diseases!

Keratinocytes and Immunity

A. Keratinocytes (KC):

• Primary role: produce protective horny layer & support outermost epithelium
• Immunological Role:
  • releases IL-1 after Injury to initiate Immune & inflammatory Cascade
  • release & synthesis AMP (anti-microbial peptides)
  • defensin & cathe-licidin => first line of immune defense
  • recognize PAMPs via toll-like receptors (TLR)
  • produce chemokine - to attract Immune Cells & Cytokines
  • y-interferon induces MHC class II expression of KC - enable them to be antigen-presenting cells

Langerhans Cells and Immunity

B. Langerhans Cells:

• dendritic cells
• location: epidermis & mucous membranes
• characteristic surface marker: „langerin“ - marker to identify in tissue section
• MHC class II - antigen-presenting cell
• key role in inducing T-cell response
• peripheral position in body (epidermis) - early defenders against infections

Dermal Dendritic Cells and Immunity

D. Dermal dendritic cells:

• located just below basement membrane in dermis
• secrete cytokines
• stimulate T-cell proliferation - travel to lymph node to perform this
• regulate humoral antibody-mediated immune response

Mast Cells and Immunity

E. Mast cells:

• present in most Connective Tissues - around blood vessels
• contain inflammatory mediators (histamin, prostaglandin)
• central role in urticaria & contact allergic responses to haptens

Haptens

• Haptens:
  • 1st need to bind a protein to induce Immune response
  • eg. of haptens - cobalt, nickel, copper (Kupfer) & penicillin

Molecular Components of Skin Immunity

2) Molecular Components:

• Antigens:
  • are recognized by immune system = provoking immune reaction - via humoral- or cell-mediated immune response
• Superantigens:
  • are bacterial toxins - bind with MHC class II from antigen-presenting cells - & induce massive T-cell proliferation & cytokine production e.g. toxic shock syndrome, guttate psoriasis
• Antibodies:
  • are immunoglobulins that react with antigens
  • 4 different types of Ab: A. IgG = long-lasting humeral immunity B. IgM = first antibody after immunization or infection C. IgA D. IgE = responsible for type I immediate hypersensitivity reactions - bind Fc-receptors of mast cells & basophils
• Cytokines:
  • secreted by lymphocytes, macrophages & keratinocytes
  • examples of cyto .: IL, growth factors, interferons
  • regulate amplitude & duration of inflammation by: a) paracrine action - acting locally on nearby cells b) endocrine action - acting on distant traget cells via circulation c) autocrine action - acting on cells that secreted cytokines itself- After binding to cell surface receptors: - regulate transcription of genes in target cell via: # signal transduction pathways

Innate Immune System

Innate Immune System

• IMMEDIATE but NOT SPECIFIC reaction to infectious agents WITHOUT activating specific lymphocytes or use antibodies, eg .:
  • defensins in epidermis => AMP
  • complement => attract neutrophils & opsonize
  • keratinocytes produce cytokines
  • non-specific cells can release chemokine
• cells of innate immune sys .:
  1. neutrophils
  2. monocytes
  3. macrophages are antigen-presenting cells => recognize PAMPs
• also have toll-like receptors => activate adaptive Immune sys.

Adaptive Immune System

Adaptive Immune System

• specific, long lasting, targeted immune response
• antigen-presenting cells eg. langerhans cells, dermal dendritic cells process antigen - present to T-cell, which binds antigen elicits inflammatory response -+ involves, cytotoxic, phagocytic and inflammatory cells.
• 4 types classified by Coombs & Gell: A. Immediate hypersensitivity reaction (type I) B. Humoral cytotoxic reaction (type II) C. Immune complex-mediated reaction (type III) D. Cell-mediated immune reaction (type IV)

Epidermis Structure and Function

3) Epidermis - structure and function Structure: - In thin skin = Consists of 4 Layers (thin skin) & has NO Blood Vessels!

Stratum Basale

1. Stratum basale = basal layer

• deepest layer . adheres to dermis at the basement membrane
• single layer of COLUMNAR Stem Cells
• Stem Cell - continuously divides/proliferates, to produce new keratinocytes (in response to damage) -Melanocytes, Merkel- & Langerhans Cells reside here too!

Melanocytes

• Melanocytes: A. dendritic cell B. form epidermal melanin unit = dendritic processes surround keratinocytes (KC) - melanocytes inject melanosomes to KC - to provide them with pigmentation to protect against UV radiation

Merkel Cells

• Merkel Cell:
  1. located close to hair follicles
  2. transducers for fine touch - associated with fine unmyelinated nerve endings

Langerhans Cells in Epidermis

• Langerhans Cells: (a) dendritic cell (b) form strike network with dendritic processes (c) key role in immune reactions (derived in Bone Marrow) i) surface receptors Cb3 & Fc portions for IgG & IgE ii) bearing MHC class II -present antigens to T-lymphocytes

Stratum Spinosum

2. Stratum spinosum = prickle cell layer

• 8-10 layers thick
• change from columnar cells to = polygonal cells
• keratinocytes synthesise keratin
• prickle cell layer due to desmosomes that look like prickles (stacheln) under light microscope (with color)
• desmosomes are attachment plaques that physically bind adjacent keratinocytes to one another

Stratum Granulosum

3. Stratum granulosum = granular layer

• 3-5- layers thick
• cells contain large irregular basophilic granules of keratohyalin # keratohyalin granules contain proteins = filaggrin, in-vo-lucrin, lori-crin -during keratinization: # granular cells collapse & convert into flattened squames, with a thick peripheral protein coating (horny envelope)

Stratum Lucidum

4. Stratum lucidum

• only in thick skin

Stratum Corneum

5. Stratum corneum = horny layer

• most superficial layer & thickest layer (20-30 layers)
• made of flattened dead cells (corneocytes) filled with keratin (stratified squamous epithelium)
• corneocytes deep in the horny layer stick tightly together - only those on surface flak off
• Epidermis constantly renews itself by shedding -> process known as epidermal turnover or transit time
• takes 30 days

Epidermis Function

Function:

• relative impermeability & constantly renewing (see box) - provides a passive barrier for microorganisms.
• maintaining the integrity and hydration of the skin.
• melanin storage
• First-line of Immune defense by: - AMP (antimicrobial peptides) e.g .: cathelicidins & defensins - who have a broad range of antimicrobial activity

Dermis Structure and Function

4) Dermis - structure and function

Dermis Function

Function:

• support epidermis structurally & nutritionally - with older age, the dermis thins & loses its elasticity .
• Thermoregulation => BLOOD VESSELS & Sweat Glands reside here!

Dermis Structure

Structure: - the dermis lies btw the upper epidermis & the lower hypodermis

Layers of Dermis

Two Layers of Dermis:

A. Papillary Layer

• UPPER layer
• arrangement of thin collagen fibres (lockeres Bindegewebe)
• Immune cells (Macrophages, Mast cells) present
• Meissners Corpuscles (mechanoreceptors), free sensory nerve endings (nociceptors)
  • noci-ceptors => detect pain & heat
  • mechano-receptors => register deformation of skin caused by pressure, vibration, touch
• Capillary Loops (superficial plexus + arterioles)

B. Reticular Layer

• LOWER layer
• thick collagen fibres arranged parallel to surface of skin (straffes Bindegewebe)
• Blood vessels (deep plexus) & Lymphatics reside here -deep plexus supply sweat glands & hair follicle
• Immune cells
• Hair follicle & associated Sebaceous (oil) gland & apocrine (scent) gland
• Eccrine (sweat) gland
• Ruffini-Receptors (slow adaptive mechanoreceptors) & Pacinian Corpuscle (Vater-Pacini C.) (fast adaptive mechanoreceptor)

Components of Dermis

Three Components of Dermis:

Dermal Fibres

1) Fibres of Dermis:

• 70-80% made of collagen
  1. 85% Type I skin collagen
  2. 15% Type III skin collagen - Diseases: Ehlers-Danlos Syndrome, Osteogenesis imperfecta (fragility of bones) - Diseases: Lathyrism (fragility of skin & CT)
• Reticular fibers - found in fatal skin, around blood vessels & appendages of adult skin. Elastic Fibres - make up 2% of skin - abnormalities: cutis laxa & pesudo-xanthoma elasticum

Ground Substance of Dermis

2) Ground Substance:

• composed largely of 2x GAGs (Glucos-amino-gylcans)
  1. Hyaluronic Acid
  2. Dermatan sulfate - complexed to core proteins named proteo-glycans
• Function of Ground substance:
  1. shock absorber
  2. lubricant during movement btw collagen & elastic fibre networks
  3. binds water - allowing nutrients, waste products & hormones to pass dermis

Cells of Dermis

3) Cells of Dermis:

1. Fibroblast

• make up majority
• synthesis of collagen, reticulin, elastin, fibronectin

1. Langerhans cells
2. Mast cells
3. Merkel cells
4. Lymphocytes

Hair Structure and Function

5) Hair - structure and function

Hair Function

Function:

1. Conservation of heat
2. protection against UV radiation
3. protection against minor injury
4. Social function (cosmetics, sexual attraction)

Hair Structure

Structure: - The hair is composed of 3 layers (from inside to outside):

A. Medulla

• innermost layer
• sometimes absent

B. Cortex

• contains melanosomes for colour
• provides strength, moisture, color & texture

C. Cuticula

• outermost layer
• protects cortex
• other structures that also belong to the hair:

Hair Follicle

• hair follicle:
  • surround hair root & bulb
  • and is fixed by dermal papilla to attach hair to skin & to blood supply (deep plexus)

Arrector Pili Muscle

• arrector pili muscle
  • originates in papillary dermis (upper most layer of dermis- adjacent to epidermis)
  • inserts to hair follicle
  • Function:
    • erect hair to protect against cold =„goose-bumps“
    • sympathetic innervation

Sebaceous Glands

• sebacous glands
  • protective lipid-film for skin & hair

Hair Growth and Loss

• Normal growth rate: 0.4mm/day
• Normal hairloss rate: 70-100hairs/day
• Development of Hair:
  1. Growing phase: # anagen - 3-8 years
  2. Resting phase: # catagen - 3 weeks
  3. Shedding phase (Haarausfall) # telogen - 3-8 months

Types of Hair

Types of hair:

I. Terminal (long hair)

• thicker & darker
• Locations: 1.scalp, 2.eyebrows, 3. eyelashes, 4. pubic-, axillary- & beard areas