W24 Skin functions, microbiota and infections (GN) Flashcards
Physiology of the skin:
What are the Main general functions? (6)
- The body’s largest organ
- Mechanical barrier to heat, injury, UV lights and infections
- Regulation of body temperature
- Retention/excretion of water
- Sensory detection
- Synthesis of essential molecules
(e.g. Vitamin D) - Outer waterproof covering of the body
What is the Structure of the skin?
Epidermidis - The outermost layer
* Varied thickness - 0.5 mm (eyelid) to 5 mm (heels)
* Composed mainly of keratinocytes
Dermis- Connective tissue containing:
* Elastin and collagen fibres (stretch & strength)
* Blood vessels and nerve terminations
* Hair follicles
* Sebaceous/sweat glands
Hypodermis/subcutaneous layer – not part of the skin
* Connect the skin to underlying bone and muscle
* Adipose tissue –resistance and thermal insulation
What are the 5 sublayers of the epidermis?
- Stratus corneum (outermost)
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale (deepest)
What are the main cells in the epidermis? (3) (no blood vessels)
What are their roles?
-
Keratinocytes ( ̃90%)
-keratinisation (secreting a fibrous protein - keratin)
-provide mechanical strength -
Melanocytes ( ̃5%)
-producing melanin = inducing skin pigmentation -
Langerhans cells
-Dendritic cell recognising threats, activating immunity
Keratinisation - summary
Multiple stages of keratinocyte cell differentiation:
Describe each layer: (5)
Which contains langerhans cells?
Which contains melanocytes?
1. S. corneum:
> 15 layers of fully keratinized squamous cells (waterproof coat) that are shed & replaced
2. S. lucidum (only present on the soles and palms):
Few layers of flattened/dead cells losing nucleus and organelles
3. S. granulosum
Cells produce keratin granules & release lipid (barrier function)
4. S. spinosum
Cells accumulate keratin precursor. It contains Langerhans cells.
5. S. basale
* Stem cells undergo mitosis forming undifferentiated keratinocytes that migrate. Melanocytes are present
Skin microbiota
What are the 4 microenvironments that human skin is categorised into?
Where are most microbes found?
Oily, moist, dry, foot
- Most microbes reside in the outermost layers of the stratum corneum
- Others in hair follicles and gland pores
- Relatively stable over time (in a healthy individual)
- Core residents are common in a population
What are skin resident species?
- Permanent inhabitants of the skin
- Crucial roles in maintaining skin health
- Establish stable populations over time
- Even after hygienic practises
- If disturbed, they are re-established promptly
- Unlikely to cause opportunistic infections
- The commensal Staphylococcus epidermidis
What are Skin Transient species?
- Temporary inhabitants of the skin (short
duration) - Their contribution is not key
- Can be easily removed by routine hygiene
- Usually not pathogenic, but can cause
opportunistic infections - Species acquired via environmental exposure
Skin normal microbiota –
What are the Major components? (3)
- Bacteria
* Diphteroirds
-Corynebacterium species
-Cutibacterium acnes = May cause acne
- Low virulence
- Responsible for body odour
* Staphylococci
- Wide range of virulence
- Staphylococcus epidermidis (low virulence – protection against infections)
- S. aureus have low/high virulent strains - Yeasts
* Malassezia species
-Harmless in healthy individuals
- Malassezia furfur causing dandruff or interfere with pigmentation - Viruses
* Combination of viruses
Skin as a barrier for infections
What are the intrinsic characteristics of the skin in creating hostile conditions for pathogen colonisation? (6)
- Low pH (4.0 - 6.0)
- Low moisture content
- Nutrient poor
- Releasing antimicrobial molecules
- Constant exfoliation of cells
- Pathogenic colonization prevention
Skin as a barrier for infections:
-what does the body have in place to inhibit pathogen growth
Benefits of low pH, low moisture content and nutrient poor?
- Low pH (4.0 - 6.0)
* Most bacteria have neutral optimum pH
* Growth inhibited at low pH - Low moisture content
* High salt concentration = Hypertonic environment = High osmotic pressure - Nutrient poor
* Stratum corneum = source of only peptides and lipids
* Sebaceous glands secrete Sebum = source of only lipids
* Sweat glands secrete sweat = salt-laden (high osmotic pressure
Skin as a barrier to infections
Releasing antimicrobial molecules:
What is released? (2)
- Antimicrobial peptides - AMPs
-Produced by sweat & sebaceous glands - Effects = direct killing & immune activation
- Lysozyme
-Product by sweat glands
-Bactericidal effect on Gram +ve only
-Hydrolysing NAM-NAG bonds of a peptidoglycan chain of their cell wall
Skin as a barrier to infections
Constant exfoliation of cells:
Why is this important?
Removing transient bacteria = Less opportunity to colonise the niche
Skin as a barrier to infections:
What is Pathogenic colonization prevention?
- Outcompeting pathogens for nutrients and binding sites (niches)
- Modulating local immunity = Langerhans cells activation
Skin normal microbiota:
What is the specific role of Cutibacterium acnes?
Digest sebum triglycerides in fatty acids (energy source) and propionic acid (maintaining a protective low pH)
Skin normal microbiota:
What is the specific role of Staphylococcus epidermidis?
- Inhibits S. aureus biofilm by secreting proteases
- Induces keratinocytes to produce antimicrobial peptides
Normal microbiota can cause opportunistic infections:
- Cutibacterium acnes
- Can trigger inflammation = acne vulgaris
- Staphylococcus epidermidis
- Low virulent if confined to the epidermidis
- It forms biofilms on plastic catheters - it
may cause catheter- associated UTIs
Mechanisms of skin opportunistic infections:
-
Cuts, lesions, changes in barrier permeability
-Microbiota can access the dermis and blood vessels -
Dysbiosis (microbiota alteration)
-Opportunity for opportunistic pathogen to outgrow
-Causes: metabolic diseases (e.g., diabetes), topical antibiotic treatments (encouraging fungal growth), inflammation
3.** Co-infections/immune deficiency**
-Within an infection, microbiota species can amplify tissue damage
Bacterial Skin pathogens
Bacterial Skin pathogens:
* Staphylococcus & Streptococcus (Gram +ve) the most frequent in skin infections
* Also, Pseudomonads (i.e. Pseudomonas dermatitis), Gram -ve
Staphylococcus aureus = mostly involved in skin infections
* Minor component in the nose and skin (4 %) microbiota
Microscopic identification
* Gram staining Gram positive (purple stained)
* Morphology spherical (cocci)
* Arrangements grape-like clusters (Staphylo)
* Colonies on Agar shining golden yellow
S. aureus virulence factors
- S.aureus pathogenic strains express a range of virulence factors:
- Proteolytic enzymes to invade tissues
- Lipases, proteases, Hyaluronidase (breaking down proteoglycans in the dermis)
- Factors to evade host defences
- Coagulase = Induces blood clotting, evading phagocytosis
- Proteins that neutralise AMPs
- Capsule: hindering cellular antigens to avoid immune recognition
- Cause host damage by producing different exotoxins
- Exfoliatins - causing blistering of the skin
- Toxic shock syndrome toxin = exacerbated inflammatory response = shock syndrome
Streptococcus pyogenes virulence factors
( for info)
Distinct Strep A strains with different virulence factors:
* Proteolytic enzymes to invade tissues
-Hyaluronidase breaking down proteoglycan in the dermis
-Streptokinase - enzyme that dissolves blood clots
* Factors to evade host defences
-M protein on the fimbriae - evades phagocytosis
-Capsule made by hyaluronic acid (host component) not targeted by immune cells
* Cause host damage by producing different exotoxins
-Streptolysins O and S, that lyse red blood cells and neutrophils
-Pyrogenic exotoxin exacerbated inflammatory response shock syndrome
What are examples of bacterial skin infections?
Impetigo
Folliculitis
Furuncles/boils
Carbuncles
Erysipelas
Cellulitis
Necrotising fascitis
Impetigo:
Causef by which bacteria?
2 clinical manifestations?
- Affect superficial layer of the skin
- Rash not painful, but may be itchy
- Typical in children = face, arms, legs
- Highly contagious = direct contact
Aetiology = mostly caused by S.aureus
* Primary infection = affecting healthy skin
* Secondary infection = after cuts or skin lesions (e.g. due to chickenpox or eczema)
Two clinical manifestations
* non-bullous impetigo – most common
* bullous impetigo (only S.aureus)
Describe Non-bullous impetigo:
Thin-walled vesicles or pustules that rupture quickly
* Leaking pus forming brownish/honey crusts
* S.aureus and/or Streptococcus pyogenes involved
Describe Bullous impetigo:
Appearance?
Where is it found on the body?
When they rupture?
Type of bacteria?
- Larger and fluid-filled blisters/bullae (>1cm)
- On the trunk, buttocks, extremities
- Their rupture leaves a flat, yellow/varnish crust.
- ONLY S. aureus = strains producing exfoliatin toxins
-Exfoliatins penetrates the unbroken skin by disrupting its barrier
What are the Bullous impetigo complications – S.aureus
(2)
- Staphylococcal Scalded skin syndrome (in newborns)
- S.aureus strains releasing exfoliatin B = causing skin blistering
- Toxin can spread in the tissue and extend the lesion
Clinical manifestations: - Initial erythematous rash resembling scalded skin = large bullae that rupture
- Resulting in a widespread painful skin peeling
Staphylococcal Toxic shock syndrome
* S.aureus strains release toxic shock syndrome (TSS) – superantigen toxin
* Induces an over-activation inflammatory cells = cytokines storm
Clinical manifestations (life-threatening)
* Rapid onset of fever, rash, hypotension, shock with multiorgan involvement
