Skin Microbial Interactions and Wound Healing Flashcards
When do skin microbial diseases arise?
Opportunity (e.g. wound)
Population imbalance
What prevents bacterial penetration to the dermis?
Keratinisation
Within the dermis, where is the site of bacterial colonisation?
Sweat glands
What does gland secretions contain?
Slightly acidic sweat from the sebaceous glands
Anti-microbial peptides
Which layer of bacterial penetration causes illness?
Hypodermis
Give an example of a disease associated with hypodermal bacterial entry
Necrotizing fasciitis
What causes necrotizing fasciitis?
bacteria from soil enters the skin through through a deep wound and colonises in the hypodermis
What are the immune defences in the epidermis?
Langerhan cells
Keratinocytes
CD8+ T cells
What is the function of keratinocytes in association with immune defence?
- Possess Toll like receptors
- Detect pathogen
- Release cytokines to induce Langerhan’s and T cell movement to site of infection
What are the immune defences in the dermis?
Dermal dendritic cells
Macrophages
Innate lymphoid cells (ILC)
What is the function of the innate lymphoid cells?
Orchestrate immune responses among T cells and can suppress attack of bacteria
What are the three phases of wound healing?
1) Inflammatory phase
2) Proliferative phase
3) Remodeling phase
What happens in the inflammatory phase?
Release of inflammatory cytokines to promote chemotaxis
Accumulation of pus
What promotes growth?
Mitogenic
Epithelial growth factor (EGF) - growth of fibroblasts and keratinocytes
What do fibroblasts do in relation to the inflammatory phase?
Cause scaring through collagen and connective tissue deposition
What do keratinocytes do in relation to the inflammatory phase?
Recreate the epidermal layer
What is the role of IL-6 in the inflammatory phase?
Induce fever
Describe the proliferative phase
- Epithelization
- Angiogenesis in the dermis
- Fibroblast proliferation in the dermis
What is epithelialisation?
Growth and division of epithelial cells from the stratum basale
What is angiogenesis?
Production of new blood vessels
Why is fibroblast proliferation important in the proliferative phase?
Deposit collagen into the dermis which provides a supportive matrix for epidermal keratinocyte growth
What do fibroblasts produce?
Dermal granulation tissue
What does dermal granulation tissue consist of?
- main signals are PDGF and EGF
- collagen type III
- Glycosaminoglycans
- Fibronectin
- Elastin fibres
What induces fibroblasts?
TGF-beta1
What happens in the remodeling phase?
- Scaring
- Collagen reorganisation
- Cross linking of collagen
What causes scaring?
The conversion of type III collagen to type I
Why is there cross linking of collagen?
Increase tensile strength
What local effects affect wound healing?
Oedema Ischemia - perfusion of the wound Impaired healing Infection Foreign bodies
where is beta-defensin secreted from?
All epithelial cells
- in the skin = keratinocytes and sebaceous duct cells
What are defensins?
anti-microbial peptides
what are defensins involved in?
Innate immune response mechanism
How do defensins function?
Permeabilise bacteria outer wall causing lysis
Give an example of a ‘good’ bacteria
Staphylococcus epidermidis
Describe the function of staphylococcus epidermidis in terms of prevention of disease
has mechanisms for host immune invasion
resists harmful yeast and bacteria colonisation
Give an example of a ‘bad’ bacteria
Staphylococcus aureus
name a pathogen associated with staphylococcus aureus
MRSA
how does the staphylococcus aureus function?
will colonise human skin, lung and gut.
opportunistic pathogen
causes boils and abscesses
give 2 examples of what staphylococcus aureus secretes?
Coagulase (blood clots)
Lipase (degrades protective sebaceous oils)
What is an infection caused by staphylococcus aureus
folliculitis
How does the infection of follicultis arise?
Staphylococcus aureus invades down the shaft of the hair follicle
Causes inflammation and infection of the hair follicle and sebaceous gland.
What is quorum sensing?
Homeostatic mechanism involving released peptide signals that keep bacterial populations stable
what peptide signals do quorum sensing detect?
Autoinducer peptides
What happens when there is a low concentration of s. epidermis?
Decrease the amount of inducer peptides Causes phosphorylation of the ArgC Activation of ArgA Growth and cell division Increase the concentration of s. epidermis
What happens if you get a s. aureus infection?
Autoinducer peptides inhibit ArgC resulting in cell death
Give an example of a fungal inhabitant of the epidermis
Malassezia - causes dandruff
What is malassezia function
Secretion of phospholipase
Cleaves sebum lipids to inflammatory signals (e.g. arachidonic acid)
how does malassezia alter skin epithelial function?
Synthesise anti-bacterial compounds from skin amino acids and peptides
Modifies keratinocyte sensitivity to UVA damage
Inhibits melanin production
Inhibits langerhans cell immune signalling
Where is acne bacteria found?
dermal pores and hair follicles
Where is the acne nutrient source from?
Sebum
Shed keratin
where does the acne bacteria proliferate in?
The sebaceous gland
how does the pustule head of acne form?
The proliferation in the sebaceous gland causes swelling of the lumen of the gland
this lumen filled with bacteria
the bacteria moves all the way up through the epidermsi
how is sebum produced?
holocrine secretion
What prevents acne?
Isotrentoin
How does isotrentoin prevent acne?
inhibits sebaceous holocrine secretion
Possible cause of acne
genetic condition involving failure of cell polarisation
What does isotrentoin release?
13cis retinoic acid
Two results of isotrentoin
Sebocyte secretion arrested
Sebocyte re-growth arrested
How does sebocyte re-growth arresting cause reduced inflammation?
-> sebaceous gland lumen unblocked -> conditions less favourable for P. Acnes growth -> inflammation subsides
