Skin diseases Flashcards
psoriasis
a complex, chronic and multi-factorial inflammatory disease which involves hyper proliferation of the keratinocytes in the epidermis. Thought to be the result of interplay between genetic predisposition and environmental factors
what can trigger psoriasis
infection, injury, allergy, extreme tips, alcohol, stress resulting in an inflammatory response
psoriasis occurs due to an increased
production of skin cells- long lasting chronic disorder.
process which causes psoriasis
1) trigger e.g. injury, infection, allergy, chemical, stress
2) langerhans cells waiting for engulfment
3) these triggers (sometimes PAMPs) will then trigger langerhans - engulfment - antigen presentation
4) langerhans migrate to the lymph nodes –> antigens presented to naive t helper cells (CD4+ cells)
5) langerhans secrete TGF-B, IL-6 and IL-23 –> stimulate T cells to turn into Th17 cells
6) Th17 cells produce IL-17 –> psoriatic skin
what can also trigger an inflammatory response
commensal bacteria
layers of the skin
outside –> inside
Stratum corneum stratum lucidum stratum granulosum stratum spinosum stratum basale
how does psoriasis affect the layers of the skin
- stratum granulosum reduced or absent
- stratum basel becomes obsessively proliferative
- quick replication of keratinocytes (no differentiated cells due to lack of apoptosis)
- nucleated undifferentiated cells one to the top layer of the skin
why is psoriasis red
due to blood vessel growth needed to satisfy vascular need of quickly reproducing cells
cells in psoriasis
dont stack very well due to being cuboidal
summary of psoriasis
auto-immune disease which involves the over activation of keratinocytes which live in the statute basal by cytokines which leads to them becoming excessively proliferative
what are SNPs
single nucleotide polymorphisms
- subsitutions
- deletion
- insertion
SNPs can be used as
biological markers
some SNPs can help predict
responses to drug or risk of developing a disease e.g. skin cancer
to find SNPs
primers extending from SNPs used
which three genes are significantly associated with psoriasis
HLA-C
IL12B
IL24R
which cytokines are produced in excess in psoriasis
TNF, IL which trigger inflammation in the skin and other organs
what effect do cytokines have
- widened blood vessels
- accumulation of WBC
- rapid multiplication of keratinocytes
normal keratinocytes
take a month to divide, mature and migrate to the skin surface and be shet
psoriatic keratinocytes
process takes 3 to 5 days, resulting in thickened, red skin, that sheds silvery scales of keratinocytes which have matured too qucikly
skin cancers
develop from abnormal cells in the skin which have he ability to spread to other parts of the body
three types of skin cancer
1) basal-cell skin cancer
2) squamous-cell skin cancer
3) melanoma
basal-cell skin cancer
arises from basal cells- slow growing and unlikely to spread to distant areas
squamous cell
more likely to spread. Uncontrolled growth of abnormal cells arising in squamous cells
melanoma
most aggressive. begins in melanocytes and is much more likely to spread to other parts of the body
TNM system
described the stage of a cancer which originates from a solid tumour
T
describes the size of the tumour and whether is has invaded nearby tissue
N
describes nearby lymph nodes which may be involved
M
describes distant metastases- if it has spread to other parts of the body
Imiquimod
topical cream immune-modualtory used to treat precancerous and cancerous sun damaged skin (basal cell carcinoma)
-also viral warts and other cancerous skin
mechanism of action of Imiquimod
binds TLR-7 and TLR-8
- -> triggers inflammation and the immune system destroys cancerous cells
- -> chemokine
- -> vasodilation= more permeable to WBCs
side effect of imiquimod
induces psoriasis like inflammation in susceptible mice and humans : IL23, IL17, Th17
where are langerhans most adapted to live
stratum spinosum
phototherapy is used to treat
psoriasis
what does phototherapy use
PUVA
PUVA
psoralen and UVA
psoralen
drug given orally- makes skin more sensitive to UV light
why is psoralen use important
means a lower dose of UV light can be given- less chance of bruning
how can psoralen be given
topically (i.e. in a bath- dosage issue and not very localised)
- usually given orally
what can phototherapy for psoriasis also be called
photochemotherpay
concerns of phototherapy
it could cause skin cancer
which are the wavelengths used in phototherapy and how high frequency are they
UVA and UVB
frequency of UVB
290-320 nm
frequency of UVA
340-400nm
which UV penetrates furtherest?
UVA- penetrates into the dermis (dermal fibroblasts, dermal dendritic cells, endothelia cells, T cels, mast cells, granulocytes)
how far does UVB penetrate
short penetration into epidermis (langerhans and keratinocytes)
how does phototherapy treat psoriasis
1) increased keratinocytes derived expression of anti-inflammatory cytokines
- increase in IL-10 (anti-inflammatory)
- increase in prostaglandins
2) Suppression of cytokine induced upregulation of ICAM-1 = less adhesion molecules = keratinocyte links restored
3) modulate keratinocyte cytokine sand growth receptor expression and function
Increase release of IL-10 because of phototherapy causes
Anti-inflammatory cytokine
Suppresses IFN-𝛄 from CD4-T cells
Decreases immune response
increase in prostaglandins because of photothepray
PGE2: immunosuppressive impact
Effects expression of co-stimulatory molecules on antigen presenting cells (APCs)
end result of phototherapy
apoptosis of T cells (Th17)
- psoriasis subsided
what is photodynamic therapies used to treat
skin cancers
photodynamic therapy simple
uses singlet oxygen to kill tumour cells and treat certain non melanoma skin cancers including basal cell carcinoma
3 essential component of PDT
photosensitiser: 5-ALA
light
oxygen
photosensitised used
5-ALA
5-ALA
selectively accumulates in tumour cells because they have:
- a higher expressionn of membrane transporters
- more iron availability
- overespression of Haem biosynthesis
- more cytosolic and mochdonrial enzymes for harm biosynthesis pathway
- leaky blood vessels
- absence of lympathic dranage
Absence of lymphatic drainage
increases permeability and retention of 5-ALA
why is singlet oxygen used in photodynamic therapy
singlet oxygen has a localised damaging effect because:
- it has a short lifespan
- only diffuses a short distance
anti tumour effect of singlet oxygen
- apoptosis- necrosis and autophage
- damage to tumour vasculature
- robust inflammtory reaction
step by step process of photodynamic therpay
- apply 5-ALA to skin
- cream is systemically distributed through the skin layers
- 5-ALA selectivelyaccuumulates in tumour cells
- tumour cells convert 5-ALA into photoporphyrin IX
- affect skin is irradiated with RED light from the visible part of the EM spectrum
- red light activates photoporphyrin IX. raises it from ground state to excited state
- excited photoporphyrin IX transfers its energy to oxygen. Causes singlets to be produced
- Singlet oxygen is cytotoxic and has many mechanisms of killing tumour cells
why use red light
- wave length of 600-800nm
- penetrates skin between 10-20mm
- enough energy to initiate photodynamic reactions
