Skin Disorders Flashcards
What are the 5 layers of the epidermis (from top to bottom)?
Stratum corneum Stratum lucideum Stratum granulosum Stratum spinosum Stratum basale
What is in the stratum corneum?
Layers of compacted dead cells
No organelles or nucleus
Full of keratin
What is in the stratum lucideum?
A transparent layer that is only present in hardened areas of skin
What is in the stratum granulosum?
Glycolipids that make the skin waterproof
Granular cells that arrange the keratin filaments
What is in the stratum spinosum?
8-10 layers
Contains Langerhan cells
Contains keratinocytes
Cells are adhered by desmosomes
What is in the stratum basale?
Single layer
Contains melanocytes
Undergoing continuous mitosis, forcing the layers upwards
What are features of melanocytes?
Produce melanin
Highly proliferative
Large nucleus
Features of keratinocytes
Produce keratin
Reach the top layer of skin in around 1 month
Become more differentiated as they rise up the layers, losing their nuclei and organelles
Features of Langerhan cells
Adapted macrophages
Can phagocytose pathogens and become APCs
Activate T helper 17 cells
Secrete proinflammatory cytokines such as IL-2
Features of T helper 17 cells
Activated by Langerhan cells
Secretes IL-17 which causes proliferation of keratinocytes
Secretes cytokines which activate leukocytes and cause production of APPs
What is psoriasis characterised by?
Formation of scaly white plaques on the skin
How are the symptoms of psoriasis formed?
Excessive proliferation of the stratum basale
Keratinocytes move towards the surface in 3-5 days
Reach the top still undifferentiated and nucleated
Still lacking desmosomes, and do not stack correctly
How is psoriasis initiated?
Caused by an inflammatory trigger such as injury, pathogen or allergen
This activates Langerhan cells
Langerhan cells activate Th17 cells by secreting IL-2 and presenting the pathogen antigen
Activated Th17 cells secrete IL-17 which causes proliferation of keratinocytes
What are the roles of cytokines in psoriasis?
Systemic symptoms (e.g. tiredness)
Activates complement
Causes inflammation, allowing neutrophils to invade tissues
What are some uses for immunosuppressive drugs?
Preventing organ rejection after transplant
Treatment of psoriasis and other autoimmune conditions
What is a disadvantage of immunosuppressive drugs?
They increase the chance of getting an opportunistic infection
What is the hedgehog signalling pathway involved in?
Transmits information about cell differentiation to embryonic stem cells
Mutations in the pathway are associated with basal cell carcinoma
What is the hedgehog signalling pathway?
The hedgehog ligand binds to the receptor, patched
This forms complex which is internalised and degraded
SMO is free to move into the cilium
SMO converts GLI to GLI-A (activated)
GLI-A translocates to the nucleus and transcribes genes for growth and development, including Wnt
What happens when the hedgehog ligand is not present?
The Patch receptor binds to and inhibits SMO
GLI remains in the cilium, as GLI-R (repressed)
No transcription of genes
What sort of mutations in the hedgehog signalling pathway could lead to development of basal cell carcinoma?
Loss of function in the patch receptor gene
Gain of function in the SMO gene
How could you use flow cytometry to get information about size and granularity of cells in a sample?
Load sample as single-cell suspension Add sheath fluid Pass in front of laser in single file Present on density plot Forward scatter = size Side scatter = granularity
How could you use flow cytometry to get information about antigen presence on cells in a sample?
Label cells with fluorophore Run through flow cytometer Emits light when excited by laser Present as peak on histogram Compare to control peak
What are antimicrobial peptides?
Peptides secreted by commensal bacteria and keratinocytes
Includes lysozymes, beta-defensins, cathelicidins
3 things that antimicrobial peptides do
- Break down bacterial cells walls and membranes, causing lysis (they are positively charged so bind to negatively charged bacterial membranes)
- Enhance toll like signalling
- Neutralise PAMPs to prevent acute inflammatory response
3 things required for TH17 activation
- Langerhan cells presents antigen on MHC II, binds to toll like receptor
- Costimulation by CD80/86 binding to B7
- Cytokines such as IL-2 allow proliferation
What is phototherapy?
Treatment for psoriasis
UV light is used to suppress the immune system
What wavelengths of light are used in phototherapy, and where do they reach?
UVA (320-400nm) - Reaches T cells and granulocytes in the dermis
UVB (290-320nm) - Reaches keratinocytes and Langerhan cells
What are the effects of phototherapy?
- Increase expression of IL-10 (anti inflammatory cytokine)
- Suppress production of IFNy from CD4 T cells
- Increase expression of immunosupressive prostaglandins
- Decrease number of Langerhan and dendritic cells
- Stop upregulation of cell surface adhesion molecules
- Reduce expression of cytokine and growth factor receptors on keratinocytes
- Induce apoptosis of skin infiltrating T cells
What is a photosensitiser?
A drug that is applied along with phototherapy, which enhances the effects of the UV so that lower doses can be used
Can be applied orally or topically
Example of a photosensitiser used during phototherapy
PUVA
What is photodynamic therapy?
Used red light (600-800nm) to treat non-melanoma skin cancer
How does photodynamic therapy work?
Photosensitiser 5-ALA applied to skin and absorbed by stratum corneum
Becomes converted into PPIX in tumour cells
Red light causes a photochemical reaction to occur
Red light + 5-ALA + O2 –> 1O2
1O2 is a ROS, causes apoptosis or necrosis of tumour cells
How are the effects of photodynamic therapy localised?
1O2 has very short half life so damage is localised
5-ALA is only converted into PPIX in tumour cells, not normal cells
Why is 5-ALA only converted into PPIX in tumour cells?
It is converted by haem biosynthesis pathway
- tumour cells have more membrane transporters
- tumour cells have higher iron availability
- tumour cells have more enzymes involved in haem biosynthesis pathway
What is Imiquimod?
Topically applied drug used to treat skin cancer, genital warts, cancerous skin lesions, HPV
How does Imiquimod work?
Binds to TLR-7 and TLR-8 to activate NFkB signalling
Triggers inflammatory immune response so immune cells attack virus/cancer cells
Also inhibits hedgehog signalling
What is 5-fluorouracil?
Topical cream
Used to treat skin cancer, warts, HPV etc
How does 5-fluorouracil work?
Inhibits synthesis of thymine, preventing DNA replication
