Skin Disorders

Question 1

What are the 5 layers of the epidermis (from top to bottom)?

Answer 1

Stratum corneum
Stratum lucideum 
Stratum granulosum
Stratum spinosum 
Stratum basale

Question 2

What is in the stratum corneum?

Answer 2

Layers of compacted dead cells
No organelles or nucleus
Full of keratin

Question 3

What is in the stratum lucideum?

Answer 3

A transparent layer that is only present in hardened areas of skin

Question 4

What is in the stratum granulosum?

Answer 4

Glycolipids that make the skin waterproof

Granular cells that arrange the keratin filaments

Question 5

What is in the stratum spinosum?

Answer 5

8-10 layers
Contains Langerhan cells
Contains keratinocytes
Cells are adhered by desmosomes

Question 6

What is in the stratum basale?

Answer 6

Single layer
Contains melanocytes
Undergoing continuous mitosis, forcing the layers upwards

Question 7

What are features of melanocytes?

Answer 7

Produce melanin
Highly proliferative
Large nucleus

Question 8

Features of keratinocytes

Answer 8

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

Question 9

Features of Langerhan cells

Answer 9

Adapted macrophages
Can phagocytose pathogens and become APCs
Activate T helper 17 cells
Secrete proinflammatory cytokines such as IL-2

Question 10

Features of T helper 17 cells

Answer 10

Activated by Langerhan cells
Secretes IL-17 which causes proliferation of keratinocytes
Secretes cytokines which activate leukocytes and cause production of APPs

Question 11

What is psoriasis characterised by?

Answer 11

Formation of scaly white plaques on the skin

Question 12

How are the symptoms of psoriasis formed?

Answer 12

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

Question 13

How is psoriasis initiated?

Answer 13

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

Question 14

What are the roles of cytokines in psoriasis?

Answer 14

Systemic symptoms (e.g. tiredness)
Activates complement
Causes inflammation, allowing neutrophils to invade tissues

Question 15

What are some uses for immunosuppressive drugs?

Answer 15

Preventing organ rejection after transplant

Treatment of psoriasis and other autoimmune conditions

Question 16

What is a disadvantage of immunosuppressive drugs?

Answer 16

They increase the chance of getting an opportunistic infection

Question 17

What is the hedgehog signalling pathway involved in?

Answer 17

Transmits information about cell differentiation to embryonic stem cells
Mutations in the pathway are associated with basal cell carcinoma

Question 18

What is the hedgehog signalling pathway?

Answer 18

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

Question 19

What happens when the hedgehog ligand is not present?

Answer 19

The Patch receptor binds to and inhibits SMO
GLI remains in the cilium, as GLI-R (repressed)
No transcription of genes

Question 20

What sort of mutations in the hedgehog signalling pathway could lead to development of basal cell carcinoma?

Answer 20

Loss of function in the patch receptor gene

Gain of function in the SMO gene

Question 21

How could you use flow cytometry to get information about size and granularity of cells in a sample?

Answer 21

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

Question 22

How could you use flow cytometry to get information about antigen presence on cells in a sample?

Answer 22

Label cells with fluorophore
Run through flow cytometer
Emits light when excited by laser
Present as peak on histogram
Compare to control peak

Question 23

What are antimicrobial peptides?

Answer 23

Peptides secreted by commensal bacteria and keratinocytes

Includes lysozymes, beta-defensins, cathelicidins

Question 24

3 things that antimicrobial peptides do

Answer 24

1. Break down bacterial cells walls and membranes, causing lysis (they are positively charged so bind to negatively charged bacterial membranes)
2. Enhance toll like signalling
3. Neutralise PAMPs to prevent acute inflammatory response

Question 25

3 things required for TH17 activation

Answer 25

1. Langerhan cells presents antigen on MHC II, binds to toll like receptor 2. Costimulation by CD80/86 binding to B7 3. Cytokines such as IL-2 allow proliferation

Question 26

What is phototherapy?

Answer 26

Treatment for psoriasis | UV light is used to suppress the immune system

Question 27

What wavelengths of light are used in phototherapy, and where do they reach?

Answer 27

UVA (320-400nm) - Reaches T cells and granulocytes in the dermis UVB (290-320nm) - Reaches keratinocytes and Langerhan cells

Question 28

What are the effects of phototherapy?

Answer 28

1. Increase expression of IL-10 (anti inflammatory cytokine) 2. Suppress production of IFNy from CD4 T cells 3. Increase expression of immunosupressive prostaglandins 4. Decrease number of Langerhan and dendritic cells 5. Stop upregulation of cell surface adhesion molecules 6. Reduce expression of cytokine and growth factor receptors on keratinocytes 7. Induce apoptosis of skin infiltrating T cells

Question 29

What is a photosensitiser?

Answer 29

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

Question 30

Example of a photosensitiser used during phototherapy

Answer 30

PUVA

Question 31

What is photodynamic therapy?

Answer 31

Used red light (600-800nm) to treat non-melanoma skin cancer

Question 32

How does photodynamic therapy work?

Answer 32

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

Question 33

How are the effects of photodynamic therapy localised?

Answer 33

1O2 has very short half life so damage is localised | 5-ALA is only converted into PPIX in tumour cells, not normal cells

Question 34

Why is 5-ALA only converted into PPIX in tumour cells?

Answer 34

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

Question 35

What is Imiquimod?

Answer 35

Topically applied drug used to treat skin cancer, genital warts, cancerous skin lesions, HPV

Question 36

How does Imiquimod work?

Answer 36

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

Question 37

What is 5-fluorouracil?

Answer 37

Topical cream | Used to treat skin cancer, warts, HPV etc

Question 38

How does 5-fluorouracil work?

Answer 38

Inhibits synthesis of thymine, preventing DNA replication