Skin Disorders Flashcards
key functions of stratum granulosum
o 3-5 rows of flattened keratinocytes starting apoptosis, terminal differentiation, organelles degenerate, keratohyalin protein and waterproof glycolipid present
How does imiquimod work
an immune-modulator
Releases cytokines which destroy skin cancer cells by modifying the immune response to stimulate apoptosis.
It may also increase lymphocytes, dendritic cells, and macrophages to the tumour lesion.
Describe psoriasis
The undifferentiated cells come to the surface as the stratum granulosum is reduced or absent.
This forms skin-scales as the keratinocytes do not stack, adhere, or secrete glycolipids.
Blood vessels are also closer to the surface layer of the skin, and so the skin has a red tinge.
What 5 factors influence peripheral tolerance
- Negative Selection in the Peripheral Immune System
- Lack of Co-stimulation
- Failure to Encounter Self Antigens
- Receipt of Death Signals
- Control by Regulatory T Cells
What are privileged sites in the body?
Tissues hidden behind anatomical barriers so T cells can’t reach them i.e.
• interior of the eye
• testes
• the brain
Key functions of stratum lucidum
Transparent layer present on palms and soles
what do the epitopes recognised by the t-cell receptor contain
- small ‘self’ proteins
- major histocompatibility complex
What are the Bcl-2 family proteins
interact with each other to determine whether a cell undergoes apoptosis or stays alive. Some Bcl-2 family proteins promote survival, and block apoptosis. Others are ‘pro-death’, and trigger apoptosis
What happens to the T cells whose receptors bind to self epitopes so tightly that they could attack the cell displaying them
they are deleted by apoptosis
What is psoralen used for
sensitises the skin, preventing side effects such as burns from the UV waves. This allows a higher, more potent dose of UV to be used.
Define proto-oncogenes
Genes which code for proteins involved in the regulation of cell growth, either coding for cell division or death.
Define psoriasis
excessive proliferation of basal cells
How do metastasis occur
cancer cells that break off from the main tumour travel through the bloodstream.
Once in the blood, they can go to any part of the body. Many of these cells die, but some may settle in a new area, start to grow, and form new tumours.
Give 2 effects of anti-microbial peptides
o Bind to bacterial cell membranes and break them down o Effect the electrostatic balance o Effect chemotactic gradient o Enhance nucleic acid recognition o Neutralise PAMPS
key functions of stratum corneum
Keratinised squamous layer, dead cells, densely packed, structural support, no nucleus, these cells form dust- filled with keratin
define keratinocyte
cell that stores and produces keratin protein
How can PUVA improve symptoms of psoriasis
- increases keratinocyte anti-inflammatory cytokine (IL-10) to supress IFN-Y from CD4 cells.
- Increases prostaglandins which have an immunosuppressive effect in the skin causing the depletion of Langerhans and dendritic cells
- Suppresses cytokine-induced upregulation of cell-surface adhesion molecules.
- Modulates keratinocyte cytokine and growth factor receptor expression and function.
- Induces apoptosis of T cells.
Give 2 side effects of immunosuppressants
- Increased susceptibility to infection
- Kidney problems
- High Blood Pressure
- GI tract problems
- Reduced production of red and white blood cells
What is imiquimod
Imiquimod cream is a cancer treatment and is also known by its brand name, Aldara
Where do t cells develop
the thymus
Define an antimicrobial
Any agent which kills microorganisms or stops their growth
If a T cell survives negative selection, what happens
They migrate throughout the immune system
Define apoptosis
cell death that prevents immune activation
What are death receptor proteins
Found on the surface of the cell.
When they are bound by certain cytokines they cause changes in the cell that can lead to cell death.
Explain the steps in psoriasis development
- A trigger e.g. pathogen causes Langerhans cells to become activated and phagocytose the trigger.
- These migrate to the lymph nodes, secreting IL-1, IL-6 and TNF a
- They present to a naive CD4 helper cell in the presence of:
a. MHC II
b. Co-stimulation with CD80/CD86
c. Cytokines IL-6 and IL-23 - This undergoes clonal expansion and proliferates into Th17 effector cells
- Th17 cells migrate to the dermis where they secrete IL-17 and activate keratinocytes
- Keratinocytes secrete further IL-17 and the cycle becomes self-perpetuating
- VEGF increases vascularisation and skin become psoriatic
What is the name given to agents which KILL microbes
microbicidal
What is the IL-23/IL-17 Inflammation Axis
IL-23 induces the differentiation of naïve CD4 cells into highly pathogenic helper T cells (Th17) which produce IL-17, IL-6 and TNF a. IL-17 recruit’s neutrophils and pathogens to infected tissue.
Il-23 promotes the proliferation and maintenance of the Th17 cells.
Explain the steps of metastasis
- primary tumour
- proliferation/angiogenesis
- detachment/invasion
- embolism/circulation
- transport
- Arrest in organs
- adherens to vessel wall
- extravasion
- proliferation/angiogenesis
Do SNPS affect disease
When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the gene’s function.
What is phototherapy
This involves exposing the skin to different types of light
Explain the steps of apoptosis
The cell activates caspases that are normally dormant. These caspases dismantle the cell from within. The apoptotic cell breaks into blebs that can be engulfed by other cells. This prevents the cell contents leaking out of the dying cell and allows the components to be recycled.
key functions of stratum basale
Bottom, single layer, highly prolific, long life span, large nuclei
Define immunosuppressants
a drugs class which suppress/reduce the body’s cellular/humoral immune response
What can Basal Cell Carcinomas be caused by
• Sporadic mutations o Hedgehog pathway • Acquired mutations o UV, immunosuppressants, smoking age and skin tones • Loss of functions mutation o Ptch 1 gene (tumour suppressor) • Gain of function o Mutations of the SMO gene (proto-oncogene)
Why is it more important to tolerise T cells than B cells
B cells cannot make antibodies to most antigens without the help of T cells
How can UVB light be useful in phototherapy
o Slows growth of affected cells
o Immunomodulatory effect
o Reaches epidermal keratinocytes and Langerhans cells
How can UVA light be useful in phototherapy
o Slows excessive skin growth
o Immunomodulatory effect
o Effects deeper dermis, fibroblasts, dendritic cells, endothelial cells, T cells, mast cells and granulocytes due to the smaller wavelength
Define DMARDs
Disease-modifying anti-rheumatic drugs – specifically for autoimmune conditions
When may necrosis occur
occurs when a cell dies due to lack of a blood supply, or due to a toxin
What is imiquimod used as a treatment for
- Basal cell skin cancer (BCC)
* Actinic (solar) keratosis
What is photodynamic therapy
A photosensitiser is injected into the bloodstream and is absorbed by the tumour cells. This can both damage blood vessels the tumour needs to grow and activate the immune system to attack the tumour cells.
A light is then exposed to the tumour e.g. a fibre optic cable via an endoscope and it produces singlet oxygen causing localised damage.
Define necrosis
The cells’ contents can leak out and damage neighbouring cells
State 2 key death control proteins
Caspases
Bcl-2
Death receptors
IAPS
What are the specific 5 layers of the skin
- Stratum Basale
- Stratum Spinosum
- Stratum granulosum
- Stratum Lucidum
- Stratum Corneum
Define metastasis
The development of secondary malignant growths at a distance from a primary site of cancer
define keratin
intracellular fibrous protein that gives hair, nails, and skin their hardness and water-resistant properties
What are IAPS
inhibitor of apoptosis proteins’ can prevent cell death, by blocking other proteins
Define SNPS
variations in the DNA sequence at certain locations
Give 2 examples of DMARDs
- Anti-TnF mABs
- Methotrexate
- NSAIDs
- Ciclosporin
- Corticosteroids
What do commensal bacteria produce to out-compete other bacteria
anti-microbial peptides
What are caspases
enzymes are switched on in apoptotic cells, and digest other proteins to bring about cell death
What is the ligand/death signal that can trigger apoptosis of T cells when bound
Fas
What is the name given to agents which INHIBIT microbes
Biostatic
What are the 3 more general layers of the skin
epidermis
dermis
hypodermis
what is self-tolerance
The failure to attack the body’s own proteins and other antigens
What are the three main classes of antimicrobials
- disinfectants
- antiseptics
- antibiotics
key functions of stratum spinosum
Keratinocytes, adds structural support, desmosomes, synthesising keratin and flatten, presence of macrophages
What is immune tolerance
The failure to mount an immune response to an antigen.
What is the order of the layers of the skin (bottom up)
- Stratum Basale
- Stratum Spinosum
- Stratum Granulosum
- Stratum Lucidum
- Stratum Corneum
