Trigger 7 Flashcards
what are the layers of the epidermus
stratum corneum (stratum lucidum) stratum granulosum stratum spinosum stratum basale
what is the epidermus composed of
keratinised = stratified squamous epithelium
what so kerinocytes do
manufacture and store keratin
what is the role of keratin
gives skin its hardness and water resistant properties
describe the stratum basale
attaches to the dermis
made up of basale cells which produce all the keratinocytes
merkele cells
melanocytes
what do merkele cells do
receptor and responsible for stimulating sensory neurons
what do melanocytes do
produce melain, which gives colour and protects against UV damage
describe the stratum spinosum
cells joined via desomosomes
8-10 layers of kerinocytes, begin keratin synthesis
langerhans interspread
describe the stratum granulosum
flatter, thick membrane
generates large amounts of keratin
describe the stratum lucidum
thin layer
keratinocytes that compose are dead and flattened
densly packed with elediden (clear protein rich lipids) which give cells their transparent apperance and provide a barrier to water
describe the stratum corncum
15 - 30 layers
dry, dead layer helps protect the penetration of microbes and the dehyration of underlying tissue and mechanical protection
cells are shed periodically and replaced by cells below
entire layer in replaced over 4 weeks
describe the dermis
contains blood, lymph vessels, nerves, hair follicles and sweat glands
made of two layers of connective tissue that compose an interconnected mesh of elastin and collagen fibres
describe the papillay layer
made of loose, arelor connective tissue - collagen and elastin fibre form a loose mesh
finger like dermal popille project into the stratum basale
contains fibroblasts, adipodcytes, immune cells, lympathetic capillaries, nerve fibres and meissner corpuscles
decribe the reticular layer
composed of dense, irregular connective tissue
layer is well vascularised and has rish sensory and sympathetic nerve supply
elastin fibres provide some eleasticty to the skin
collagen fibres provide structure and tensile strength
collagen also binds water keeping it hydrated
what is psoriasis
skin condition that causes red flaky, crusty patches of skin covered with silvery scales
how does psoriasis happen
undifferienated nucleated cells in the stratum corneum
startum basale becomes excessively proliferated
scales - kerinocytes dont stack
normally takes 1 month for cells to surface, in psoriasis only takes 3-4 days
topical treatments
creams and ointemts you apply to affected areas
photothearpy treatment - UVB therapy
slows down the production of skin cells effects keratinocytes and langerhans cells
photothearpy treatment - psoralen plus UVA
take a tablet or cream containing psoralen which makes your skin more sensitive to light
penetrates more deeply, affecting dermal fibrobalsts, dermal dendtric cells, endothelial cells and skin-inflitrating inflammatory cells such as T-lymphocytes
single neuclotide polymorphism
significant associations between 3 genetic regions
HLA-C may be involed in antigen presentation to CD8 and T cells
IL12B - encode p40, component of IL-12 and IL-23
Il23R - encodes a component of IL23 receptor
methotrexate
slows production of skin cells, suppresses inflammation
folic acid antagonist (interfers with folic acid metabolism in the liver)
adverse effects - liver toxicity - blood cell changes
- GI tract - nausea, vomiting, diarrhoea
NSAIDS - sulfasalaine
DMARDs - immunosalocilate
- may act as a free radical scavenger of ROS produced by neutophils
adverse effects - Gi distrubances - reduction in gastic mucosa protective prostaglandins
disease modifying drug
cirlospoin
immunosupressant
inhibits IL2 gene transcription = decrease T cell proliferation
kidney/liver toxicity
describe the development of psoriasis
inflammatory trigger
stimulates langerhan to produce IL-1, IL-6, TNF-a
activated langerhan migrates
recognised by naive T-cell via TGf-b, IL-6, IL-23
Th-17 activated via antigen presentation
colonal expansion
Th-17 home to skin and invade dermis, activating keratinocytes
seceret cytokines
proliferated state
psoriasis
what is the effetc of Th-17
stimulates
- IL-17 –> macrophages and neutorphils
- IL-6 & IL-22 –> hepocyte –> CRP, binds to phosphocholine on bacteria –> phagocytosis
- IL-22 –> cytotoxic differientaion –> natural killer an dCD8
Where are Th1 cells produced and what do they do
produced by denritic cells
preTh cells form an immunological synaphses in which the dendritic cells
- present antigenes to the T cell receptor for antibodies
- secrete IL-12 and IFN-y
What is the effect of INF-y and TNF-B secrted by TH1
stimulate macrohpages to kill englufed bacteria
recruit other leukocytes to the side prodcuing inflammation
act on B cells to promote antibody class switching
help cytotoxic t cells
Where are Th2 cells produced and what do they do
produced when antigen presenting cells present antiges to the T cell receptor along with
- the co-stimulating molecule B7
- the pancreatic stimulants IL-4 and IL-12
What is the effcte of IL-4 secreted by Th2
stimluated B cells class swiching
acts as a poistive feedback promoting more phe-Th cells to entre the Th2 pathway
block INF-y receptors from entering the immunlogical synaphses
the effect of phototherapy
increase IL-10, keratinocytes - dervided antiinflammatory cytokine
increases prostagandins
= delpletion of LCs and demal DCs
supress cytokine induced upregualtion of cell surface adhesion molecules (ICAM-1)
modulate kerationcyte cytokines and groeth factor receptor (EGF) expression and function
induce apoptosis of skin infiltrating T cells
what can Reactive oxygen species do
cause damage iniate signalling pathways - JAK/STAT induce receptor clustering induce kinase activity activate nuclear receptors induce prolifertaion, apoptosis, inflammation
ROS and inflammation
inital oxidative burst that makes ROS (happens in phagosome)
if phagosome fuses with a lysosome you can get HOCL
results in bacteria killing
inflammation
Use of ROS
growth
- hydorgen peroxide is required in the thyroid gland to oxidise iodide to iodine via the NADOH oxidase system
- iodine is then used to produce T3 and T4
inflammation
- NFkB signalling - produces ROS
- ROS inhibit kinase inhibitor of NFkB
- activates NFkB pathway
- NO - relaxes smooth muscle, allows immune cells into tissues
interleukins
released by leukocytes
chemokines
protein cytokines mainly involved in facilitaing chemotaxis
guide leukocyte along chemotaxic gradient to site
interferons
protein cytokines that have antiviral functions
activate macropahges and natural killer cells
tumour necrosis factor
cytokines that induce apoptosis
released by NK cells, macrophages and helper T cells
IL-1B
secreted by monocytes and macrophages
injured endothelial cells and fibroblasts
causes fever, inflammation and pain
INFy
secreted by lympocytes
activates macrophages and many other functions
IL-6
secreted by T-cells and macrophages
causes fever, acute phase protein response
TNFa
secreted monocytes and others
activates macrophages and endothelium and NFkB
causes fever, inflammation and pain
Apoptosis inducing factor
protein normally located in the intermembrane space of mitochondria
AIF is released from mito through holes
migrates to nucleus
binds to DNA
triggers destruction of DNA and cell death
cyclin dependant kinases
mulifuctional enzymes that can modify various protein substrates involved in cell cycle progression
require the presence of cyclins to become active
exists in similar amounts throughout the cycle while cyclin conc tends to vary
protooncogenes
groups of genes that cause normal cells to become cancerous
mutated version - oncogenes
normally encode proteins that function to stimulate cell divison, inhibit cell differentaion and halt cell death
onocogeens increase these processes
protooncogenes –> oncogenes
point mutation which pernamently activate proteins which can be switched on/off
chromosonal translocation –> occur when pieces of broken chromosomes are reattached haphazardly leading to the formation of a fusion protein containing the N-terminus of one protein and the C-terminus of another leading to altered regulation
tumour supressor
code for proteins that operate to restrict cellular growth and division and can promote apoptosis
can cause cancer when they are inactivated
P53
transcription factor that activates expression of proliferation inhibiting and apoptosis promoting protein in response to DNA damage
critical role in G1 - S cell cycle check point
if p53 inactive - cell cycle progesses even if there is damage
pRb
pRb stops the expression of genes required for progression to S phase
if inactivated causes uncontrolled cell division
normally caused by frameshift in the RBI gene causing premature introduction of stop codon
G1 checkpoint
determines whether all conditions are favourable for cell divison to proceed
- appropriate size and adequate energy levels
- DNA damage
G2 checkpoint
cell size and protein reserves
DNA replication
DNA damage
M checkpoint
determines whether all of the sister chromatids are correctly attached
Non melanoma skin cancer
cancer that slowly develops in the upper layers of the skin
usually a lump or discoloured patch on the skin
most cases cancerous lump are red and firm while cancerous patches are usually flat and scaly
melanoma skin cancer
can spread to other organs of the body
found in the lowest epidermus layer in melanocytes
metastasis
when cancer spreads away from the original site in the body
this is often known as stage IV
TNM staging
a cancer is alwast refered to by the stage it was given at diagnosis
T refers to the size and extent of the main tumour
N refers to the number of lymph nodes that have cancer
M refers to whether the cancer had metastasised
primary tumour T
TX main tumour cannot be measured
TO main tumour cannot be found
T1,T2 etc refer to the size and extent of tumour
Regional lymph nodes N
NX cancer in nearby lymph cannot be measured
NO no cancer in lymph
N1, N2 etc refers to number and location of lymph nodes that contains the cancer
Distant metastisised M
Mx cannot be measured
MO cancer has not spread
M1 cancer has spread
Imiquimod
Topical cream immuno-modulator used to treat pre-cancerous & cancerous (basal cell carcinoma, BCC) sun-damaged skin
Also viral (genital/non-genital) warts & other cancerous skin lesions
Binds TLR-7 & TLR-8 (ssRNA).
Triggers inflammation – immune system destroys cancerous cells.
Induces psoriasis-like inflammation in susceptible mice & humans: IL-23, IL-17, Th17
