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DDT > Trigger 7 > Flashcards

Trigger 7 Flashcards

1
Q

what are the layers of the epidermus

A 
stratum corneum 
(stratum lucidum)
stratum granulosum 
stratum spinosum 
stratum basale
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2
Q

what is the epidermus composed of

A

keratinised = stratified squamous epithelium

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3
Q

what so kerinocytes do

A

manufacture and store keratin

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4
Q

what is the role of keratin

A

gives skin its hardness and water resistant properties

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5
Q

describe the stratum basale

A

attaches to the dermis
made up of basale cells which produce all the keratinocytes
merkele cells
melanocytes

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6
Q

what do merkele cells do

A

receptor and responsible for stimulating sensory neurons

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7
Q

what do melanocytes do

A

produce melain, which gives colour and protects against UV damage

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8
Q

describe the stratum spinosum

A

cells joined via desomosomes
8-10 layers of kerinocytes, begin keratin synthesis
langerhans interspread

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9
Q

describe the stratum granulosum

A

flatter, thick membrane

generates large amounts of keratin

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10
Q

describe the stratum lucidum

A

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

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11
Q

describe the stratum corncum

A

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

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12
Q

describe the dermis

A

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

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13
Q

describe the papillay layer

A

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

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14
Q

decribe the reticular layer

A

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

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15
Q

what is psoriasis

A

skin condition that causes red flaky, crusty patches of skin covered with silvery scales

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16
Q

how does psoriasis happen

A

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

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17
Q

topical treatments

A

creams and ointemts you apply to affected areas

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18
Q

photothearpy treatment - UVB therapy

A

slows down the production of skin cells effects keratinocytes and langerhans cells

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19
Q

photothearpy treatment - psoralen plus UVA

A

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

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20
Q

single neuclotide polymorphism

A

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

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21
Q

methotrexate

A

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

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22
Q

NSAIDS - sulfasalaine

A

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

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23
Q

cirlospoin

A

immunosupressant
inhibits IL2 gene transcription = decrease T cell proliferation
kidney/liver toxicity

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24
Q

describe the development of psoriasis

A

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

25
Q

what is the effetc of Th-17

A

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
26
Q

Where are Th1 cells produced and what do they do

A

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

27
Q

What is the effect of INF-y and TNF-B secrted by TH1

A

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

28
Q

Where are Th2 cells produced and what do they do

A

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
29
Q

What is the effcte of IL-4 secreted by Th2

A

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

30
Q

the effect of phototherapy

A

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

31
Q

what can Reactive oxygen species do

A 
cause damage
iniate signalling pathways - JAK/STAT
induce receptor clustering 
induce kinase activity 
activate nuclear receptors 
induce prolifertaion, apoptosis, inflammation
32
Q

ROS and inflammation

A

inital oxidative burst that makes ROS (happens in phagosome)
if phagosome fuses with a lysosome you can get HOCL
results in bacteria killing
inflammation

33
Q

Use of ROS

A

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
34
Q

interleukins

A

released by leukocytes

35
Q

chemokines

A

protein cytokines mainly involved in facilitaing chemotaxis

guide leukocyte along chemotaxic gradient to site

36
Q

interferons

A

protein cytokines that have antiviral functions

activate macropahges and natural killer cells

37
Q

tumour necrosis factor

A

cytokines that induce apoptosis

released by NK cells, macrophages and helper T cells

38
Q

IL-1B

A

secreted by monocytes and macrophages
injured endothelial cells and fibroblasts
causes fever, inflammation and pain

39
Q

INFy

A

secreted by lympocytes

activates macrophages and many other functions

40
Q

IL-6

A

secreted by T-cells and macrophages

causes fever, acute phase protein response

41
Q

TNFa

A

secreted monocytes and others
activates macrophages and endothelium and NFkB
causes fever, inflammation and pain

42
Q

Apoptosis inducing factor

A

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

43
Q

cyclin dependant kinases

A

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

44
Q

protooncogenes

A

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

45
Q

protooncogenes –> oncogenes

A

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

46
Q

tumour supressor

A

code for proteins that operate to restrict cellular growth and division and can promote apoptosis
can cause cancer when they are inactivated

47
Q

P53

A

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

48
Q

pRb

A

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

49
Q

G1 checkpoint

A

determines whether all conditions are favourable for cell divison to proceed

  • appropriate size and adequate energy levels
  • DNA damage
50
Q

G2 checkpoint

A

cell size and protein reserves
DNA replication
DNA damage

51
Q

M checkpoint

A

determines whether all of the sister chromatids are correctly attached

52
Q

Non melanoma skin cancer

A

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

53
Q

melanoma skin cancer

A

can spread to other organs of the body

found in the lowest epidermus layer in melanocytes

54
Q

metastasis

A

when cancer spreads away from the original site in the body

this is often known as stage IV

55
Q

TNM staging

A

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

56
Q

primary tumour T

A

TX main tumour cannot be measured
TO main tumour cannot be found
T1,T2 etc refer to the size and extent of tumour

57
Q

Regional lymph nodes N

A

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

58
Q

Distant metastisised M

A

Mx cannot be measured
MO cancer has not spread
M1 cancer has spread

59
Q

Imiquimod

A

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

DDT (10 decks)

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