7 - skin disorders Flashcards
1
Q
integumentary system
A
organ system made up of skin and accessory structures
- exocrine glands, hair, nails etc
2
Q
vascularised
A
contains blood vessels
3
Q
3 main layers of skin
A
epidermis
dermis
hypodermis - subcutaneous tissue
4
Q
dermis structure
A
middle layer
dense, irregular connective tissue
houses blood vessels, hair follicles, sweat glands, and other structures
5
Q
epidermis
A
outermost layer
keratinized, stratified squamous epithelium
4/5 layers of cells
avascular - no blood vessels
6
Q
5 layers of epidermis
A
stratum basale stratum spinosum stratum granulosum stratum lucidum stratum corneum
7
Q
keratinocyte
A
cell that stores and produces keratin protein
8
Q
keratin
A
intracellular fibrous protein that gives hair, nails, and skin their hardness and water-resistant properties
9
Q
stratum basale
A
attaches epidermis to basal lamina (which lies below dermis)
keratinocytes are produced from a layer of basal cells
merkel cells and melanocytes present
10
Q
merkel cells
A
responsible for stimulating sensory nerves that the brain perceives as touch
especially abundant on surface of hands/feet
11
Q
melanin
A
produced by melanocyte
gives hair and skin its colour
helps protect living cells of epidermis from UV radiation damage
12
Q
stratum spinosum
A
spiny in appearance due to the protruding cell processes that join the cells via a structure called a desmosome
langerhans cells present
13
Q
desmosomes
A
interlock and strengthen bonds between cells
14
Q
langerhans cell
A
type of dendritic cell
functions as a macrophage by engulfing bacteria, foreign particles, and damaged cells in stratum spinosum
15
Q
movement of keratinocytes in the skin layers
A
As new keratinocytes are produced on top of the stratum basale, the keratinocytes of the stratum spinosum are pushed into the stratum granulosum.
16
Q
stratum granulosum
A
middle layer - above stratum spinosum
keratinocytes are flatter
lots of fibrous keratin produced
17
Q
stratum lucidum
A
middle layer - above stratum granulosum
only found in thick skin
keratinocytes are dead and flattened
eleiden protein present
18
Q
stratum corneum
A
uppermost layer - above stratum lucidum - exposed to outside
dry, dead layer of keratinocytes
mechanical protection
cells are shed and replaced over a 4 week period
19
Q
papillary layer
A
part of dermis
loose connective tissue
finger-like projections into stratum basale of epidermis
cells include: fibroblasts, adipose cells, blood vessels, phagocytes
20
Q
reticular layer
A
under the papillary layer
much thicker
vascularized connective tissue
elastin and collagen fibres
21
Q
hypodermis
A
subcutaneous layer below dermis connects skin to bones and muscle fascia tissue well vascularised fat storage
22
Q
pigments
A
influence skin colour
e.g. melanin, carotene, haemoglobin
23
Q
increased melanin accumulation
A
protects DNA from UV damage and break down of folic acid
24
Q
albinism
A
inability of melanocytes to produce melanin
25
dermis
connects epidermis to hypodermis
provides strength and elasticity (collagen/elastin)
2 layers- papillary layer and reticular layer
26
when are ROS produced
during mitochondrial oxidative metabolism
| in response to bacterial invasion and cytokines
27
how does hydrogen peroxide cause cancer
causes cell damage and uncontrolled growth
28
MAPK ROS pathway
```
ROS activates Raf in plasma membrane
Raf phosphorylates MEK
MEK phosphorylates ERK
activated ERK translocates to nucleus
transcription
```
29
photodynamic therapy
treatment of skin cancer using ROS
30
what causes the photosensitizing agent to produce ROS
the correct wavelength from the light source
31
how does phototherapy cause death of cancer cells
causes damage to blood vessels
which starves cells of nutrients
produces ROS
32
how does ROS kill cancer cells
highly cytotoxic
| initiates cellular apoptosis and necrosis
33
red light
long wavelength
| penetrates deeper to layers of epidermis
34
which layer of the skin absorbs the topical cream e.g. 5-ALA
stratum corneum
35
how do tumour cells convert 5-ALA to photosensitizer
via haem biosynthesis pathway
| tumour cells have many enzymes for this
36
what is required if the photosensitiser is injected
tube needed to guide the light
37
advantages of 5-ALA
short-half life
diffuses over short distances
localised damage
38
what is imiquimod
topical cream
| immunomodulator
39
what is an immunomodulator
stimulates immune response
40
example of non-melanoma skin cancer
basal cell carcinoma
41
what is imiquimod used to treat
non-melanoma skin cancer
genital warts
actinic keratosis
42
mechanism of imiquimod
binds to TLR-7 receptors of langerhans cells in epidermis
activates NF-kappaB pathway
causes production of pro-inflammatory cytokines
antigen presentation to naive t cell
effector cytokines produces by t helper cells
apoptosis of basal cell carcinoma cells
43
which cells take up and process basal cell carcinoma antigens
langerhans cells
44
where do langerhans cells migrate to once they have bound to the antigens
regional lymph node
45
proto-oncogenes
genes that cause normal cells to become cancerous when they are mutated
activated version causes cancer
46
tumour-suppressors
genes that normally inhibit cancerous cell proliferation by terminating cell cycle or causing apoptosis
47
normal function of proto-oncogenes
regulating apoptosis
| preventing cell differentiation
48
mutations that activate proto-oncogenes
dominant mutations
point mutations - inserts/deletions
gene amplification - additional copies of the gene
chromosomal translocation - gene moves to different site on chromosome
49
examples of proto-oncogenes
HER-2
MYC
p53
Ras
50
inactivation of tumour-suppressors
allows uncontrolled cell proliferation causing tumour formation
51
mutations that inactivate tumour-suppressors
recessive - both alleles need to be mutated
| germline mutations
52
examples of tumour -suppressors
APC
Rb
p53
DDC
53
what are cyclins
family of proteins that control regulation of the cell cycle
54
what does cdk stand for
cyclin dependent kinase
55
what activates cdks
cyclin binding
56
what are cdks important for
cell cycle progression
57
p53 detects damaged DNA...
causes release of cdk inhibitor e.g p21
| binds to cdk-cyclin complex and blocks activity
58
G1/S cyclins
activate cdks in late G1
| commitment to cell cycle entry
59
S-cyclins
binds cdks and stimulate late chromosome duplication
60
M-cyclins
activate cdks
| stimulate entry into mitosis at G2/M transition
61
dysregulation of Shh leads to
tumour formation
basal cell carcinoma
shh is important in differentiation of skin cells
62
2 types of mutations in hedgehog signalling
tumour suppressor gene - loss-of-function mutation in Ptch 1
| proto-oncogene - activating mutations in Smo
63
what is the signalling transducing molecule in hedgehog signalling
Smo
64
what happens in absence of Shh
Smo is blocked and cannot bind to Ptch
Gli is converted into repressor form
no transcription
65
where does hedgehog signalling take place
primary cilium
66
what happens in presence of Shh ligand
```
Shh binds to Ptch
Shh-Ptch complex is internalised and degraded
SMo translocates to cilium
Gli is converted into active form
transcription initiated
```
67
role of wnt signalling in colon cancer
APC gene is a tumour suppressor
mutation in APC gene inhibits GSK-3B
B-catenin is not degraded and translocates to the nucleus
uncontrolled growth and cell proliferation
68
wnt signalling leads to ...
gene transcription
69
no ligand bound to frizzled receptor in wnt signalling
B-Catenin destruction complex gets phosphorylated and ubiquitinated
degraded in the proteosome
transcription is inhibited
70
ligand bound to frizzled receptor in wnt signalling
dishevelled protein inhibits APC
B-catenin complex not phosphorylated/ubiquitinated
B-catenin complex translocates to nuclues
transcription initiated
71
flow cytometry measures
how granulated cells are
| size of cells
72
role of laser in flow cytometry
excited fluorescently labelled cells to emit light at varying wavelengths
73
uses of flow cytometry
```
cell counting
cell sorting
biomarker detection
protein engineering
diagnosis
```
74
example of using flow cytometry as diagnostic tool
increased WBC count seen in leukemia
75
how can you distinguish immune cells using flow cytometry
```
graph
side scatter (granularity) on y-axis
forward scatter (size) on x-axis
```
e.g. neutrophils are large and granulated
76
central tolerance
process by which b-cells and t-cells are destroyed if they are reactive to 'self'
77
importance of immune tolerance
ensures immune system does not attack self peptides
78
where does central tolerance take place
primary lymphoid organs
79
peripheral tolerance
mechanisms that take place outside of primary lymphoid organs
aim to prevent immune system from carrying out an immune response against self tissues or harmless material e.g. food/commensal organisms
80
immune response against 'self' causes
autoimmune disease
81
4 mechanisms of peripheral tolerance
1. clonal deletion
2. immune ignorance
3. anergy
4. immune regulation
82
why does peripheral tolerance occur after central tolerance
ensures t and b cells that have escaped central tolerance do not mount an immune response against self
83
clonal deleton
most common mech of peripheral tolerance
| apoptosis of T and B cells that have escaped central tolerance
84
Anergy
T cells made non-responsive to antigens
85
autoimmunity
when own immune cells recognise self-antigens and mount an immune response
- failure of central and peripheral tolerance
86
Treg cells function
```
T regulatory cells
(T repressor cells)
regulate immune system
maintain immune tolerance
prevent autoimmune disease
```
87
treg cells in autoimmunity
not enough
| overwhelmed
88
example of systemic autoimmune disease
rheumatoid arthritis
89
example of organ-specific autoimmune disease
Type 1 diabetes
| immune cells attack the pancreatic insulin-producing beta cells
90
what are Th17 cells
pro-inflammatory cytokines
| produced by activated t cells
91
overall effect of Th17 cell activation
recruitment of neutrophils via epithelial and stromal cells
92
what causes Naive t cell to differentiate into Th17 cells
IL-23
IL-6
TGF-B
93
how do epithelial cells (activated by Th17) recruit neutrophils
release chemokines and antimicrobial peptides
94
how do stromal cells (activated by Th17) recruit neutophils
release chemokiens
95
chemokines
chemotactic cytokines
96
role of Th17 cells at mucosal barriers
maintain mucosal barriers
| contribute to pathogen clearance
97
Th17 cells in auto-immune disease
th17 cells are overactivated in autoimmune disease
| cause excessive inflammation
98
what do Th17 cells produce
IL-17
| IL-22
99
which layer of the skin would you find sweat glands and hair follicles
dermis
100
where are blood vessels found in the skin
spread from the subcutaneous layer to rest of body
| reach up to vascularise dermis
101
2 layers of dermis
1- papillary layer
| 2- reticular layer
102
main feature of psoriasis
excessive proliferation of keratinocytes in stratum basale
103
what makes keratinocytes
basal cells in stratum basale
104
what triggers psoriasis
inflammatory trigger
- activation of immune langerhans cells
- injury/infection/allergy/stress
105
mechanism of psoriasis from activation of langerhans cells
```
migrate to lymph node
differentiate into th17 cells
secrete IL-17
reduced or absent stratum granulsom
excessive proliferation of keratinocytes
nucleated, undifferentiated cells move to top layers of skin
```
106
what causes redness in psoriasis
blood vessels growth near surface of skin
107
what is the problem with undifferentiated keratinocytes in the top skin layers
they dont secrete glycolipids - dry less waterproof
| they dont stack well so form a scale
108
what do keratinocytes produce
chemokines and antimicrobial peptides
| to increase cutaneous immune response
109
treatment of psoriasis
immunosuppressants - DMARDs
phototherapy - PUVA
topical cream
oral/injection
110
main effect of antimicrobials
kill or inhbit growth or microorganisms
111
what mediates release of AMPs
cytokines
112
example of cytokines triggering AMP release
IL-17 and IL-22 produced by Th17
| trigger release of AMPs in gut, skin, lungs
113
3 types of AMP
B-defensins
cathelicidins
lysozymes
114
B-defensins
AMP
cationic peptide
enhances resistance of epthelial surfaces
secreted at mucosal surfaces
115
cathelicidins
found in macrophages, granulocytes, keratinocytes
| punctures pathogen cell membranes
116
lysozymes
hydrolyse bacterial cell wall
| cause cell lysis
117
phototheraphy
treatment using light
118
features of UVA
longer wavelength
350nm
penetrates into dermis
affects fibroblasts, dendritic cells
119
features of UVB
sshorter wavelength
around 300nm
penetrates epidermis
affects keratinocytes and langerhans cells
120
3 types of phototheraphy
broadband UVB
narrow band UVB
PUVA
121
PUVA
psoralen and UVA
122
psoralen
topical or oral photosensitizer
| increases sensitivity to UV radiation
123
what is PUVA used to treat
chronic plaque psoriasis
| after UVB treatment
124
celllular effects of PUVA treatment
increases production of anti-inflammatory cytokines
increases prostaglandins - suppress langerhan cells co-stimulation
decrease cytokine-induced ICAM-1 upregulation
induce apoptosis of skin infiltration lymphocytes
module keratinocyte, cytokine and growth factor receptr ezpression
125
missense
snp where different polypeptide is produced
126
nonsense
snp where protein production is halted
127
causes of SNPs
stochastic process
INDELs
substitutions
point mutations
128
how do you identify SNPs
GWAS
129
where are SNP mutations found in psoriasis
CARD14 gene
130
what do DMARDs stand for
disease modifying anti-rheumatic drugs
131
what are DMARDs used for
treatment of autoimmune disorders
| eg. rheumatoid arthritis
