KEY NOTES WK 2 Flashcards
layers of epidermis in order and key features
CLGSB
stratum corneum (dead keratin and filaggrin)
stratum lucidum (thick skin- soles, palms)
stratum granulosum (lamellar granules rich in lipids, associate keratin and filaggrin)
stratum spinosum (synthesize keratin and filagrin)
stratum basale (stem cells and melanocytes, sensory receptors, langerhans cells for immune)
dermal layers (2)
papillary layer- type I and III collagen (loose CT) with papillae to interlock with epidermis
reticular layer- type I collagen and elastic fiber (dense CT) with nerves, arteries, glands, hair follicles
T cell activation
T cell has T cell receptor and CD4 co-receptor that interact with HLA2 on APC
the co-stimulate of CD28 on T cell with CD80 on APC
ILCs
type I ILC secretes IFNy and TNFa –> does Th1
type II ILC secretes IL4, IL5, IL9, IL13 –> does Th2
ILC3 secrete IL17, IFNy for extracellular bacteria (Th17 response)
what activates ILC2 cells
alarmins
what are alarmins
IL25, IL33, TSLP
early release cytokines on skin that push a Th2 response and activate ILC2
promote mast cell survival and migration
IgE, IL4, IL22
inhibited by IFNy
how are mast cells activated
sensitized by IgE
degranulation in response to an allergen (ie.. atopic dermatitis, allergic rhinitis, asthma) and cause relapse of histamine, serotonin, heparin, proteases, TNFa, IL4
type II inflammation
cytokines to induce proliferation and activation of eosinophils
then what promotes migration from blood to peripheral tissues
IL5
eotaxin
when do eosinophils accumulate
type 2 inflammation
alarmins (TSLp, IL33, iL25) activate ILC2
granule content of eosinophils
major basic proteins; cationic proteins, eosinophil peroxidase, IL4, IL13, TNFa
neutrophil granules
defensives and cathelicidins (pore forming –> lysis)
cathepsin
lysosome
lactoferrin (iron)
myeloperoxidase
neutrophil function
NET (neutrophil extracellular trap)
sticky chromatin to trap bacteria
histone are toxic to bacteria
classical vs alternative macrophage activation
classic= via IFNy –> inflammation - kill microbes
alternative (IL4, IL13)- repair and anti-inflame
NK cells do what
apoptosis via fas-fas ligand
secrete perforin (poke holes) and granzyme (apoptosis)
PAMPs
PAMPs on bacteria, recognized by PRRs (i.e. TLR, NOD, RIG)
skin cell glands and keratinocytes can secrete
AMPs
* Defensins, RNA-ase, dermicidin, cathelicidin, psoriasin
keratinocytes express
TLRs and RIGs and respond to alarmines, cytokines, chemokines
types of psoriasis
plaque psoriasis (most common): Well-demarcated salmon-pink papules or plaques with a silvery-white scale (on extensors, scalp, soles, palms, nails)
also guttate psoriasis (via strep infection) and pustular psoriasis (pus)
Th type causing psoriasis
Th17
–> IL17 from Th17 and ILC3
–> IL23 from dendritic cells
allergic contact dermatitis
I.e. nickel, cosmetics, poison ivy
get itching and erythema 48hrs to days after exposure
need sensitization (hapten initial exposure) then elicitation phase and subsequent exposure will cause rxn
what molecule causes allergic contact dermatitis
hapten
stick to skin and make it look foreign
activate inflammasome, IL1, TLR4 (nickel)
type of Th response in allergic contact dermatitis
Th1
allergic contact dermatitis vs psoriasis Th_
ACD= Th1
P= Th17
normal commensal bacteria in skin after birth
Coagulase-negative Staphylococci (Staph epidermidis)
staph aureus can cause
MRSA- methicillin resistance staph aureus
Staph Soft Tissue Infection (SSTI)
toxins
pore forming toxins
phenol soluble modulins
exfoliative toxins (serine proteases target desmosomal cadherin and cause intraepithelial bullae in skin or staph-scalded skin syndrome if systemic)
staph superantigens
Toxic shock syndrome toxin 1 (TSST-1), enterotoxins …..
non specific activation of T cells via HLA2 on APCs (activate CD4+ T cells)
TSST-1 (toxic shock syndrome) (staph superantigen) causes
high fever, hypotension, scarlet fever-like rash, desquamation of skin, multiorgan dysfunction
staph neutrophil invasion (1st line of defence)
Chemotaxis inhibitory protein (CHIPS) or staphopain A –> block complement
Staph-superantigen-like 5 and 11
Staphylococcal nuclease
protein A –> block phagocytosis
NOT HELPFUL LOL
immune response against staph
AMPs (keratinocytes)
neutrophil recuited by PRRs (TLR2, NOD2)
caspase 1
Th17 - IL-17
exfoliative toxins in staph auereus cause
blistering skin disorder
ET-A: bulls impetigo (local)
ET-B: staph scalded skin syndrome (systemic)
exfoliative toxins (serine proteases) in staph aureus bind ___ to cause loss of cell-cell adhesion between stratum ____
bind CAM desmoglein-1
stratum spinous and granulosum
group A streptococcus skin infection have 200 subtypes and are identified by _____.
types that cause skin infection
M protein
type D and E
M protein in strep
binds complement
binds IgG and inhibits antibody mediated phagocytosis
TLR2
bind fibronetin on keratinocytes
strep pore forming toxins
streptolsyin O (forms pores –> lysis)
steptolysin S (disrupt cell membrane, cytolytic)
strep superantigens
streptococcal pyrogenic exotoxin (non specifically activate T cells)
strep neutrophil evasion
make antioxidants (glutathione peroxidase and superoxide dismutase) to inhibit ROS mediated killing
nuclease A and DNase Sda1 breakdown NETs
what type of IFN response to strep
type 1 IFN response –> TLR9 activation
strep and staph superantienic toxin dont need to
be processed by APCs;
bind outer wall, not HLA2
non specific activation of T cells
increase CLA for skin homing
cytokine storm; TNFa, IL1, IL6 (i.e. toxic shock)
pseudomonas aeruginosa key colour and door
Sweet, grape-like odor and blue-green colour
cutaneous infections from pseudomonas aeruginosa
= HOT AND WET
Green nail syndrome, toe web infection, folliculitis, hot-foot syndrome, external otitis, perichondritis
if get pseudomonas aeruginosa and immunocompromised can get
bacteremia (bacteria in blood stream)
ecthyma gangrenosum (necrotic black lesion from invading veins and arteries and then skin)
what do pseudomonas aeruginosa need to get into the skin
some type of damage (i.e. burn, trauma, dermatophyte infection)
how does pseudomonas aerugiona degrade skin
alkaline protease, protease IV and elastase
then use exoenzymes
eotoxin A
Procyanin
LPS
key communication of pseudomonas aerugionsa so they can coordinate gene transcription
quorum sensing –> biofilm formation
2 things pseudomas aeruginosa produces
alginate (mucoid substance)
biofilm
antibiotic restistant mechanisms of psuedomonas aeruginosa
multidrug efflux pumps
beta-lactamases
down regulate porins
most common bacteria causing external otitis
pseudomonas aeruginosa
dermatophytoses are ____ that attack _____
fungal infection that have spores that adhere to keratin and change gene expression
germinating final release proteases and lipases to digest keratin and prevent proliferation
what component of dermatophytes activate TLRs in keratinocytes to trigger AMPs, cytokines, proliferation of keratinocytes
mannan
type of hypersensitivity rxn to clear fungus in dermatophytes
Th1, Th17 (delayed)
what is a dermatophytid reaction
inflammatory dermatitis at distant site from primary infection
Criteria to establish ID eruption:
(1) dermatophytosis is confirmed on another body part
(2) there is no fungal elements within the ID eruption
(3) the ID eruption goes away once the primary dermatophyte infection clears
onychomycosis
nail fungal infection
onychomycosis common causes
Trichophyton rubrum and T. interdigitale, Candida spp
tinea barbae caused by
beard final infection
T. interdigitale, T. verrucosum
tinea corporis and cause
dermatophytosis of labours skin (hairless- i.e bum, top of foot)
t. rubrum
tinea cruris
dermatophytosis of groin, genital, perineal
T. rubric and Epidermophyton floccosum
tinea pedis and tinea mannum
dermatophytosis of feet (pedis) and hands (mannum)
. rubric, T. interdigitale and Epidermophyton floccosum
measles
cause
transmission
sx
ssRNA from paramyxoviridae family
contact or airborne
morbilliform rash for 3-5 days; kopek spots, fever, cough
rubella
cause
transmission
sx
+ strand RNA togaviridae family
nasopharynx droplets
rash and lymphs
Erythema Infectiosum - Parvovirus B19
sx
5th disease/ slapped cheeks
poly arthritis
papular purpuric glove and sock syndrome
what can Erythema Infectiosum - Parvovirus B19 cause if bad
transient aplastic crisis –> suppress eryhtropoesis (RBC production)
Human Herpesvirus 6 (HHV-6)
sx
6th disease/ roseola infant
febrile seizures without rash in kids
all herpes virus
chronic; latent stage and reactivate
Herpes Simplex Virus
2 types
sx
HSV1 oral
HSV2 genital
mostly asymptomatic
effect skin then get into nerves and be latent
Varicella-Zoster herpes virus (VZV) presentation
chicken pox (initial) to shingles (reactivate)
when Varicella-Zoster virus (VZV) becomes latent and reactivates what does it cause
shingles - effects sensory and autonomic neruons (latent) and causes pain with the rash –> postherpetic neuralgia
where is Varicella-Zoster virus (VZV) latent in
trigeminal nerve, spinal
sensory ganglia T1-L2
how does varicella herpes zoster virus as shingles spread
antidromically (from nerves to skin) –> zoster vesicles
Human Papillomavirus (HPV)
which types are high risk
infects
E6 and E7 (oncogenic)
infects keratinocytes
HPV common warts
butchers warts from (wet meat)
HPV-2, 27, 57 and HPV-4 and HPV-1
HPV7
which UV is worst
UVA
signature UV mutation
C>T transition in TP53 (tumor suppressor gene)
what protect skin cells from UVR
scale for burning and tanning and more melanin
melanin
Fitzpatrick scale
basal cell carcinoma from which UV
UVB
basal cell carcinoma mostly on which area
head and neck (rarely metastatic)
pathogenesis of basal cell carcinoma
UVB mutates p53 and PTCH1 (tumor suppressors)
malfunction in sonic hedgehog singaling (PTCH1) –> SMO not inhibited –> transcription of target genes
squamous cell carcinoma more common in
darker skin and immunosuppressed
viral carcinogens
HPV (16 and 18) turn off tumor suppressor TP53
immunosuppression increases risk of cancer
especially squamous cell carcinoma
via medications, HIV
chronic inflammation resulting in squamous cell carcinoma
chronic ulcers, burns, inflammatory skin condition (i.e. discoid lupus)
malignant melanoma
high mortality risk
risks: genes (CDKN2A, CDK4, POT1, TERT), UV exposure, melanocytic nevi/moles (if atypical and large and congenital)
hair follicle cycle
ACTEE
anagen (growth for 2-8 years)
catagen (involution)
telogen (rest for 3 months)
exogen (shedding)
androgenic alopecia
shorten anagen (growth) phase
genetics, male, after puberty, androgens (DHT), hormonal dysregulation in female (estrogen), cytokines
male pattern: frontal hairline and vertex
female pattern: centropariteal thinning and Christmas tree
telogen effluvium
diffuse hair loss
early termination of anagen (growth) and more % of hairs in telogen (rest)
increased shedding of club hairs (i.e. late stage of telogen, lack sac and pigmentation)
cause of telogen effluvium
psychophysiologic stressors (remove trigger to resolve)
subtypes of telogen effluvium
acute (2-4 months) i.e. rash diet, surgery
chronic (>6 months) i.e. thyroid, malnutrition, STI, zinc and iron deficient
chronic (4th and 6th decade); age
stage changes of hair in telogen effluvium
premature termination of anagen (growth) ie. stress
prolong anagen and stop abrupt i.e. post partum
short anagen ie. drugs
what is elevated in telogen effluvium from stress
elevated interferon levels, heparin
alopecia areata
autoimmune hair loss, esp kids,
well demarcated patches of hair loss
cytotoxic CD8 T cells
increase catagen and telogen, inflammatory infiltrate around follicular bulbs
oncychomycosis
nail fungi from dermatophytes mostly
toes and distal lateral
hyperkeratosis and separate nail from bed
psoriasis can effet
nails (esp if arthritis)
hyperkeratosis, leukonychia, pitting, nail separation (oil or salmon spot)
