week 2 lec 2 Flashcards
normal epidermis is colonized by what commensal bacteria after birth
Coagulase-negative Staphylococci (Staph epidermidis)
most common purulent skin infection and what its caused by
pyoderma from staph aureus
what can cause staphylococcal skin infections
Immunosuppressive disorders, diabetes, atopic dermatitis, preexisting tissue injury (surgical sites, burns)
which staph is commensal and which is pathogenic
Staph epidermidis – mostly commensal
Staph aureus- commensal and aggressive/ pathogenic
–> MRSA- methicillin resistance staph aureus
risk factors for staph soft tissue infection
lack IL-17
defective neutrophil function or # (cancer, chemo, genes)
pathogenesis of staph soft tissue infection (3)
- pore-forming toxins (i.e. alpha and gamma toxin) –> lyse neutrophils and macrophages
- phenol-soluble modulins –> lyse leukocytes and erythrocytes
- exfoliative toxins (from bacteriophages) –> serine proteases target desmosomal cadherin –> intraepithelial bullae (skin) OR staphylococcal-scalded skin syndrome (systemic)
staph superantigens examples
I.e. toxic shock syndrome toxin 1, enterotoxins…
staph superantigens nonspecifically activate
T cells via HLA-2 on APCs and beta-subunit of TCR –> CD4+ T cells activated
what does toxic shock syndrome toxin 1 (TSST-1) rxn cause
high fever, hypotension, scarlet fever-like rash, desquamation of skin, multiorgan dysfunction
staph- neutrophil evasion
what does protein A block?
(expressed on surface of S. aureus)–> blocks antibody-mediated phagocytosis by both neutrophils and macrophages
staph- neutrophil evasion
what does staphylococcal nuclease destroy?
destroys neutrophil extracellular traps
staph- neutrophil evasion
what does catalase, alkyl hydroperoxidase reductase and staphyloxanthin inhibit?
inhibit ROS-mediated killing of S. aureus
staph- neutrophil evasion
what does staph-superantigen-like 5 and 11 block?
block P-selecting and ICAM-1 which normally allow neutrophils to adhere to the endothelium and enter tissue
staph- neutrophil evasion
what does chemotaxis inhibitory proteins (CHIPS) or staphopain A (ScpA) block?
block complement receptors and CXCR2 neutrophil-
attracting chemokines
what (antimicrobial peptides) AMPs fight against staph?
Beta-defensins 2 and 3, cathelicidin, RNase 7
–> bacteriostatic or bactericidal activity
which neutrophils via PRRs fight against staph?
TLR-2 –peptidoglycan and lipoproteins
NOD-2 –muramyl dipeptide
staph has a pore forming toxin that helps promote neutrophil recruitment and fight against the bacteria. how?
Staph’s pore-forming toxin actually activate caspase-1 and result in activation of IL-1Beta –> promote neutrophil recruitment
IL-17 also for neutrophil recruitment
what do the exfoliative toxins in staph aureus cause
blistering skin disorders
what are the 2 exfoliative toxins in staph and what do they cause
ET-A causes bulleux impetigo (localized)
ET-B causes staphylococcal scalded-skin syndrome (SSSS) (cutaneous tenderness and widespread superficial blistering)
what is the mechanism of action of exfoliative toxins in staph aureus
ETs are serine proteases that bind to cell adhesion molecule desmoglein-1 –> loss of cell-cell adhesion between stratum spinous and granulosum –> making it easy to blister
how do staph exfoliative toxins worse
bind desmoglein-1 (cell adhesion molecule) and cause loss of cell adhesion and easy blistering
common cause of superficial purulent skin infections
group A streptococcus (GAS) (i.e. strep pyrogens)
local and invasive problems from group A strep
local: impetigo, ecthyma, intertrigo
invasive: erysipelas, cellultiis, necrotizing fasciitis, deep tissue necrosis –> sepsis, shock, multi organ failure, death
a group A strep infection can trigger an immune mediated disease like
Guttate psoriasis, acute rheumatic fever, rheumatic heart disease, glomerulonephritis
risk factors for strep
environmental: hygiene, poverty, corwding
pre-existing condition: tissue damage and inflammation i.e. eczema and fungal infections
where to non-GAS species (other strep, not group A) infect
areas with poor blood flow (e.g., ischemia or venous stasis).
which strep are linked to skin infections
D and E
what is the protein that differentiates the 200 subtypes of GAS (group A strep)
m-protein
M-protein in strep inhibits immune defesnes by
bindings regulators of complement system –> no activation of classical and alternative path
inhibit antibody-medicted phagocytosis by binding Fc region of IgG
inflammation via TLR-2 on monocytes –> increase IL-6, IL-1 beta and TNFalpha
where can m protein of strep bind on keratinocytes
fibronectin and CD46
2 pore forming toxins in strep
steptolysin O and steptolysin S
steptolysin O vs steptolysin S
these strep pore-forming toxins act on
O= large pore formation cause apoptosis of neutrophils, macrophages and epithelial cells
S= cytolytic against neutrophils, lymphocytes, erythrocytes and platelets (inflammation, vascular injury and necrosis)
what is the strep superantigen? effect?
Strep pyrogenic exotoxin serotype A, C, G to M, mitogenic exotoxin SMEZn
non-specifically activates T cells
Streptococcal Pyrogenic Exotoxins (superantigen) causes what
streptococcal toxic shock syndrome, scarlet fever, erysipelas and invasive presentations
how does strep do neutrophil invasion?
make antioxidants (glutathione peroxidase, superoxide dismutase) to inhibit ROS mediated killing
nuclease A and DNase Sda1 breakdown neutrophil extracellular traps
how does the immune system respond to strep?
AMPs made by keratinocytes (beta-defensins 1 and 3, cathelicidin)
neutrophil recruitment (TLR-2 peptidoglycan and lipoproteins and NOD-2 for muramyl dipeptide)
type 1 IFN response (TLR-9 activation –> oxidative burst)
adaptive T and B response (but so many M proteins and types of strep that immunity to 1 type doesnt protect against others)
super antigenic toxins from which bacteria
staph aureus or group A strep
super antigenic toxins lead to a cytokine storm of which cytokines? what does this cause?
TNF alpha, IL-1, IL-6
Capillary leak syndrome and other systemic problems (i.e., toxic shock syndrome)
do super antigenic toxins need APCs to exert effects on T cells
no
where to super antigenic toxins bind on APCs?
HLA-2 but outer walls
so recognition is not specific to HLA-2 or T cell receptor
= greater T cell response
how do super antigenic toxins cause cutaneous manifestations?
increase # of T cells with CLA (skin homing)
*cutanoeus lymphocyte-associated antigen
pseudomonas aeruginosa characteristics
gram negative rod
in aqeusous envo
sweet grape odor
blue green color
oxidase positive
non lactose fermenting
obligate aerobic bacteria
likes warm (42 celcisu)
primary cutaneous infections from pseudomonas aeruginosa
Green nail syndrome, toe web infection, folliculitis, hot-foot syndrome, external otitis, perichondritis
pseudomonas in immunocompromised patietns
bacteria and ecthyma gangrenosum
how can pseudomonas aeruginosa get into skin
if damage i.e. infection, catheter, trauma
what factors in pseudomonas aeruginosa degrade skin and parts of immune system
alkaline protease, protease IV, elastase
what does pseudomonas aeruginosa release after contacting the host
exoenzymes
ExoS –> TLR’s –> TNF-alpha production
ExoT –> binds adenosine diphosphate ribosyltransferase
ExoU –> damages cell membranes
ExoY –> binds adenylate cyclase
other factors in pseudomonas aeruginosa
Exotoxin A –> interferes with protein synthesis! cell death
Procyanin –> pro-inflammatory and oxidative effects
LPS –> activates TLR4 –> septic shock mediator
Quorum sensing –> intercellular signaling to coordinate gene transcription and possible biofilm formation
pseudomonas aeruginosa pathogenic feature
makes alginate to scavenge free radicals, impair phagocytosis, inhibit neutrophil chemotaxis, inhibit complement activation
biofilm production (protect against antibiotics and AMPs)
how do pseudomonas aerguinoa be antibiotic resistnant
Multidrug efflux pumps (pump it out), beta-lactamases (breakdown the antibiotic), downregulation of porins on the outer membrane (then antibiotic can’t get in)
pathogenesis of pseudomonas aeruginosa
- green nail syndrome
- toe web infection
- folliculitis and hot-foot syndrome
–> all if it water
- external otitis
- bacteremia (in bloodstream) and ecthyma gangrenosum (veins and arteries then to skin invasion- inside out)
how do you get Bacteremia and Ecthyma Gangrenosum from psuedomonas aeruginosa
Hospitalized patients with neutropenia, hematological malignancy or low CD4+ count
what are dermatophytoses and what do they thrive on
fungal infections that use keratin (spores adhere to it and change gene expression)
fungi releases proteases, lipases and ceramidases to digest through the keratin
interfere with keratinocyte proliferation and cell mediated immunity
immune response to dermatophytes
mannan (fungal component) activates TLR (causes keratinocyte proliferation, AMP secrete, pro-inflammatory cytokine)
delayed-hypersensitivity- Th1 and Th17 to clear fungus
dermatophytid reaction is
inflammatory dermatitis at a distance site from primary infection
-delayed hypersensitive, eruption is polymorphic
criteria to establish dermatophytid (ID) eruption
- dermatophytosis is on another body part
- no fungal elements in ID eruption
- ID eruption goes away once primary dermatophyte infection clears
Onychomycosis
fungal infection of nail
common causes of onychomycosis
90% caused by Trichophyton rubrum and T. interdigitale, Candida spp are often culprits of fingernail infections
tine barbae
fungal infection of the beard
causes of tinea barbae
zoophilic strains of T. interdigitale, T. verrucosum
tinea corporis AKA ringworm
dermatophytosis of glabrous skin (except palms, soles and groin)
tinea corporis AKA ringworm cause
T. rubrum
Head, neck and arms
tinea cruris
Dermatophytosis of groin, genitalis, pubic area, perineal and perianal skin
causes of tinea cruris
T. rubric and Epidermophyton floccosum
tinea pedis and tinea mannum
Dermatophytosis of feet (pedis) or palmar and interdigital areas of hands (mannum)
pathogen for tinea pedis and tinea mannum
T. rubric, T. interdigitale and Epidermophyton floccosum
measles
Highly contagious, single-stranded, enveloped RNA virus of the Paramyxoviridae family
how are measles transmitted
person- person (contact or airborne respiratory droplets)
Koplik spots, fever, cough, coryza,
conjunctivitis with possible severe
complications of pneumonia and encephalomyelitis in which disease
measles
rubella
Enveloped positive-stranded RNA virus of the Togaviridae family
family for measles vs rubella
rubella- togaviridae family
measles- paramyxoviridae family
how is rubella trasnmitted
direct or nasopharynx droplets
features of rubella
Enlarged cervical, suboccipital and postauricular lymph nodes
rash
rubella and immunity
lifelong
erythema infectious aka fifth disease is causesd by which virus and what does it look like?
parvovirus B19 (Parvoviridae, no envelope, single-stranded DNA virus)
slapped cheeks
Erythema Infectiosum - Parvovirus B19
cheek rash then lacy eruptions on extremities, polyarthritis, papular purpuric glove and sock syndrome
what is the crisis that can be caused by Erythema Infectiosum - Parvovirus B19
Transient aplastic crisis – can infect and destroy erythroid progenitor cells
Human Herpesvirus 6 (HHV-6) causes what in infants
Exanthem subitum/ roseola infantum, 6th disease
fevers (usually no rash in kids)
what is true for all herpesviruses
Chronic infection with latent stage and possibility to reactivate
what causes Human Herpesvirus 6 (HHV-6)
Herpesviridae family, double-stranded DNA
where does Human Herpesvirus 6 (HHV-6) replicate in the body and get transmitted
replicate in salivary glands and trasmitted through saliva
herpes simplex virus- where does it infect
1st infects skin or mucosa then to local nerve ends and ganglia to be latent and reactivated
types of herpes simplex virus and where they infect
HSV-1 oral
HSV-2 genital
symptoms of herpes simplex virus
Most primary infection are asymptomatic, and most transmission occurs during asymptomatic shedding
herpes simplex virus pathogenesis depends on
immune function/ competence
IFN and TLR2 mutations increase lesions or encephalitis
dendritic cells and CD8+ T cells localize to sites of reactivation
humeral immunity to reduce viral titers at inoculation sites
varicella herpes zoster virus is what initially and upon reactivation turns into what
chicken pox –> shingles
varicella herpes zoster virus spread?
highly contageous
chicken pox on face and scalp then spread to trunk
rose coloured macules to papules
how does shingles present (reactivation of Varicella Herpes Zoster Virus)
unilateral dermatomal pain and rash
postherpetic neuralgia
how does varicella herpes zoster virus (chicken pox) enter the body?
mucosa of respiratory tract and oropharynx
disseminated via blood and lymph
how long to show sx of chicken pox
10-14 days after infection –> larger viremia (post replication)
which sensory nerves and ganglia does chicken pox (Varicella Herpes Zoster Virus) travel
trigeminal nerve, spinal
sensory ganglia T1-L2
how does chicken pox (Varicella Herpes Zoster Virus) circulate
via lymphocytes
to end and go into latency for Varicella Herpes Zoster Virus (chickenpox) infection what is needed
T cell mediated immunity
how does Varicella Herpes Zoster Virus get reactivated
T cell mediated immunity fails
spread in ganglion
neuropathic pain
destroy neurons and sensory nerves
spread antidromically via sensory nerve and into skin endings –> zoster vesicles
human papillomavirus type
DNA virus of the Papillomaviruses, nonenveloped, double stranded DNA virus
many types of human papillomavirus.. which are high risk for malignancy
E6 and E7 proteins have oncogenic effects
what does human papillomavirus infect
keratinocytes
replicate when in basal epidermal keratinocytes (E6 and E7 proteins for amplification)
human papillomavirus causes what skin symptoms
Common warts:
HPV-2, 27, 57 and HPV-4 and HPV-1
Butcher’s warts (wet meat handling) - HPV-7
