9. TA lectures Flashcards
Atopic dermatitis can be caused by…
microbial dysbiosis, genetic mutations, skin barrier disruption, immune dysregulation, allergen exposure
physical burden of atopic dermatitis
skin pain
sleep disturbance
depression and anxiety
asthma, allergies, hay fever
allergic contact dermatitis
infections
cardio-metabolic disorders
skin microbial dysbiosis in atopic dermatitis
skin barrier disruption causes a decrease in commensals and AMP
results in an increase of IgE, eosinophils, and CCL17
Mast cells in Atopic dermatitis
- IgE bound to mast cell can cause imflammation (immunological)
- pathogen detection and surveillance in barrier tissues
- have a spatial and temporal advantage over other leukocytes
MRGPRX2/b2 mediated mast cell activation
- MRGPRX2 is expressed in human connective tissue mast cells
- are receptors of cationic ligands
- cause non-immunologic mast cell activation (IgE independent)
how do mast cells and S.aureus interact in the occurrence of AD
- increases s.aureus = decreased microbial diversity
- s.aureus produces d-toxin which activates mast cells and induces AD-like inflammation
what renders mast cells “sentinels” of the body
- tissue-resident cells found in host-environment junctions
- possess a broad repertoire of receptors to detect a variety of molecules
- activation occurs in seconds to minutes
- roles in allergy and infection
MRGPRX2/b2 receptor expression and activation
- found in connective tissue mast cells
- activated by a variety of cationic (positive) compounds
- mediates susceptibility to bacterial infection
what are examples of cations (bacterial molecules) that the MRGPRX2 receptor binds
- quorum-sensing molecules
- neuropeptides
- anti-microbial peptides
what is catestatin
a neuroendocrine AMP which has antimicrobial and immunomodulatoy properties
its activation and improve the process of healing infected wounds
catestatin induces…
MC histamine and PGD2 release through MRGPRX2
effects of S.aureus toxins
activates T-cells
leukocyte lysis
host cell lysis
compromise physical barriers
examples of toxins from s.aureus
TSST1
staphylococcal enterotoxins
leukocidins
a-hemolysin
how does s.aureus evade the immune system
interferes with complement activation
fibrin sheild
what does SCIN do
stabilizes inactive C3 convertase to prevent further action of the complement cascades