Deck 4 Flashcards
(59 cards)
Stimulatory cytokines for ILC-2s
IL-33 (strong response) and IL-25 (moderate response)
How does T2 immunity lead to helminth expulsion?
In addition to signals that activate the `epithelial escalator’, the type 2 cytokines IL-4, IL-5, IL-9 and IL-13 contribute to increased muscle contractility, diarrhea and changes to the mucus that lines the gastrointestinal tract
What are the steps of tissue repair after damage in epithelial layer?
Following cellular stress or tissue damage, adenosine is released at the site of inflammation, which can induce up-regulation of the alarmin IL-33 and enhance the development of tissue- protective M2 macrophages and eosinophils at the site of parasite infection. IL-33 activates ILC2s which release amphiregulin.
What is a role for amphiregulin?
Amphiregulin from ILC2s leads to tissue repair and protection from DSS-induced damage as well as damage from influenza infection.
UCP-1
thermogenic protein in beige adipose tissue that is critical for burning calories and preventing obesity.
What is a phenotype of ILC2- or IL-33-deficient mice?
Reduced beige adipose, increased obesity. Loss of tissue repair mechanisms.
How do ILC2s regulate adipose beiging?
ILC2-derived enkephalin peptides promote beiging and tissue protection of white adipose. This leads to an increase in energy expenditure and a decrease in adiposity.
What cytokines activate ILC2s and which cytokines do they produce in response?
ILC2s are activated by IL-25, IL-33, and TSLP, and produce Amphiregulin, IL-13, IL-5, and IL-9,
What is the effect of ILC2 cytokines on other cells?
Epithelial cells - mucus production “weep and sweep”
Eosinophil activation and production of cytokines
Mast cell activation
M2 polarization
inflammatory ILC2s phwnotype
KLRG1-high, IL-25R-high
IL-33 required for their generation
Tryptophan hydroxylase (Tph)
rate-limiting enzyme of the biosynthesis of serotonin (5-HT) from its precursor L-tryptophan
2 isoforms of Tph
Tph1 - Non-neuronal cells: Enterochromaffin cells and mast cells (and ILC2)
Tph2 - Neurons: brainstem and myenteric plexus
Which mRNAs are upregulated in ILC2 after IL-33 treatment?
mki67 il5 il13 Areg Tph1
What is the phenotype of mice lacking Tph1 in lymphocytes?
reduced inflammatory ILC2s, reduced worm expulsion in helminth infections.
ILC2 main transcription factor
GATA3
Nmur1
Neuromedin U (Nmur1) is selectively expressed by ILC2s and not expressed by eosinophils, mast cells, basophil or other hematopoietic cells.
ILC2s co-localize with NMU-expressing neurons in the intestinal submucosa.
Stimulation of Nmur1 on ILC2s leads to production of IL13 and IL5
What cells do ILC2 co localize with in the intestinal submucosa?
NMU-positive cholinergic neurons
Role of NMU in the gut
directly stimulates ILC2s,
promotes type 2 responses and accelerates worm expulsion and type 2 inflammation in the lung.
Beta-2 adrenergic receptors in ILC2ss
Relatively upregulated expression on ILC2s. ILC2s are closely colocalized with neurons that produce the ligand for this receptor (norepinephrine) , and receptor KO mice have enhanced ILC2 responses, suggesting that B2 adrenergic receptor signaling may suppress ILC2s
What might be the neuronal ILC2 ‘rheostat’?
Cholengeric neurons activate ILC2s through NMU/Nmur1 signaling, and Catecholaminergic neurons inhibit ILC2s through norepinephrine/B2AR signaling.
enzyme involved in cell wall (septum) synthesis in E. coli
FtsI
Five tasks that bacteria must content with when exporting proteins
discriminate the cytoplasmic-resident proteins from those that are destined for export;
deal with the inherent tendency of polypeptides to fold rapidly;
target exported proteins to the membrane with specificity and fidelity;
achieve transmembrane crossing of these elongated, heteropolymeric substrates, which are several times as long as the membrane is wide; and finally,
manage a second sorting event that releases membrane proteins into the lipid bilayer and secretory proteins to the trans side of the membrane
Which secretion pathway is ubiquitous and essential for all three domains of life?
the Sec pathway, which additionally acts as the entry point for many of the other protein export and sorting pathways
What are the two pathways for protein targeting for secretion via the Sec pathway?
SRP-mediated targeting (co-trasnlational)
SecB-mediated targeted (co- and post-translational)