Antigen uptake and innate immune responses
33 important questions on Antigen uptake and innate immune responses
Which two forms of DCs are there and what is the difference between both?
There are migrant and resident DCs. Migrant DCs have an immature phenotype in peripheral tissues where they are surveying the environment and eventually migrate to the lymph nodes where they mature.
Resident DCs are found in lymph nodes and the spleen where they spend their entire life immature until they encounter a pathogen or inflammatory signals.
Which receptors can be found on immature DCs and which actions do they cause?
C-type lectins and TLRs can be found. TLRs activate certain patterns in the cell which lead to upregulation of production of adhesion-molecules, cytokines and co-stimulatory molecules and DC maturation. Activation of C-type lectins leads to internalization of the pathogen and processing.
How is LPS recognized by cells?
TLR 4 with MD 2 and CD14
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Which patterns can be recognized by TLR-2?
A broad range of patterns, including peptidoglycan and zymosan. It usually works together with other TLRs like TLR 6 and TLR 1
Which receptor recognizes unmethylated CpG motifs?
TLR 9
What do C-type lectins and TLRs have in common, what are differences?
Both are endocytic, but TLRs can discriminate between self and non-self.
What is the crucial difference between type 1 and type 2 CTLs?
Type 2 CTLs contain only one CRD at their carboxy-terminal extracellular domain.
Which motifs on CTLs are important for antigen uptake?
tyrosine-containing coated-pit intracellular targeting motif
triad of acidic amino acids
dileucine motif
How can CTLs induce tolerance?
If a CTL is targeted without TLR activation, the antigen is taken up and processed without maturation of the DC, which induces tolerance.
How can mycobacteria be tolerated?
They can induce tolerating signals via CTLs, which are usually overruled by TLR. However, if the concentration of mycobacteria is too high, the suppressing signal of the CTL (DC SIGN) can induce tolerance by inhibiting the signal of the TLR (4)
How activates TLR4 NF kappa b dependent signalling?
LPS activates TLR4, leading to activation of NF kappa b via TRAF-6 and leading to endocytosis and termination of MyD88 signalling. In the endosome a second TRAM-TRIF-mediated signalling is initiated, which leads to production of IFN gamma and a second phase of MAPK and NF kappa B activation and cytokine (IL-6, IL-12) production.
What is recognized by CD14 and CD36?
lipoteichoic acid and diacylated lipopeptides
Which other molecules are needed for TLR-4 signalling?
LPS-binding protein, which presents LPS to CD14.
MD2 helps TLR-4 binding LPS and homodimerize.
Which complex uses C36?
TLR4-TLR6 to respond to altered self patterns like oxLDL or amyloid beta
Which TLRs use CD14 and HMGB for which nucleic acid delivery?
dsRNA to TLR3
ssRNA to TLR7
ssDNA to TLR9
Which membrane bound C-type lectins are important for antigen capturing?
MMR, DEC205, BDCA2, DC SIGN
Which c-type lectins may be secreted and why?
MMR and DC SIGN to act as agglutinins and opsonins.
Which c-type lectins may be important for DC-T-cell interaction?
DC SIGN and dectin-1
Which are the 7 mammalian REL-related proteins?
RELA/p65, c-REL, RELB, p105, p50, p100 and p52
What do all REL proteins have in common?
They all contain REL-homology domains. Its amino-terminal is responsible for backbone and sequence-specific contact whereas the carboxy-terminal mediates dimerization.
Which REL-proteins contain carboxy-terminal transactivation domains?
RELA, RELB, c-REL
Which REL-proteins contain gycerine-rich regions and why?
The GRRs are important for co-translational processing of p105 to p50 (Ref. 97) and post-translational processing of p100 to p52
How do acetylation and phosphorylation affect RELA?
phosphorylation is required for optimal NF b transcriptional activity, acetylation regulates distinct functions of NF b like IB association.
How is NF kappa B activated?
serine residues of IxB are phosphorylated by the Signalosome, leading to phosphorylation of IxB and its ubiquilation and degradation by 26S proteasome, which liberates the p50/RELA heterodimer (NFkappaB) which then is translocated to the nucleus.
Which other pathway is there next to NF kappa b?
NFKB2 (p100), which can be activated by BAFF and CD40, which in turn selectively activate NIK and IKK1.
Which serine residue is phosphorylated after encountering TNF and LPS by the cell?
S267
Which serine residue is phosphorylated when the cell encounters IL-1 and TNF?
S311 and S529
Which lysine residues have to be acetylated for optimal working of RELA?
K310
Which lysine residues have to be acetylated to prevent assembly of RELA with IxB?
K211, K218
Which lysine residues have to be acetylated to impair RELA's transcriptional activity?
K122 and K123
Next to RELA, which molecules are also affected by the same kinases?
Histone tails.
Which diseases can be caused by NFkappaB?
too much: rheumatoid arthritis, asthma, IBD
constitutive active: acute lymphoblastic leukemia, breast cancer
Which medicines can inhibit NF kappa B?
aspirin salicylate or cyclosporin
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