Immune responses to glycolipids and polysaccharides Flashcards
What is the difference between T-dependent and T-independent antigens?
T-independent antigens are recognized by B-cells but not presented to T-cells, so there will be only a IgM response and no class switching. T-dependent antigens do induce a T-cell response and the B-cells will undergo class switching.
For which processes do CD4 T-cells provide help to B cells?
Germinal center formation, isotype switching and affinity maturation.
Are carbohydrates T-dependent or T-independent antigens?
In general, carbohydrates are T-cell independent antigens, so only IgM production and no memory B cell formation. There’s no recognition by CD4 so no help for plasma cell formation and/or class switching!
What is the effect of a Glycoconjugate vaccin?
Coupling the polysaccharide to a protein carrier, so the protein with a part of the glycan will be presented to the T-cell which will provide help to the B-cell. This will result in an IgG response to the carbohydrate and memory B cell formation.
What are Tcarb?
The T-cells that respond to glyoconjugates are called Tcarb.
What is glycosylation and where is it present?
Glycosylation is glycans attached to polypeptides, in the ER & Golgi but also in the cytosol & nucleus. Almost all surface proteins are glycosylated.
What are Zwitterionic polysaccharides?
Zwitterionic polysaccharides are an exception of carbohydrates that dó give a CD4 T-cell response and activate APCs directly. But they still only give IgM responses, because they can’t be processed in B-cells.
What is the Zwitterionic charge motif and what does it cause?
CD4 T-cell activation depends on the zwitterionic charge motif, because this forms a helical shape which resembles the alpha-helix in protein peptides
How are Zwitterionic presented?
The zwitterionic polysaccharides are internalized by DCs via the C-type lectin DC-SIGN, cut into small pieces by nitric oxide and then presented on MHC II.
What is polysaccharide A (PSA) and what does it do?
PSA (an example of zwitterionic polysaccharide) maintains host-microbe symbiosis and induction of Tregs. A dysregulation of PSA can result in autoimmune disease.
PSA vaccination can protect against colitis (and other inflammation) due to the Tregs they induce and the IL-10 secretion.
What does CD1 recognize and on which cells is it expressed?
The CD1 molecule recognizes glycolipids. Humans have 5 CD1 molecules (CD1De is a chaperone) and mice only have 1 (CD1D). CD1 has also limited polymorphisms so we all have the same.
CD1 is present on APCs: DCs, macrophages and B cells, also when they’re immature.
Do CD1 molecules recognise lipids exogenous or endogenous?
Both, in the endocytic pathway the lipids are recycled via the cell surface membrane into the endosomes. The lipids can be both self or foreign.
Which CD1 molecules are recognized by CD4 and CD8 T-cells?
Conventional CD4+ and CD8+ T cells recognise CD1a, CD1b and CD1c.
By which cells is CD1d recognized?
CD1d is recognized by a special subset of NKT cells, which express both T cell and NK cell markers and have an Innate-like rapid response. A prototypic CD1d ligand is a-GalCer.
What is the effect of NKT cells?
The NKT cells have a fast and robust production of cytokines and chemokines, are cytotoxic and modulate behaviour of other effector cells.