Lesson 7 Flashcards
Which cells are antigen presenting cells (APCs)?
the main cell types involved are macrophages, dendritic cells and B cells but all our cells can be APCs
Which is the function of APCs?
it is to show up the MHC class I and II molecules.
Describe generally the maturation of the naive T cell
This process happens inside the lymphoid organ for the naïve T cells (a T cell that has never encountered an antigen to which has a specific receptor): T cells exit from the thymus and circulate in our body through the blood or the lymphatic circulation. The APCs, loaded with all the stranger peptides, start to be contacted by many T cells, each with different TCR. The one with a specific TCR able to recognize the peptide and the MHC will start to contact in a stronger way the APCs, even contacting other molecules on the APC.
How can a dendritic cell phagocytise its target?
they can easily phagocytise through the normal PRR, but they can also phagocytise everything that is opsonised by the complement
Describe generally the maturation of the dendritic cells
1- They are able to migrate, so they are not stacked in the tissues.
2- After the migration they start a program of maturation (in the tissues they are immature cells)
3- To perform the maturation, they start to express a very important chemokine receptor (CCR7) useful for the migration to the lymphoid organ
4- During the travelling they change the expression of some membrane molecules (class I or class II)
5- Then they’re contacted by several T cells but only those with the compatible TCR will interact
6- Once mature, they transform themselves in antigen presenting cells. They have to migrate where the T cells are more abundant in the lymphoid organ
Comparison: dendritic cells, macrophages, B cells. LOCALIZATION
The location is different, in fact the dendritic cells are everywhere, the macrophages are found in different tissues (the lymphoid tissue, connective tissue, the pleura, the pericardium, etc.) and the B cells are only present in the lymphoid tissue.
Comparison: dendritic cells, macrophages, B cells. LEVEL OF EXPRESSION OF MHC COMPLEX
The level of expression of the MHC complex is different: all of them constitutively expressed it but the macrophages and the B cells start to express this molecule after having received some signals (inducible).
Comparison: dendritic cells, macrophages, B cells. EFFECTS
The effects are quite different: the dendritic cells are the only one able to activate the naïve T cells, while macrophages and B cells can activate only the T cells which are pre-activated by the dendritic cells (not naive T cells).
Which proteins can be shown by the MHC molecules?
- Endogenous proteins (class I): our proteins, endogenous bacteria, viruses or some tumoral antigens. CD8T cells (cytotoxic T cell) recognize intracellular peptides and this recognition leads to the direct target cell disruption
- Exogenous proteins (class II): generated by phagocytosis. CD4T cells (helper T cell) recognize it and secrete cytokines in order to communicate with all the immune cells
How does the structure of the proteasome changes during an infection?
The structure of the proteasome can change during the infection: the interferon-γ (usually produced during viral or endogenous bacterial infection) is able to increase the expression of two different components of the proteasome: LMP2 and LMP7.
LMP2 and LMP7 are slightly polymorphic genes located inside the HLA class II complex, they can change the proteasome in an immunoproteasome, which is able to cut the hydrophobic residues necessary to the binding of these peptides on APCs. The immunoproteasome is more prone to produce the peptides allocated in the MHC class I groove.
Which is the main difference between a proteasome and an immunoproteasome?
proteosomes are able to cut only proteins targeted by the ubiquitin, immunoproteasomes, in presence of cytoines, became able to cut non-ubiquitinated protein
How does a MHC class I obtain the peptide to show? (process)
1- The peptides come out from the proteasome and are quickly digested in the cytosol by peptidase or aminopeptidase
2- Some peptides manage to rescue themselves thanks to the presence of specific transmembrane transporters located on the ER membrane
3- These transporters allow the entrance of the peptides in the reticulum: they’re made by two molecules (TAP1 and TAP2) whose genes are located in the MHC class II complex.
4- Then, class I molecules are synthesized
5- They are initially associated to some chaperonin (to maintain the 3D structure) called calnexin and calreticulin
6- β2-microglobulin substitutes the chaperonins
7- Another chaperonin called tapasine supports MHC class I molecules. The binding with the tapasine allows all the peptides to enter the reticulum thanks the TAP transporters.
8- All the molecules, MHC class I, β2 and the peptides, are presented to the cellular membrane through normal vesicles transport, which implies Golgi for post-translational modifications.
HLA class I and class II: which kind of proteins are shown?
- Endogenous proteins (class I)
- Exogenous proteins (class II)
How does a MHC class I obtain the peptide to show? (process)
When something is phagocyte, the phagosome will fuse with the lysosome and the proteins are degraded (without the involvement of the proteasome).
In the meanwhile, there is the synthesis of the MHC class II molecules inside some vesicles, these vesicles will fuse with the ones containing the peptides and a bound will be formed.
Then, through the process of exocytosis they can be exposed on the cell surface.
Which is the role of DP, DM and DO in the presentation of exogenous peptides?
BOHHH
