MHC and APC jon Flashcards
Are PAMPs and antigens the same?
No, antigens what recognised by TCR and BCR. PAMPs recognised by PRRs.
What do TCRs and antibodies recognise?
TCRs recognise exogenous and endogenous pathogens via their presentation as a peptide sequence (sequential epitope)
Antibodies recognise the conformational epitope.
How is LPS recognised?
LPS binds to LPS binding protein (LBP) which associates with CD14. This LPS, LPB CD14 complex then associates with TLR4 which recognises portions of LPS.
Need to kill infected cells, but don’t want to kill phagocytic cells, what have they developed?
MHC I and MHC II pathway for presentation of exogenous (in endo-lysosomal compartments) and endogenous antigens.
What portions do CD8 and CD4 bind of MHC?
To invariant chains.
How many peptides in MHC class I? Which MHC has a larger groove?
nonomer in MHC I, MHC II has larger groove.
Where do the CDR variable regions bind to?
They bind to portions of the MHC and also to peptide antigen. CD3 most diverse formed at join regions.
Subunits of MHC I and II?
MHC I a1,2 and 3 with B2m. B2m also binds to CD1 and MR1 and (CMV UL18).
MHC II has a1 and 2 and B1 and 2.
class I classical and non-classical genes?
Class II classical?
HLA-A, B and C. non classical are HLA-E F and G.
HLA-DP, DQ DR. (DM involved in MHC II loading)
Is it likely that two individuals will have the same MHC haplotype?
NO because huge polymorphisms in each HLA gene. And both are co-expressed.
Are MHC specific?
NO they can bind a huge number of peptides.
What proteins associate with the MHC I after newly synthesised in the ER?
BiP initially binds, then calnexin chaperone binds along with ERp57. B2m then associates with the complex and calreticulin will replace calnexin.
Tapasin then associates with ErP57/calnexin and MHC-1 and brings it into association with the TAP transporter.
Roles of calnexin and ErP57?
Calnexin stabilises and prevents MHC I aggregation.
ErP57 catlyses the formation of disulphide bonds.
Roles of tapasin?
bridge betweeen TAP and MHC1 peptide loading complex.
Stabilises TAP transporter (which is ATP driven)
widens MHC I groove, so that only high affinity binding peptides are sufficient to close and release tapasin.
What kind of immunoproteasome is it? and what subunits? What cytokine induces its upregulation?
26S proteasome, 20S and 19S (cap) subunits.
IFN-y upregulates its formation.
What XYZ catalytic units of the proteasome are replaced?
X to LMP-7, Y to LMP2, and Z to MECL-1.
This allows it to cleave peptides preferentially at certain C terminal residues.
This helps TAP transport and MHC I anchoring.
What does ERAAP do>
IN ER after TAP transport will cleavepeptide at preferential N- terminal sites.
Hlep stable binding of peptides to MHC I.
4 ways that viral infections may inhibit MHC I expression?
By interfering with ERAP. US4-1 from CMV does this.
By directing MHC-1 for degradation within the ER. US11 (From CMV)
Reroutes the MCH -1 from to prevent expression on surface.
Creates proteins that prevent TCR Ab binding through steric hindrance.
What 3 things do all jawed vertebrates have?
GALT, thymus and spleen.
Classical and non classical MHC II?
HLA- DP DQ DR. non classical (low polymorphisms) HLA-DM HLA DO.
Function of HLA-DM and DO?
Regulate peptide laoding onto the MHC II.
HLA-DM binds MHC II in the endo-lysosome and CLIP is released. Opens MHC II wide enough so that only high affinity peptides bind.
HLA- DO regulates HLA-DM.
Steps of MHC II presentation?
Newly synthesised MHC II binds wiht the invariant chain trimer in the ER. This sterically inhibits binding of other peptides from the cytosol.
Invariant chain tail guides to endo lysosomal pathway
Here invariant chain is cleaved in a step wise manner to CLIP.
HLA-DM binds MHC II to release CLIP fragment and mediate antigen peptide binding.
HL
4 ways that viruses subvert MHC II presentaion.
- Inhibit acid mediated protease degradatino of antigen.
- modulate the MHC peptide complex.
- Interefere with the invariant chain.
- they interfere with CIITA (the transactivatory that binds to SXY enhancesome to reguate MHC II gene expression.
Where do antigens and DC and lymphocytes enter the lymph nodes and spleen.
Antigens and DCs through afferent lymph into subcapsular sinus. Lymphocytes mainly from the HEVs and leave through the efferent lymph.
In spleen they both come through blood and via the marginal zone.
Where do cells and molcules exit into interstitial fluid, and where do it then go?
Exit in capillaries and post capillary venules, interstital fluid goes into the blind ended lymphatics.
What three sections make up the white pulp in the spleen?
The marginal zone, the PALS and the primary follicle.
