Antigen Capture and Presentation Flashcards
MHC polymorphism
More than 150 separate alleles have been identified within MHC gene
Many alternative versions of each MHC gene
Co-dominant MHC expression
Haplotypes from both mom and dad are expressed simultaneously, creating more diversity
Structure of MHC class I
a-chain encoded by MHC locus, forms 3/4 globular domains (a1, a2, a3)
B2 microglobulin- non-MHC encoded. Forms fourth domain
MHC one binds peptides how long
About 8-10AAs in length
Synthesis/expression of peptide-MHC I complexes
Synthesized on the ER as a-chain glycoprotein, interacts with B2 microglobulin to form MHC I.
Protein broken down into peptides in cytosol are transported by TAP into the ER and loaded on to the MHC I
Then transported to Golgi and out to membrane
MHC II structure- binds peptides of what length
Two alpha and two beta chains- binds 13-18AAs long MHC class II has greater range of peptides that it can bind to than MHC I
CD8 binds what part of MHC I
a3 domain
CD4 binds what part of MHC II
B2 domain
Antigens entering peripherally are filtered by the ______ while antigens in the blood are filtered by
Periphery- lymph nodes
Blood- spleen
Major cytokines produced by classical dendritic cells
TNF, IL-6, IL-12, IL-23
Function/major cytokines produced by plasmacytoid DCs
Antiviral innate immunity and induction of T cell responses against viruses
Type I interferons
Activated DCs- what happens
Lose adhesive markers and upregulate CCR7
Increase expression of MHC and CD80
Travel to secondary lymphoid tissue
Present Ag to T cells
Presenting Ag on Class II MHC
Protein Ag is endocytosed and processed
Class II MHC synthesized in ER
Ii occupies the peptide binding cleft, MHC-II-Ii complex loaded into vesicle
Ii degraded to CLIP by lysosomal enzymes, HLA-DM facilitates exchange of CLIP for peptide Ag (in late endosome/lysosome)
Unbound MHCs are not displayed
Ankylosing spondylitis
Inflammation of the spine
Over 88% express the HLA-B27 allele
Possible that HLA-B27 cannot bind a critical antigenic peptide/present that peptide against the agent causing the disease
Rheumatic fever
Sequelae of streptococcus pyogenes infection
Generation of Abs against stept. cross react with cardiac tissue
More prone to develop this if you have HLA-DR4 allele