Flashcards in Activation of Adaptive Immunity Deck (29):
What are the two ways an APC (macrophage or dendritic cell) can activate a T cell?
1. TLR binds a PAMP then produces cytokines (IL12, 6, TNF alpha)
2. takes in pathogen/Ag, chews it up, throws it out on an MHC for TCR to see
Where are type 2 HLA found?
APCs: Dendritic cells, macrophages, b cells and T helper
Where is HLA controlled from?
How many haplotypes does a human have for HLA?
2, one from mom, one from dad
What are the class 1 HLA genes?
HLA-A, HLA-B, HLA-C
Where are class 1 expressed? What do they do?
All nucleated cells, present antigen to CTL and inhibit NK cells
What are the parts of HLA 1?
Three alpha units and 1 beta unit
What regions of HLA 1 are encoded by HLA?
a1, a2, a3
What limits the size of HLA1 peptides?
Closed ends on the protein, limits to 8-10 AA
Where is HLA 1 made?
In the ER as a glycoprotein, in the ER the beta subunit associates, then in the ER the peptide binds to the receptor and moves to the cell surface
What are the HLA 2 subtypes?
HLA-DP, HLA-DQ, HLA-DR
What is the structure of HLA2?
It is made of an alpha and beta unit which are roughly mirrors of each other
How many peptides does HLA2 bind?
Between 13-18 because the ends are open
What domains of HLA2 have the greatest polymorphism? Where are they from?
a1, b1, they come from DQ
What binds to HLA2 in the ER? What does it do?
Invariant chain, it directs the protein to an endosome where the invariant protein is removed and the peptide is allowed to bind
How many alpha and beta chains do we have for HLA2?
6a and 6b; you get 3 from each parent and they can combine in any combination of a and b
What are the features of peptide binding to HLA
They are slow to bind and even slower to come off because you want T and B cells to be able to recognize the protein as problematic before it is removed
What are our antigen presenting cells?
B cells, macrophages, dendritic cells
What is the HLA2 pathway for antigen processing?
The protein is taken into the cell-> endosome and lysosome bind and degrade the protein -> HLA2 is made in ER and invariant chain is attached -> endosome carrying degraded protein and HLA2 are fused -> CLIP removes portion of invariant chain -> HLA-DM removes CLIP from HLA2 -> protein binds to HLA2 -> whole complex is transported to cell surface
What is the pathway for HLA1 antigen processing?
Protein inside cells is degraded by proteasome -> degraded pieces are taken up by TAP which moves it into the ER lumen -> TAP is connected to HLA1 by tapasin on the lumen -> the complex forms -> moves to golgi -> vesicles dumps complex in cell surface
What is cross presentation?
When one thing is recognized by both CD8+ and CD4+ t cells
What is Ankylosing spondylitis associated with?
Inflammation of the spine based on overexpression of HLA-B27
What is rheumatic fever?
After effect of S. Pyogenes infection; Ab created cross react with the heart
patients with HLA-DR4 allele are more likely to get it
What is sjogren’s syndrome?
Associated with HLA-DR3
Defect in salivation and lacrimation
What HLA is Type 1 DM associated with?
What HLA is psoriasis associated with?
What cancer has an antigen processing defect?
Renal cell carcinoma
Down regulated TAP protein (transports peptides into ER lumen)
What is bare lymphocyte syndrome?i
Defect in TAP protein that doesn’t transport peptides in so there are no peptides expressed on the cell surface (no HLA1 on cell surface)