Lecture 8 Flashcards
How many signals do T cells need to get activated? Name them.
- TCR-peptide+MHC
- Costimulation: CD28-B7
- Cytokine
How do dendritic cells change with PAMP binding?
↑MHC 1 AND2
↑B7 = costimulatory molecule
Change chemokine receptors to move toward lymph node for T/B cell stimulation
From phagocytosis role –> processing machine
Do APCs always express costimulatory molecules?
NO - must undergo maturation to express these
DC & macrophages ↑costim molecules after binding PAMPs, getting proinflam cytokines of CD40-CD40L
B cells must be induced by T cells via CD40-CD40L
Do all T cells require co-stimulation?
NO
Naive - always
Memory - sometimes
Effector - no
What are plasmacytoid DCs?
Innate immunity
Make a lot of type IFNs when activated
What are fDCs?
@ secondary lymph organs
Not - MHC restricted
Display antigen to B cells
What are CD8+ DC cells?
DC cells that can express MHC1
Which has higher precursor frequency: pathogens or non-self MHC?
Non-self MHC = higher precursor frequency
For MHC2, which chains are MHC encoded - alpha or beta?
BOTH
For MHC1, which chains are MHC encoded? Alpha or beta2 microglobuin?
Alpha aka the heavy chain ONLY
What are superantigens?
Creates peptide non-specific TCR/MHC interactions
General T cell activation - cytokines aren’t antigen specific = non-specific inflammation
What 5 molecules are critical for MHC1 antigen processing?
- Chaperones = calnexin, calreticulin
- Tapasin - holds MHC 1 near TAP
- TAP brings in peptides
- Proteosome - unique to MHC1!
- ERAAP - customizes peptides for the specific MHC
Describe the proteosome used for MHC1 peptide presentation.
20s core
Alpha & beta subunits = proteolytic
C term creates peptides that are more likely to bind MHC 1 molecules
Fxn upregulated by IFN gamma
- + PA28 cap to speed up peptide production
What is the source of protein antigens for MHC 1 vs 2?
1: Sometime phagosomes but usually proteins in the cytosol
2: Endosomal/lysosomal proteins internalized from extracellular environment
What is cross priming?
CD8 DCs!!!!!
The ability of APCs to present on MHC1s
TAP dependent
B/C NEED COSTIM
What is alloreactivity?
Reaction to non-self MHC
Think of transplant
MHCa + MHCa - identical match vs small DNA differences due to polymorphisms
Which viruses block peptide entry into the ER to evade immune response?
Herpes simplex 1
Human cytomegalovirus
Bovine herpes
Which viruses retain MHC1 in the ER to evade immune response?
Adenovirus
Human cytomegalovirus
Murine “ “
Which viruses degrade MHC 1 to evade immune response?
Human cytomegalovirus
Murine gamma herpes
What virus binds MHC 1 at cell surface to evade immune response?
Murine cytomegalovirus
How can you increase avidity?
Tetramer of MHC-peptide with TCR
Why would you have a MHC2 deficiency? What is the net effect?
Lacking TFs
NO CD4 cells
EX: Coeliac
Why would you have a MHC1 deficiency? What is the net effect?
TAP mutation
Beta2 microglobulin mutation
NO CD8 cells
Why do we care about peptide anchor residues?
Predict which peptides will bind well to particular MHC alleles
- Vaccination
- Looking for antigen-specific T cells
- Tumor immunology
