part 6 Flashcards
what is the endomembrane system
ER, Golgi, transport vesicles, endosomes, lysosomes.
what are the functions of the endomembrane system
transportation, storage, degradation, and production
what are clathrin
a set of proteins that allow for the formation of the endosome as a pathogen is being taken in.
Found on the surface of the cell.
what is cathepsin
Cysteine proteases
S, L, B, D
Need an acidic environment to be activated (acidification).
what are the four types of cathepsin
S: almost all APCs express this enzyme
L: expressed in thymic cortisol cells (T cell training in thymus)
B and D: plays a role, but not much.
what pathogens bind to MHC I
cytosolic
what pathogens are are presented to CD8 cells
cytosolic
cell death
what pathogens are presented on MHC II
intravesicular and extracellular
what pathogens are presented to CD4 cells
intravesicular and extracellular
how are intravesicular pathogens neutralized
activates killing; endocytic vesicles (low pH)
how are extracellular pathogens neautralized
presenting cell activates B cells to secrete Ig; endocytic vesicles (low pH)
what are TAPs
transports peptides from the cytosol into the endoplasmic reticulum, thereby selecting peptides matching in length and sequence to respective MHC class I molecules
how many TAPs are there
1 and 2
how long are the peptides TAP transports
8-16 AAs long
what are the physical properties of TAP
TAP 1 and 2 transversing the membrane, with ATP binding cassesttes exposed on cytosol side
what is the proteasome complex
Tube-like complex
Degradation complex
Takes chains of amino acids and chops them.
Main type of proteasome completely degrades proteins.
what are the parts of the proteasome complex
The catalytic chamber (20S Core) is where digestion takes place.
Made up of 7 columns; 4 proteins per column.
Ubiquitin protein: highly-conserved, about 73 amino acids long
Targets proteins for degradation (tagging).
19S regulatory particle of proteasome binds to ubiquitin
what is ubiquitin? why is it important
a protein found in most tissues (ubiquitous)
Proteins are marked for degradation by the attachment of ubiquitin to the amino group of the side chain of a lysine residue
what is the immunoproteasome complex for
antigen presenting
what does interferon secretion upregulate
upregulates the amount of MHC I presented on the surface, which allows for upregulation of TAP LMP2 and LMP7, (MECL-1) (core protein)
PA28 (regulatory proteins)
what is the first step of MHC I expression
Partially folded MHC class I alpha chains bind to calnexin (chaperone protein) until B2-microglobulin binds.
what is the second step of MHC I expression
MHC class I alpha:beta complex is released from calnexin, binds to chaperone complexes (calreticulin and ERp57) and binds to TAP via tapasin
what does tapasin do
associates with TAP
what is ERp57
thioreductase (breaking disulfide bonds)
what are DRiPs
About 30% of all proteins are defective (DefectiveRibosomalProducts)
DRiPs are chopped up by proteasome
what is the third step of MHC I expression
Cytosolic proteins and DRiPs are degraded to fragments by proteasome. TAP delivers peptides to ER.
what is TRiC
protects peptides from being degraded as they move to TAP.
what is ERAAP
cuts and modify TriC from peptides
what is the fourth step of MHC I expression
Peptide binds to MHC and the MHC finishes its folding. MHC is released from the TAP complex, is transported, and is expressed on cell membrane.
how do viruses evade being destroyed by the immune system
by messing with the MHC, TAP, and MHC chaperone complex
Herpes, adenovirus
what happens in early endosomes when antigen is first taken in
pH is neutral and endosomal proteases are inactive.
Chloroquine prevents acidification of endosomes.
what is the first step of MHC II expression
Antigen is taken into the cytosol by vesicle
what is the second step of MHC II expression
Acidification within the vesicle activates proteases to degrade antigen into peptide fragments.
what is the third step of MHC II expression
Vesicles containing peptides fuse with vesicles containing MHC II molecules, where the MHC II is later expressed on the surface of the cell.
what happens to the MHC II vesicle as it moves to the surface of the cell
it moves through different vesicles
what maintains MHC II when not bound to pathogen proteins
bound to invariant protein
what is the structure of an invariant protein
9 protein complex
where is the invariant protein bound on MHC II
binds in the groove of MHC II
what is the first step of invariant cleaving
Ii is cleaved initially to leave only a fragment bound to MHC II and membrane
what is the second step of invariant cleaving
Ii is further cleaved into CLIP, which is only bound to the MHC II molecule
what swaps the invariant with the antigen for MHC II
HLA-DM swaps invariant chains with the antigen (peptide editing)
what does HLA-DM resemble
resembles MHC II with no binding site.
where/when is the invariant switched with the antigen
MIIC (a compartment) is where HLA-DM swaps CLIP with antigen
During second step
what produces more HLA-DM
IFN a, b, and g
what does HLA-DO do
it is an inhibitor to HLA-DM and competitor of HLA-DM
when are self-peptides expressed
presented on MHC II in order for cell replacement in the periphery
Tolerance
what is special about dendritic cells
A dendritic cell (swallows cell) can take an antigen presented on MHC and present it on themselves.
