Test 3 Flashcards
How does the exposure to pathogens select for MHC polymorphism?
unique presentation of a key antigen keeps the population alive
MHC Class I peptide derivation
cytosol
MHC Class II peptide derivation
endocytic vesicles
Proteasome
1 20S and 2 19S components
20S component
made up of 4 rings, 7 subunits each; hollow core lined with proteolytic subunits
protealytic subunits
B1, B2, and B5
What does the proteasome recognize?
polyubiquination
Enzyme for ubiquitinization: E1
ubiquitin activating enzyme; adds ubiquitin to Lysine
Enzyme for ubiquitinization: E2
ubiquitin conjugating enzyme; adds ubiquitin to Lysine
Enzyme for ubiquitinization: E3
ubiquitin ligase
Trigger for the Immunoproteasome
IFN-y secreted by NK and T-cells
Immunoproteasome: instead of proteolytic units
LMP2, LMP7, and MECL 1
MECL1
DIFFERENCE from proteasome; allows to cut after hydrophobic resides
PA 28 Caps
allow for increased rate of releasing peptides and helps get peptides to proper length
TAP
transporters associated with antigen-processing; heterodimer in ER membrane that shuttles peptides into ER; requires ATP
Calnexin
what MHC Class I a-chains binds to in the ER
MHC Class I peptide loading complex
calreticulin, tapasin, Erp-57
calreticulin
holds MHC in partially folded state
tapasin
holds MhC close to TAP
Erp-57
protects disulfide bonds in MHC
invariant chain
forms a trimer; final destination info is found on this; the final destination is endocytic vesicles
cathepsin S
cleaves Ii until the CLIP remains in the peptide binding cleft
HLA-DM
NEVER FOUND AT THE SURFACE; governs the removal of CLIP and finding of correct peptide
HLA-DO
NEVER FOUND AT THE SURFACE; acts as a negative regulator of HLA-DM; expression NOT increased by IFN-y
Cross presentation
ability to understand that the peptide is form a virus infected cell so it puts it in an MHC Class I instead of Class II
What changes the chemokine receptors expressed on dendritic cells?
toll-like receptors
CCR7
expressed when it enters the lymph node; sensitive to CCL19 and CCL21
CCL19 and CCL21
secreted from lymphoid tissue; attract T-cell to lymph node
What is shutoff while dendritic cells are circulating?
phagocytosis
Dendritic cell in the lymph node
high expression of MHC I and II because of high levels of B7.1 and B7.2
CCL18
secreted to bring T-cells into lymph nodes
naive T-cell
out of the thymus and not activated
L-selectin
binds to GlyCAM-1 and CD34 to allow rolling adhesion
CCL21
strengthens the LFA-1 and ICAM-1 interactions
sulfated sialyl Lewis-X moity
has to do with extravasation and diapedesis of T-cells
T-cell Dendritic Interaction: 1
T-cell/Dendritic LFA-1/ICAM-1
T-cell Dendritic Interaction: 2
T-cell/Dendritic ICAM-3/DC-SIGN
S1P
highest concentration found at the exit of lymph node to keep T-cell moving
Protein kinase
phosphorylation at serine, threonine, and tyrosine activated by dimerization
scaffold proteins
large, many interaction domains
adaptor proteins
smaller, less interaction domains
G-proteins
small GTPases; inactive: bound to GDP, active: bound to GTP
GEF
Guanine Exchange Factor; inactive to active
GAP
GTPase Activating Protein; active to inactive
second messengers
small biochemical mediators
phosphotidyl kinases
PIP2 to PIP3; Pleckstrin Homology Domain binds to PIP3
ITAM
intracellar domain of T-cell receptor and CD3 complex; phosphorylated and triggers next events
Lck
activated upon correct binding and will activate ITAM
ZAP-70
2 SH2 domains; binds to zeta tails and is phosphorylated by Lck
Phosphorylation of ZAP-70
triggers the recruitment of LAT and SLP76
Gads
linker between LAT and SLP76
Gads:SLP76:LAT complex
recruits Phospho-lipase C
B7.1 B7.2 and CD28
phosphorylated by LCK and recruits PI3K
PI3K
changes PIP2 to PIP3
PIP3
recuits Itk
Itk
phorphylates Phospho-lipase C
DAG
only different within membrane; made from the breakdown of PIP2; 2 transcription factors
IP3
completely different; made from the breakdown of PIP2; 1 transcription factor
Activation of NFAT
draw it
Activaiton of DAG
draw it
Activation of NFkB
draw it
Dendritic cytokines
triggers the T-cell into the G1 phase of the cell cycle
IL2
important for cell proliferation
Naive T-cell IL2 receptor
only B and y domains
Activated T-cell IL2 receptor
a, B, and y domains
T-cells
proliferate multiple times per day for multiple days
What allows effector T-cells to be recruited to infected tissues?
changes in surface proteins
VLA-4
expressed instead of L-selectin, binds with VCAM-1 that is upregulated on infected cells
VCAM-1
upregulated on infected endothelial cells
LFA-1
important for contacting target cells; conformational change increases the interaction with ICAM-1
T-cell immunity
cell-mediated immunity
Cytoskeleton rearrangement at the site of contact
microtubule organization center lines up with the Golgi
site of contact
SMAC and immunological synapse
What does a CD8 need extra for costimulation?
it must also bind to a CD4 effector T-cell
B7 interaction
CD4 and Dendritic; causes production of Il-2 by CD4; causes upregulation of Cd40 ligand to bind to CD40 receptors on dendritic
Upregulation of B7
dendritic now upregulates B7 molecules to help the CD8 get activated
CD8: Apoptosis
nuclear and membrane blebbing and fragmentation of DNA (200 bp)
CD8: Cytotoxic Granules
perforin, granulysin, serglycin, and granzymes
perforin and granulysin
get inside the target cell
serglycin and granzymes
keeps everything together
granzymes
5 different ones; they’re all serine proteases
Granzyme B: Pathway 1
cleaves and activates BID; TBID interacts with mitochondria to exocytose cytochrome C
Granzyme B: Pathway 2
cleaves and activates Caspase 3; caspase cascade leads to the activation of CAD
CAD
fragments DNA
TH1 cells
activate microphages
TH17
(REGULATORY) enhance neutrophil response
TH2
activates cellular and antibody response to parasites; only Ab is IGE
TFH
help B-cells secrete their Ab
Treg
(REGULATORY) keeps the T-cells in control by stopping dendritic cells from activating T-cells
