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51 Cards in this Set
- Front
- Back
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What does histcompatible mean?
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Tissue compatible
If in a transplant, the tissues are HLA compatible, good chance that the transplant will work |
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What is the fct of MHC I?
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Show self, process and present peptides to CD8+ T cells and restricts CD8+ T cells to MHC I
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What kind of Ag are found ass't with class I molecules?
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Virus fragments
Toxins Cancer Ag |
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What does CD8+ do?
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Enhances signallig
Key element of anchoring |
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What influences the decision of the T cell?
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What is picked up by dendritic cells and macrophages in the environment
The T cell can then decide whether or not to send more reinforcements, deal with the Ag or not, become a Th or Tc |
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What is the fct of MHC II?
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Process and present Ag to Th (CD4+)
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Wht is the tissue distribution of MHC II?
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APC:
Dendritic cells B cells Macrophages Activated T cells |
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What is the source of antigenic peptides for MHC II?
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Extrinsic to the cell
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Why is there a difference btw class I and II?
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Control
If any cell in the body could activate Th, would have a lot more trouble controlling what happens |
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Cytosolic pathogens:
are degraded in? peptides bind to? presented to? effect on presenting cell? |
Cytosolic pathogens:
Degraded in the cytosol Peptides bind to MHC Presented to effector CD8 T cells Presenting cell causes cell death |
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Cross-presentaton of exogenous antigens:
are degraded in? peptides bind to? presented to? effect on presenting cell? |
Cross presentation of exogenous Ag:
Degraded in the cytosol Peptides bind to MHC I Presented to Naive CD8 T cells Th presenting cell (usually a dendritic cell) activates the CD8 T cell |
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Intravesicular pathogens:
are degraded in? peptides bind to? presented to? effect on presenting cell? |
Intracellular Pathogens:
Degrade in endocytic vesicles (low pH) Peptides bind to MHC II Presented to CD4 T cells Activates presenting cell to kill intravesicular bacteria and parasites |
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Extracellular pathogens and toxins:
are degraded in? peptides bind to? presented to? effect on presenting cell? |
Extracellular pathogens and toxins:
degraded in endocytic vesicles (low pH) peptides bind to MHC II Presented to CD4 T cells Causes presenting cells to activate B cells to secrete Ig to eliminate extracellular bacteria/toxins |
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Describe Ag processing.
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Class I Ag are made in the cytosol
TAP ptn complex are constitutive and inducible ptns lined to the formation of the MHC (TAP 1/2) Intracellular ptns are degraded in the ctosol in the proteosome |
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How is TAP constitutive?
Inducible? |
Constitutive: Cstly facilitate mov't into ER that allows packaging into MHC I
Inducible: Can increase signal of Ag presentation |
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What happens in the proteosom?
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Ptns are degraded into peptides
These peptides are transported to the ER by the ATP dependent TAP ptns and packaged into MHC I |
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What is the structure of TAP?
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Has a hydrophobic transmb domain (extends into the lumen of the ER and across the ER mb)
ATP binding cassette (ABC) domain in the cytosol |
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What happens to MHCI after they are synthesized?
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1-Partly folded MHC I α chains bind to calnexin (mb bound ptn) until the β2-microglobulin binds
2- The MHC I αβ2m complex is released from calnexin, binds a complex of chaperone ptns (calreticulin, Erp57) and binds to TAP (a transporter) via tapasin 3-Cytosolic ptns and defective ribosomal products (DRiPs) are degraded to peptide fragments by the proteasome. TAP delivers peptides to the ER 4- The peptide binds the MHC I molec and completes its folding. The MHC I molec is released from the TAP complex and exported to the cell mb |
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What happens if TAP is inhibited?
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Cell can't present antigen
Tcyt won't know cell is infected |
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What happens if MHC I is retained in the ER?
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Ag doesn't go to the cell surface
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What happens if MHC I is degraded?
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Won't be stable, can't spend much time on the surface
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What happens if MHC I is not bound to a peptide?
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It is less stable, .: it must ass't with other ptns like chaperones, to help temporarily stabilize it
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How are MHC II processed?
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1) Ag is taken up into intracellular vesicles
2) In early endosomes of neutral pH, endosomal proteases are inactive 3) Acidification of vesicles activates proteases to degrade Ag into peptide fragments 4) Vesicles containing peptides fuse with vesicles containing MHC II molecules |
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How are MHC II formed?
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Made in the ER, but bind peptides in vesicles outside the ER
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How are MHC II prevented from binding peptides in the ER?
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Put in chaperones
Acts as surrogates, goes to ER and waits -> an invariant peptide chain binds in and blocks the groove in the newly formed MHC (class II thinks its complete and ends up in a secretory vesicle) |
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What happens to the invariant chain?
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-Invariant chain binds the groove of MHC II molec
-Invariant chain is initially cleaved toleave a fragment bound to the class II molec and to the mb -further cleavage leaves a short peptide fragment (CLIP) bound to he MHC II molec (end up with just the clip in the groove. ) (Invariant chain can act as a chaperone) |
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Where are MHC molec located?
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Specialized compartment called MIIC
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What are HLA-DM class II-like ptns? Where are they located?
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They are ptns that stabilize the MHC II ptns and facilitate peptide loading
Located in MIIC |
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How is MHC II stabilized?
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1)Invariant chain complexes with MHC II, blocking the binding of peptides and misfolded ptns
2) The invaraint chain is cleaved in an acidified endosome, leaving CLIP still bound to the MHC II 3) Endocytosd Ag are degraded to peptides in the endosome, but the CLIP peptide blocks the binding of peptides to MHC II 4) HLA-DM bind to MHC II, release CLIP and let other peptides bind. Then the MHC II can go to the cell surface |
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What are the characteristics of MHC?
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Polymorphic
Polygenic |
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How many dif MHC I are there on CHR? How many dif MHC II are there on CHR?
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MHC I:3
MHC II: 3-4 have 2 of each CHR .: 12-14 MHC's on CHR 14 dif pockets, 14 dif peptides |
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How many HLA are there on each MHC?
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3 HLA I: A, B, C (class I only has α chain)
class II has α and β |
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When is MHC expression increased?
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When faced with inflammation
-> MHC I and II genes upregulated by IFN-γ |
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What does IFN-γ upregulate?
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TAP1/2
MHC II and DM ptns: occurs via production of a class II transactivator (CIITA) |
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What happens if CIITA is missing?
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SCID
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What happens when you add IFN-γ to MHC I? MHC II?
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MHC I: hit cells with IFN-γ, start producing MHC I
MHC II: restricted to APC, .: IFN-γ acts on CIITA which will turn on MHC II Need this 2nd step of control |
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What are HLA 1B genes?
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Don't restrict T-cell fct
Group of MHC I-like cell surface ptns Involved in NK cell recognition Involved in iron metabolism |
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What are MIC molec?
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Part of the Class 1B genes
MHC-like molec can be induced in response to stress MIC A and B Are expressed in epithelial and fibroblast cells and may play a role in innate immunity NK, γδ T cells andsome CD8 have receptorss for MICs and can be activated by these ptns |
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What happens whe you sense danger?
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Inc stress
Inc MIC Inc innate .: inc NK |
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What are HLA-G/E?
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Class 1b ptns involved in NK activity
HLA-G expressed on fetal-derived placental cells. NK activity is inhibited by HLA-G on these cells (this is how fetus is kept alive) HLA-E inhibits cytotoxic activity of NK cells and .: cels expressing IgE are immune to NK killing |
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Why are NK cells more tightly regulated?
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Because they can go anywhere
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What happens to HLA-G/E during pregnancy?
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HLA-G is upregulated
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Are HLA polymorphic or monomorphic?
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Polymorphic
(only the DRα locus is monomorphic, all the others have many alleles) |
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Where is most of the variability in class I and II?
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In the pocket
specific sites in the amino terminal domains |
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What is alloreactivity? Ho many T cells does it affect?
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T cells reacting to dif MHC that does not belong to us
Affects up to 10% of T cells |
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What are 2 modes that may expain alloreactivity?
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1) Peptides bound to the allogeneic MHC molec fit well to the TCR, allowing binding even if there isn't a good fit with the MHC molec
2) Allogeneic MHC molec may provide a better fit to the TCR, tight binding that is less dependent on the peptide that is bound to the MHC (less common) |
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What are superantigens?
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Bacterial and viral ptns that stimulate T cell reponses without direct MHC processing
Can activate multiple (2-20%) T cell bearing similar Vβ regions Results in massive production of T cell cytokines and is ultimately immunosuppressvie |
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What is the ultimate superAg?
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anti-CD28
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What is the problem with superAg?
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Can activate the T-cells non specifically
Get massive inflammation signals Can get cytokine storm Multi-organ failure and cell death Virus/bact damage to turn immune system on itself |
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Where does the superAg bind?
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Outside of the groove (holds on tight)
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What are CD1 molec?
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MHC-like
Expressed on dendritic cells and monocytes Can present glycolipids to specific T cell (hard to present fat cells) Can present longer peptides Possibe evolutionay advantages for recognition of microbial lipids and glycolipids |
