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Q: What is MHC?
A: major histocompatiability complex
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Q: What is a syngeneic graft?
A: graft b/w genetically identical animals
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Q: What is the human equivalent to a syngeneic graft?
A: autologous graft
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Q: What is an allogeneic graft?
A: graft b/w individuals with dissimilar genetics
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Q: How do human transplants (allogeneic) work?
A: the immune response must be suppressed
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Q: What is a graft vs. host disease?
A: the graft attacks the host, usually marrow
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Q: What are the 2 classes of genes involved in graft rejection?
A: MHC Class I and MHC Class II
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Q: What are MHC Class I proteins in humans?
A: HLA antigens ( human leukocyte antigens)
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Q: What are MHC Class II proteins in humans?
A: DR, DQ, DP
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Q: Where are the MHC gene products found?
A: On cell surfaces
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Q: Are MHC gene products secreted?
A: No, they are cell surface receptors
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Q: What are the MHC Class I gene products (3)?
A: HLA-A, HLA-B, HLA-C
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Q: What is beta2 microglobulin
A: A protein that forms a heterodimer with class I protein
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Q: How many different Class I chains do humans have on each cell?
A: 6, due to co-dominant expression, A=B=C
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Q: List the MHC Class I protein domains (5)
A: Extracellular (3), alpha 1, 2 & 3, transmembrane, cytoplasmic
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Q: What domains houses the cleft?
A: the extracellular domains
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Q: How long is the peptide that fits in the Class I cleft?
A: approximately 9 amino acids
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Q: What domains are polymorphic on MHC I?
A: alpha 1 and alpha 2
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Q: Why is the alpha 3 domain constant, on MHC I?
A: so beta2 microglobulin can attach, as well as CD8 binding
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Q: Can we ever see the MHC I cleft empty?
A: No, either self, virus or degraded
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Q: What domain is polymorphic on MHC II?
A: alpha 1 and beta 1
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Q: What domains are constant on MHC II?
A: alpha 2 and beta 2
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Q: Where do the peptides for a Class I protein come from?
A: self or viral proteins synthesized in the cell
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Q: Class II proteins present peptides from?
A: extracellular entities
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Q: Enzymes that create peptides presented on the MHC II are?
A: endosomal/lysosomal proteases
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Q: Enzymes that create peptides presented on MHC I are?
A: cytosolic proteasomes
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Q: What is the site of peptide loading in the MHC II?
A: specialized vesicular compartments
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Q: What is the site of peptide loading in the MHC I?
A: endoplasmic reticulum (ER)
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Q: What is TAP?
A: tranporter associated with antigen presentation, class I
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Q: Which way does TAP transport peptides?
A: cytosol to inside the ER, backwards
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Q: What happens if an MHC doesn't have a peptide in the cleft?
A: it is degraded
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Q: Where does CD4 bind to MHC II?
A: beta 2 domain
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Q: What is a CLIP?
A: self peptide that is removed from MHC II so it can bind foreign peptides
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Q: What are TAP 1 & 2?
A: peptide transporters in the ER, for MHC I
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Q: What is co-dominant expression?
A: both parental alleles of each MHC gene are expressed
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Q: What does co-dominant expression do?
A: increase the number of different MHC molecules that can present peptides to T cells
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Q: What does antigen presentation refer to?
A: Peptides presented within MHC class I/II clefts to the T-cell receptor (TCR).
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Q: For T cell recognition of a foreign element, T cell will only recognize:
A: Peptides, linear sequences and the peptide in context.
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Q: What is MHC restriction?
A:Specific T cells recognize foreign peptide sequences within the cleft of a self MHC molecule.
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Q: Can MY T cells recognize a peptide in the cleft of YOUR class I/II proteins?
A: No, unless we have identical class I/II proteins.
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Q: How has the immune system solved the problem of killing both extracellular and intracellular pathogens?
A: It kills infected cells with cytotoxic T cells, and produces antibodies to neutralize extracellular pathogens.
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Q: What kind of cells have MHC class II molecules?
A: Antigen presneting cells (Accessory cells): B cells, Macrophages, Dendritic cells.
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Q: How do B cells take up protein? Is this method efficient?
A: Proteins is taken up through Ig complexes and complement receptors on the surface of the cell. This is very efficient, as Ig bind antigen with high affinity.
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Q: What are Langerhans cell, and where are they located?
A: They are dendritic cells, and are located in the skin.
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Q: What do dendritic cells do upon the uptake of antigen?
A: Process it and migrate from the periphery into lymph nodes for activation of T cells.
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Q: What organelle is responsible for digestion of antigen into peptides for the exogenous pathway?
A: lysosome
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Q: Which MHC molecule has an invariant chain prior to being loaded with a peptide?
A: MHC II
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Q: Where is the MHC II loaded with peptides and, are these peptides derived from endogenous or exogenous proteins?
A: The MHC II is loaded in the vescle formed by the fusion of the lysosome with the MHC vesicle. The peptides are of exogenous origin.
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Q: Where is the MHC I loaded with peptides, and what organelle generates these peptides?
A: The MHC I is loaded in the RER with peptides that have been generated from the proteasome.
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Q: How long do peptide expressing MHC I/II exist on the cell surface?
A: MHC II lasts about 12 hours, MHC I has a half-life of 10-15 hours.
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Q: MHC II is loaded with what peptides?
A: exogenous
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Q: MHC I is loaded with what peptides?
A: endogenous
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Q: What is the origin of most peptides found in the MHC I in a healthy person, and in a person with a cold?
A: self proteins, viral proteins.
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Q: What is the origin of most peptides found in the MHC II in a healthy person, and in a person with strep throat?
A: self proteins, bacterial proteins.
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Q: What cells express class I proteins?
A: virtually all cells.
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