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97 Cards in this Set
- Front
- Back
T-cells only recognize processed Ag presented on what?
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Only processed Ag presented on MHCs.
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Ag presented on an MHC may also be referred to as what?
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May be referred to as an HLA complex in humans and H-2 in mice.
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In what mammalian species are genes that constitute MHCs present in?
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They are present in EVERY mammalian species.
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MHCs are implicated in susceptibility to ? and ?.
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Implicated in susceptibility to disease and autoimmunity.
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MHCs are important for discrimination between what?
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Important for discrimination between self and non-self.
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When were MHCs discovered?
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They were discovered during studies of rejection to transplanted tissue.
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MHC encodes how many classes of molecules?
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MHC encodes 3 major classes of molecules.
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Name the 3 major classes of molecules that are encoded by MHC.
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1. Class I MHC genes
2. Class II MHC genes 3. Class III MHC genes |
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Describe class I MHC genes.
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They encode glycoproteins found on the surface of nucleated cells. It present Ags to Cd8/TC cells.
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Describe class II MHC genes.
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It encodes glycoproteins on APCs to present processed Ags to CD4/Th cells.
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Describe Class III MHC genes.
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They encode various secreted proteins that have immune functions. (ie, complement and other inflammatory mediators)
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In both humans and mice how is MHC organized?
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It is organized into regions.
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Class I MHC genes and Class II MHC genes have common ? features.
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They have common STRUCTURAL features.
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Class III MHC genes are flanked by what? What do class II MHC genes encode?
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They are flanked by I and II regions. They encode molecules critical to immune function (ie, complement and cytokines)
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?, ?, and ? arranges in pairs encoding alpha and beta chains.
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DP, DQ, and DR arrange in pairs encoding alpha and beta chains.
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MHC gene expression is related to a cluster of genes found where?
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A cluster of genes found on CHROMOSOME 6.
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Chromosome 6, as it relates to gene expression, could be described as what? Why?
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It is polygenic and polymorphic. It has several gene loci. It has many alleles (gene versions)
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All alleles are not found with ? ? in humans.
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All alleles are not found with equal frequencies in humans.
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MHC diversity is a ? ?.
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It is a population diversity.
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What is a set of MHC genes inherited from each parent called?
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It is called a HAPLOTYPE.
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What is the probability of siblings inheriting identical haplotypes from both parents?
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Sibling have a 1 in 4 probability of inheriting the same haplotypes.
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What makes tissue matching between unrelated relative very unlikely?
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MHC polymorphism makes this very unlikely.
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Why is MHC polymorphism so powerful?
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It is powerful because it enable different allelic class I and Class II products to bind an ALMOST infinite array of peptides.
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A class I molecule has a ? ?, while class II has a ? ?.
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Class I has a deep socket, II has an open pocket.
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Class I has an ? chain with ? domains.
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Class I has an alpha chain with 3 domains.
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In class I which alpha chain is highly conserved and has a sequence of amino acids that interacts with Tc/CD8.
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alpha 3
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Class I has ? microglobulin.
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It has Beta 2 microglobulin.
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What is Beta 2 microglobulin required for?
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It is required for Class I expression.
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Class II is composed of two ?-? chains.
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Composed of two non-identical chains.
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What are the two non-identical chains of class II composed of?
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They are composed of two alpha domains and two beta domains.
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It could be said that MHC molecules are what? Explain.
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They are promiscuous. They do not exhibit the specificity of Abs and TCRs.
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How many allelic variants of MHC are there in humans?
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There are several hundred allelic variants in humans.
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How many class I and class II molecules are expressed by an individual?
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Every individual only expresses up to 6 different class I molecules and up to 12 different class II molecules.
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Peptide binding sites are ?.
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They are POLYMORPHIC.
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What is an anchor residue?
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Amino acids that anchor the peptide into the MHC groove. It should be noted that all peptides that binds to Class I molecules contain a carboxyl terminal anchor that are usually hydrophobic (leucine, isoleucine).
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The peptide binding domain of Class I molecules?
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Alpha 1/ Alpha 2.
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The peptide binding domain of class II molecules?
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Alpha 1/ Beta 1
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The nature of the peptide binding cleft of class I molecules?
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It is closed at both ends.
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The nature of the peptide binding cleft of class II molecules?
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It is open at both ends.
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The general size of bound peptides of Class I molecules?
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8-10 amino acids.
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The general size of bound peptides of Class II molecules?
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13-18 amino acids.
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The peptide motifs involved in binding to MHC molecule for class I molecules?
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Anchor residues at both ends of peptide; generally hydrophobic carboxyl-terminal anchor.
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The peptide motifs involved in binding to MHC molecule for class II molecules?
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Anchor residues distributed along the length of the peptide.
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The nature of the bound peptide for class I molecules?
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Extended structure in which both ends interact with MHC cleft but middle arches up away from MHC molecule.
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The nature of the bound peptide for class II molecules?
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Extended structure that is held at a constant elevation above the floor of MHC cleft.
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MHC molecules are ? diverse. Explain.
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They are ENORMOUSLY diverse. This diversity is seen within a species and within an individual.
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Is MHC diversity for the same reasons that Abs and TCRs are diverse? Explain.
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No, it is not the same. Abs and TCR are dynamic and changing. MHCs are fixed in the genes and do not change.
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MHC expression is dependent upon ? type.
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Dependent upon CELL-TYPE.
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Where is MHC I found?
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On all NUCLEATED CELLS.
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Where is MHC II found?
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Found only on APCs.
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Where are the highest levels of MHC I found?
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The highest levels are found on lymphocytes.
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Name 4 cell types that express low levels of MHC I?
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1. Neural cells
2. Fibroblasts 3. Muscle cells 4. Hepatocytes |
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Which cells appear to lack MHC?
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Neurons and sperm cells (at certain stages) appear to lack MHC.
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MHC II is found only on APCs. What does expression depend upon? Explain.
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Expression varies depending on cell differentiation stage. Pre-B-cells lack MHC II. Low levels on monocytes and macrophages until activation by Ag and then level of expression dramatically increases.
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Is MHC expression regulated.
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Yes, it is regulated.
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List 3 things that are involved in the regulation of MHC expression?
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1. Transcription Factors
2. Various cytokines 3. Viruses |
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How are transcription factors involved in the regulation of MHC expression?
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MHCs are flanked by 5' promoter sequences. They are mediated both positively and negatively.
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How are various cytokines involved in the regulation of MHC expression?
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INFs and TNF increase MHC I expression. IL-4 increases the expression of MHC II on resting B-cells.
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Name 3 viruses that are involved in the regulation of MHC expression.
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1. CMV
2. HPV 3. AD12 |
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Bare lymphocyte syndrome is the result of what?
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It is the result of a defect in TRANSCRIPTION.
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How many MHCs do BLS patients express?
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Bare lymphocyte syndrome patients express little to no MHCs.
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BLS patients expression of little to no MHCs leads to an increased susceptibility to what?
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They have an increased susceptibility to viral and opportunistic infections.
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What are the symptoms seen in BLS patients?
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The symptom range from none to SCID (Severe combined immunodeficiency).
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A defect in what 2 genes is involved in BLS syndrome? Explain.
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A defect in TAP1 and TAP2 genes. These TAP proteins are required for the loading of peptides.
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List 5 diseases that compromised MHC leaves you susceptible to?
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1. Autoimmune disorders
2. Some viral diseases 3. Complement disorders 4. Neurological disorders 5. Some allergies |
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Give an example of an autoimmune disorder that a person with compromised MHC expression is susceptible to?
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HLA B27 allele (Ankylosing Spondylitis)
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Give an example of a neurological disorder that a person with compromised MHC expression is susceptible to?
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HLA-DR2 (Narcolepsy)
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In the 1970s it was discovered that both ? and ? T-cells could recognize Ag only when couple with a ?-? molecule.
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Both CD4 and CD8 T-cells could recognize Ag only when coupled with a self-MHC molecule. This is related to self-MHC restriction.
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T-cells require ? Ag.
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T-cells require PROCESSED Ag.
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The target cells involved in Ag processing and presentation display what?
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They are cells that display peptides associated with MHC I to CD8/Tc cells.
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APCs associated with Ag processing and presentation display what?
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They display peptides associated wtih MHC II to CD4/Th cells. (However, sometimes APCs can present Ag on MHC I).
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APCs must express ? ? and deliver a ? signal.
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APCs must express MHC II and deliver a co-stimulatory signal.
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List 3 professional antigen presenting cells.
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1. Dendritic cells (several types)
2. Macrophages 3. B cells |
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What are the most effective professional antigen presenting cells?
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Dendritic cells
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What must macrophages be activated by before they become an antigen presenting cell?
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They must be activated by phagocytosis.
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B-cells constitutively express ? but require activation before they express ? molecules.
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They express MHC II but require activation before they express costimulatory molecules.
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Dendritic cells express MHC II. What else do they have the ability to use?
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They can also use MHC I.
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Dendritic cells are ?. Why is this fortunate?
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They are NUCLEATED. This is fortunate because most viruses infect cells other than APCs. This relates to "altered self-cells".
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Give 3 examples of altered self-cells that can serve as targets for viruses?
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Cancer cells, aging body cells or allogenic cells from a graft can serve as targets for dendritic cells that use MHC I.
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How are intracellular and extracellular Ags trafficked?
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They are trafficked through separate intracellular compartments.
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List two intracellular compartments by which intracellular and extracellular Ags may be trafficked through.
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1. Cytosolic Pathway
2. Endocytic Pathway |
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The cytosolic pathway is responsible for processing which Ags? Where is it presented?
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Responsible for processing endogenous Ags. (Like viruses replicating within a nuceate host cell). It is presented on membrane with MHC I.
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The endocytic pathway is responsible for processing which Ags? Where is it presented?
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Processes exogenous Ags. It is presented on the membrane with MHC II.
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In eukaryotes, ? levels are regulated.
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Protein levels are regulated.
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In the cytosolic pathway for endogenous Ags intracellular proteins are degraded into ? ? by ?.
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Intracellular proteins are degraded into SHORT PEPTIDES by PROTEOLYSIS (PROTEOSOME).
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In the cytosolic pathway for endogenous Ags, the protein targeted for proteolysis has what associated with it?
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It has UBIQUITIN associated with it.
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List the 5 steps for the pathway of class I MHC-associated antigen presentation.
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1. Production of proteins in the cytosol.
2. Proteolytic degradation of cytosolic proteins. 3. Transport of peptides from cytosol to ER. 4. Assembly of peptide-class I complexes in ER. 5. Surface expression of peptide-class I complexes. |
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What do chaperone molecules help peptides assemble?
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They help peptides assemble with MHC-I.
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What does MHC I require the presence of for stability?
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MHC-I requires the presence of a PEPTIDE for stability.
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When peptides are assembled with MHC-I what, at the cell surface, recognizes Ag?
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At the cell surface CD8/Tc cells recognize Ag.
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Where are the alpha chain and beta2-microglobulin made? What protein are they associated with?
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They are made in the RER. They are associated with the ER membrane protein CALNEXIN.
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In the endocytic pathway for exogenous Ags what happens to the exogenous Ags? What is involved?
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Exogenous Ags are internalized by APCs and are phagocytosed and processed for presentation with MHC-II. This involves endosome action, MHC transport, and MHC-peptide binding.
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List the 5 steps of the pathway of class II MHC-associated antigen presentation.
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1. Uptake of extracellular proteins into vesicular compartments of APC.
2. Processing of internalized proteins in endosomal/lysosomal vesicles. 3. Biosynthesis and transport of class II MHC molecules to endosomes. 4. Association of processed peptides with class II MHC molecules in vesicles. 5. Expression of peptide-MHC complexes on cell surface. |
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What is "cross-presentation" necessary for?
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It is necessary for immunity against most tumors and viruses that avoided APCs.
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What does "cross-presentation" play a role in?
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It plays a role in HPV, Influenza, CMV, EBV, Listeria, Salmonella, and E. Coli. Also seen in tumors of the brain, pancreas, melanoma, and leukemia.
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Where is the clearest example of "cross-presentation" seen?
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The clearest example is found on dendritic cells.
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Describe the mechanism of cross-presentation?
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The mechanism is not totally clear. It involves transportation by TAP to ER where association with MHC I occurs. The MHC I complex goes to cell surface where it can be detected by CD8/Th cells.
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