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36 Cards in this Set
- Front
- Back
What are the 2 distinct components of the adaptive immune response and what are they mediated by?
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1. Humoral immunity
Mediated by: antibodies produced by B lymphocytes 2. Cellular immunity Mediated by: T lymphocytes and components of the innate immune system (macrophages) |
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Describe the structure of an MHC class I molecule
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Heavy chain: α1, α2, α3
Light chain: β2-microglobulin (β2m) - has Ig folds The heavy and light chain interacts noncovalently. Heavy chain is polymorphic, but light chain is not. |
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Identify the functional regions in an MHC class I molecule
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Peptide-binding region: α1, α2 - has β-pleated sheets and parallel walls of α helices
Immunoglobulin-like domain: part of α3 and β2m (Hydrophobic) transmembrane region: part of α3 Cytoplasmic region: part of α3 |
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Describe the structure of an MHC class II molecule
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α chain: α1, α2
β chain: β1, β2 Both α and β chains are polymorphic. |
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Identify the functional regions in an MHC class II molecule
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Peptide binding region: α1 and β1
Immunoglobulin-like region: part of α2 and β2 Transmembrane region: part of α2 and β2 Cytoplasmic region: part of α2 and β2 |
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What are the differences in the binding of MHC I and MHC II
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MHC I: binds peptides 8-9 residues long
(bc antigen binding cleft is closed) MHC II: binds peptides 13-20 residues long (bc antigen binding cleft is open at both ends) |
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Bacteria such as Staphylococcus and viruses such as murine mammary tumor virus release superantigens, which do not bind to the MHC peptide groove. How do they work?
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Superantigens directly bind to the outer surface of specific MHC II molecules (without antigen processing) and the Vβ region of the T cell receptor (irrespective of the Vα chain).
This induces massive production of cytokines and functionally inactivates responding T cells, causing general immunosuppresion. |
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What are the loci encoding the MHC class I genes in humans?
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HLA-A, HLA-B, HLA-C
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What are the loci encoding the MHC class II genes in humans?
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HLA-DPα, HLA-DQα, HLA-DRα
HLA-DPβ, HLA-DQβ, HLA-DRβ1, HLA-DRβ2 |
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What do the MHC class III genes encode for?
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Components of the complement system
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Other than restriction elements for T cells, what other genes are encoded in the human MHC region?
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Heat shock proteins
Cytokines (eg: TNF) Gene products involved in antigen processing: - TAP - LMP - tapasin - DM |
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List 3 properties of the MHC genes that contribute to the diversity of MHC molecules expressed by an individual
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1. polymorphism
2. co-dominant expression 3. polygeny |
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A human cell may express as many as how many Class I molecules?
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6
3 heavy chain genes (A, B, C) inherited from mother; 3 heavy chain genes inherited from father |
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A human cell may express as many as how many Class II molecules?
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15
3 α chain genes (DPα, DQα, DRα) and 4 β chain genes (DPβ DQβ, DRβ2, DRβ1) from mother 3 α chain genes (DPα, DQα, DRα) and 4 β chain genes (DPβ DQβ, DRβ2, DRβ1) from father That makes 14. And some maternal and paternal α and β chains can bind with each other. |
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The genes that encode the MHC class I α chains and the MHC class II α and β chains are the most polymorphic of all known genes.
Where are polymorphic residues within MHC molecules clustered at? |
In the MHC molecule's antigen-binding site
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What does it mean that the block of MHC genes is a haplotype?
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MHC molecules are inherited as an entire block of genes.
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On which cells are MHC I molecules expressed?
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All nucleated cells (ie: not on RBCs)
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Considering that the function of MHC II is to communicate with other cells, on which cells are MHC II molecules expressed?
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Most hematopoietic cells in lymphoid tissues:
- B cells - Macrophages - Other antigen-presenting cells - Epithelial cells of the thymus (Not really T cells) |
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How are endogenous antigens (proteins synthesized in the cytoplasm, such as those derived from a virus that has infected the cell, or those being made by tumor cells) processed?
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Endogenous antigens in the cytoplasm are processed and presented on Class I molecules to be recognized by CD8+ T cells
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How are exogenous antigens (those derived from bacteria, viruses) processed?
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Exogenous antigens are endocytosed and presented on Class II molecules to be recognized by CD4+ T cells, which will activate macrophages to destroy the intracellular microorganisms
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Summarize the steps in MHC class I-restricted antigen presentation
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1. virus replicates
2. cytoplasmic viral protein is degraded by proteasome 3. TAP1/2 transport degraded peptides into the ER 4. peptide in ER binds to new MHC I molecules, helped by - calnexin, tapasin, and calreticulin (chaperones) - ERp57 (a thioloxidoreductase - opens and closes disulfide bonds) 5. The Class I-peptide complex is exocytosed onto the cell surface and presented to CD8+ T cells LMP = low molecular weight protein (proteasome subunits) TAP = transporter associated with antigen processing (LMP2, LMP7, TAP1/2, tpn are encoded within the MHC) |
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Processing of antigens by MHC I and II occurs for both foreign antigens and self antigens. Is this a problem?
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No. T cells do not recognize self antigens complexed with self MHC because T cells are tolerant against them. T cells learn to ignore self antigens during their selection in the thymus
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Summarize the steps in MHC class II-restricted antigen presentation before the peptide-containing endosomes fuse with MHC II/Ii-containing vesicles
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1. Antigens are endocytosed
2. Antigen-containing endosomes fuse with lysosomes; antigens are degraded by lysosomal protases called cathepsins Meanwhile: 1. New MHC II molecules in the ER are complexed with a 3rd chain, an Invariant chain (Ii) 2. The MHC II/Ii complex is targeted to the endocytic pathway The Ii has 2 functions (1) transport signaling (2) the CLIP (class II-associated invariant chain peptides) region shields the antigen binding groove of MHC II from peptide binding while it's still in the ER and Golgi |
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Summarize the steps in MHC class II-restricted antigen presentation after the peptide-containing endosomes fuse with MHC II/Ii-containing vesicles
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3. Fusion of endosome and vesicle
4. Lysosomal proteases degrade the Ii until only the CLIP fragment is left intact 5. DM, which looks like MHC II, binds to MHC II to catalyze the release of CLIP and the loading of high-affinity peptides. This happens in the MHC class II compartment (MIIC) 6. The MIIC fuses with the plasma membrane, allowing peptide presentation to CD4+ T cells |
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T cell receptors resemble antibody molecules in that they have both variable and constant regions. What are some differences?
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T cell receptors
- are never secreted - have a single antigen-binding domain - recognize antigen in the context of self-MHC molecules |
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Describe the structure of a T cell receptor
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α and β chains covalently linked by disulfide bonds.
Each chain has a variable and constant region. 1-5% of T cells in blood are γδ T cells - they're made of γ and δ chains. |
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Expressed on?
Ab: ____ TCR: ___ |
Ab: B cells
TCR: T cells |
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Has cell surface forms?
Ab: ____ TCR: ___ |
Ab: Yes
TCR: Yes |
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Has secreted forms?
Ab: ____ TCR: ___ |
Ab: Yes
TCR: No |
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What kind of chains?
Ab: ____ TCR: ___ |
Ab: 2 heavy, 2 light
TCR: α and β, or γ and δ |
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Members of Ig superfamily?
Ab: ____ TCR: ___ |
Ab: Yes
TCR: Yes |
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Has isotypes with distinct functions?
Ab: ____ TCR: ___ |
Ab: Yes
TCR: No |
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Number of antigen binding sites?
Ab: ____ TCR: ___ |
Ab: 2
TCR: 1 |
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Antigens recognized?
Ab: ____ TCR: ___ |
Ab: protein, sugar, lipid, etc
TCR: MHC+peptide |
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Diversity generated by DNA rearrangement?
Ab: ____ TCR: ___ |
Ab: Yes
TCR: No |
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Diversity generated by somatic hypermutation?
Ab: ____ TCR: ___ |
Ab: Yes
TCR: No |