Term
| Name the type classes of TCR. |
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Definition
| "alpha-beta" TCR and "gamma-delta" TCR |
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Term
| What type of TCR recognizes linear, processed peptides bound to MHC molecules? |
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Definition
|
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Term
| Which T cell responds to extracellular pathogens? |
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Definition
|
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Term
| How can MHC molecules bind such a wide range of peptides? |
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Definition
| they exhibit promiscuous binding specificity AND there is great polymorphism between individual MHC molecules |
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Term
| What do we know about gamma delta TCR? |
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Definition
| enriched at mucosal sites, have a limited repertoire, can recognized non-peptide antigen, and are not restricted by MHC |
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Term
| Name the two regions of a TCR. |
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Definition
| variable or V region and constant or C region |
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Term
| Where does the variability of TCR specificity come from? |
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Definition
| gene rearrangement (similar to B cells but there is no other mutation) |
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Term
| How many antigens can one T cell receptor bind simultaneously? |
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Definition
| there is only one binding site so TCR can only bind one antigen at a time |
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Term
| T/F TCRs can exhibit the same affinity but have different avidity. |
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Definition
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Term
| Where in the body do T cells undergo gene rearrangment? |
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Definition
|
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Term
| What gene segments rearrange to make up the alpha chain? |
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Definition
|
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Term
| What gene segments rearrange to make up the beta chain? |
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Definition
| V beta, D beta, and J beta |
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Term
| Which enzymes are responsible for the process of gene rearrangment for TCRs? |
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Definition
| RAG-1 and RAG-2 (recombinase-activating genes) |
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Term
| In what organelle are the alpha and beta chains of the TCR joined together? |
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Definition
|
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Term
| A RAG knockout mice will develop what syndrome? |
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Definition
| SCID (severe combined immunodeficiency syndrome) |
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Term
| What is the definition, presentation treatment, and prevelence of SCID? |
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Definition
| Immune deficiency disease in which neither antibodies or T cell responses are made. Characterized by lymphopenia, agammaglubulinemia, and life threatening infections. Tx with bone marrow transplant (fatal in infancy without one). 1:50-75,000 births |
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Term
| What types of mutations cause Omenn syndrome? |
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Definition
| missense mutations in RAG genes that result in partial enzymatic activity, IL-7Ralpha deficiency, and deficiency in artemis |
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Term
| Symptoms of Omenn Syndrome |
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Definition
| early onset of erythroderma, failure to thrive, protracted diarrhea, infections (staph aureus, candida albicans and pneumocystis carinii |
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Term
| What might you find on physical exam of a patient with Omenn Syndrome? |
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Definition
| enlarged liver, spleen, and lymph nodes |
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Term
| What would blood work of a pt with Omenn Syndrome show? |
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Definition
| eosinophilia, lack of B cells, low Ig apart from IgE, marked decrease in T cells |
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Term
| What is the treatment for Omenn syndrome? |
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Definition
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Term
| How does the TCR leave the ER? |
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Definition
| it associates with 4 invariant membrane proteins that are collectively known as the CD3 complex and the zeta chain (they are responsible for signal transduction |
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Term
| What is the function of a T helper 1 cell? |
|
Definition
| activate macrophages to phagocytose extracellular pathogens and kill them |
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Term
| What is the function of T helper 2 cells? |
|
Definition
| stimulate B cells to make antibodies |
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Term
| What is the function of a TH17 cell? |
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Definition
| help other cells recruit inflammatory cells (particularly neutrophils) mostly to mucosal surfaces |
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Term
|
Definition
| A CD4+ T regulatory cell that helps protect cells and tissues from autoimmunity |
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Term
| Name the type of cells that aren't leukocytes and that express MHC class II. |
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Definition
|
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Term
| What soluble molecules increase the presentation of MHC molecules during an infection? |
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Definition
| interferons, a type of cytokine |
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Term
| Describe the structure/parts of the MHC class I molecule. |
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Definition
| transmembrane alpha chain with three parts (alpha 1,2,or 3) that is non-covalently complexed with beta 2 microglobulin. The peptide binding site is formed from the a1 and a2 domains of the chain |
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Term
| Describe the structure/parts of the MHC class II molecule |
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Definition
| 2 transmembrane proteins (alpha 1 & 2 and beta 1 & 2 chains) both of which contribute to the peptide binding site, made up of beta 1 and alpha 1 |
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Term
| How long are the peptides that MHC I binds? |
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Definition
| 8-10 aas (length is very defined because the two ends of the peptides are grapsed by pockets situated at the end of the deep groove) |
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|
Term
| How long are the peptides that MHC II binds? |
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Definition
| 12-25 (variable in length because the ends are not pinned in by pockets) |
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Term
| MHC I binds pathogens that come from where in the cell? |
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Definition
|
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Term
| MHC II binds pathogens that come from where in the cell |
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Definition
| in lysosomes and other vesicles of the endocytic pathway |
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Term
|
Definition
| found in the cytosol of all cells. have proteolytic activity. degrade cellular proteins taht are poorly folded, damaged or unwanted |
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Term
|
Definition
| transporter protein that brings peptides from the cytosol into the lumen of the ER (like viral peptides for MHC I) |
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Term
| Immediately after leaving the ER, where does the MHC I/peptide compelx go? |
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Definition
| the golgi body (then the cell membrane) |
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Term
| How is a pathogen in a vesicle degraded? |
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Definition
| vesicle travels inwards from plasma membrane and becomes acidify. Then they fuse with a lysosome forming a phagolysosome. Lysosomes contain hydrolases and proteases that become activated by these acidic conditions |
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Term
| Where does MHC II bind its peptide? |
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Definition
| MHC II leaves the ER/golgi and travels in a vesicle that fuses with the vesicle containing the peptides |
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Term
| Which chromosome encodes the MHC molecules? |
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Definition
|
|
Term
| Variations in what molecules are responsible for graft rejection and graft versus host disease? |
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Definition
|
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Term
| The human MHC is often called the ________. |
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Definition
| HLA complex (human leukocyte antigen) |
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Term
| Inherited diversity of MHC molecules is achieved in what 2 ways? |
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Definition
| gene families (individuals express several different genes for MHC) and genetic polymorphism (lots of different alleles in a population) |
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Term
| Name the three highly polymorphic isotypes of MHC I. |
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Definition
|
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Term
| Name the three OLIGOmorphic isotypes of MHC I. |
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Definition
|
|
Term
| Which MHC I isotypes present to NK cells? |
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Definition
|
|
Term
| Which MHC I isotypes present to CD8 T cells? |
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Definition
|
|
Term
| Name the three MHC II isotypes that present antigens to CD4 T cells. |
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Definition
|
|
Term
| Which MHC II isotypes are polymorphic? |
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Definition
| HLA-DP and HLA-DQ have polymorphic alpha and beta chains. |
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|
Term
| Which MHC II isotypes are oligomorphic? |
|
Definition
| HLA-DR (alpha chain), HLA-DM, and HLA-DO |
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Term
| How many different genes encode the DR beta chain? |
|
Definition
| Four (DRB1, DRB3, DRB4, and DRB5) |
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Term
| Name the MHC II isotypes taht function to regulate loading of HLA-DP, HLA-DR, and HLA-DQ. |
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Definition
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Term
| The different encoded proteins of alleles are termed ____. |
|
Definition
|
|
Term
|
Definition
| the combination of MHC alleles you inherit. Also known as your HLA type |
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Term
| Where on the MHC molecule are the most variations between MHC isotypes? |
|
Definition
| on the sites that bind the peptide and the T cell receptor |
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Term
| What are anchor residues? |
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Definition
| amino acid sequences common to most of the peptides that bind any particular MHC |
|
|
Term
| what is the peptide binding motif? |
|
Definition
| combinations of anchor residues common to peptides that all bind a particular MHC isoform |
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Term
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Definition
| When a T cell responding to a peptide presented by one MHC allotype rarely/never responds to that peptide bound to another MHC type. |
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Term
| What is balancing selection? |
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Definition
| selective process that helps maintain the variety of MHC isoforms in a population |
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Term
| Directional selection of an MHC allele occurs due to... |
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Definition
| deadly, specific, epidemic disease |
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Term
| Self-MHC isoforms are described as ______________ and all other MHC isoforms as __________. |
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Definition
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|
Term
| What are alloreactive T cells? |
|
Definition
| T cells that can respond to complexes of peptide and allogeneic MHC class I and II molecules that are present on cells from other individuals |
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|
Term
|
Definition
| antigen that binds to alloreactive T cells |
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Term
|
Definition
| When alloreactive T cells are activated by alloantigens on a allogeneic transplant/graft |
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|
Term
| How do you prevent an alloreaction? |
|
Definition
| make sure transplant donors and recipients have similar or identical HLA types |
|
|
Term
| What is the dominant genetic factor affecting suceptibility to autoimmune disease? |
|
Definition
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