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57 Cards in this Set
- Front
- Back
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What does it mean to say that antigen receptors on T and B cells are clonally expressed?
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The lymphocyte populations are made up of a variety of distinct clones; each clone expresses many identical receptors specific for one epitope.
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What is the main difference between TCRs and BCRs?
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The type of epitopes that they bind are chemically different.
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What type of epitope do TCRs bind?
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Only peptide complexed with MHC
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What type of epitope do BCRs bind?
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Undegraded antigens of many types
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Are TCRs and BCRs capable of transmitting signals to their cellular interiors independently?
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No; they require additional non-covalently linked components which make TCR complexes or BCR complexes.
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How many types of B and T cell clones are in each human?
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A ton! billions..
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How can we contain all the genetics necessary for making so many different clones?
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By gene rearrangements
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Which have effector functions; immunogloblins or TCRs?
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Ig's
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What are the effector functions of immunoglobulin?
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-Complement fixation
-Opsonization |
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What are the effector functions of immunoglobulins mediated by?
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Constant regions (Fc)
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In what forms are macromolecules recognized by B cell receptors?
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Linear or conformational
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In what forms are peptides displayed on MHC recognized by T cells?
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Only linear
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What are the helper molecules that aid the BCR in signal transduction?
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Proteins Ig-alpha / Ig-Beta
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What are the helper molecules that aid the TCR in signal transduction?
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CD3 and psi
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What is the structure of a BCR immunoglobulin composed of?
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-2 heavy chains
-2 light chains |
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What is each light chain made of?
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2 immunoglobulin domains
-one variable -one constant |
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What is each heavy chain made of?
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4 or 5 immunoglobulin domains
-one variable -3 or 4 constant |
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What holds the light and heavy chains together?
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Disulfide bonds
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What do the variable regions constitute?
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The Fab region
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What do the constant domains below the hinge region constitute?
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The Fc region
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What is the special feature of the variable regions on light or heavy chains?
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3 regions of hypervariability - CDR1, 2, 3
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Which CDR is most variable?
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CDR3
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What is the TCR structure composed of?
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-one alpha chain
-one beta chain each is made of 2 immunoglobulin domains |
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What makes the variable regions of the TCR variable?
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3 regions of hypervariability, just like on the BCR; called CDR1, 2, or 3
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Which requires accessory molecules in order to bind the antigen it's specific for; BCR or TCR?
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TCR
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What are the accessory molecules?
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CD4 or CD8
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What do the accessory molecules CD4 or CD8 bind to?
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Polymorphic residues of MHC
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On the TCR, what is equivalent to the light or heavy chain?
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Alpha chain = light
Beta chain = heavy |
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How is the required diversity for antigen receptors generated with minimal use of DNA?
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Via VDJ gene recombination, then recombination with a constant region gene segment.
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What are the steps in genetic recombination for generating variability?
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1. Heavy chain D/J
2. DJ recombines w/ V 3. VDJ recombines with C Then expression occurs at the cell surface w/ a surrogate light chain. |
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What has to happen in order to replace the surrogate light chain with a real one?
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VJ recombination, then combination with a Constant gene segment, then transcription of light chain.
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On what chromosome are the genes for heavy chain located?
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14
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On what chromosome are the genes for light chain located?
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2
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On what chromosome are the genes for TCR beta chain located?
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7
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On what chromosome are the genes for TCR alpha chain located?
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14
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What is the general nature of somatic recombination of the variable genes for TCR/BCR?
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Random
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What determines whether a clone's expressed DNA will be from maternal or paternal sources?
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Whichever chromosome gets successfully rearranged within frame for transcription first.
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What happens once one of the parental DNA's genes are successfully recombined and readable?
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The other parent's DNA will be silenced by allelic exclusion.
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What is allelic exclusion?
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Expression of the heavy chain gene product of either maternal or paternal chromosomes, but not both.
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In which gene segment for BCRs is there the most potential for variability?
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In the V gene segment of the heavy chain.
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In which gene segment for TCRs is there the most potential for variability?
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On the V gene segment of the Beta chain.
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What is combinatorial diversity?
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The mechanism of generating diversity in clones by VDJ somatic recombination.
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What is junctional diversity?
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The mechanism for generating diversity in clones by adding or removing nucleotides at junctional regions in the genes.
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So what are the 4 mechanisms for generating diversity in immunoglobulins BCRs?
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1. Multiple variable gene regions
2. Mix/match pairing of heavy and light chains (kappa vs lam) 3. Junctional diversity 4. Somatic hypermutation |
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What is the process by which Bcells with self-reactive BCRs are removed from the lymphocyte population?
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Negative selection
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What is the process by which immature cells fail to recognize with self antigen at all are killed?
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Positive selection
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Where does Tcell maturation occur?
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In the thymus
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What determines the T cell repertoire in an individual?
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Positive and negative selection in the thymus
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What determines whether a Tcell will mature to become CD4+ or CD8+?
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The medullary dendritic cell that presents self peptide on its MHC - MHCI vs MHCII
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So if a medullary dendritic cell presents self peptide on MHC I to an immature Tcell and it binds with high avidity what will happen?
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Negative selection; Apoptosis - this is a cell with potential for autoimmunity
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If a medullary dendritic cell presents self peptide on MHC I to an immature Tcell and it binds with weak avidity what will happen?
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Positive selection - this cell does bind, but not overly strong.
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When T cells differentiate into CD8+ versus CD4+ cells, what happens?
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First they are double positive, then they become single positive.
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Where in the thymus does positive selection mostly occur?
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Near the cortex
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Where in the thymus does negative selection mostly occur?
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In the medulla
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What do anti-allotypic antibodies differentiate?
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Antibodies that are from two different individuals, based on single AA differences in the constant regions.
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What do anti-isotype antibodies differentiate?
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Just different isotypes of antibodies, based on the common variations that make each isotype unique (IgG vs IgM)
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What do anti-idiotypic antibodies differentiate?
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One B-cell clone's BCRs or immunoglobulins, from a different clone's.. within the same individual.
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