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57 Cards in this Set

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