Immune sensing 2: Adaptive Immunity Flashcards
Which of these could be recognised by T cells and/or B cells?
-Proteins
-Carbohydrates
-Linear peptide sequence
-Native structure of molecule
-Ag containing discontinuous epitopes
-Repeating epitopes
-Host molecules
quiz
- T and B
- B
- T and B
- B
- B
- B
- T and B
T cells recognise linear peptide sequences (8-25 amino acids long) that are presented to them by an Antigen Presenting Cell, thus they can only recognise protein fragments and do not recognise the native structure of the protein.
B cells can recognise almost any organic molecule and so could recognise both proteins and carbohydrates. Surface bound Ab serves as the B cell antigen receptor and as Ab contain two identical Ag binding sites (one on each arm) and so can bind to Ag simultaneously allowing them to bind to repeating epitopes. Ab generally recognise the native structure of the molecule on its own and can recognise both linear and discontinuous epitopes.
T and B cells are both able to recognise host Ag as well as microbial Ag.
Which of these are properties of the T cell receptor (TCR), B cell receptor (BCR), or both?
-Has two Ag binding sites
-Has one antigen binding site
-Created from two different chains
-Can be soluble or membrane bound
-Has immune effector functions
-Only recognises antigen presented by Antigen Presenting Cells
quiz
- BCR
- TCR
- BCR and TCR
- BCR
- BCR
- TCR
A T cell receptor can only recognise Ag that are presented to it by Antigen Presenting cells. A TCR has no immune effector functions and is solely used for antigen recognition and activation of T cells. This means that it is only found as a membrane bound form, and only has one Ag binding site.
Antibodies have a membrane bound form that plays the role of a B cell receptor, and a soluble form that has immune effector functions. Antibodies have two identical Antigen binding sites and so can bind two identical Ag simultaneously. The ability to bind two antigens is important for mediating their effector functions and will be discussed further in the lecture on B cells.
Both the TCR and Ab are created from two different chains; heavy and light chain for Ab, and α and β chain for the TCR. These two chains are joined together to form the antigen-binding site. As antibodies have two antigen binding sites they are created from two identical heavy chains and two identical light chains. The heavy chain of Ab also mediates the Ab effector functions.
Which of these process is involved in creating Ab diversity?
-Addition or deletion of nucleotides within J (joining) gene segments
-Joining of multiple randomly selected V gene segments to a D or J gene segment
-Precise alternative splicing of V, D, and J mRNA
-Differential mRNA processing
-Precise somatic recombination of V, D, and J gene segments
-Imprecise somatic recombination of V, D, and J gene segments
-Addition or deletion of nucleotides at joins of V, D, and J genes
-Imprecise alternative splicing of V, D, and J mRNA
quiz
- Imprecise somatic recombination of V, D, and J gene segments
- Addition or deletion of nucleotides at joins of V, D, and J genes
The antigen-binding site of an antibody is formed where the variable regions of the heavy and light chain are brought together. Chromosome 14 contains multiple different versions of V, D, and J gene segments. The variable regions of the Ab heavy and light chains are created by the somatic recombination of a random V gene segment, with a random D gene segment (heavy chain only), and a random J gene segment. Thus a heavy chain variable domain consists of one V segment, one D segment, and one J segment, whilst a light chain Ag binding domain consists of one V segment and one J segment. The random selection of different V, D and J gene segments creates one level of diversity.
To create additional diversity the joining of the V, D, and J segments is imprecise, and nucleotides can be added or removed at the junctions of the different gene segments during recombination. Nucleotides are only changed at junctions and not deleted or added in the middle of J (or V or D) segments.
Alternative splicing or differential mRNA processing would not result in a permanent change to the DNA sequence of the B cell meaning that the B cell receptor could change over time. These processes are not used to create Ab diversity. By permanently changing the DNA sequence coding the Ab (or T cell receptor) this ensures that the B cell (or T cell) and all its daughter cells can only express one Ag receptor
Why is clonal expansion required?
quiz
We have a huge number of T and B cells in our body, each with a different receptor capable of recognising a different Ag. This ensures that our T and B cell populations can recognise a huge range of microorganisms, and means that when we are infected with a microorganism we will always have at least one B or T cell present in our body capable of specifically recognising that microorganism. However, whilst this means as a whole population our T and B cells can respond to any microorganism, there will only ever be a few individual T or B cells capable of recognising any one Ag (estimated at 30 B cells in our body capable of recognising any one specific antigen). This is not enough to mount an effective immune response. Thus, once a T (or B) cell is activated (recognises its Ag and is deemed specific for a pathogen) it then divides multiple times to produce a large population of T (and B) cells all with identical TCRs (BCRs) and all with the same Ag specificity. This is referred to as clonal expansion. The requirement for clonal expansion is one of the reasons why adaptive immune responses are slower than innate immune responses.
Select whether the following statements about T and B cells are true or false.
-Each T and B cell has one unique receptor
-All self-reactive T and B cells are deleted through central tolerance
-The majority of BCR and TCR created will be non-functional
-T cell clonal expansion is driven by TNF-α
-Clonally expanded T and B cells can have a different TCR from their parent cell
-An antigen can contain multiple epitopes
quiz
- True
- False
- True
- False
- False
- True
An antigen is a molecule (or molecule fragment) that can be recognised by a T or B cell. The precise section of the Ag that the T or B cell receptor binds to is called the epitope. If an antigen is large then it can contain multiple T and/or B cell epitopes. Every T and B cell has one unique receptor and so can bind to one unique epitope within an Ag. Different T or B cells with different receptors can bind to different epitopes within the same Ag. Thus, two T cells with different receptors can recognise the same Ag by binding to different epitopes within it.
Somatic recombination of V, D, and J genes is a random process and because of this the majority of recombination events do not end up coding for a functional protein. If the T or B cell fails to produce a functional TCR or BCR then it will die by apoptosis. Because the creation of TCRs and BCRs by somatic recombination results in a permanent change in the DNA, all daughter cells (as produced by clonal expansion) will have identical BCR or TCR to the parent cell. Activated T cells produce IL-2 that acts as an autocrine growth factor to promote their own proliferation resulting in their clonal expansion.
The majority of self-reactive T and B cells are deleted during the process of central tolerance. However, the process is not perfect and so we all have T and B cells circulating within our body that are capable of recognising self-antigens
Whats the definition of an antigen?
a molecule recognized by adaptive immune cells
- binds TCR or antibody or both
Whats an epitope?
part of the antigen recognized by T or B cell receptor
What is a paratope?
Part of the antibody or TCR that binds the epitope
How do T and B cells differ in recognizing antigens?
T cells only recognize antigens on APC’s whereas B cells
Whats the difference between TCR and Antibodys (B cell receptors)?
Both are membrane bound, only antibodies can also be secreted though as Ab or Ig. Mem
what are the advantages of adaptive sensing?
- Adaptable (VDJ somatic rearrangement)
- Very specific
- Immune memory
What are the disadvantages of adaptive sensing?
- Slow (takes time to activate + clonally expand)
- Easy for pathogen to evade bc so specific can just change its antigenic structures
- Receptor cannot distinguish between pathogens and self/innocuous molecules (eg pollen)
