Lecture 3.
A. Explain the principle of antibody diversification which occurs for vaccination to be
effective.
Vaccination is a simple, safe and effective protection against harmful diseases which involves
the training of the immune system to create antibodies just like it does when it is exposed to
a disease. The ideal vaccine has a sterilising immunity, is effective at site of infection, induces
a cell mediated response, is effective against all serotypes and variants in a target population,
is long lasting and has a simple vaccination schedule. In this essay, we will explain the
principles of vaccination by discussing the roles of B cells, antibodies and T cells in mounting
an effective immune response upon vaccination.
Vaccination must induce a cell-mediated response where CD4 and CD8 T cells kill infected
cells once the pathogen is taken up. For this to happen, B cells must be activated and produce
antibodies against specific antigens. B cells are antigen presenting cells that internalise and
process antigens, cut it down using specific enzymes and present it on MHCs. The T cells will
then recognise the peptide bound to the MHC via their T cell receptor, leading to activation
signals causing differentiation and activation of T cells. B cells produce antibodies which
undergo antibody recombination and class switching, somatic hypermutation and affinity
maturation for antibody diversification.
B cell activation occurs upon BCR binding the antigen. This induces a signal transduction
cascade where the activating signal requires the clustering and cross-linking of BCRs. This will
cause the cell to rapidly divide, producing plasma B cells and a small number of memory B
cells. The BCR binds the antigen via its Fab receptor which is made up of 1 V region per arm
which pair together to form 2 identical antigen binding sites. This allows the antibody to cross-
link with the antigen more stably and at higher affinity. In its germline configuration, the
antibody gene locus is made up of multiple VDJ segments. Following VDJ antibody
recombination, the mature antibody will only contain one segment for each. At first, in the
pro-B cell stage, the heavy chain is recombined such as 1 D and 1 J segments recombine
together, followed by 1 V and DJ recombination. This productive H chain rearrangement will
lead to an IgM-H chain expression. As the pro-B cell transitions to the small pre-B cell stage,
first a kappa Light chain VJ recombination occurs and if this is unsuccessful a lambda
recombination occurs. Successful pairing of a L chain with the IgM-H chain results in BCR
expression at the cell surface.
Once this occurs, class switching in mature B cells in response to antigen stimulation and co-
stimulation signals results in the deamination of cytosine to uracil by Activation-induced
cytidine deaminase in the S region of H chains. The H chains are replaced with those of
different isotypes, modifying their effector activity but not their antigen specificity. Naïve B
cells can switch to an isotope directed by different cytokines secreted by T cells and other
cells. The B cell antigen can switch to either of the other 4 isotypes, IgG (either of its 4
subtypes), IgA, IgE or IgD. The most abundant in serum is IgG.
Then, somatic hypermutation and affinity maturation occur, where SHM alters the V regions
of IgG genes to enable affinity maturation. This is aided by AID and as the deaminated cytosine
A. Explain the principle of antibody diversification which occurs for vaccination to be
effective.
Vaccination is a simple, safe and effective protection against harmful diseases which involves
the training of the immune system to create antibodies just like it does when it is exposed to
a disease. The ideal vaccine has a sterilising immunity, is effective at site of infection, induces
a cell mediated response, is effective against all serotypes and variants in a target population,
is long lasting and has a simple vaccination schedule. In this essay, we will explain the
principles of vaccination by discussing the roles of B cells, antibodies and T cells in mounting
an effective immune response upon vaccination.
Vaccination must induce a cell-mediated response where CD4 and CD8 T cells kill infected
cells once the pathogen is taken up. For this to happen, B cells must be activated and produce
antibodies against specific antigens. B cells are antigen presenting cells that internalise and
process antigens, cut it down using specific enzymes and present it on MHCs. The T cells will
then recognise the peptide bound to the MHC via their T cell receptor, leading to activation
signals causing differentiation and activation of T cells. B cells produce antibodies which
undergo antibody recombination and class switching, somatic hypermutation and affinity
maturation for antibody diversification.
B cell activation occurs upon BCR binding the antigen. This induces a signal transduction
cascade where the activating signal requires the clustering and cross-linking of BCRs. This will
cause the cell to rapidly divide, producing plasma B cells and a small number of memory B
cells. The BCR binds the antigen via its Fab receptor which is made up of 1 V region per arm
which pair together to form 2 identical antigen binding sites. This allows the antibody to cross-
link with the antigen more stably and at higher affinity. In its germline configuration, the
antibody gene locus is made up of multiple VDJ segments. Following VDJ antibody
recombination, the mature antibody will only contain one segment for each. At first, in the
pro-B cell stage, the heavy chain is recombined such as 1 D and 1 J segments recombine
together, followed by 1 V and DJ recombination. This productive H chain rearrangement will
lead to an IgM-H chain expression. As the pro-B cell transitions to the small pre-B cell stage,
first a kappa Light chain VJ recombination occurs and if this is unsuccessful a lambda
recombination occurs. Successful pairing of a L chain with the IgM-H chain results in BCR
expression at the cell surface.
Once this occurs, class switching in mature B cells in response to antigen stimulation and co-
stimulation signals results in the deamination of cytosine to uracil by Activation-induced
cytidine deaminase in the S region of H chains. The H chains are replaced with those of
different isotypes, modifying their effector activity but not their antigen specificity. Naïve B
cells can switch to an isotope directed by different cytokines secreted by T cells and other
cells. The B cell antigen can switch to either of the other 4 isotypes, IgG (either of its 4
subtypes), IgA, IgE or IgD. The most abundant in serum is IgG.
Then, somatic hypermutation and affinity maturation occur, where SHM alters the V regions
of IgG genes to enable affinity maturation. This is aided by AID and as the deaminated cytosine
