Humoral Immunity: B-Cell Activation, Affinity Maturation and Class Switching Flashcards
In summary, describe the phases of the humoral immune response
- resting mature naive B cell, makes IgM on cell surface
- activated B cell (antigen binds, helper T cells, cytokines)
- clonal expansion + differentiation
- form plasma cells -> IgM secreted (plasma cells make lots of Ig)
- class/isotype switching occurs -> make IgG instead
- B cells start to make high-affinity antibodies - affinity maturation
- eventually generate memory B cells
Describe Ig expression during B cell maturation & how this activates the B cell
- functional Ig expressed as membrane (cell surface) IgM (sIgM)
- membrane IgM acts as a B cell receptor (together w IgD)
- binding of antigen to IgM activates tyrosine kinase
- this activates signal transduction pathways for cell division + differentiation
What 3 things does B-cell activation require?
- antigen binding to B-cell receptor (sIgM), resulting in stimulation of signal transduction pathways
- co-stimulation by T cells
- co-stimulation by cytokines
What are the 2 forms of IgM?
- membrane bound on B cell surface -> antigen receptor
- secreted (circulation, tisues, mucosa)
The activated B-cell begins to secrete soluble IgM. What is this mechanism called?
Differential splicing
Describe the process of differential splicing
- mechanism required for soluble IgM to be secreted
- Cμ is not coded for by single exon
- there are 4 exons w/ 2 alternative versions of exon four
- differential splicing gives 2 diff mRNAs coding for 2 proteins which differ at the C terminal end
- note V region, coded by VDJ complex, is identical
so splicing can occur at 2 places on the pre-RNA, to give rise to either secreted μ chain OR membrane μ chain - protein.
What is the difference in structure between secreted IgG and membrane IgG?
- secreted has tail piece
- membrane has hydrophobic transmembrane region + cytoplasmic tail
Secreted antibodies circulation i the blood and access various sites to deal w/ pathogens. What are 3 effector functions of antibodies?
- neutralisation of microbes + toxins (block entry)
- opsonisation of microbes to enhance phagocytosis
- activation of complement (pathogen killing) (lysis)
Different classes of antibodies work best at certain sites, examples?
- IgM, IgG - blood
- IgA - mucosa
Different classes of antibodies work best against certain pathogens. Give one example
IgE - parasites
What is class (isotype) switching?
During an immune response B cells become capable to produce antibodies of different classes but without changing specificity (respond to the same Ag)
- ability to perform diff effector functions
- can deal better w/ pathogens
- isotype switch needs signal from helper T cells
IgM switch to -> IgG, IgA, IgE
IgG switch to -> IgA, IgE
Which 2 things are not altered in class switching?
- specificity for antigen
- the light chain
Different classes of antibody have different constant (Fc) regions to carry out different functions, but first Ig made is always IgM. What are the 2 main mechanisms of class switching called?
- Minor - IgD only, by differential splicing, made at same time as IgM
- Major - all other classes, by DNA rearrangement
Describe minor class switching
- Cμ and Cδ are transcribed as part of single precursor RNA
- differential splicing can remove Cμ exons
- so the Cδ exons are now used
- result is same VDJ is now joined to Cδ -> making IgD
Describe major class switching
- endonuclease recognition site (switch region) before each CH segment
- cut before Cμ + cut before alternative C segment
- original VDJ now transcribed along with new C region
- note: no change in light chain
