Selection & function of antibodies Flashcards
How does activated B-cells improve specificity?
Through somatic hypermutation and affinity maturation.
Antibody function: Fab dependent
Neutralisation of pathogens eg. by blocking viral receptors.
Neutralisation of toxins by irreversible binding
Pro/cons with long hinge regions
Flexibility to better bind Ag, complement, Fc-gamma receptors and transport receptors.
/ Higher susceptibility to degradation
Antibody function: Fc dependent
Opsonization, activation of complement, diffusion to extravascular sites.
Affinity maturation
Centrocytes die unless they bind CD40L on a cognate TFH cell. Higher affinity is selected for in competition with other centrocytes
Can isotype switch occur more than once?
Yes, but only one way.
AID mode of action i isotype switching
AID nicks the switch regions , which causes a DNA bend and loops out the region between the nicks, causing a different heavy chain constant region to be downstream to the heavy chain variable region.
Binding of CD40L happens because of…
When a centrocyte binds antigen hold by FDC, which causes internalisation and presenting to a cognate TFH cell.
Which cell direct B cell differentiation and how?
Cognate TFH cells. By secreting either IL-10 (plasma) or IL-4 (memory) depending on cytokine microenvironment when TFH cell got activated.
Best isotypes for toxin neutralisation and why
IgG & IgA because they are small for diffusion, have undergone affinity maturation. IgG is specifically transported to tissues.
Memory cells
High affinity, class-switched surface Ig, don’t secrete soluble Ig.
IgA isotype switch is induced by
TGF-β
Antibody function: Opsonization
Antigen with IgG bound fix C1q, resulting in C3b deposition on both Ab and Ag.
C3b are picked up by erythrocyte CR1 and brought to a professional phagocyte.
Centrocytes, centroblasts; which are expressing surface IgM?
Centrocytes.
Isotype switching
Switching of constant regions in heavy chain.
Antibody function: Complement activation.
Depends on antibody hinge-region to bind C1. IgM and IgG3 (long, flexible hinge) are good at binding of the multiple sites of C1.
What takes place in the light zone
Affinity maturation, isotype switching, differentiation
IgE isotype switch is induced by
IL-4
The 2 survival signals for centrocytes are:
- Binding of antigen on FDC
2. Binding to CD40L on cognate FTH that recognises that processed antigen.
Switch region
Short DNA sequence preceding each heavy-chain constant region segment. Works to increase transcription before the segment, leaving the single-stranded DNA vulnerable to AID.
Which cell directs isotype switching?
TFH effector
What happens if a memory cell bind Ag?
Cloning and differentiation into plasma cells, outnumbering the original memory cells.
Plasma cells
Don’t express BCR, MHCII. Can’t grow, hypermutate or switch isotype. Secretes alot of soluble Ig.
When do B cells express AID?
As centroblasts and centrocytes
B cell differentiation
Differentiation of B cells into either plasma cells or memory cells
IgG isotype switch is induced by
INF-γ
