11 Antibodies Flashcards
what are the types of binding antibody family to proteins
conformational determinant
linear determinant
Conformational determinant
when denatured determinant lost by denaturation
- antibodies bind only when the protein
Linear determinant
when denatured:
- Ig binds to determinant in denatured protein only
- Ig binds to determinant in both native in denatured protein
Antibody diversity
B cell precursor
Antibody rearrangement is random (only one of each segment)
Two segments join in heavy chain gene (D-J, then V to D) and the DNA in between is cut
Remove introns
Forms mRNA
mRNA translates into light chain
Antibody binding diversity
DNA segments of heavy chain are rearranged to produce gene V, D, J and C
Can B cells expressed more than one VH domain
VH domain is rearranged the other loci stops rearranging = Allelic exclusion
Therefore, a given B cell clone only expresses ONE Variable domain
Why during second response the antibody is ‘better’
- secondary response is mainly mediated by memory cells
- memory cells are product of T and B cell differentiation
- after second activation with antigen memory cells undergo the process of somatic mutation of their variable region gene
- after affinity selection, positive selected clones expand and differentiate into memory cells
- somatic mutations
Do Vh domains improve with time
Accumulating mutations
Increasing binding affinity to the molecule
Why there are sometimes more vaccinations – to try improve the affinity towards the antigen
Events that change Ab response from just IgM
- after antigen encounter some B cells switches irreversibly to other downstream antibody isotopes (IgG, A and E)
- once switched cells lose ability to express IgM and IgD
- those alterations occurs at DNA level similar to V gene rearrangement
what drives class switching
cytokines
specific opsonins
antibodies
non-specific opsonins
complement system, fibronectin, lectins, fibrinogen, C-reactive proteins
Recognition driven by complement
complement activation (labelling and lysis) - immune adherence