Humoral Immunity; Antibodies and the life cycle of B cells Flashcards
what does CDR mean
Complementarity Determining Regions
4 main effector function of antigen binding to antibody
prevents pathogen-host binding
phagocytosis
lysis
NK-induced apoptosis
different classes of antibody
IgG IgD IgA IgM IgE
Heavy chain class switching
• Only affects heavy chain CONSTANT region
• Different effector functions — deal with different pathogens
• Minor: Differential splicing (mRNA level)
— lgM and lgD (last lecture)
• Major: DNA recombination
- lgM to lgG, lgA, lgE
- lgG to lgA, lgE
Class switch recombination (CSR)
1) Cytokine signal;
2) Switch regions;
3) AID and DSB repair proteins
• Recombination between switch regions
• Switching only proceeds downstream
— lgM to lgG, lgA, lgE
— lgG to lgA, lgE
during class switching which region changes
heavy chain constant region changes
during class switching what cuts and forma the new one
AID + DSB repair proteins
whats included in somatic recombination
V(D)J recombination
Tdt nucleotide addition
Somatic hypermutation
Class switching
whats included in Differential splicinq
lgM and lgD
Membrane bound
and secreted lg
is class switching reversible
NO
One-turn/two-turn rule (12/23 rule)
Recombination only occurs between a segment with a 12bp spacer and a 23bp spacer
Generation of antibody diversity
Multiple germline V, D and J gene segments
Combination V-J and V-D-J joining
Junctional flexibility
P-nucleotide addition
N-nucleotide addition
Combinatorial association of heavy and light chains
Somatic hypermutation during affinity maturation (next lecture)
Allelic exclusion b cells
Two copies Of each lg gene — one from mother and one from father
In Other cells, both genes are expressed
Antibody genes different — Only one heavy chain allele and one light chain allele is expressed
Order of rearrangement: Heavy>kappa>lambda; 1st allele then 2nd
Ensure each B cell makes one type of antibody
where does affinity maturation occur
in the germline centre
B cell activation requires 3 signals
antigen binding to BCRs
co -stimulation by activated Th cell specific to same antigen
Th cell-derived cytokines