properties of antibodies L24 Flashcards
Isotope/class swithcing
AB change in constant regions allows for different effector functions, changing the class types
swapping constant Fc regions changes Ab function without changing specificity for Ag, this is independent of whether the antibody is membrane bound or secreted
difference between membrane and secreted Ab
differential RNA processing
cells can always produce both forms
membrane = cell surface Ag receptor
secreted = effector functions
IgM and IgD
first isotopes produced
IgM and IgD are produced by differential RNA splicing so the DNA is not changed
switching for IgG, IgE, IgA
irreversible change in DNA, can only produce one isotope at a time
AID - activation induced deaminase cuts to do this
IgM = first line of defence
initial response on first challenge
produced prior to affinity maturation so lower affinity than other isotopes
IgM forms pentamers via J chain
very good at binding repeating epitopes
very efficient at activating complement system
opsonises via complement
IgA = mucosal surfaces
J chain facilities transport across intestinal epithelium
resistant to low Ph and digestive enzymes
good at cross-linking Ag/pathogen
keeps pathogens away from epithelium by clumping them together for expulsion
weak ADCC function and complement fixation so less likely to cause collateral damage
opsonises
FcR that link Ab functions to innate cells
FcyR = binds IgG
FcaR = binding IgA
FceR = binds IgE
different innate cells express different types of FcR
innate cell expression of FcR defines which Ab isotope they work with and so defines effect function
macrophages express FcyR and FcaR
mast cells express FceR
FcR stimulates antibody dependent cellular cytotoxicity ADCC
ADCC process where antibodies direct innate immune cells to kill infected cells using Fc receptors
IgG binds to infect cell then binds to FcyR on NK cells to trigger to kill
antigen antibody cross linking
required to bind to and activate FcyR and FcaR
helps distinguish Ab that are bound to pathogen or infected cell
how does IgE help kill extracellular pathogens?
IgE binds to parasite/allergnes and then cross links FceR on mast cells to trigger release of toxic granules or histamine
why are two antigen binding sites important on Ab
enables cross linking of antigens
improves neutralisation of toxins/pathogens
enables activation of FcR on immune cells
allow aggregation for better clearance
What is antigen–antibody (Ag-Ab) cross-linking, and why is it important?
When multiple antibodies bind multiple antigens, they cross-link, which is required to:
Activate FcγR or FcαR
Distinguish between pathogen-bound antibodies (danger) vs free antibodies (no infection)
Prevent inappropriate immune activation by free IgG
Why doesn’t free IgG activate immune cells via FcγR?
Free IgG has low affinity for FcγR → doesn’t bind unless cross-linked by antigen, which ensures that only antibody-bound pathogens trigger immune responses.
How do antibodies neutralize pathogens and toxins?
Clump (agglutinate) pathogens/toxins
Block entry into host cells
Create immune complexes for easier phagocytosis and clearance
What are immune complexes and their role?
Clusters of antigens bound to antibodies → facilitate phagocytosis and clearance by immune cells.
IgE makes innate cells into memory cells
FceR has high affinity for IgE
binds monomeric IgE, does not need Ag-cross linking
FceR becomes loaded with IgE
gives mast cell an Ag-specific receptor
IgE
non opsomoisers
kill parasite helminths
cause allergies
reason why anaphylaxis is so fast
affinity maturation and mutation
mutations in Ag binding site to increase affinity for Ag in Fab region
somatic hypermutation does this as mutation rate of V D J regions of activated B cells so large
mutation change sequence of Ag binding site, increase affinity via AID
after somatic hypermutation of B cells
can loose ability to bind to Ag and B cell dies
can bind Ag with worse affinity, B cell survives but is outcompeted
or
Binds Ag with higher affinity - selects for B cells producing Ab with highest affinity
Affinity maturation
overall process by which activated B cells increase their Ab affinity for Ag
via somatic hypermutation
tends to occur after or same time as class switch from IgM
tightly controlled to prevent accidental creation of self-reactive Ab
summary of all processes together for B cell
Activation of B cells and migrate to germinal centre
B cell proliferates
Somatic mutation and affinity maturation - isotype switching
exit of high affinity, antibody secreting and memory cels
