Lecture 6 - Antibody Effector Function Flashcards
Direct and indirect antibody effector functions
Direct - Function of Fab, neutralisation
Indirect - Involves Fc, targets bound antigen for phagocytosis, etc
Example of antibody direct mechanism
Antibody binds to influenza haemagglutinin
Influenza is now unable to enter host cell
Example of antibody indirect mechanism
Antibody binds to target antigen
If IgE, stimulates mast cell degranulation
Opsonisation
1)
2)
3)
1) Antibody binds to taret antigen
2) Bind to phagocyte by FcR
3) Phagocytosis
What does ADCC stand for?
Antibody-dependent cell-mediated cytotoxicity
Another name for FcgRIII
CD16
What is CD16?
IgG receptor on the surface of NK cells
What triggers NK cell killing?
Crosslinking of CD16/FcgRIII receptors
Mast cell degranulation
1)
2)
3)
1) Mast cell is ‘sensitised’ - IgE coats mast cell, binds to FceR
2) IgE Fab region comes into contact with allergen
3) Crosslinking of FceR leads to degranulation
Does a mast cell have a monoclonal or polyclonal antibody coating?
Polyclonal.
Can respond to several different allergens
Probably clumps o fmonoclonal antibodies in different places to allow crosslinking, clumping of antibodies
FcgRI affinity
High
FcgRIIA affinity
Low
FcgRIIB affinity
Low
FcgRIIIA affinity
Low
FcgRIIIB affinity
Low
FcgRI cell distribution
Macrophages, neutrophils
FcgRIIA cell distribution
Macrophages, neutrophils
FcgRI function
Cell activation, phagocytosis
FcgRIIA function
Cell activation, phagocytosis
FcgRIIB cell distribution
B cells
FcgRIIB function
B cell inhibition
FcgRIIIA cell distribution
NK cells
FcgRIIIA function
NK cell antibody-dependent cell-mediated cytotoxicity
FcgRIIIB cell distribution
Neutrophils
FcgRIIIB function
Neutrophil phagocytosis
FceRI cell distribution
Mast cells
FceRI function
Mast cell degranulation
FceRI affinity
High
Why are many Fcg receptors low affinity?
To keep serum IgG levels high.
If they were high affinity, IgG would be sequestered on cells, like IgE is.
High avidity antibodies
Multimeric IgM, IgA
Which FcgR can stably bind monomeric IgG
FcgRI (high affinity).
Can bind a single IgG bound to an antigen
Which FcgR need multiple antibodies bound to a pathogen in order for stable binding?
FcgRIIA, fcgRIIB, FcgRIIIA, FcgRIIIB
What kind of cells do NK cells kill?
Virus-infected cells
Not really extracellular bacteria
What is the secretory component?
Part of the polymeric-Ig receptor on secretory IgA
Is IgA dimeric in the blood?
Yes
How is the classical complement cascade initiated?
C1q component of C1 binds to exposed region of IgM or IgG bound to antigen
What is C1q?
Part of the C1 complex.
C1 is made up of three components, one of which is C1q
Which antibody is best at activating complement?
IgM.
IgG1, 2 and 3 are capable of activating complement, but need several antibodies bound to antigen to activate it, whereas pentameric IgM only needs one
Can free antibodies activate complement?
No. Only IgG and IgM complexes can activate complement
Which antibodies neutralise?
IgG, IgA
Which antibodies opsonise?
IgG1 > IgG3 > IgG4, IgA
Which antibodies induce antibody-dependend cell-mediated cytotoxicity?
IgG1, IgG3
Which antibodies activate the complement cascade?
IgM»_space; IgG1, IgG3 > IgG2, IgA
Which antibody degranulates mast cells?
IgE
Antibody variability types
1)
2)
3)
1) Isotype
2) Allotype
3) Idiotype
What is allotype?
Differences in antibody gene genetic code.
Heritable
Results in different Ig alleles
Doesn’t encode any noticeable difference in function
What is idiotype?
Diversity in antibody binding sites
~10^7 different binding sites in each individual
An equation to quantify proteinomic variability
Number of different amino acids at a given position/Frequency of most common amino acid at a given position
What are complement proteins very good at killing?
Extracellular bacteria
What is the most variable region of an antibody?
CDR3