Properties and Functions of Antibodies Flashcards
How do the two regions of an antibody relate to its function?
- variable Fab region defines Ag specificity
- constant Fc region defines function
Why does an antibody have two Ag binding sites?
permits cross linking (forming immune complexes)
improves neutralisation and controls innate cell activation
is required to bind to and activate FcγR and FcαR
distinguishes Ab that are bound to pathogen/infected cell from free antibody
Why can the Fc region change?
allows different effector functions
swapping constant Fc regions changes Ab function without changing specificity for Ag
What is a difference in function between a membrane Ab and a secreted Ab?
secreted Ab = effector functions
membrane = cell surface Ag receptor
How are IgM and IgD produced and what is their function?
only isotypes that can be produced simultaneously by a B cell
they are the first isotypes produced
are produced by differential RNA splicing
IgD = secreted in small quantities, function unknown
IgM = first response Ab
What is Class/Isotype switching?
mechanism by which B cells start producing IgG. IgA, or IgE
irreversible change in DNA, once switched you cannot go back
can only produce one isotype at a time
What cells control class switching?
Th cells
tell B cells which isotype to produce
State the different antibody classes and their properties.
IgM = great complement fixer, first antibody made
IgA = resistant to stomach acid, protects mucosal surfaces
IgG = helps NK cell kill, can cross placenta
IgE = defends against parasites, causes allergies
How does IgM make up for its lower affinity?
IgM forms pentamers via J chain
compensates for lower affinity (as they are produced prior to affinity maturation)
v good at binding repeating epitopes
v efficient at activating complement
(J chain is different from J gene segement)
How is IgA adapted to mucosal surfaces?
forms a dimer via J chain which facilitates transport across intestinal epithelium
resistant to low pH and digestive enzymes
keeps pathogens away from epithelium by clumping them together for expulsion with faeces
Weak ADCC function and complement activation - avoids collateral damage in gut
What is an FcR?
Fc Receptors
present on innate cells such as macrophages which bind to Fc region of Ab
gives specificity of adaptive immunity to innate immune cells
innate cell expression of FcR defines which Ab isotypes they work in partnership with and so defines effector function
Different Ab isotypes bind different FcR. What are they?
FcγR - binds IgG (gamma binds G)
FcαR – binds IgA (alpha binds A)
FcεR – binds IgE (epsilon binds E)
What is opsonisation and what antibodies induce it?
an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes
opsonisers: IgG, IgA, (IgM via complement)
non-opsoniser: IgE
How does IgE make innate cells into memory cells?
FcεR has high affinity for IgE
binds monomeric IgE (doesnt require Ag cross linking)
receptors become loaded w IgE
gives the mast cell an Ag-specific receptor
How does somatic hypermutation select for B cell producing Ab w highest affinity for Ag?
after somatic hypermutation, B cell was tested to see if it can still bind its Ag:
1. loses ability to bind Ag - B cell dies
2. binds Ag with lower affinity - B cell survives but is outcompeted
3. binds Ag w higher affinity - B cell outcompetes those w lower affinity
Define affinity maturation.
the overall process by which activated B cells increase their Ab’s affinity for Ag
Somatic hypermutation (100,000x greater mutation rate in V D J genes) occurs to slightly modify Ag binding region
How is affinity maturation controlled so that self-reactive Ab’s are not created?
B cells require T cell permission to undergo affinity maturation and to survive thereafter
after affinity maturation a B cell must present the Ag it recognises to a T cell
- if T cell recognises the Ag, B cell is still microbe specific and is
allowed to survive
- if T cell no longer recognises the Ag then affinity maturation has likely changed the B cells specificity for Ag. B cell is no longer useful or is potentially self reactive so is deleted
Membrane vs secreted Ab production?
Differential RNA splicing for transmembrane Ig vs secreted Ig gives them different carboxylate termini
IgE specialisation?
FcR has high IgE affinity
Main antibody for linking with innate cells
FcR binds monomeric IgE (doesn’t require cross linking)
Gives mast cells Ag specific receptor
Aids in killing helminths
Doesn’t opsonise
How do Clonal expansion, isotype switching and affinity maturation for together?
B cells activated and migrate to germinal centre
B cell proliferation
Somatic mutation, affinity maturation and isotype switching occur
Exit of high affinity antibody secreting cells and memory cells
Difference in antibodies in primary and secondary response?
Increased number of Ag specific B cells present
B cells usually class switched to IgG,A, or E
Ab produce by B cells has higher Ag affinity
What are the antibody isotypes?
IgA
IgD
IgE
IgG
IgM
= MAGED 🦑
So true 🐮
Why does IgA have higher affinity?
Peyer’s patch (gut immune centres) B cells have higher rates of somatic hypermutation
Components of mucosal immunity?
Gentler approach
Tight junctions prevent epithelium penetration
Mucus layer prevents microbes reaching epithelium
Anti microbial peptides in mucus layer damage microbes that get too close
IgA gentler activity
Passive approach allows living with commensals