Lecture 15: Immunoglobulin Structure and Function Flashcards
What happens when a B cell recognises the epitope of an antigen?
B cells undergo clonal selection, proliferation and generation of plasma cells which secrete antibody + memory cells which persist to combat next infection
How many different encoded specificities of B cells are there in humans?
~10^7 different encoded specificities
What does a given antigen bind to on its specific B cell?
surface Ig
What is surface Ig?
immunoglobulins which are embedded in the B cell membrane
What is the role of surface Ig?
acts as the B cell antigen receptor and can transduce activation signals upon antigen binding
How many copies of surface Ig does each B cell express?
multiple copies ~10^5 per cell that bind the same antigen
What is secreted Ig secreted by?
activated B cells (plasma cells)
What is the difference between secreted IgG and membrane IgG?
secreted IgG has all the same regions as membrane IgG except it has a tail piece and membrane IgG has a cytoplasmic tail + a hydrophobic transmembrane region
What is the structure of immunoglobulins? How are they held together?
consists of two heavy and two light chains
chains are held together by disulphide bonds
What is the structure of the Ig domains?
~110 amino acids long
2 layers of beta-pleated sheet, 3-5 antiparallel strands
What do inward pointing hydrophobic residues form?
a stable core
What are light chains consisted of?
two Ig domains
What are heavy chains consisted of?
four to five Ig domains (depending on the class of antibody)
What regions do chains have? What is the function of these regions?
variable (V) and constant (C) regions
variable - antigen binding
constant - effector function
What is the role of the hinge which links antigen-binding arms?
allows flexibility in binding to multiple antigens
What are the two functionally distinct parts of Ig?
the Fc part and the Fab part
What is the Fc part of Ig?
tail constant region, can be 1 of 5 isotypes
What is the Fab part of Ig?
antigen binding, hypervariable (humans can make ~10^12 antibody specificities)
What can the immunoglobulin molecule be readily cleaved into using specific enzymes?
functionally distinct fragments
How does pepsin cleave Ig?
separates both Fab regions from digested Fc region
How does papain cleave Ig?
releases individual Fab and Fc fragments
What is most of the variability between different Igs within? What do these form?
three regions of Vh and Vl (hypervariable regions)
these form the antigen binding site
How long are hypervariable regions?
~10 amino acids in length
What are hypervariable regions also known as?
CDRs or complementarity determining regions
In which CDR region is there the most variability?
in the CDR3 region
How can immunoglobulins differ in their light chain?
either have a kappa or a lambda light chain
the same type of light chain is found on both arms of a single Ig molecule
How can immunoglobulins differ in the constant region of their heavy chain?
different class or isotype e.g. mammals have 5 isotypes: IgA, IgD, IgG, IgE and IgM (designated by Greek letter)
What are the properties of IgG?
high affinity monomer (bivalent)
major class in secondary response
large hinge region (i.e. flexible arms)
What are the properties of IgM?
has extra constant Ig domain pentamer (10 valency) Ig oligomerization via J-chain first Ig produced high avidity although low affinity
What is affinity?
the strength of binding of one molecule to another at a single site
What is avidity?
sum total of the strength of binding between two molecules or cells to one another (where multiple binding sites are involved)
Do multimeric Ig have high or low avidity?
Do monomeric Ig have high or low avidity?
multimeric Ig have high avidity
monomeric Ig have low avidity
What are the properties of IgA?
dimer (tetravalent)
major Ig secreted into GI and respiratory tracts
26aa tailpiece links to J-chain
What are the properties of IgD?
low abundance and mainly cell-associated
What are the properties of IgE?
involved in response to parasites and allergic reactions
binds to mast cells, induces degranulation
extra C domain
Where are the different Ig isotypes distributed?
IgG = serum and lymph IgM = serum IgA = serum and secretions (e.g. tears, GI tract) IgD = serum? IgE = beneath epithelial surfaces
What does the constant region confer?
functional specialisation on the antibody
What are different classes of Igs distinguished by?
the structure of their heavy-chain constant regions
What are antibody effector functions?
neutralisation, opsonization and complement activation
What is the role of the Fab region?
involves antigen recognition
direct mechanism
What is the role of the Fc region?
indirect / targeting mechanisms
What is neutralisation (direct mechanism)? -> IgG, IgA, IgM
Ab binding to proteins used by viruses or bacteria which are essential for attachment
can block infection
What is opsonization (indirect mechanism)? -> IgG1 > IgG3 > IgG4 = IgA
coating of pathogen with specific Ab -> binding to phagocytes via FcR -> enhanced phagocytosis of bound particle
What is antibody-dependent cell-mediated cytotoxicity (indirect mechanism)? -> IgG1 = IgG3
Ab binds to target cell via variable region e.g. virus infection cell
Ab binds to NK cell via FcyRIII receptor (CD16)
cross-linking of FcR triggers NK cell killing
What is degranulation and what is it carried out by (indirect mechanism)? -> IgE
IgE binds to parasite or allergen and FceR on immune cell
cross-linking of FceR triggers degranulation -> release of inflammatory mediates such as histamine
carried out by eosinophils, basophils and mast cells
What is complement activation (indirect mechanism)? -> IgM > IgG1 = IgG3 > IgG2 = IgA
Ab binding to component C1q via Fc initiates the classical complement cascade
only IgG and IgM complexes can bind C1q and free Ab does not activate C1q
