Chemistry of Immunoglobulins
Ig class IgM structure
1. 10 Ag binding sites --> highest avidity 2. monomer on surface of mature B cell
Ab structure
1. 2 identical heavy chains 2. 2 identical light chains 3. heavy chains joined by disulfide bonds in the hinge region 4. light chains joined to heavy chains by disulfide bonds in Cl region 5. 5 classes of heavy chains include IgG, IgM, IgA, IgE, and IgD 6. 2 types of light chain (k or l) 7*. both heavy and light chains have interchain disulfide bonds 8*. Ab binds Ag at the N-terminal end (Fab)
effector functions of IgE
1. Binds to basophils and mast cells. Causes degranulation --> allergic reaction. 2. has lowest concentration in serum 3. short half-life, but long when on surface of mast cell 4. Protection against worms by causing inflammatory reaction
effector functions of IgM
1. Heaviest isotype 2. appears first during primary immune response 3. best at C' activation 4. best agglutinating Ab
effector functions of IgD
1. Monomer 2. second receptor on B cell after IgM 3. UKNOWN FUNCTION
effector functions of IgG
1. Most prevalent isotype in human serum (blood and lymph) 2. longest half life 3. appears in late primary and early secondary response can activate C' 4. opsonin and mediates ADCC (antigen dependent cellular cytotoxicity)
effector functions of Ig A
1. monomer on B cell surface, dimer when secreted 2. secretory antibody has protective protein (secretory component). The component is added by epithelial cells once the secreted IgA has bound to a poly-Ig receptor on the submucosal side of an epithelial cell. Added so it can be protected in harsh environments. 3. highest concentration in body of all isotypes
Ig class IgG structure
1.Always a monomer 2. 2 Ag binding sites
Ig domain
Ab molecule is made of Ig domains, each about 100-110 amino acids long. Each contains an intrachain disulfide bond. Fold is important in making it apart of the Ig gene superfamily.
Allotype
Allelic forms of same protein that can vary within a species. Usually 1-2 a.a changes
F_c
Area of antibody with biological activity. Comprises total C region. Note: IgG and IgA have subclasses due to minor amino acid difference in the C region.
Fab
Area of the antibody which binds the antigen. Comprised of variable light and heavy chain regions plus C_H1 and C_L regions). Note: Ab will have only one of the two possible light chain types.
framework region
Areas of less variability. They simply provide a framework for the hypervariability region to do the business.
C
C = constant.
What is the biologically active part of an antibody?
Fc (C' activation, ADCC)
What is an immunoglobulin?
Ig = antibody = Ab = gamma globulins. They are synonymous! Ig is a generic term. Ab specifies an Ig with particular specificity.
Which isotypes can be transported via mucus?
IgA and IgM
Which isotypes can induce mast-cell degranulation?
IgE
Which isotypes are able to activate the classical compliment pathway?
IgG and IgM
Which isotypes are present on the membrane of mature B cells?
IgM and IgD
Significance of multiple myeloma
Isolation of monoclonal Abs from myeloma patients allowed for characterization of generic Ig structure
hypervariable region
Regions that determine complementarity to the antigen. Concentrated in three regions called CDR (complement determining regions) including CDR1, CDR2, CDR3. Usually exposed so they can more easily contact the antigen. CDR3 is most important in contacting antigen.
Ag specificity
The Ag specificity of B cells is because of their membrane bound Ig. A single Ab can only bind to ONE antigen. After the initial binding of the Ag to a membrane bound Ig, the B cell is activated and can develop a plasma cell. The plasma cell secretes soluble Abs specific to ONE antigen. Specificity possible because of clonal selection and proliferation.
Isotype
These are the 5 classes of heavy chains. Determined by C (constant)-regions of H-chains
V_h
Variable part of the heavy chain
Do the membrane and secreted forms of Ab differ?
Yes. IgG, IgD, and IgE stay as monomer. IgA becomes a dimer joined by a j chain. IgM becomes a pentamer joined by a j-chain and multiple disulfide bonds.
C_H
constant part of the heavy chain
Idiotype
due to the variable region (e.g. CDRs) of the Ig (differences in a.a. sequences due to variable binding to Ags) essentially a clonal marker for a given B cell
Significance of Bence-Jones proteins
light chains released into urine. Helped characterize generic Ig structure.
Which isotypes can cross the placenta?
some subclasses of IgG
V_l
variable part of the light chain