Immunoglobulin Structure Flashcards
Describe the following classes of immunoglobulins:
IgG IgA IgM IgD IgE
Where are the predominant/mostly found or involved with?
IgG - predominant Ab induced in secondary response
IgA - predominant Ig in external secretions
IgM - predominant Ab induced in primary response
IgD - found mainly on surface of B cells
IgE - involvement in allergic hypersensitivities
Describe the basic immunoglobin structure.
All antibodies have a common core structure of two identical light chains (about 24 kilodaltons [kD]) and two identical heavy chains (about 55 or 70 kD) (Fig. 1). One light chain is attached to each heavy chain, and the two heavy chains are attached to each other. Both the light chains and the heavy chains contain a
series of repeating, homologous units, each about 110 amino acid residues in length, which fold independently in a common globular motif, called an immunoglobulin domain.
What determines the Ig type? (IgA, IgG, IgM, IgD, IgE)
Describe chain type.
The H chains determine the Ig isotype, IgA, IgG, IgM, IgD, or IgE.
IgG- gamma IgA-alpha IgM-mu IgE-epsilon IgD-delta
What two classes or isotopes do all antibody light chains fall into?
K and (see h/o)
Each member of a light-chain isotype shares complete amino acid sequence identity of the carboxy terminal C region with all other members of that isotype. In man, antibodies of each light chain type are present in equal number
Studies of which proteins resulted in identification of variable (V) and constant (C) regions (domains)?
myeloma
Is the variable region the C or N terminal region of both H and L chains?
The N-terminal region of both H and L chains are considered variable regions; the remainder of H and L chains are considered the constant regions.
What makes up the variable region of the antigen binding site of an immunoglobin?
Variable Region: The combination of the variable region of the H chain and the variable region of the L chain make up the antigen binding site of an immunoglobulin.
What effector functions are carried out by constant domains?
Other effector functions of Ig are carried out by the constant domains.
These include the ability to cross the placenta, sites for attachment to Fc receptors of macrophages, monocytes, mast cells and sites for binding complement.
What are CDRs?
Describe their folding.
What is responsible for the specificity of their antigen binding?
Most of the amino acid sequence variation among different heavy and light chains that as part of an Ig molecule bind different antigens, is confined to three separate locations in the V region. These are called hypervariable segments, or CDRs.
When VH and VL regions fold into an Ig domain, the CDRs are present on the surface as projecting loops (Fig. 3.5); VH and VL CDRs are in close proximity in 3D. Sequence differences contribute to variation in the chemical
surface of the loops.
The amino acid sequences of the CDRs are primarily responsible for the specificity of antigen binding.
How are immunoglobulin classes (isotopes) identified?
by the constant region of H chains
Describe IgM.
Ab?
How is it elicited?
Describe the structure of its secreted form.
Where and how is it expressed? (On what type of cell?)
What complement pathway is it a part of?
Does it cross the placenta?
What is the serum concentration?
Of what receptor is it part of?
- Ab of primary response for protein Ag administered parenterally.
- Major class of Ab elicited by T-independent antigen (polysaccharide).
- Pentameric in its secreted form, m.w. = approx. 900,000 daltons.
- J chain (mw = 15,000 daltons) joins the subunits
- Expressed on the surface of B-cells as a monomer
- Effective complement fixation - classical pathway.
- Does not cross the placenta of man or other species.
- Serum concentration = approx. 100 mg/dl in adult.
- Part of B cell receptor (BCR)
Describe IgG.
Ab class characteristic of what type of response?
Describe the structure and weight of the secreted form.
Is there variability in complement fixation? According to what?
Does it cross the human placenta?
Describe the serum concentration.
- Ab class characteristic of secondary response for most protein (T-dependent) Ag.
- Monomeric in its secreted or membrane form; m.w. = approx. 150,000 daltons.
- Variability in complement fixation according to subclass.
- Crosses the human placenta due to the presence of FcRn on the placenta.
- Serum concentration = approx. 1200 mg/dl in adult.
Describe IgD.
What is the usual form? More common in membrane or plasma?
As what type of Ag receptor does it function?
Describe serum concentration.
- Usual form is the membrane form; very few IgD plasma cells.
- Functions as B-cell Ag receptor along with IgM
- Serum concentration of adults = approx 3 mg/dl
Describe IgE.
What is it involved in?
Describe its interaction with mast cells and basophils.
How is it secreted?
Describe serum concentration?
- Class of antibody involved in allergic hypersensitivities, such as ragweed allergy.
- IgE Ab(s) fix to mast cells and basophils via an Fc receptor on the cells
- Secreted as a monomer; m.w. approx. 190,000 daltons; CHO rich.
- Very low concentrations in serum of normal adults ( approx. 30 μg/dl).
Describe IgA.
Role?
What is predominant form?
By which pathway does it fix complement?
Does it cross the placenta?
Describe its concentration in serum.
- Predominant Ig class in external secretions; occurs as a dimer.
- J chain joins the two subunits
- Predominant form in serum is monomeric; serum IgA is approx 160,000 daltons.
- Function of serum IgA is not clear.
- Does not fix complement by classical pathway; can usually fix complement by alternative pathway.
- Does not cross placenta.
- Serum concentration = approx 300 mg/dl in adult.
- Key role in mucosal immunity
