Immunoglobulins
How is secretory component added to IgA?
A plasma cell secretes a dimeric IgA antibody which interacts with a poly-Ig receptor on the basement side of mucous epithelial cells. This unit is transported across the cell via a vesicle and undergoes enzymatic cleavage to release secretory IgA in the lumen.
What are allotypes and idiotypes?
Allotypes are allelic forms of the same protein that can vary within a species (usually 1-2 amino acid changes). Idiotypes part due to the variable region of the immunoglobulin and are essentially a clonal marker for a given B cell.
Describe the structure of an antibody.
An antibody is a Y-shaped protein. It is made up of 2 identical heavy chains extending from top to bottom and 2 identical light chains where the protein branches. The 2 heavy chains are joined together by disulfide bonds in the hinge region. The light chains, each to the outside of the heavy chains, are joined to the heavy chain by disulfide bonds in the CL region. Both the heavy and light chains have intra-chain disulfide bonds in the middle 60 amino acids.
What are the regions of an antibody and their activities?
Before the hinge region, the heavy chains each have 2-3 constant regions. After the hinge, the heavy and light chains each have one constant region and one variable region. The entire constant region of the antibody, Fc, is the area of biological activity. This is responsible for complement activation and antigen dependence cell-mediated cytotoxicity (ADCC). The variable region at the end of the antibody, Fab, is the antigen binding site. Antigen binds at the N-terminal end.
What are Bence-Jones proteins and how are they used clinically?
Bence-Jones proteins are produced in urine of patients with overproduction of light chains of an antibody molecule. The excreted free light chains allow for characterization of the immunoglobulin structure.
Describe Fab and Fc.
Fab is the antigen binding site (VH/VL and CH1/CL(?)). There are 2 light chain types, kappa and lambda. Fc is the biological activity region which has 5 classes (G, A, M, E, D). G and A have subclasses with slightly different functions.
Describe the secreted form of the isotypes.
G, D, and E are monomeric. A is dimeric and M is pentameric. A and M are also multivalent and are held together by the J-chain (a polypeptide).
Which human isotopes are involved in mucosal transport?
IgA and IgM are involved in mucosal transport, especially IgA.
Which human isotype has a wide variety of molecular weight? Which isotype is the largest?
IgA has a wide range of molecular weights (150,000-600,000). IgM is the largest isotype (900,000)
What are the characteristics of IgA
IgA is a monomer on the surface of B cells and a dimer (can be tetramer) in secretions. It has 2 subclasses and is the major immunoglobulin in the body. It has a secretory components which is a mucophilic, protective protein that attaches to epithelium and traps antigens in mucous where lysozyme can help degrade them.
What are the characteristics of IgD?
IgD is a monomer and the 2nd receptor on a B cell (after IgM). It essentially tags along with IgM and has no known function.
What are the characteristics of IgE?
IgE binds the basophils and mast cells. When it binds to an antigen, it causes degranulation of mast cells which induces an allergic reaction. It acts as protection against parasitic worms and causes an acute inflammatory response. It is the lowest concentration isotype in the body.
Which isotypes activate the classical complement pathway?
IgG and IgM both activate the classical complement pathway.
What are the characteristics of IgG?
IgG is a monomer with 2 antigen binding sites. It has 4 subclasses (some of which may cross the placenta) and is predominant in blood and lymph. It appears in late primary and early secondary immune response and can activate the complement cascade. It is an opsonin (stimulates phagocytosis) and mediates antigen dependent cell-mediated cytotoxicity (ADCC - destruction due to chemical mediators).
Which isotype induces mast cell degranulation?
Immunoglobulin E induces mast cell degranulation.
Which isotype crosses the placenta?
Immunoglobulin G may cross the placenta.
Which isotype is present on the membrane of mature B cells?
Immunoglobulin M and D are present on the membrane of mature B cells.
What are the characteristics of IgM?
Immunoglobulin M is a monomer on the surface of mature B cells and a pentamer when secreted from plasma cells. The pentamer is joined together by the J chain and has 10 antigen binding sites. Immunoglobulin M appears 1st during the primary immune response and is best at complement activation and agglutinating antibodies.
What are immunoglobulin domains?
Immunoglobulin domains make up the antibody molecule. Each domain is 100 to 110 amino acids long and contains intrachain disulfide bonds. These molecules are members of the immunoglobulin gene superfamily which plays a role in host defense.
What is the difference between an immunoglobulin and antibody?
Immunoglobulin is used as a generic term while antibody specifies an immunoglobulin with a particular specificity.
What are isotypes and what are the examples in humans?
Isotypes are classes of antibodies that have differences in amino acid sequence and function. They are determined by C-regions of the H-chain. Humans have IgM, IgG, IgA, IgE, and IgD. Immunoglobulins M and E differ from the others in that they have an additional domain (4 constant regions instead of 3) and no hinge region.
What is multiple myeloma and what is its effect on the immune system?
Multiple myeloma is a B cell cancer which produces high levels of an antibody with a single specificity.
What are the classes of heavy chains and types of light chains?
The classes of heavy chains are IgG, IgM, IgA, IgE, and IgD. The types of light chains are kappa and lambda.
What are the parts of the variable region?
The end of the antibody has an N-terminal region where the antigen binds (VH and VL). Variability is concentrated in the complementarity determining regions: CDR 1, CDR 2, and CDR 3 (hyper variable regions). Framework regions are less variable.
What is the role of immunoglobulin in antigen specificity?
When a B cell is activated, it develops into a plasma cell to secrete soluble antibodies. B cells have membrane-bound immunoglobulin that are specific to one antigen. Therefore, only those B cells specific to a present antigen will proliferate and produce identical antibodies. This is called clonal selection.
