Untitled - D Ank Unlimited

immunoglobulin A (IgA) 367 immunoglobulin A deficiency
The immunoglobulin molecule consists of heavy (H) and
light (L) chains fastened together by disulfide bonds. The
molecules are subdivided into classes and subclasses based
on the antigenic specificities of the heavy chains. Heavy
chains are designated by lower case Greek letters (μ, γ, α, δ,
and ε), and the immunoglobulins are designated IgM, IgG,
IgA, IgD, and IgE, respectively. The three major classes are
IgG, IgM, and IgA, and the two minor classes are IgD and
IgE that together comprise less than 1% of the total immunoglobulins.
The two types of light chains (κ and λ) are
present in all five immunoglobulin classes, although only
one type is present in an individual molecule. IgG, IgD, and
IgE have two H and two L polypeptide chains, whereas IgM
and IgA consist of multimers of this basic chain structure.
Disulfide bridges and noncovalent forces stabilize immunoglobulin
structures. The basic monomeric unit is Y-shaped,
with a hinge region rich in proline and susceptible to
cleavage by proteolytic enzymes. Both H and L chains
have constant regions at their carboxyl termini and variable
regions at their amino termini. The two heavy chains are
alike, as are the two light chains, in all immunoglobulin
molecules. Approximately 60% of human immunoglobulin
molecules have κ light chains, and 40% have λ light chains.
The five immunoglobulin classes are termed isotypes based
on the heavy chain specificity of each immunoglobulin
class. Two IgA and IgG classes are further subdivided into
subclasses based on H chain differences. The four IgG
subclasses are designated as IgG 1 through IgG 4, and the
two IgA subclasses are designated IgA 1 and IgA 2. Digestion
of IgG molecules with papain yields two Fab and one Fc
fragments. Each Fab fragment has one antigen-binding site.
By contrast, the Fc fragment has no antigen-binding site
but is responsible for fixation of complement and attachment
of the molecule to a cell surface. Pepsin cleaves the
molecule toward the carboxyl terminal end of the central
disulfide bond, yielding an F(ab′) 2 fragment and a pFc′ fragment.
F(ab′) 2 fragments have two antigen-binding sites. L
chains have a single variable and constant domain, whereas
H chains possess one variable and three to four constant
domains. Secretory IgA is found in body secretions such as
saliva, milk, and intestinal and bronchial secretions. IgD
and IgM are present as membrane-bound immunoglobulins
on B cells, where they interact with antigen to activate B
cells. IgE is associated with anaphylaxis, and IgG, which is
the only immunoglobulin capable of crossing the placenta,
is the major human immunoglobulin.
IgA1.
J chain
IgA2.
Secretory piece
Secretory IgA that consists of two IgA monomers, a J chain, and a
secretory piece that is believed to protect the molecule from enzymatic
digestion in the gut.
immunoglobulin A (IgA)
Immunoglobulin A (IgA) comprises 5 to 15% of the serum
immunoglobulins and has a half-life of 6 days. It has a
molecular weight of 160 kDa and a basic four-chain monomeric
structure; however, it can occur as a monomer, dimer,
trimer, or multimer. It contains α heavy chains and κ or λ
light chains. The two subclasses of IgA are designated IgA 1
and IgA 2. In addition to monomeric serum IgA, a dimeric
secretory or exocrine variety appears in body secretions
and provides local immunity. For example, the Sabin oral
polio vaccine stimulates secretory IgA antibodies in the
gut that provide effective immunity against poliomyelitis.
IgA-deficient individuals have an increased incidence of
respiratory infections associated with a lack of secretory
IgA in the respiratory system. Secretory or exocrine IgA
appears in colostrum, intestinal, and respiratory secretions;
saliva; tears; and other secretions.
immunoglobulin A deficiency
The most frequent human immunodeficiency that affects
1 in 600 persons in the United States. Even though the
B cells of these individuals have IgA on their surfaces, they
do not differentiate into plasma cells that secrete IgA. IgA
levels are decreased from a normal value of 76 to 390 mg/
dL to a value below 5 mg/dL. Almost half develop anti-IgA
antibodies that are subclass-specific. IgA-deficient individuals
with heightened susceptibility to infection by pyogenic
microorganisms also are deficient in IgG 2 and often IgG 4.
The administration of a blood transfusion to IgA-deficient
patients possessing anti-IgA antibodies can lead to anaphylactic
shock due to IgE antibodies specific for IgA or
to a fatal hemolytic transfusion reaction. Patients may also
H
L
I