Immunoglobulins and immunoglobulin deficiency syndromes WORLD OF MICROBIOLOGY AND IMMUNOLOGY300•
The molecular understanding of how the diverse repertoire of
these receptors is generated came with the discovery of
somatic recombinationof receptor genes, which is the para-
digm for studying generearrangement during cell maturation.
The most important influence on the development of
immunogenetics is, however, the studies of a gene family
known as the MCH, or major histocompatibility complex.
These highly polymorphic genes, first studied as white-cell
antigens of the blood and therefore named human leukocyte
antigens (HLA), influence both donor choice in organ trans-
plantation and the susceptibility of an organism to chronic dis-
eases. The MHCis also linked with most of all the important
autoimmune diseases such as rheumatoid arthritis and diabetes.
The discovery in 1972 that these MHC molecules are
intimately associated with the specific immune response to
virusesled to an explosion in immunogenetic studies of these
molecules. This has led to the construction of very detailed
genetic and physical maps of this complex and ultimately to its
complete sequence in an early stage of the human genome-
sequencing project.
Other clusters of immune recognition molecules that are
well established at the center of the immunogenetics discipline
are the large arrays of rearranging gene segments that deter-
mine B-cell immunoglobulins and T-cell receptors.
Immunoglobulins, which mediate the humoral immune
response of the adaptive immune system, are the antibodies
that circulate in the bloodstream and diffuse in other body flu-
ids, where they bind specifically to the foreign antigen that
induced them. This interaction with the antigen most often
leads to its clearance. T cell receptors, which are involved in
the cell-mediated immune response of the adaptive immune
system, are the principle partners of the MHC molecules in
mounting a specific immune response. An antigen that is taken
up by specialized cells called antigen presenting cells is usu-
ally presented on the surface of this cell in complex with either
MHC class I or class II to T cellsthat use specific receptors to
recognize and react to the infectious agent. The reacting T
cells can kill the host cells that bear the foreign antigen or
secrete mediators (cytokines and lynphokines) that activate
professional phagocytic cells of the immune system that elim-
inate the antigen. It is believed that during disease epidemics,
some forms of class I and class II MHC molecules stimulate
T-cell responses that better favor survival. Which MHC mole-
cule is more favorable depends on the infectious agents
encountered. Consequently, human populations that were geo-
graphically separated and have different disease histories dif-
fer in the sequences and frequencies of the HLA class I and
class II alleles.
Other immune recognition molecules that were studied
in great details in immunogenetics are two families of genes
that encode receptors on the surface for natural killer (NK)
cells. These large lymphocytes participate in the innate
immune system and provide early defense from a pathogens
attack, a response that distinguish them from B and T cells
which become useful after days of infection. Some NK-cell
receptors bind polymorphic determinants of MHC class I mol-
ecules and appear to be modulated by the effects that infectious
agents have upon the conformation of these determinants.One of the most important applications of immuno-
genetics in clinical medicine is HLA-typing in order to help
match organ donors and recipients during transplantation sur-
gery. Transplantation is a procedure in which an organ or tis-
sue that is damaged and is no longer functioning is replaced
with one obtained from another person. Because HLA anti-
gens can be recognized as foreign by another person’s immune
system, surgeons and physicians try to match as many of the
HLA antigens as possible, between the donated organ and the
recipient. In order to do this, the HLA type of every potential
organ recipient is determined. When a potential organ donor
becomes available, the donor’s HLA type is determined as
well to make absolutely sure that the donor organ is suitable
for the recipient.See alsoAutoimmunity and autoimmune diseases; Immunity,
active, passive and delayed; Immunity, cell mediated;
Immunity, humoral regulation; Immunologic therapies;
Immunosuppressant drugs; In vitro and in vivo research;
Laboratory techniques in immunology; Major histocompati-
bility complex (MHC); Medical training and careers in
immunology; Molecular biology and molecular genetics;
Mutations and mutagenesis; Oncogenetic research;
Transplantation genetics and immunology; Viral geneticsIMMUNOGLOBULIN DEFICIENCY• see
IMMUNODEFICIENCY DISEASE SYNDROMESIMMUNOGLOBULINS AND IMMUNOGLOBU-
LIN DEFICIENCY SYNDROMESImmunoglobulins and immunoglobulin deficiency syndromesImmunoglobulins are proteins that are also called antibodies.
The five different classes of immunoglobulins are formed in
response to the presence of antigens. The specificity of an
immunoglobulin for a particular antibodyis exquisitely precise
The five classes of immunoglobulins are designated
IgA, IgD, IgG, IgE, and IgM. These share a common structure.
Two so-called heavy chains form a letter “Y” shape, with two
light chains linked to each of the upper arms of the Y. The
heavy chains are also known as alpha, delta, gamma, epsilon,
or mu. The light chains are termed lambdaor kappa.
The IgG class of immunoglobulin is the most common.
IgG antibody is routinely produced in response to bacterial and
viral infections and to the presence of toxins. IgG is found in
many tissues and in the plasma that circulates throughout the
body. IgM is the first antibody that is produced in an immune
response. IgA is also produced early in a body’s immune
response, and is commonly found in saliva, tears, and other
such secretions. The activity of IgD is still not clear. Finally, the
IgE immunoglobulin is found in respiratory secretions.
The different classes of immunoglobulins additionally
display differences in the sequence of amino acids comprising
certain regions within the immunoglobulin molecule. For
example, differences in the antigen-binding region, the variable
region, accounts for the different antigenbinding specificitieswomi_I 5/6/03 3:23 PM Page 300