3 5
Molecular Immunology
unique proteins of the immune system. Although new
components and new functions for known components of
the immune system continue to be discovered, the princi-
pal groups of molecules of immunity are immunoglobu-
lins, T-cell receptors and coreceptors, cytokines, and the
proteins of the complement system. Discrimination be-
tween self and nonself, which is the result of the elimina-
tion of B and T cells that recognize self-molecules, reflects
the actions of substances that regulate programmed cell
death. Recognition of epitopes on foreign substances and
foreign cells by immunoglobulin molecules and T-cell re-
ceptors occurs because of complementarity between spe-
cialized “lock-like surface” regions of an immunoglobulin
or T-cell receptor molecule and the “key-like” epitopes of
an antigen molecule.
Cell proliferation in response to foreign antigens in-
volves receptors, coreceptors, and intracellular process-
ing of the antigens by proteolytic enzymes. The trans-
port and binding of the processed antigens is directed
by proteins that are encoded by genes of the major his-
tocompatibility complex. Finally, T-cell receptor recog-
nition of the processed, antigen-derived peptides results
in the synthesis and release of cytokines.
pleiotropic protein molecules with functions for each cy-
tokine molecule determined both by the structure of the
cytokine molecule and the cells and cell receptors with
which the cytokine interacts. Cytokines act as the mes-
sengers through which communication and coordination
among the cells of the immune system are obtained. Com-
plement proteins act on the cell membrane of foreign or-
ganism by assembly of the MAC, which causes permeabil-
ity changes that destroy the cell. In a highly coordinated
manner, the cells and molecules of the immune system pro-
tect the organism from pathogenic organisms and bacterial
In the newborn infant, resistance to infectious agents
is first achieved by maternal antibodies that cross the
placenta during fetal development or antibodies from
mammary gland secretions transferred to a nursing in-
fant. Subsequent antibody-mediated protection is pro-
vided by antibodies synthesized by the B cells of the in-
dividual as described above. Following this natural se-
quence, the focus on molecules and how molecular struc-
tures account for biological function begins with antibody
35.6 Immunoglobulin Structure and Function
Antibodies, i.e., immunoglobulin molecules, account for
approximately 15-20% of the mass of proteins in human
serum, the protein solution that remains after blood or
(Also see color figure.) Structural motif of the immunoglobulin family.
Each domain of the immunoglobulin or other molecule of the
immunoglobulin family is composed of a collection of /3 strands that form
a globular structure. There are seven strands in the constant-region
domains that form two /J sheets; one sheet contains three antiparallel
strands and the other four antiparallel strands. The orientation illustrates
the two sheets that together create the /3 sandwich or immunoglobulin
plasma has clotted. The immunoglobulins can be divided
into five classes—IgG, IgM, IgA, IgE, and IgD—based on
their polypeptide chain sequences. The immunoglobulin
classes are divided as follows: ~80% IgG, 5-10% IgM,
~15% IgA, and <0.2% for IgE and IgD combined.
The most common type of molecule of the immunoglob-
ulin family is IgG (p-immunoglobulin or p-globulin). IgG
will be used as the reference molecule for describing the
other classes of Ig molecules. An IgG immunoglobulin
molecule contains four polypeptide chains; two heavy
polypeptide chains (H chains), ~50,000 Da each, and two
light polypeptide chains (L chains), ~25,000 Da each.
The difference between this “simple” immunoglobulin
and more complex forms of immunoglobulin molecules,
i.e., IgM and IgA, are described later (Figure 35-11). Be-
cause of a common motif in the immunoglobulins and
some immune system cell membrane receptor molecules,
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