Chapter 13
Innate and Adaptive Immunity
295
Immunoglobulins
Antibodies are protein molecules also known as
immunoglobu-
lins
. Igs are classified into five different categories based upon
their role in the humoral defense mechanisms. The five classes
include IgG, IgA, IgM, IgD, and IgE (Table 13.4). The classic
structure of Igs is comprised of four-polypeptide chains with
at least two identical antigen-binding sites (Fig. 13.9). Each Ig
is composed of two identical light (L) chains and two identi-
cal heavy (H) chains that form a characteristic “Y”-shaped
molecule. The “Y” ends of the Ig molecule carry the antigen-
binding sites and are called
Fab
(
i.e.,
antigen-binding) frag-
ments. The tail end of the molecule, which is called the
Fc
fragment, determines the biologic and functional characteris-
tics of the class of Igs.
The heavy and light chains of the Ig have certain amino
acid sequences, which show constant (C) regions and variable
(V) regions. The
constant regions
have sequences of amino
acids that vary little among the antibodies of a particular class
of Ig and determine the classification of the particular Ig (
e.g.,
IgG, IgE). The constant regions, therefore, determine the
effector function of the particular antibody. For example, IgG
can tag an antigen for recognition and destruction by phago-
cytes. In contrast, the amino acid sequences of the
variable
regions
differ from antibody to antibody. They also contain the
antigen-binding sites of the particular molecule. The different
amino acid sequences found in these binding sites allow this
region of the antibody to recognize its complementary epit-
ope (antigen). The variable amino acid sequence determines
the shape of the binding site, forming a three-dimensional
pocket that is complementary to the specific antigen. When
B lymphocytes divide, they form clones that produce antibod-
ies with identical antigen-binding regions. During the course
of the immune response, class switching (
e.g.,
from IgM to
IgG) can occur, causing the B cell clone to produce one of the
different Ig types.
IgG
(gamma globulin) is the most abundant of the Igs
making up 75% of the total circulating antibodies. It is a large
molecule with a molecular weight of approximately 150 kDa
complement receptors expressed on the cell membrane.
During development Ig gene rearrangement takes place to
insure that only B lymphocytes are capable of producing
antibodies (Ig). At each stage of development, a cell-specific
pattern of Ig gene is expressed, which then serves as a pheno-
typic marker of these maturational stages. The B lymphocyte
progenitors are known as pro-B and pre-B cells and develop
into both mature and naive B lymphocytes in the bone mar-
row. Naïve (or immature) B lymphocytes display IgM on the
cell surface. These immature cells respond to antigen differ-
ently from a mature B cell. They can be functionally removed
from the body as a result of interaction with a self-antigen, by
undergoing programmed cell death (apoptosis) or by the pro-
cess of anergy where they become nonresponsive in the pres-
ence of the antigen. Naïve B lymphocytes can leave the bone
marrow and migrate to peripheral or secondary lymphoid tis-
sues such as the spleen and lymph nodes where they complete
the maturation process. Once B lymphocytes become fully
mature, they become capable of expressing IgD, in addition
to the IgM on the cell membrane surface. Mature B lympho-
cytes are fully responsive to antigens and are capable of inter-
acting with T cells.
The commitment of a B-cell line to a specific antigen is
evidenced by the expression of the membrane-bound Ig recep-
tors that recognize the specific antigen. Initially, when mature
B lymphocytes encounter antigens that are complementary
to their encoded surface Ig receptor and in the presence of
T lymphocyte antigen presentation, they undergo a series of
conformational changes that transform them into antibody-
secreting plasma cells or into memory B cells (Fig. 13.8).
Both cell types are necessary for the ultimate success of the
humoral response. The antibodies produced by the plasma
cells are released into the lymph and blood, where they can
then bind and remove their specific antigen with the help
of other immune effector cells and molecules. The memory
B lymphocytes have a longer life span and are distributed to
the peripheral tissues in preparation for subsequent antigen
exposure.
B-cell antigen
receptor on
surface of
immunoglobulin
Proliferation
TCR
TCR
CD4
Antigen MHC-II
B
cell
Plasma
cell
Differentiation
Antibody
B
cell
Memory
B
cell
B
cell
Cytokines
Helper
T cell
FIGURE 13.8
•
Pathway for B-cell differentiation.
