Defense Mechanisms of the Body
What are the mechanisms of clonal deletion and inac-
tivation during fetal and early postnatal life? Recall that full
activation of a helper T cell requires not only an antigen-
specifi c stimulus but a nonspecifi c costimulus (interaction
between complementary nonantigenic proteins on the APC
and the T cell). If this costimulus is
provided, the helper
T cell not only fails to become activated by antigen, but dies
or becomes inactivated forever. This is the case during early
life, although what accounts for the costimulus not being
delivered is unclear. B cells can also undergo clonal deletion
and inactivation.
This completes the framework for understanding specifi c
immune defenses. The next two sections utilize this framework
in presenting typical responses from beginning to end, high-
lighting the interactions between lymphocytes and describing
the attack mechanisms used by the various pathways.
Antibody-Mediated Immune Responses:
Defenses Against Bacteria, Extracellular
Viruses, and Toxins
A classical antibody-mediated response is one that results in
the destruction of bacteria. The sequence of events, which is
quite similar to the response to a virus in the extracellular
uid, is summarized in
Table 18–6
Figure 18–14
Antigen Recognition and Lymphocyte Activation
This process starts the same way as for nonspecifi c responses,
with the bacteria penetrating one of the body’s linings and
entering the interstitial fl uid. The bacteria then enter the lym-
phatic system and/or bloodstream and are carried to the lymph
nodes and/or the spleen, respectively. There a B cell, using its
immunoglobulin receptor, recognizes the bacterial surface
antigen and binds the bacterium.
In a few cases (notably bacteria with cell-wall polysac-
charide capsules), this binding is all that is needed to trigger
B-cell activation. For the great majority of antigens, however,
antigen binding is not enough, and signals in the form of
cytokines released into the interstitial fl uid by helper T cells
near the antigen-bound B cells are also needed.
For helper T cells to react against bacteria by secreting
cytokines, they must bind to a complex of antigen and class II
MHC protein on an APC. Let us assume that in this case the
APC is a macrophage that has phagocytized one of the bacte-
ria, hydrolyzed its proteins into peptide fragments, complexed
them with class II MHC proteins, and displayed the com-
plexes on its surface. A helper T cell specifi c for the complex
then binds to it, beginning the activation of the helper T cell.
Moreover, the macrophage helps this activation process in two
other ways: It provides a costimulus via nonantigenic plasma
membrane proteins, and it secretes IL-1 and TNF.
IL-1 and TNF stimulate the helper T cell to secrete
another cytokine named
interleukin 2 (IL-2)
and to express
the receptor for IL-2. IL-2, acting as an autocrine agent, then
provides a proliferative stimulus to the activated helper T cell
(see Figure 18–14). The cell divides, beginning the mitotic
cycles that lead to the formation of a clone of activated helper
T cells, and these cells then release not only IL-2 but other
cytokines as well.
Certain of these cytokines provide the additional sig-
nals required to activate nearby antigen-bound B cells to pro-
liferate and differentiate into plasma cells, which then secrete
Thus, as shown in Figure 18–14, a series of protein mes-
sengers interconnects the various cell types, the helper T cells
serving as the central coordinator. The macrophage releases
IL-1 and TNF, which act on the helper T cell to stimulate the
release of IL-2, which stimulates the helper T cell to multiply.
The activated progeny then release still other cytokines that
help activate antigen-bound B cells.
As stated earlier, however, some of the B-cell progeny do
not differentiate into plasma cells but instead into memory cells,
whose characteristics permit them to respond more rapidly
Table 18–6
Summary of Events in Antibody-Mediated Immunity Against Bacteria
1. In secondary lymphoid organs, bacterial antigen binds to specifi c receptors on the plasma membranes of B cells.
2. Simultaneously, antigen-presenting cells (APCs), for example, macrophages, (a) present to helper T cells processed antigen complexed to
class II MHC proteins on the APCs, (b) provide a costimulus in the form of another membrane protein, and (c) secrete IL-1, TNF, and
other cytokines, which act on the helper T cells.
3. In response, the helper T cells secrete IL-2, which stimulates the helper T cells themselves to proliferate and secrete IL-2 and other
cytokines. These activate antigen-bound B cells to proliferate and differentiate into plasma cells. Some of the B cells differentiate into
memory cells rather than plasma cells.
4. The plasma cells secrete antibodies specifi c for the antigen that initiated the response, and the antibodies circulate all over the body via
the blood.
5. These antibodies combine with antigen on the surface of the bacteria anywhere in the body.
6. Presence of antibody bound to antigen facilitates phagocytosis of the bacteria by neutrophils and macrophages. It also activates the
complement system, which further enhances phagocytosis and can directly kill the bacteria by the membrane attack complex. It may
also induce antibody-dependent cellular cytotoxicity mediated by NK cells that bind to the antibody’s Fc portion.
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