Immune Defense against Bacterial Pathogens: Adaptive or Acquired Immunity (page 4)
(This chapter has 6 pages)
© Kenneth Todar, PhD
Induction of primary immunological responses
Induction of a primary immunological response begins when an
antigen
penetrates epithelial surfaces. It will eventually come into contact
with
macrophages
or certain other classes of Antigen Presenting cells (APCs),
which
include B cells, monocytes, dendritic cells, Langerhans cells
and
endothelial cells. Antigens, such as bacterial cells, are internalized
by endocytosis and "processed" by the APC, then "presented" to
immunocompetent
lymphocytes to initiate the early steps of the immunological response.
Processing by a macrophage (for example) results in attaching antigenic
materials to the surface of the membrane in association with MHC II
molecules on the surface of the cell . The antigen-MHC II complex
is presented to a T-helper (TH2) cell
which is able to
recognize
processed antigen associated with a class II MHC molecule on the
membrane
of the macrophage. This interaction, together with stimulation by Interleukin
1 (IL-1), produced by the macrophage, will activate the TH2 cell.
Activation
of the TH2 cell causes it to begin to produce Interleukin
2
(IL-2),
and to express a membrane receptor for IL-2. The secreted IL-2
auto stimulates
proliferation of the TH2 cells. Stimulated
Antigen stimulated TH2 cells produce a variety
of lymphokines including IL-2, IL-4, IL-6, and gamma
Interferon, which mediate various aspects of the immune response.
For
example, IL-2 binds to IL-2 receptors on other T cells (which have
bound
the Ag) and stimulates their proliferation, while IL-4 causes B cells
to
proliferate and differentiate into antibody-secreting plasma cells
and memory B cells. IL-4 activates only B cells in the vicinity
which themselves have bound the antigen, and not others, so as to
sustain
the specificity of the immunological response.
As previously mentioned, B cells themselves behave as APCs. Antigens
bound to antibody receptors on the surface of a B cell cause
internalization
of some of the antigen and expression on the B cell membrane together
with
MHC II molecules. The TH2 cell recognizes the
antigen together with the
Class II MHC molecules, and secretes the various lymphokines that
activate
the B cells to become antibody-secreting plasma cells and memory B
cells.
Even if the antigen cannot cross-link the receptor, it may be
endocytosed
by the B cell, processed, and returned to the surface in association
with
MHC II where it can be recognized by specific TH2
cells which will
become
activated to initiate B cell differentiation and proliferation. In any
case, the overall B-cell response leads to antibody-mediated
immunity
(AMI).
The antigen receptors on B cell surfaces bear the specificity of
antibodies that they are genetically-programmed to
produce.
Hence, there are thousands of sub-populations of B cells
distinguished
only by their ability to produce a unique (reactive) type of antibody
molecule.
A B-cell can react with a homologous antigen on the surface of the
macrophage or with soluble antigens. When a B-cell is bound to Ag, and
simultaneously is stimulated by IL-4 produced by a nearby TH2 cell, the
B cell is stimulated to grow and divide to form a clone of identical B
cells, each capable of producing identical antibody molecules. The
activated
B cells further differentiate into plasma cells which
synthesize
and secrete large amounts of antibody, and into a special form of B
cells
called memory B cells.
The antibodies produced and secreted by the
plasma
cells react specifically with the homologous antigen that induced
their formation. Many of these reactions lead to host defense and to
prevention
of reinfection by pathogens. Memory cells a role in
secondary
immune responses.
Plasma cells are relatively short-lived (about one week) but produce
large amounts of antibody during this period. Memory cells, on the
other
hand, are relatively long-lived and upon subsequent exposure to Ag they
become quickly transformed into Ab-producing plasma cells.
Generation of cell mediated immunity (CMI) begins when (for
example)
a Tc cell recognizes a processed antigen associated with
MHC
I on the membrane of a cell (usually an altered self cell, but
possibly
a transplanted tissue cell or a eucaryotic parasite). Under stimulation
by IL-2 produced by TH2 cells the Tc
cell becomes
activated
to become a cytotoxic T lymphocyte (CTL) capable of lysing the
cell
which is showing the new (foreign) antigen on its surface, a primary
manifestation
of CMI.
The interaction between an antigen-presenting macrophage and a TH
cell
stimulates the macrophage to produce and secrete a cytokine called Interleukin-1
(IL-1) that acts locally on the TH cell. The
IL-1 stimulates the TH cell
to differentiate and produce its own cytokines (which in this case
might
be called lymphokines because they arise from a lymphocyte).
These
lymphokines have various functions. Interleukin-4 has an immediate
effect
on nearby B-cells. Interleukin-2 has an immediate effect on T cells as
described above.
Time is required before a primary immunological response to be
effective as a
host defense. Antigens have to be recognized, taken up, digested,
processed
and presented by APCs; a few select TH cells
must react with Ag and
respond;
preexisting B or T lymphocytes must encounter the Ag and proliferate
and
differentiate into effector cells (plasma cells or CTLs). In the case
of
AMI, antibody level has to build up to an effective physiological
concentration
to render its host resistant. It may take several days or weeks to
reach
a level of effective immunity, even though this immunity may persist
for
many months, or years, or even a lifetime due to the presence of the
antibodies.
In natural infections, the inoculum is small, and even though the
antigenic
stimulus increases during microbial replication, only small amounts of
antibody are formed within the first few days, and circulating antibody
is not detectable until about a week after infection.
Induction of a secondary immunological
response
On re-exposure to microbial antigens (secondary exposure to
antigen),
there is an accelerated immunological response, the secondary or memory
response. Larger amounts of antibodies are formed in only 1-2 days.
This
is due to the activities of specific memory B cells and memory T cells
which
were formed during the primary immune response. These memory cells,
when
stimulated by homologous Ag, "remember" having previously seen the Ag,
and are able to rapidly divide and differentiate into effector cells.
Stimulating
memory cells to rapidly produce very high (effective) levels of
persistent
circulating antibodies is the basis for giving regular "booster"-type
vaccinations
to humans and pets.

Figure 4. Primary and
Secondary
Immunological Responses. Following the first exposure to an antigen the
immune
response (as evidenced by following the concentration of specific
antibody
in the serum, called "titer") develops gradually over a period of days,
reaches a low
plateau
within 2-3 weeks, and usually begins to decline in a relatively short
period
of time. When the antigen is encountered a second time, a secondary
(memory)
response causes a rapid rise in the concentration of antibody, reaching
a much higher level in the serum, which may persist for a relatively
long
period of time. This is not to say that a protective level of antibody
may not be reached by primary exposure alone, but usually to ensure a
high
level of protective antibody that persists over a long period of time,
it is necessary to have repeated antigenic stimulation of the immune
system.
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