Biomedical Engineering Reference
In-Depth Information
response. Many of the functions of NF-
κ
B in adaptive immunity are analogous to
the functions of NF-
B is necessary for the
hematopoietic development of lymphocytes (T and B cells); lymphocyte survival
and maturation; and lymphocyte effector functions. Like the innate immune system,
the adaptive immune system requires continual replenishment of its cellular com-
ponents and careful regulation of these cells during and after the immune response.
As was alluded to in
Chapter 6
, adaptive responses rely on signaling events that
occur within carefully organized primary and secondary lymphoid organs that require
NF-
κ
B in the innate immune system. NF-
κ
B for their development and maintenance.
Of its many functions, one of the most critical roles of NF-
κ
B in the adaptive
immune system is the regulation of antiapoptotic genes. This supposition is based
on genetic studies demonstrating that deficits in adaptive immune responses in NF-
κ
B
knockout mice can be rescued by either removal of proapoptotic stimuli or forced
expression of antiapoptotic genes. However, as is often the case, careful examination
reveals unexpected complexities — NF-
κ
B may protect from or facilitate apoptosis
depending on the timing, target, and context of a given signaling event. NF-
κ
B-
regulated cytokines are also critical to the adaptive response, while the regulation of
organogenic chemokines by NF-
κ
B is crucial for lymphoid organogenesis. Conse-
quently, analyzing the role of NF-
κ
B in adaptive immunity requires not only dis-
secting overlapping functions in lymphocyte development and activation, but also
looking at the organization and formation of the tissues that support these processes.
κ
7.2
LYMPHOID ORGANOGENESIS
B function in the adaptive immune system with a brief
discussion of the development and function of tissues that are central to lymphocyte
biology. These tissues can be broadly divided into two categories: primary and
secondary lymphoid organs. Primary (central) lymphoid organs include the bone
marrow and thymus, where B cell and T cell development occur, respectively. B and
T cells develop continuously over the mammalian lifespan. The bone marrow
remains active throughout life, while thymic activity dwindles with the onset of
adulthood. Secondary (peripheral) lymphoid organs include the lymph nodes, Peyer's
patches, mucosal-associated lymphoid tissue (MALT), and spleen. These tissues are
associated with the maintenance and activation of mature lymphocytes, and in some
cases these tissues also can contribute to lymphocyte development. As discussed in
Chapters 6 and
8
, the peripheral lymphoid organs provide an environment within
which the interaction of lymphocytes and other leukocytes can be carefully orches-
trated. Deletions of NF-
We begin our look at NF-
κ
B family genes have revealed a multitude of defects in
lymphoid organogenesis, although in some instances it has remained unclear whether
the deficit is in the development of the tissue itself or in the hematopoietic cells that
populate the fully differentiated tissue.
κ
7.2.1
NF-
κ
B
IN
P
RIMARY
L
YMPHOID
O
RGANS
NF-
B function is critical in the development and maintenance of the central lym-
phoid organs, bone marrow, and thymus. Although, there has been relatively little
κ
