Lymphoid Organs
The
central and peripheral lymphoid organs are responsible for the production,
maturation, and storage of large numbers of immune system cells including the B
and T lymphocytes. These organs and tissues are widely distributed throughout
the body and provide different, but often overlapping, functions (Fig. 13.12).
The central lymphoid organs are comprised of the bone marrow and the thymus and
are responsible for immune cell production and maturation. The tissues and
cells of the peripheral lymphoid system store the cells of the immune system
where they function to concentrate and process antigen as well as support
cellular processes necessary for development of fully functioning, adaptive
immune responses. The peripheral lymphoid tissues are comprised of the lymph
nodes, spleen, tonsils, appendix, Peyer patches in the intestine, and
mucosa-associated lymphoid tissues in the respiratory, gastrointestinal, and
reproductive systems. Networks of lymph channels, blood vessels, and
capillaries connect the lymphoid organs and transport immune cells, antigens,
and cellular debris
throughout the body.
Thymus
The thymus
is an elongated, bilobed structure
located in the mediastinum above
the heart and serves as a specialized immune system organ. Each lobe is
surrounded by a connective tissue capsule layer and is divided into lobules.
The lobules can be divided into an outer cortex and a central medulla, which
play different roles in the process of T-lymphocyte maturation. The outer
cortex contains densely packed immature T lymphocytes (thymocytes). The inner
medulla is a less dense area of tissue that contains fewer but more
histologically mature lymphocytes. The medulla is comprised of Hassall
corpuscles but also stores DCs and macrophages (Fig. 13.13).
The thymus
is essential to the development of the immune system because it is responsible
for the production of mature, immunocompetent T lymphocytes. The thymus is a
fully developed organ at birth, weighing approximately 15 to 20 g. It is most
active in the neonatal and preadolescent periods. At puberty, when the immune
cells are well established in peripheral lymphoid tissues, the thymus begins to
atrophy and is replaced by adipose tissue. Nevertheless, residual T-lymphocyte
production continues throughout adult life. Precursor T (pre-T) cells enter the
thymus as functionally and phenotypically immature T cells. They then mature
during different cycles and then move from the cortex to the medulla until they
are released into the peripheral lymphoid tissues. Rapid cell division,
maturation, and selection occur in the cortex under
the influence of thymic hormones and cytokines.
As the T cells mature, they develop the TCRs that differentiate them from other
types of T cells. The majority of the thymocytes die in the cortex during the
process of gene rearrangement and maturation because they fail to develop the
appropriate receptor types on their cell membranes. Only those T cells capable
of recognizing foreign antigen displayed by self-MHC are allowed to mature. This
process is called thymic selection. Mature, immunocompetent T-helper and
T-cytotoxic cells leave the thymus in 2 to 3 days and enter the peripheral
lymphoid tissues through the bloodstream.
Lymph
Nodes
Lymph
nodes are small aggregates of lymphoid tissue located along lymphatic vessels
throughout the body. The lymphatic vessels carry lymph, which is a clear
sometimes yellow-tinged fluid that contains a variety of white blood cells (pre-dominantly
lymphocytes) and transports cellular debris and organisms to the lymph modes to
be removed from the body. Each lymph node processes lymph from a discrete,
adjacent anatomic site. Lymph nodes are congregated in the axillae and groin
and along the great vessels of the neck, thorax, and abdomen. The lymph nodes
receive lymph from the collecting ducts, which ultimately drain into the
thoracic duct located in the left side of the chest at the level of the
subclavian vein. Lymph nodes have two functions: removal of foreign material from lymph before it enters the bloodstream and serving as centers for proliferation and
response of immune cells.
Lymph
nodes are bean-shaped, encapsulated tissues, approximately 0.5 to 1 cm in
diameter. Lymph enters the node through afferent lymph channels and leaves
through the efferent lymph vessels located in the deep indentation of the
hilus. Lymphocytes and macrophages move slowly through the lymph nodes so that
they have adequate time to engulf microorganisms and interact with circulating
antigen. The lymphatic system provides a large surface upon which macrophages
and DCs can more easily present antigens to T lymphocytes.
Lymph
nodes are divided into three distinct and specialized areas—an outer cortex, a
paracortex, and an inner medulla (Fig. 13.14). The T lymphocytes predominate in
the paracortex and the B lymphocytes predominate in the follicles and germinal
centers of the outer cortex. The T lymphocytes proliferate when antigens enter
the paracortex of the lymph node. They then migrate to the outer cortex so that
they can interact with B lymphocytes that are stored there. Within the
follicles the lymphocytes continue to mature, replicate, and interact with the
PACs present in the nodes (macrophages and follicular DCs). Activated B cells
then migrate to the medulla of the lymph node, where they complete their
maturation into plasma cells. Large quantities of antibodies are then released into the systemic circulation.
The
spleen is a large, ovoid secondary lymphoid organ located high in the left
upper quadrant of the abdominal cavity between the diaphragm and the stomach.
The spleen filters antigens from the blood and is important in the response to
systemic infections. It is divided into two systems: the white pulp and the red
pulp. The red pulp is well supplied with arteries and venous sinusoids and is
the area where senescent and injured red blood cells are removed. The white
pulp contains lymphatic nodules and diffuse lymphoid tissue where concentrated
areas of B and T lymphocytes permeated by macrophages and DCs exist. The
lymphocytes (primarily T cells) that surround the central arterioles form the
area called the periarterial lymphoid sheath. There is also a diffuse
marginal zone that contains the follicles and germinal centers and is rich in B
cells. This separates the white pulp from the red pulp and allows lymphocytes
to move easily between the blood and the lymphatic tissue. A sequence of
activation events similar to that seen in the lymph nodes occurs in the spleen.
Other
Secondary Lymphoid Tissues
Other secondary
lymphoid tissues include the mucosa- associated lymphoid tissues, which
are nonencapsulated clusters of lymphoid tissues located around membranes
lining the respiratory, digestive, and urogenital tracts. These organ systems
constantly came in contact with pathogens and toxins and, therefore, require
the presence of immune cells in order to respond to the potential invasion by
pathogens and harmful substances. In some tissues, the lymphocytes are
organized in loose, nondescript clusters, but in other tissues such as the
tonsils, Peyer patches in the intestine, and the appendix, their structure is
better organized. These tissues contain all the cellular components (i.e., T
cells, B cells, macrophages, and DCs) required to mount an immune response.
Immunity at the mucosal layers helps to exclude many pathogens from the body
and, as a result, protects the more vital internal structures.
