 ORGANS
OF THE IMMUNE SYSTEM Primary Lymphoid Organs: Sites of lymphocye maturation In Most Mammals: bone marrow
& thymus PRIMARY LYMPHOID ORGANS BONE MARROW
Because there is not a discrete site, the process is very difficult to study. Stromal cells in the bone marrow very important in this process. Soluble factors are not as well characterized in the bone marrow but IL-7 is known to be an important signal. **There also is known to be a negative selection process. Many pre-B cells die in the bone marrow. If they do not form functional Ig molecules or if they possess Ig molecules which recognize and bind to self antigens they will undergo death by Apoptosis. As many as 90% of differentiating B cells are believed to have this fate. B cells that survive this selection process leave the bone marrow through efferent blood vessels. THYMUS Cortex and Medulla are both crisscrossed by a 3D network of stromal cells composed of:
These cells physically interact with the developing T cells (thymocytes) as well as secreting soluble factors which influence T cell maturation. In the cortex, the network is densely packed with thymocytes. Cells are less dense in medulla. In medulla, the epithelial cells are more visible and you also find HASSAL's Corpuscles. -Function Unknown. The thymus is at its largest
relative size at birth and its largest actual size is at puberty.
Following puberty the thymus begins to shrink. In elderly individuals
it is usually less than 3 grams in weight. Please see figure of thymus from lecture or in text. Histology images from BIO 324 Lab
The complete process of thymic
education is a two-step process in which Thymic cortical epithelial
cells function as the In positive selection, T cells which bear a TcR which can bind SELF-MHC are selected to survive and proliferate. Cells which are not positively selected are triggered to undergo APOPTOSIS (T cells which lack a functional TcR, or T cells which possess a TcR without affinity for self-MHC) Positively selected thymocytes must go through a second phase of selection known as NEGATIVE SELECTION. Functionally, during negative selection any T cell that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS. The self peptides encountered
in the thymus are derived from proteins expressed in thymus + other
proteins brought to the thymus via the blood stream. Of course not all
potentially auto-reactive T cells can be deleted and peripheral deletion
of autoreactive T cells is also Most importantly:: thymic macrophages and dendritic cells serve as APCs in the process of negative selection The surviving T cells migrate to the medulla where they continue maturation and finally leave the thymus through the postcapillary venules or efferent lymphatics. Stromal cells secrete soluble factors which are important in T cell maturation. Some examples include: Individual roles not well known but all are relatively small 1-15kDa. In addition, *IL-7 also known to play a role in T cell maturation within the thymus. PEYER'S PATCHES Actually: Two types of Peyer's patches seem to occur: one with primary lymphoid function and one type with secondary lymphoid function. SECONDARY LYMPHOID ORGANS Sites where lymphocytes encounter antigen and interact with other cells of the immune system. Such organs enlarge in response to antigenic stimulation and are poorly developed in germ-free animals. LYMPH NODES 3 regions to the lymph node: Cortex (outermost layer- contains mostly B lymphocytes, plus both follicular dendritic cells and macrophages all arranged in clusters called primary follicles). Following antigenic stimulation they primary follicles become secondary follicles consisting of concentric rings of densely packed lymphocytes and central lymphocytes, macrophages, and dendritic cells. The GCs (germinal centers) contain large proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells. A smaller population of Th lymphocytes is also present to provide Th regulatory activity. The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory cells. Paracortex - (layer just
beneath the cortex) This region is sometimes called the T dependent
region of the lymph node. Medulla- inner most region,
more sparsely populated by cells. Please see figure from lecture or in text. -Afferent lymphatic vessels
pierce the capsule of a lymph node at various sites and empty into the
subcapsular sinus. There is a This huge increase in the number of lymphocytes is due to:
-There is an affferent artery which enters the lymph node. Lymphocytes can enter the node by passing between specialized capillary endothelial cells in the postcapillary venules. This region of the venules contains modified vascular endothelial cells which are taller and more pronounded. Therefore, these areas of the postcapillary venules are termed HIGH ENDOTHELIAL VENULES (HEVs) The extravasation of lymphocytes across the HEVs increases dramtically during antigenic stimulation. Antigenic stimulation can enhance this process 10X. Clearly, the concentration of lymphocytes in the lymph nodes can increase greatly following antigenic stimulation accounting for "swelling of lymph nodes". -LYMPH- fluid from the tissues flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of larger collecting vessels called lymphatic vessels. Lymphatic vessels converge into the thoracic duct, which returns the fluid to the circulatory system by dumping into the left subclavian vein. SPLEEN The spleen is a large, oval
secondary lymphoid organ positioned high in the left abdominal cavity.
The spleen is adapted to filter the blood, it responds
therefore to systemic infections. It is surrounded by a capsule,
which sends trabeculae into the interior to form a Red Pulp- Network of sinusoids populated with macrophages and numerous erythrocytes. Site where old RBCs are destroyed and removed. White Pulp- Surrounds the splenic arteries, forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes. Clusters of B lymphocytes in the White Pulp form primary follicles occupying a more peripheral position. Upon antigenic challenge, these primary follicles develop into characteristic secondary follicles containing germinal centers. The spleen is NOT supplied
by afferent lymphatics. Blood-borne cells and antigens are carried
into the spleen through the splenic artery, which empties into the marginal
zone. Antigen enters the marginal zone, it is trapped by interdigitating
dendritic cells, which
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In
addition: Bone Marrow serves as site of maturation of B lymphocytes
in most mammals studied to date.
Precursor
T cells enter thymus from the blood (there are no afferent lymphatic
vessels] and mature into functional T lymphocytes. Precursor T cells
first enter the cortex which is densely packed with cells due to tremendous
degree of proliferation. However, the vast majority of these cells are
destined to die due to (APOPTOSIS) - programmed cell death. The T cells
(thymocytes) go through a selection process in the thymus based upon
the TcR that they possess.
of
lymphatic vessels and serve as the first organized structures to encounter
most antigens. The major function of the lymph nodes is to filter
antigen from the lymph.
