Lymphatic System

Most lymphocytes are found in blood and lymph, representing recirculating immunocompetent cells. Cells of the lymphatic tissue possess unique cell surface molecules called cluster of differentiation (CD) molecules. These are designated by numbers and can be visualized by immunohistochemistry.

T lymphocytes (T cells) differentiate in the thymus. They represent 60-80% of circulating lymphocytes. They are involved in cell-mediated immunity and express T-cell receptors (TCR) and CD markers. They are subclassified into:

• Helper CD4+ T lymphocytes, which express the CD4 and TCR markers. They secrete cytokines and interact with CD8+ cells, B lymphocytes, and macrophages. They are involved in cell-mediated and antibody-mediated immunities. They are restricted to recognizing antigen presented only on MHC II (major histocompatibility complex molecule II).
• Cytotoxic CD8+ T lymphocytes, which express the CD8 and TCR markers. They kill virus-infected cells, cancer-transformed cells, and transplanted cells (allograft) via the action of perforins and fragmentins secretions. They are restricted to recognizing antigen presented only on MHC I (major histocompatibility complex molecule I).

B lymphocytes (B cells) are named because they were first recognized in the bursa of Fabricius in birds or bursa-equivalent organs (e.g. bone marrow and GALT). Represent 20-30% of circulating lymphocytes and express various CD markers, B cell receptors (BCRs), which are membrane-bound immunoglobulin that serve as antigen-binding sites, and MHC II (allowing them to present antigens to helper CD4+ cells). Upon interaction with helper CD4+ cells B cells are activated, divide, and differentiate into plasma cells and memory B cells.

Natural Killer lymphocytes (NK cells, Null cells) are lacking T and B lymphocyte markers, hence the name null cells but they develop from the same precursor. They are programmed to recognize and kill transformed cells (i.e. virus infected and tumour cells). They kill cells in antibody-dependent cell mediated cytotoxicity. NK cells possess FC receptors on their membranes that bind antibodies on the surface of the virus-infected or transformed cells. Interaction of the FC receptors with the Ab-antigen complex stimulates NK cells to secrete perforins and fragmentins (aka granzymes) to destroy the target.

Most antigen-presenting cells (APC) belong to the mononuclear phagocytic system, which macrophages, perisinusoidal macrophages (kupffer cells), langerhans cells in the epidermis, and dendritic cells of the spleen and lymph nodes. Exceptions include B lymphocytes, and Type II, III, and V epithelioreticular cells of the thymus (which are of non-monocytic origin).

Diffuse lymphatic tissue (MALT) is the accumulation of lymphatic tissue not enclosed by a capsule. It is located in the lamina propria of the gut (GALT), respiratory passages (BALT), and genitourinary tract. It guards the body against pathogens. It contains lymphocytes and other free cells (e.g. macrophages and plasma cells). These cells intercept antigens and initiate the immune response.

Lymphatic nodules are discrete concentrations of lymphocytes in a meshwork of reticular cells and fibers. They are sharply defined but not encapsulated and include darkly stained masses of nuclei of lymphocytes. There are no afferent lymph vessels, but there are efferent ones. They usually develop a germinal center and are surrounded by a mantle zone (corona). They occupy specific locations in the gut, including the tonsils, distal small intestine (Peyer’s patches in the ileum), cecum, and appendix. There are two forms:

• Primary nodules, which consists chiefly of inactive T lymphocytes and immature B lymphocytes.
• Secondary nodules, the most common form. The exhibit the following features:
• Germinal center, which is located in the central region of the nodule. It develops when a B lymphocyte that has recognized an antigen returns to a primary nodule to undergo proliferation. Proliferation gives rise to large lymphocytes, which is the reason for the lighter staining feature. Germinal centers contain activated B lymphocytes (APC), plasma cells, macrophages, and follicular dendritic cells.
• Mantle zone, which is an outer ring of small lymphocytes around the germinal center.

Events of B Lymphocyte Maturation following Antigen Transportation by M cells:

• Sequence of events is clearest in Peyer's patches
• B lymphocytes are activated upon contacting antigen
• Undergo proliferation in the germinal center of the lymphatic nodule
• Progeny cells leave nodules via efferent lymph and are carried to the regional (mesenteric) lymph nodes, where they proliferate further and differentiate into plasma cells. Antibodies are produced and distributed via lymph to the whole body
• Some B cells formed in lymph nodes are carried via lymph to blood
• B cells leave blood and return to the lamina propria
• Differentiate into plasma cells and produce antibodies