The immunological system is comprised of the lymphoid tissues and organs of the body. Lymphoid tissues are widely distributed: they are concentrated in bone marrow, lymph nodes, spleen, liver, thymus, and Peyer's patches scattered in linings of the GI tract. The lymphoid system is encompassed by the system of mononuclear phagocytes. Lymphocytes are the predominant cells, but macrophages, dendritic cells, and plasma cells are also present. Lymphocytes are cells which circulate, alternating between the circulatory blood stream and the lymphatic channels. The distribution of lymphatic tissues that make up the immunological system in humans is illustrated in the figure below.

Figure 1. Anatomy of the Immunological System. (A): The major components of the immunological system are lymph nodes connected by lymph ducts, Peyer's patches (masses of lymphocytes in the lower gastrointestinal tract), thymus, spleen, and bone marrow. (B): A lymph node. Afferent lymph ducts bring lymph-containing antigens into the lymph node. Macrophages, dendritic cells and  B-cells in the cortical region make contact with the antigen and process it for presentation to immunocompetent B-cells and T- cells, thereby initiating an immune response. As a result, B-cells are stimulated to develop into antibody-secreting plasma cells, and T-cells are stimulated to develop into effector T cells of various classes. Antibodies leave the lymph node by the efferent ducts that empty into the blood stream. Lymphocytes can also leave the node by the efferent duct and travel to other sites in the lymphatic system or enter into the blood circulation. A single lymphocyte completes a circuit through the circulating blood and lymphatic systems once every 24 hours.

Organs comprising the immune system

Bone Marrow  All cells of the immune system are initially derived from the bone marrow. During hematopoiesis, bone marrow stem cells develop into either mature cells or precursors of cells that migrate out of the bone marrow to continue their maturation elsewhere. The bone marrow produces lymphocytes  (B-cells, immature T-cells, and natural killer cells), granulocytes (including neutrophils, monocytes and dendritic cells), in addition to red blood cells and platelets.

Thymus T-cells mature in the thymus. Immature T-cells, also known as pre-T cells (or prothymocytes), leave the bone marrow and migrate into the thymus. In a maturation process sometimes referred to as "thymic education", T cells that are beneficial to the immune system are spared, while T cells that might evoke a detrimental autoimmune response are eliminated. The mature T cells are then released into the bloodstream.

Spleen The spleen is is made up of B cells, T cells, macrophages, dendritic cells, natural killer cells and red blood cells. The spleen filters antigens directly from the blood that passes through it, and migratory macrophages and dendritic cells bring antigens to the spleen via the bloodstream. An immune response is initiated when a macrophage or dendritic cell "presents antigen" to appropriate B or T cells. In the spleen, B cells become activated and produce large amounts of antibody.

Lymph Nodes The lymphatic system parallels the circulatory blood system. It is periodically guarded by  lymph nodes, which are found throughout the body. Composed mostly of T cells, B cells, dendritic cells and macrophages, the nodes drain fluid from most tissues. Antigens are filtered out of the lymph in the lymph node before returning the lymph to the circulation. In a similar fashion as the spleen, macrophages and dendritic cells capture antigens and present them T and B cells, consequently initiating an immune response.


Figure 2. Origin and differentiation of cells of the immune system.

Cells of the immune system

B-cells The major function of B lymphocytes is to develop into antibody-secreting plasma cells following stimulation by foreign antigens of bacteria, viruses and tumor cells. Antibodies are specialized proteins that specifically recognize and bind to specific antigens that caused their stimulation. Antibody production and binding to foreign antigens is often critical as a means of signaling other cells to engulf, kill or remove that substance from the body.

T-cells T lymphocytes are usually divided into two major subsets that are functionally and phenotypically different. T helper (TH) cells, also called CD4+ T cells, are involved in coordination and regulation of immunological responses. They function to mediate responses by the secretion of lymphokines that stimulate or otherwise affect other cells involved in the immune responses.

The second subset type of T lymphocytes are cytotoxic T lymphocytes ( Tc cells or CTLs) or CD8+ T cells. These cells are involved in directly killing certain tumor cells, virus-infected cells, transplant cells, and sometimes eucaryotic parasites. CD8+ T cells are also important in down-regulation of immune responses.

Both types of T cells can be found throughout the body, most conspicuously in lymphoid organs (lymph nodes and spleen) but also the liver, lung, blood, and the intestinal tract.

Natural Killer cells Natural killer cells, known as NK cells, are similar to CTLs (CD8+ T cells). They function as effector cells that directly kill certain tumors such as melanomas, lymphomas and virus-infected cells, most notably herpes and cytomegalovirus-infected cells. However, NK cells, unlike the CD8+ (Tc) cells, kill their target cells without need for recognition of antigen in association with MHC molecules.  NK cells that have been activated by secretions from CD4+ T cells will kill their tumor or viral-infected targets more effectively.

Macrophages Macrophages are important in the regulation of immune responses. Besides their role in phagocytosis, they may function as antigen-presenting cells (APCs) because they ingest foreign materials and present these antigens to other cells of the immune system such as T-cells and B-cells. This is one of the important first steps in the initiation of an immunological response. Macrophages, stimulated by certain lymphokines, exhibit increased levels of phagocytosis and are also secrete cytokines that modulate immune responses.

Dendritic cells Dendritic cells also originate in the bone marrow and function as antigen presenting cells (APCs). In fact, the dendritic cells are more efficient APCs than macrophages. These cells are usually found in structural compartments of the lymphoid organs such as the thymus, lymph nodes and spleen. However, they are also found in the bloodstream and other tissues of the body. It is believed that they capture and process antigens in lymphoid organs where an immunological response is initiated. Of particular interest is the recent finding that dendritic cells bind large numbers of HIV particles, and may be a reservoir of virus that is transmitted to CD4+ T cells.