Anatomy of Immune System and Cellular Immune Response

Cells participating in the cellular immune response are organized into discrete associated lymphoid tissues and organs which are spread through the connective tissues of non lymphoid organs. Lymphocyte cell are responsible for the specificity of the cellular immune response. Approximately 2 x 1012 lymphocytes constitute the mature lymphoid system in humans together with a variety of ‘accessory’ cells which include epithelial cells, monocyte or macrophages cells and other antigen-presenting cells. Accessory cells are neede both for the maturation and for the effector cells functions of lymphocytes.

Lymphocytes are derived from hematopoietic progenitors which mature within the bone marrow and the fetal liver. It is giving rise to B lymphocytes, or seed to the thymus where they differentiate into T lymphocytes. The bone marrow and the thymus are therefore the primary or central lymphoid organs. Mature lymphocytes then leave central organs via the blood vessels, and migrate to secondary or peripheral tissues and organs where they exert their effector cell functions in response to antigen. Peripheral lymphoid tissues include the spleen and lymph nodes (look at the picture) and MALT (mucosa associated lymphoid tissue) which is associated with the respiratory, genitourinary and gastrointestinal tracts, accounting for approximately 50% of the total lymphoid cells in the body.

Central Lymphoid Organs

The bone marrow, and earlier in fetal life, the liver, and the thymus provide the microenvironments for the differentiation of B and T lymphocytes respectively, and for the production of mature cells responsible for humoral or cellular immune response. During B and T cell maturation, similar events occur in the bone marrow and in the thymus, namely the rearrangement of the genes encoding antigen receptors (immunoglobulin (Ig) or T cell receptors (TCRs)) and the expression of these receptors on the cell surface. A variety of other cell surface marker molecules appear in an orderly sequence which defines the maturational stages of both H and T cells.

The bone marrow provides the microenvironment for B lymphocyte differentiation. This process rakes place through the direct interaction of B cell progenitors with ill-defined ‘stroma’ cells and with the help of soluble factors, notably interleukin 7 (IL-7), which supports the growth of pre-B cells and possibly of their progenitors.

The thymus provides the microenvironment for differentiating bone marrow-derived precursors seeding into the epithelial rudiment during ontogeny. The complete sequence of maturational events leading to the production of mature T cells takes place within this organ. Maturing T cells interact with nonlymphoid thymic cells, namely epithelial cells and macrophages/interdigitaring cells. Intrathymic T cell maturation results from these cellular interactions and from the resulting cytokines (IL-I, IL-2, IL-6) produced by them. Thymocyte proliferation leads to polyclonal expansion of T cells and is the result of a direct interaction between thymocytes and epithelial cells. Positive selection favors the expansion of those cells equipped with TCRs that have proven able to hind self MI-IC molecules weakly, even in the absence of antigen. Those developing T cells which display the best fit between their TCRs and class I and class II MHC molecules expressed by nonlymphoid thymic epithelial cells have a growth advantage.

Peripheral Lymphoid Organs

The effector cell functions of B or T cells responsible for humoral or cellular immune responses are carried out in the lymphoid periphery which consists of discrete organs or associated lymphoid tissue, and of lymphocytes dispersed in the interstitial areas of nonlymphoid organs (e.g. liver, lung and the lamina propria of mucosae). The frequency of appropriate encounters between antigens and cells bearing specific antigen receptors is increased by the active recirculation of lymphocytes via blood and lymph vessels. Thus, the structural organization of peripheral lymphoid tissues is dynamic, with actively renewing mature cell populations supported by the thymus and bone marrow.