We have all seen the familiar diagram of the immune system with its T cell limb and В cell limb. It seems that as soon as one becomes familiar with it, new information is made available that makes it outdated, particularly because of the known interactions of the В and T cell systems. The circulating cells of the immune system include the granulocytes, composing about 50 percent of the peripheral white blood cells; the monocytes, composing about 10 percent; and the lymphocytes, composing about 40 percent. The lymphocytes can be further divided into three classes: the T lymphocytes, the В lymphocytes and the null lymphocytes, composing about 70 percent, 10 percent, and 20 percent of the circulating lymphocytes, respectively. Morphologically these lymphocytes are indistinguishable.
The granulocytes are the first line of defense against microbial infection. They phagocytize and ingest organisms and particulate matter, often aided by the complement and antibody systems, which coat (opsonize) the organisms, facilitating phagocytosis. Defects of granulocyte and complement function can lead to immunodeficiency syndromes, but those are beyond the scope of this article.
The second major cell type is the monocyte, the circulating member of the mononuclear phagocytic system. This system also includes fixed tissue macrophages, such as the Kupffer cells and the alveolar macrophages. As noted in Table 1, these cells have multiple functions, including a reserve bactericidal function similar to that of the polymorphonuclear granulocytes. More importantly, they engulf and “process” antigen prior to a specific antibody or T cell immune response. In this process they synthesize a substance termed interleukin 1, which plays an important role in T cell activation. Monocytes also are recruited by T cells to participate in cellular immune reactions such as delayed cutaneous hypersensitivity responses.
Lymphocytes are nonphagocytic, nonadherent mononuclear cells composing 40 percent of the peripheral blood leukocytes. В lymphocytes are characterized by the presence of surface membrane immunoglobulin, best identified using a fluorescent antibody to human immunoglobulin. В cells are the precursors of the plasma cells, the chief source of circulating antibody, and they circulate as long-lived memory cells. In addition to surface membrane immunoglobulin, В cells have receptors for the Epstein-Barr virus, lipopolysaccharide, and Staphylococcus protein A. The presence of circulating В cells does not mean that there is adequate immunoglobulin synthesis. Neonates and patients with certain immunodeficiencies have adequate В cell numbers but few plasma cells and deficient antibody production.
The T lymphocytes are usually identified by their ability to bind sheep red blood cells (RBCs) to form a characteristic rosette. The function of the sheep RBC receptor is not known, but it permits both the enumeration and the separation of T cells from other lymphocytes.
The T lymphocytes develop from stem cells after they pass through the thymus gland; here they develop distinct properties and surface antigens. Monoclonal antibodies are now available that react with T cells, and are used to identify and separate them. T lymphocytes (Table 2) are important in killing fungi, intracellular bacteria and virus, in graft rejection, in delayed hypersensitivity reaction, and in rejection of tumor cells. T cells also regulate other immune functions, including В cell differentiation and T cell proliferative and cytotoxic responses.
Different subsets of T cells are responsible for their diverse functions. We recognize at least three different kinds of T cells: (1) effector cells, those that are responsible for delayed hypersensitivity reactions, cytotoxic reactions, and graft rejection; (2) suppressor cells, those that inhibit other immune responses; and (3) helper cells, those that augment other immune responses. Monoclonal antibodies are available to both helper and suppressor cells. Helper cells have surface antigens that react with Leu 3 and OKT4 monoclonal antibodies, while suppressor cells react with Leu 2 and OKT8 monoclonal antibodies. Using immunofluores-cent techniques or an automated fluorescent-activated cell-sorter machine, the proportion of helper to suppressor cells can be determined. Ordinarily, there are about two helper (TJ cells for each suppressor (T8) cell, so the TJTt ratio is about 2:1. In certain illnesses, notably acquired immunodeficiency syndrome (AIDS), this ratio is reduced.
Null cells make up a third type of lymphocyte. Among the null cells, two distinct subpopulations are recognized, natural killer cells and killer cells. The killer cell is a nonadherent cell with a receptor for the Fc (nonantibody) portion of IgG globulin; killer cells react with an antibody-coated cell and lyse it. This is termed antibody-dependent cellular cytotoxicity (ADCC) and derives its specificity from the antibody.
A second null cell is the natural killer cell (NK). These nonadherent cells can kill certain tumor or viral-infected cells without prior sensitization. Interferon enhances their activity, predominantly by converting inactive pre-NK cells to active NK cells. In conjunction with cytotoxic T cells, these cytotoxic mechanisms(Table 3) provide a formidable defense system against virus infection, tumor cells, or foreign or antibody-coated cells.
Table 3—Types cf Cytotoxicity
|ТУре||Time of Onset||Effector Cell||Specific||Augmenting Factors||Deficiency States|
|Natural killer||Immediate||NK cell||No||IFN||SCID, newborn, IFN deficiency, Ch6diak-Steinbrinck-Higashi syndrome|
|T cell||1-3 wk||T cytotoxic cell||Yes||?||SCID, T-IDD|
|Antibody dependent (ADCC)||>3 wk||К cell, monocyte||Yes||Antibody||SCIDAgammaglobulinemia|