Lymphocytes, the second most numerous of the several types of white cells in the peripheral blood (see Table 1-4), are essential components of the immune system. Diseases affecting lymphocytes frequently manifest as an inability to protect the individual against environmental pathogens (immune deficiency disorders) or as the development of immune reactions to the individual's own cells.2
The lymphocytes in the circulation represent only a small fraction of the total body pool of these cells. The majority are located in the spleen, lymph nodes, and other organized lymphatic tissues. The lymphocytes in the blood are able to enter and leave the circulation freely. Thus, the movement of cells from one area or compartment to another is continuous. Despite this process, the number of lymphocytes in the blood and tissues is kept quite constant. Lymphocytes have been divided into two major categories based on their immunologic activity: T lymphocytes and B lymphocytes. There also is a third group of lymphocytes that lack the characteristics of either T or B cells; they are called null cells.3
T lymphocytes are primarily responsible for cell-mediated immunity, which requires direct cell contact between the antigen and the lymphocyte. This immune reaction occurs at the local site and generally develops slowly. Examples of cell-mediated immune responses include reactions against intracellular pathogens such as bacteria, viruses, fungi, and protozoa; positive tuberculin skin test results; contact dermatitis; transplant rejection (acute and chronic reactions); and tumor immunity.
As with other blood cells, T lymphocytes develop from stem cells (see Fig. 1-2) and then migrate to the thymus, where they proliferate and mature. Thymopoiesis is, however, an ineffective process, and many T lymphocytes die either within the thymus or shortly after leaving it. Only a small portion of the T lymphocytes reaches the peripheral tissues as mature T cells capable of effecting cell-mediated immunity.4
Note that the thymus functions primarily during fetal life. The peripheral T-lymphoid system is fully developed at birth and normally does not require a constant input of new cells for maintenance after birth. Thus, it is possible to surgically remove the thymus (e.g., as is done to treat myasthenia gravis) without impairing the individual's cell-mediated immune system. In contrast, failure of the thymus to develop during fetal life leads to a severe defect in cellular immunity (Di George's syndrome), usually resulting in death during infancy as a consequence of repeated infections.5
Two subsets of T lymphocytes have been identified: helper T cells and suppressor T cells. Helper T cells promote the proliferation of T lymphocytes, stimulate B-lymphocyte reactivity, and activate macrophages, thereby increasing their bactericidal and cytotoxic functions. Suppressor T cells limit the magnitude of the immune response. In normal individuals, there is a balance between helper and suppressor activities. Many immune diseases are associated with deficiencies or excesses of the T-lymphocyte subtypes (Fig. 3—1).6
The B lymphocytes are responsible for humoral immunity through the production of circulating antibodies. Examples of humoral immunity include elimination of encapsulated bacteria, neutralization of soluble toxins, protection against viruses, transplant rejection (hyperacute reaction), and possible tumor immunity. Pathological alterations in antibody production are responsible for disorders such as autoimmune hemolytic anemia, immune thrombocytopenia, allergic responses, some forms of glomerulonephritis and vasculitis, and transfusion reactions.7
Actual production of antibodies (immunoglobulins) occurs in plasma cells, the most differentiated form of B lymphocyte. All B lymphocytes have immunoglobulins (Ig) on their surfaces. These serve as receptors for specific antibodies. Five classes of immunoglobulins are currently identified: IgG, IgM, IgA, IgD, and IgE. Immune activation requires interaction not only of surface Ig with the specific antigen but also of B lymphocytes with the helper T cells. The activated B lymphocytes undergo transformation into immunoblasts that replicate and then differentiate into either plasma cells, which produce antibodies, or memory cells ("small lymphocytes"), which retain the ability to recognize the antigen. Similar memory cells have been found in the T-lymphocyte system.8
The relationships between the T-lymphocyte and B-lymphocyte systems are diagrammed in Figure 3-2. In both cellular and humoral immune responses, initial exposure to specific antigens initiates the primary immune response. Depending on the nature and quantity of the antigen, it may take days, weeks, or months for the cells to recognize and respond to the antigen. Subsequent exposure to the same antigen, however, elicits the secondary (anamnestic) response much more rapidly than the primary response.9
Tests of lymphocyte functions include T- and B-lymphocyte assays, immunoblast transformation tests, and immunoglobulin assays.