The peripheral blood contains two large populations of cells: the red cells, whose main physiological role is to carry oxygen to tissues, and the white cells, which have as their main physiological role the elimination of potentially harmful organisms or compounds. Among the white blood cells, lymphocytes are particularly important because of their cen-tral role in the immune response. Several subpopulations of lymphocytes have been defined:
1. B lymphocytes, which are the precursors of antibody-producing cells, known as plasma cells.
2. T lymphocytes, which can be divided into several subpopulations:
a. Helper T lymphocytes (TH), which play a very significant amplification role in the immune responses. Two functionally distinct subpopulations of T helper lymphocytes emerging from a precursor population (TH 0) have been defined: 1) TH1 lymphocytes, which assist the differentiation of cyto-toxic cells and also activate macrophages (activated macrophages, in turn, play a role as effectors of the immune response), and 2) TH 2 lymphocytes,which are mainly involved in the amplification of B-lymphocyte re-sponses.
These amplifying effects of helper T lymphocytes are mediated in part by soluble mediators—cytokines—and in part by signals delivered as a con-sequence of cell-cell interactions.
b. Cytotoxic T lymphocytes, which are the main immunological effector mechanism involved in the elimination of nonself or infected cells.
c. Immunoregulatory T lymphocytes, which lack unique membrane markers but have the ability to downregulate the immune response through the re-lease of cytokines such as interleukin-10 (IL-10).
3. Antigen-presenting cells, such as macrophages and macrophage-related cells and dendritic cells, play a significant role in the induction stages of the immune response by trapping and presenting both native antigens and antigen fragments in a most favorable way for the recognition by lymphocytes. In addition, these cells also deliver activating signals to lymphocytes engaged in antigen recogni-tion, both in the form of soluble mediators (interleukins such as IL-1, IL-12, and IL-18) and in the form of signals delivered by cell-cell contact.
4. Phagocytic cells, such as monocytes, macrophages, and granulocytes, also play significant roles as effectors of the immune response. One of their main func-tions is to eliminate antigens that have elicited an immune response. This is achieved by means of antibodies and complement, as discussed below. However, if the antigen is located on the surface of a cell, antibody induces the attachment of cytotoxic cells that cause the death of the antibody-coated cell (antibody-de-pendent cellular cytotoxicity, ADCC).
5. Natural killer (NK) cells play a dual role in the elimination of infected and ma-lignant cells. These cells are unique in that they have two different mechanisms of recognition: they can identify malignant or viral-infected cells by their de-creased expression of histocompatibility antigens, and they can recognize anti-body-coated cells and mediate ADCC.