Cell-Mediated Adaptive Immune System

CELL-MEDIATED ADAPTIVE IMMUNE SYSTEM

Cell-mediated adaptive immune responses are mediated by T-lymphocytes which arise from bone marrow progenitor cells and undergo maturation in the thymus before release into the systemic blood and lymph circulations (Figure 9.1). A number of parallels can be drawn between the B-lymphocyte-mediated immune response and the T-lymphocyte-mediated response. First, membrane-bound antibodies serve the cognitive function for B-lymphocytes, while the cognitive function for T-lymphocytes is served by T-lymphocyte receptor (TCR) present on the cell’s plasma membrane surface. Second, in response to antigen T-lymphocytes, like B-lymphocytes, will undergo clonal proliferation and form a population clone of memory T-cells specific for a single epitope. Third, each single B-lymphocyte and plasma cell that derives from it is capable of producing antibodies that will only recognize a single epitope. In the same manner each single T-cell is programmed to make TCR of only a single specificity able to recognize only a single specific set of chemical features within a T-cell epitope. This is achieved for the TCR in a similar manner to that for antibodies in that different gene segments termed V-D-J are brought together by the process of gene rearrangement into single RNA products. The recombined RNA will code for the polypeptide chains that make up the TCR. When all the possible recombinations are considered, the number of different TCR molecules that an individual can make is in excess of 109, a number similar to the primary antigen recognition repertoire of T-cells. There are two general classes of T-lymphocytes: helper T-lymphocytes and cytotoxic T-lymphocytes. The latter function to kill host cells that have undergone a transformation such as a viral infection or cancer and they recognize specific antigens on the surface of host cells that have arisen as a result of such cell transformation. Through this specific antigen recognition, the cytotoxic T-cell becomes closely apposed to the target host cell and is activated to synthesize and release cytotoxic secretory products (e.g. pore-forming molecules such as perforins) leading to lysis of the affected host cell. In contrast, the helper T-cell can be viewed as the coordinator of the adaptive immune system, providing appropriate activation signals, in the form of secreted cytokines, to promote the functioning of both the cytotoxic T-cell populations and that of the antibody-producing B-lymphocyte and plasma cell populations. The actions of the helper T-cell populations also promote the function of the innate immune system, for example IFN-γ released by helper T-cells increases the phagocytic activity of macrophages. The helper T-cells are further divided into T_H1 or T_H2 subpopulations depending on the nature of cytokines they secrete and, as a consequence, the arms of the immune system they predominantly influence. The T_H1 helper T-cells mainly regulate cell-mediated immunity while T_H2 helper T-cells regulate humoral immunity.