Immune Response (Molecular Biology)

The immune response is a complex sequence of events initiated by the introduction of an immunogen in an organism. In vertebrates, it is the consequence of the stimulation of B and/or T lymphocytes, leading either to the production of specific antibodies from B cells or to the occurrence of effector T cells—for example, cytotoxic T lymphocytes. Immunologists classically make a clear distinction between immune responses that are characterized by antibody production and those that result primarily in the emergence of cytotoxic T cells or delayed-type hypersensitivity, which are depicted as humoral and cellular immunity, respectively. In fact, penetration of complex antigens, such as most bacteria and viruses, trigger both types of immune responses. Furthermore, antibody responses directed against T-dependent antigens, the most common case, require cellular cooperation between B and T cells, and the humoral and cellular responses are quite intricate.

It must be realized that both the nature and the intensity of the immune response is largely dependent on the nature, dose, and mode of penetration of the antigen. For example, when given subcutaneously or intravenously, proteins stimulate a good circulating antibody response, provided that they are given in an immunogenic range of doses. If given orally, mucosal antibody production will occur preferentially. By contrast, intradermal injection will induce delayed hypersensitivity, mediated by T lymphocytes. The level of response may be substantially increased by admixing antigen with adjuvants that ensure a long-lasting liberation of antigen, in addition to providing nonspecific stimulation of the immune system.

Whatever the nature of the response, it always follows basic principles that are most simply quantified in a classical humoral response. Following antigen administration, two parameters may be followed: One is the disappearance of antigen from the body fluid, and the other is the occurrence of circulating antibodies. After a first immunization, the blood concentration of antigen decreases rapidly within a few hours, remains somewhat steady for a few days, and then rapidly decreases again, until it is no longer detectable. This occurs after 5 to 7 days, when antibodies start to be produced. As they circulate in the bloodstream, they bind to the remaining antigens, and the immune complexes are eliminated (which may be a major problem for individuals suffering renal failure). The antibodies that first appear are IgM. Their yield increases for a few days, until they are replaced by IgG antibodies that result from class switching of the isotype. The antibody titer slowly diminishes and becomes barely detectable. This is a typical primary response. As B cells start making IgG antibodies in germinal centers of peripheral lymph nodes, they rapidly accumulate somatic hypermutations so that antibodies with higher affinity will occur and be positively selected by antigen. A fraction of these B cells will constitute the long-lived memory cells that will react immediately upon a second administration of antigen. The secondary response then takes place, characterized by a rapid elevation of the IgG antibody titer, which will remain high for a much longer period of time. If a different antigen were used instead of the first one, a typical primary response would have been observed, and this is illustrative of the high specificity of the immune response. Antigen may be given several times, ensuring a successive boost of responses, leading to a hyperimmunized state.

The general kinetics described above are typical of T-dependent soluble antigens. With polysaccharides, there is no secondary response, and the antibodies remain essentially of the IgM type (with some IgG2a and IgA2 in humans). The immune response to particulate antigens, such as bacteria, is generally more complex, due to antigenic diversity. The respective contribution of humoral and cellular responses is largely dependent on the microorganism.

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