Immune System

Lymphoid organs, vessels, and recirculation. Mature lymphocytes constantly travel through the blood to the lymphoid organs and then back to the blood. This constant recirculation insures that the body is continuously monitored for invading substances. The major areas of antigen contact and lymphocyte activation are the secondary lymphoid organs. These include the lymph nodes, spleen, and tonsils, as well as specialized areas of the intestine and lungs. Appropriate recirculation and compartmentalization is essential to vigorous immune function, since this provides appropriate surveillance of the host for antigens, as well as the appropriate juxtaposition of all cellular elements to insure fruitful interaction.

Cell interactions in immune responses. Although antigen binding is necessary to activate a B or T cell, that alone is insufficient to induce an immune response. Instead, both humoral and cell-mediated responses require interactions between three cell types: antigen-presenting cells (APCs), Th cells, and either a B cell or Tc cell. Generally, the interaction between the APC and Th cells involves not only the binding of the TcR by the antigenic peptides in association with the MHC, but a series of second signals. These requisite second signals are afforded by the interactions of both membrane-bound ligand receptor pairs, known collectively as costimulators, as well as a variety of soluble growth and differentiation factors secreted by the antigen-presenting cells.

Humoral immune responses involve several events following the entry of antigen. First, antigen-presenting cells take up some of the antigen, attach pieces of it to Class II MHC molecules, and present it to T-helper cells. Binding the presented antigen activates T-helper cells, which then divide and secrete stimulatory molecules called interleukins. These stimulatory molecules in turn activate any B lymphocytes that have bound the antigen, and these activated B cells then divide, differentiate, and secrete antibody. Finally, the secreted antibodies bind the antigen and help destroy it through a variety of so-called effector mechanisms, including neutralization, complement fixation, and opsonization.

Cell-mediated immune responses involve several events following the entry of antigen. Helper T cells are required, so some of the antigen must be taken up by APCs and presented to T-helper cells. Binding the presented antigen activates the T-helper cells to divide and secrete interleukins. These in turn activate any cytotoxic T cells that have bound pieces of the antigen presented by class I MHC molecules on infected cells. The activated cytotoxic cells can then serially kill cells displaying antigen presented by class I MHC molecules, effectively eliminating any cells infected with the antigen.

Age-associated changes in recirculation, interaction, and immune responses. The patterns of compartmentalization and recirculation may vary with age, and again likely reflect a combination of factors. These probably include relative increases in memory-cell populations, whose recirculation and compartmentalization properties differ from primary lymphocytes, as well as alterations in the efficacy and structure of the lymphatics caused by either intrinsic or extrinsic factors. Of course, these shifts may alter the handling and recognition of antigens by APCs and lymphocytes, consequently impacting heavily on all negative and positive selective processes. It is also clear that the strength and duration of immune responses can change with age. Most reports of such changes are largely descriptive and subject to great variability.