Initiation of the Immune Response

INITIATION OF THE IMMUNE RESPONSE

The effector cells are really divided into two types: B cells and T cells. B cells are primarily responsible for antibody produc-tion, whereas T cells act as effector cells and may function as both helpers and suppres-sors, depending on the stimulus provided by APCs.

The first step in initiation of the immune response to an antigen must necessarily involve modification of the antigen, and these specialized cells are called APCs. Without such processing, T cells cannot recognize antigen. Thus, it is the secretion of cytokines by APCs activated by antigen presentation that further activates antigen- specific T cells. This interaction between APCs and T cells is strongly influenced by a group of molecules called co-stimulators. For example, it is CD80 (B7-1) and CD86 (B7-2) on the APC cells with receptors CD28 and CTLA-4 on the T cell that pro-vides this interaction. The absence of these co-stimulators leads to T-cell unrespon-siveness. The importance of this pathway is emphasized by the fact that antagonists to these co-stimulators do interrupt the immune response in both in vitro and in vivo experiments. For example, mice with a severe form of lupus exhibit a milder dis-ease following a CTLA-4 antagonist.

As stated before, processed antigen is presented to the T cells in the context of the MHC complex present on the surface of APCs. In this regard, the most efficient APCs are the dendritic cells. These cells have high concentrations of MHC class I and II antigens, co-stimulatory molecules, and adhesion molecules on their surface.

These cells may be divided into two major groups. The dendritic cells of the skin are called the Langerhans cells and play an important role in immune defenses since they are present in the largest protec-tive organ of the body. Because they are mobile, Langerhans cells can capture anti-gen in the periphery and migrate to sec-ondary lymph nodes where they become mature dendritic cells and interact with naïve T cells.

In contrast, the follicular dendritic cells reside in the follicular germinal cen-ter (B-cell area) of a lymph node. These cells have receptors for complement and immunoglobulins and their function is to trap immune complexes and feed them to B cells. This processed immune complex containing antigen is closely associated with MHC class II molecules on the APC surface and thus activates B cells.