Once the immune response is initiated, the end result depends on the nature and localization of the antigen, on whether the predominant response has been humoral or cell mediated, on the types of effector T cells and/or antibodies provoked and on whether the augmentation processes have been involved.
Killing of target cells (virally infected/tumour cells)
Target cells killed as a result of an immune response include organisms and cells bearing virally altered or tumour- specific antigens on their surfaces. They may be killed directly by antigen- specific mechanisms such as antibody and complement, ADCC following binding of specific antibody or antigen- specific CTL.
Cytokine production results in activation of NK cells, neutrophils and macrophages and subsequently non- specific killing by mechanisms similar to those in adaptive immunity.
Direct functions of antibody
Although some forms of antibody are good at neutralizing particulate antigens, many other factors, such as the concentration of antigen, the site of antigen entry, the availability of antibody and the speed of the immune response, may influence antigen removal (Box 1).
Box1. Some factors affecting immune responses
Neutralization is one direct effect of antibody and IgM and IgA are particularly good at this. A number of antigens, including diphtheria toxin, tetanus toxin and many viruses, can be neutralized by antibody. Once neutralized, these substances are no longer able to bind to receptors in the tissues; the resulting antigen–antibody complexes are usually removed from the circulation and destroyed by macrophages.
Although the physiological function of IgE antibody is unknown, it may have a role in the expulsion of parasites from the gastrointestinal tract. IgE antibody is normally bound to tissue mast cells. Attachment of antigen to IgE antibodies results in mast cell triggering, and release of a number of mediators of tissue damage (see Fig. 1).
Fig1. Mechanisms in immunoglobulin (Ig)E- mediated hypersensitivity.
Indirect functions of antibody
Opsonization is the process by which an antigen becomes coated with substances (such as antibodies or complement) that make it more easily engulfed by phagocytic cells. The coating of soluble or particulate antigens with IgG antibodies renders them susceptible to cells that have surface receptors for the Fc portions of IgG (FcRIII) (Fig. 2). Neutrophils and macrophages both have these Fc receptors and can phagocytose IgG- coated anti gens; however, this process is relatively inefficient if only Fc receptors are involved. The activation of complement by antibody (via the classical pathway) or by bacterial cell walls (via the alternative pathway) generates C3b on the surface of microorganisms and makes them susceptible to binding by several types of C3 receptors on macrophages and neutrophils (see Fig. 2). C3 receptors are very efficient in triggering phagocytosis.
Fig2. Opsonins and the relationship to phagocytosis.
Regulation
As discussed previously, termination of an ongoing immune response and regulation of the size of the response are crucial if collateral damage is to be prevented. While much is known of the regulation of the complement pathways, the science of cell- mediated regulation is in its infancy (after a false start in the 1980s). Several cell types are thought to have a regulatory function, involving at least three possible mechanisms (cell lysis, induced apoptosis or downregulation via cytokines). Natural and induced T regs seem to be the most important cells at present; absence of these cells, or excess of their counterparts, Th17 cells, results in autoimmune diseases, severe inflammation and allergies. Other cell types involved also include NKT cells.
