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It was recognized early last century that small molecules, known as haptens, can be made immunogenic after conjugation to carrier proteins (1). This principle has since been applied successfully to improve the immunogenicity of (poly)saccharides (2,3). We now know that the carrier proteins ensure the involvement of T-helper lymphocytes in the activation of the hapten- or polysaccharide-specific antibody-producing B lymphocytes (Fig. 1). In contrast to small molecules or haptens, polysaccharides (or other macromolecules with a repeating structure) are able to induce an immune response, most likely by directly activating B-lymphocytes. Antigens that are able to induce an immune response without the involvement of T-helper lymphocytes are referred to as TI (thymus-independent) antigens (4) (Table 1). TI-2 antigens, such as plain polysaccharides, are not able to activate relatively immature B-cells. This is in contrast to TI-l antigens, which can activate immature B-cells because of their mitogenic activity. Lipopolysaccharides (LPS) are examples of TI-l antigens. Conventional T-cells recognize peptide sequences in association with the major histocompatibility complex (MHC). Recently, unconventional T-cells were found to recognize (glyco) lipids in a CD1-restricted way, γδT-cells were shown to respond to non-proteinaceous microbial ligands (that may include carbohydrates) in a virtually MHC-unrestricted way (5). The findings of T-cell regulation of the immune response against polysaccharides (6-8) without biochemical demonstration of the specificity of the molecular interactions can best be explained by assuming a role for anti-idiotypic antibodies and T-cells specific for the idiotopes (carbohydrate mimotopes) or via the newly discovered unconventional T-cells. [ABSTRACT FROM AUTHOR]

There are many in vitro systems for the study of meningococcal pathogenesis, but it is only in animal models of infection that the interactions of the bacteria with whole tissues and the humoral and cellular immune systems can be assessed. Animal-infection models are also of great importance for the assessment of the protective efficacy of existing and candidate vaccines. However, the relevance of these animal models to human disease and how well protection assessed in them corresponds to protection against human disease, must always be considered. Animal models for pathogenic Neisseria have been previously reviewed (1). [ABSTRACT FROM AUTHOR]