Antibodies directed to capsular polysaccharides form an essential component in the defence against infections with encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae type b. Immune responses to polysaccharide antigens can occur in the absence of a functional thymus and the antigens are therefore designated as thymus independent. However, regulatory T cells may influence the magnitude of the antibody response to capsular polysaccharide antigens. So-called thymus independent type 2 antigens share several features of their immune response such as late development of antibody synthesis in ontogeny, no memory formation and a restricted isotype (IgM, IgG2) and idiotype usage. In infants and young children up to the age of 2 years the antibody response to capsular polysaccharides is inadequate resulting in an increased incidence of diseases such as pneumonia, meningitis, otitis and other forms of bacteremic disease. Anti-capsular polysaccharide antibody deficiency does occur in a number of well defined immunodeficiency syndromes including hypo- or agammaglobulinaemia, selective IgA and/or IgG subclass deficiency, Wiskott-Aldrich syndrome, DiGeorge anomaly and also in acquired immune deficiencies such as AIDS, and some forms of lymphoid malignancies. In elderly and in conditions such as splenectomy an increased incidence of infections with encapsulated bacteria does occur, sometimes but not always on basis of a defect in antibody formation. Clinicians are often confronted with young patients older than 2 years of age suffering from recurrent severe bacterial infections of the respiratory tract. In these patients no overt immunodeficiency is demonstrable but recent results indicated that a small percentage may show a selective defect in the antibody response since upon vaccination with polysaccharide vaccines no increase in antibody titer does occur. Though antibodies to polysaccharide antigens in young children are mainly of the IgM and IgG1 (IgG3) isotype, in older children and adults the polysaccharide antibodies are predominantly localized in the IgG2 subclass. The bridge between IgG2 type antibodies and phagocytosis of encapsulated bacteria is constituted by Fc gamma receptors for IgG2 on effector cells. The recent finding that allotypes of Fc gamma RIIa do exist that either bind or do not bind IgG2 type antibodies strongly suggests that the defence of a given individual to encapsulated bacteria apart from an intact antibody formation and the complement system also is determined by the allotype of the appropriate Fc gamma receptor.(ABSTRACT TRUNCATED AT 400 WORDS)