Generation and characterization of cytotoxic activity against tumor cell lines in human peripheral blood mononuclear cells stimulated "in vitro" by a glucomannan-protein preparation of Candida albicans.

Human peripheral blood mononuclear cells (PBMC) proliferated and generated non-specific cell-mediated cytotoxicity (CMC) after stimulation with a cell-wall glucomannan-protein (GMP) fraction of Candida albicans or chemically-inactivated intact microrganism. No effects were observed using other fungal cell wall components such as glucan or alkali-acid treated glucomannan. The highest CMC level was detected after 7-10 days of PBMC incubation in the presence of 50 micrograms/ml of whole Candida cells and the cytotoxic immunoeffectors elicited by these antigenic stimulations equally affected NK-susceptible (K562) and NK-resistant (Raji, Daudi and Jurkat) tumor cell lines. Both Interleukin-2 (IL-2) and gamma interferon (IFN-gamma) were produced by GMP-stimulated PBMC, the IL-2 peak production constantly preceding that of IFN production. GMP-induced generation of natural CMC was potentiated by the addition of IFN-gamma and a monospecific anti IFN-gamma serum totally abrogated both IFN activity and CMC generation. The cytolytic effectors were shown to be OKT3-, OKT8- and HLA-DR-. They did not possess typical NK markers (e.g. Leu-7 and AB8.28) but were partially recognized by A10, a IgG2a monoclonal antibody reacting to PBMC-NK lymphocytes and activated T cells. These results suggest that the antitumor cytolytic effectors generated in PBMC cultures exposed to Candida material belong either to a discrete subset of natural effectors lacking classical NK markers or to other lymphokine-activated cells. This study also suggests that the human indigenous microrganisms C.albicans may play a role in raising nonspecific antitumor effects in normal host

Switched memory B cells maintain specific memory independently of serum antibodies : the hepatitis B example

The immunogenicity of a vaccine is conventionally measured through the level of serum Abs early after immunization, but to ensure protection specific Abs should be maintained long after primary vaccination. For hepatitis B, protective levels often decline over time, but breakthrough infections do not seem to occur. The aim of this study was to demonstrate whether, after hepatitis B vaccination, B-cell memory persists even when serum Abs decline. We compared the frequency of anti-hepatitis-specific memory B cells that remain in the blood of 99 children five years after priming with Infanrix \uae-hexa (GlaxoSmithKline) (n=34) or with Hexavac \uae (Sanofi Pasteur MSD) (n=65). These two vaccines differ in their ability to generate protective levels of IgG. Children with serum Abs under the protective level, <10mIU/mL, received a booster dose of hepatitis B vaccine, and memory B cells and serum Abs were measured 2wk later. We found that specific memory B cells had a similar frequency in all children independently of primary vaccine. Booster injection resulted in the increase of memory B cell frequencies (from 11.3 in 10 6 cells to 28.2 in 10 6 cells, p<0.01) and serum Abs (geometric mean concentration, GMC from 2.9 to 284mIU/mL), demonstrating that circulating memory B cells effectively respond to Ag challenge even when specific Abs fall under the protective threshold

Approximability of integer programming with generalised constraints

Given a set of variables and a set of linear inequalities over those variables, the objective in the Integer Linear Programming problem is to find an integer assignment to the variables such that the inequalities are satisfied and a linear goal function is maximised. We study a family of problems, called Maximum Solution, which are related to Integer Linear Programming. In a Maximum Solution problem, the constraints are drawn from a set of allowed relations, hence arbitrary constraints are studied instead of just linear inequalities. When the domain is Boolean (i.e. restricted to {0, 1}), the maximum solution problem is identical to the well-studied Max Ones problem, and the approximability is completely understood for all restrictions on the underlying constraints [Khanna et al., SIAM J. Comput., 30 (2000), pp. 1863-1920]. We continue this line of research by considering domains containing more than two elements. Our main results are two new large tractable fragments for the maximum solution problem and a complete classification for the approximability of all maximal constraint languages. Moreover, we give a complete classification of the approximability of the problem when the set of allowed constraints contains all permutation constraints. Our results are proved by using algebraic results from clone theory and the results indicates that this approach is very useful for classifying the approximability of certain optimisation problems