Since the first studies showing that the zymosan was able to activate a population of white blood cells, it has been postulated that specific receptor(s) on the cells, recognizing the beta-1,3/1,6-glucan structures, was/were facilitating the action of zymosan. During recent years the term Pathogen Associated Molecular Pattern (PAMP) Receptors have been used to describe receptors on cells of the innate immune system, recognizing conserved microbial structures like beta-1,3/1,6-glucans.
Several different receptors on phagocytic cells that recognize beta-glucans have been identified: the CR3 (CD11b/CD18) (Xia et al. 1999), the dimers of the Toll like receptors 2 and 6 (Ozinsky et al. 2000), and the Dectin-1 (Brown & Gordon 2001). The exact specificity of the different receptors have still not been fully elucidated, but there are studies showing that the non-reducing terminal end of beta-1,3-linked glucan chain is likely to be a main target for recognition by the receptors (Engstad & Robertsen 1994).
It has been demonstrated that the ability to induce an immune response is largely dependent upon the ability of beta-glucans to cross-link several receptors, implicating that beta-glucan preparations that present multiple receptor binding epitopes would be the most potent immunostimulants (Poutsiaka et al. 1993; Goldman 1995)
In addition to the beta-glucan recognition receptors, it has been shown that particulate beta-glucans interact with serum opsonins (Konopski et al. 1991).
Interactions with the beta-glucan receptors on cells of the innate immune system initiate the reactions by which beta-1,3/1,6-glucans modulate immunity. Such receptors exist also on epithelial cells of the alimentary tract where interaction with beta-glucans may cause signal transduction to underlying immune cells (Nagler-Anderson 2001). This explains why beta- 1,3/1,6-glucans are also active when administered orally. Beta-glucans of different origins and different structure are all believed to act through the same route, i.e. through an initial interaction with beta-glucan receptors. Their efficacy as immune-modulators, however, is determined by differences in receptor affinity towards the different beta-glucan preparations and also their ability to cross-link receptors (Williams 1997; Müller et al. 2000).
Oral administration of micro-particulate yeast beta-1,3/1,6-glucan to mice caused a marked increase in number of intraepithelial lymphocytes in the gut, in particular of the gamma-delta T-cell population. In addition, the endothelial lymphocytes in the gut switched on high IFN-gamma production (Tsukada et al. 2003). Micro-particulate yeast beta-1,3/1,6-glucan has a direct effect on innate immunity, and, in particular, it enhances cellular immunity, strengthening resistance against viral infections. It also shows that the beta- 1,3/1,6-glucan is possibly skewing the immune response in Th-1 direction. If so, it is in accordance with observations that beta- 1,3/1,6-glucans counteract allergy and asthma despite their stimulating effects on immunity.
Both micro-particulate and soluble native beta-1,3/1,6-glucan from yeast have systemic effects on the immune system when administered onto mucosal surfaces, either in the nasal cavity or in the gut. A striking illustration is the effects of the micro-particulate beta- 1,3/1,6-glucan preparation when administrated together with influenza vaccine antigens into the nasal cavity of mice (Raa et al. 2002). While the influenza virus antigen alone caused a moderate "priming" of antigen specific T-cells in the spleen, co-administration with the micro-particulate beta-1,3/1,6-glucan (occurs also with the soluble preparation) caused up to a 30-fold increase (depending on dosage) in the ability of spleen T-cells to respond to later exposure to the same antigen. This response was not correlated with the IgG-antibody response to the influenza virus antigen, indicating an effect primarily directed towards enhanced cellular immunity. Such studies have shown that beta-1,3/1,6-glucan can also modulate and downregulate certain immune responses.
To protect suckling piglets from bacterial gut infections, sows are vaccinated by injections of antigens from such bacteria in order to get a highest possible antibody level in the milk. It has been demonstrated that beta-1,3/1,6-glucan from yeast, given in the sow diet, results in a higher specific IgG secretion in the milk compared to the vaccination alone (Decuipere et al. 1998).