The nature of each antigen, its concentration, and its location determine the positive or negative response of the immune system, which are known as immunity and tolerance, respectively. Immunity is mediated by stimulatory signals provided by antigen-specific soluble and membrane-anchored factors, which also determine the stimulatory effects of immune cells. Stimulatory mechanisms are evoked against most pathogenic microorganisms, which are meant to clear up infection from the organism. In contrast, tolerance is mediated by suppressive signals provided by antigen-specific soluble and membrane-anchored factors, which also determine the suppressive effects of immune cells. By means of repressive mechanisms, tolerance to self antigens is maintained to avoid attack against the organism itself.

Equilibrium between stimulatory and suppressive mechanisms ensures homeostasis and consequently, health. Breaking homeostasis leads to pathological conditions. Stimulation and suppression often deviate from the normal course. In autoimmunity, for example, self antigens induce stimulation of immunity, rather than tolerance. In contrast, in sepsis, immunosuppressive mechanisms prevail and prevent immunostimulatory reactions against generalized infections.

Both immunostimulation and immunosuppression are controlled by the antigen presentation process by antigen-presenting cells and the type of signals they deliver to T cells.

ImmunoRec, is actively involved in R&D projects, where using the technology of Personalized Implantable Vaccines, aims to develop strategies to lead the immune system towards stimulation or suppression.

Recently, using peptidoglycan as an antigenic stimulus, which has been shown to display a mild mitogenic activity to the organism [1], the application of Personalized Implantable Vaccine technology could inhibit immunosuppression and rescue sepsis in an animal experimental model [2].

[1] Zerva, I., Katsoni, E., Simitzi, C., Stratakis, E., Athanassakis, I. Laser micro-structured Si scaffold implantable vaccines against Salmonella Typhimurium.  Vaccine 37: 2249-2257 (2019)

[2] Zerva I, Bakela K, Athanassakis I. Immunotherapy-on-chip against an experimental sepsis model.  Inflammation 2021 (in press)