The role of mannose binding lectin associated serine protease MASP-3 in complement mediated haemolysis and the utility of recombinant properdin in fighting Streptococcus pneumoniae infection

Complement is a part of our innate immune defence system and plays an important role in fighting infection and maintaining the integrity of our body. Complement activation is tightly regulated through complement regulators, which allow their activation on foreign cells, like pathogens and stop their activation on self-cells. In states that complement activation causes damage to the self-cells (unwanted complement activation on self-cell) that arises due to deficiency of complement regulators, down regulating complement system is essential. In this condition, targeting specific pathway of complement system that mediates the pathology and allowing other pathways functioning is important. For example, results in this thesis show complement mediated haemolytic activity in human, mouse and chicken is mediated by the alternative pathway and, MASP-3 deficiency in human and mouse abolishes their haemolytic activity, thus targeting MASP-3 by monoclonal antibody may be of therapeutic value in the treatment of the AP mediated diseases e.g. Paroxysmal Nocturnal Haemoglobinuria. By this, the functions of both classical and lectin pathways of the complement system in these patients will be preserved. On the other hand, it is of therapeutic value to enhance complement activation in a state that complement activation is necessary for promoting their immune functions like on pathogen surfaces. For example, results of this thesis demonstrate that enhancing complement functional activity through the addition of small quantities of highly active recombinant properdin (Pn) provides significant therapeutic benefits in models of S. pneumoniae infection.