The goal of this thesis was to find agonists of Toll-like recptors that would interact with ligands of phagocytic receptors synergistically, would cause a strong suppresion of tumour growth, and could be safely used in human medicine.

Tick saliva contains a lot of molecules with antihemostatic and immunosupressive effects.The goal of this thesis is to test the effects of tick salivary cystatins from I.ricinus and I.scapularis on TLR - induced maturation of bone-marrow derived dendritic cells and production of chosen cytokines. Over all, the supressive effect of tick cystatins was observed in relation to TLR-induced maturation of DC. In addition, cystatins enhanced production of IL-10 and attenuated induction of IL-12 cytokines.

Recent studies have shown elevated neuroinflammation in a large subset of individuals diagnosed with schizophrenia. A pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), has been directly linked to this neuroinflammation. This study examined the effects of two TNFα modulators (PD2024 and PD340) produced by our collaborators at P2D Bioscience, Inc., to alleviate auditory sensorimotor gating deficits and reduce microglial cell activation present in the polyinosinic:polycytidylic (Poly I:C) rodent model of schizophrenia. Auditory sensorimotor gating was assessed using prepulse inhibition and microglial activation was examined and quantified using immunohistochemistry and confocal microscopy, respectively. Both PD2024 and PD340 alleviated auditory sensorimotor gating deficits and reduced microglia activation and thereby demonstrated the ability to treat both the behavioral and neuroinflammatory aspects of the disorder. These results are significant and suggest that neural TNFα is a potential pharmacological target for the treatment of schizophrenia.

No description available.

No description available.