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Plasmodium falciparum malaria remains one of the most serious health problems globally. Immunization with attenuated parasites elicits multiple cellular effector mechanisms capable of eliminating Plasmodium liver stages. However, malaria liver stage immunity is complex and the mechanisms effector T cells use to locate the few infected hepatocytes in the large liver in order to kill the intracellular liver stage parasites remain a mystery to date. Here, we review our current knowledge on the behavior of CD8+ effector T cells in the hepatic microvasculature, in malaria and other hepatic infections. Taking into account the unique immunological and lymphogenic properties of the liver, we discuss whether classical granule-mediated cytotoxicity might eliminate infected hepatocytes via direct cell contact or whether cytokines might operate without cell-cell contact and kill Plasmodium liver stages at a distance. A thorough understanding of the cellular effector mechanisms that lead to parasite death hence sterile protection is a prerequisite for the development of a successful malaria vaccine to protect the 40% of the world’s population currently at risk of Plasmodium infection.

Liver resection exposes the remaining sinusoids to an over-proportional blood flow. This mechanism may aggravate ischaemia/reperfusion damage and rejection in partial liver transplants. We studied the potential relevance of this mechanism for the pathogenesis of partial liver transplant dysfunction. Eighty-four isogeneic Lewis rats were divided into four groups: (I) sham operation; (TI) partial liver resection (30% residual liver volume); (III) orthotopic transplantation of a full-size liver; (IV) transplantation of a reduced-size liver (30% transplant volume). Microcirculation was determined by intravital microscopy 90 mm after surgery. Survival rates, liver function and morphology were monitored over a period of 14 days. Lowest survival rates and impaired liver function were observed after partial liver transplantation (group IV). These transplants displayed the lowest perfusion rate and an increased rate of leukocyte-endothelium interactions in the presence of a significantly increased sinusoidal blood flow velocity compared with those in groups I and Il. Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium lesions. Sinusoidal overperfusion seems to be a significant factor impairing liver function after liver resection. In addition to other adverse factors, such as ischaemia/ reperfusion injury, it can contribute to the pathogenesis of postoperative dysfunction of partial liver transplants. [ABSTRACT FROM AUTHOR]