Plasmodium falciparum malaria is an infectious disease that on despite of the ongoing eradication efforts is still endemic in more than 100 countries, sometimes causing severe disease that leads to the death of around half a million people per year. Malaria pathology is tightly associated with the parasite cycle inside the human red blood cells (RBCs). Central to this cycle is the initial invasion by the merozoite and the extensive RBC modifications induced by the parasite, transporting proteins to the RBC cytoplasm and membrane. The P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) transported to the surface of the parasitized RBC (pRBC) and the surface-associated interspersed protein 4.2 (SURFIN4.2) present both at the pRBC surface as well as at the merozoite apex and surface, are the major focus of this thesis. PfEMP1 is the major surface antigen and mediates rosetting (binding of parasitized RBCs (pRBCs) to two or more RBCs), a parasite phenotype associated with the development of severe disease. The most N-terminal segment of this protein (the NTSDBL1α domain) has been identified as the ligand for rosetting and naturally acquired antibodies targeting this particular protein protect against severe disease development. In this study we wanted to address the specific regions in PfEMP1 and in other protein targets recognized by rosette-disrupting antibodies (generated upon immunization with recombinant PfEMP1 or naturally acquired during P. falciparum infection). We also wanted to explore other functional roles of these antibodies. A panel of antibodies (monoclonal and polyclonal) against rosette-mediating NTS-DBL1α domains was produced by animal immunization. The antibodies were analyzed with particular attention to their capacity to recognize the surface of the pRBC, disrupt the rosettes formed by homologous parasites and induce phagocytosis by monocytic cells. Additionally, the specific epitopes recognized by the majority of these antibodies were successfully mapped to a specific region of subdomain 3 ...