Fig. 1. Schematic view of Plasmodium sporogonic (sexual) cycle and mosquito defence reactions during midgut invasion. (1) Exflagellation of microgametocytes soon after ingestion of infectious blood, giving rise to eight flagellated microgametes; (2) fertilization of macrogametes to form the zygote; (3) zygote development to a motile ookinete that invades the midgut epithelium at approximately 24 h post infection; (4) ookinete invasion arrests at the basal lamina where the parasite rounds up to form the non-motile oocyst. Several mitotic divisions within the oocyst give rise to thousands of sporozoites dramatically amplifying the parasite load; (5) oocyst rupture, at approximately 12 days post infection, and release of sporozoites into the haemolymph; (6) sporozoite migration through the haemolymph and invasion of the salivary gland. The sporozoites reside in the salivary gland lumen from where they are injected into the vertebrate host during the next bite. (a) Major parasite losses occur during the first 24 h post infection; (b) killing and subsequent melanization of ookinetes in a refractory strain, a process involving several mosquito factors including POs, LRIM1 and TEP1; (c) killing of ookinetes inside the cytoplasm of midgut epithelial cells through TEP1- and possibly LRIM1-mediated lysis; (d) ookinetes protected from killing by mosquito factors, including CTL4 and CTLMA2, successfully reach the basal lamina and develop into oocysts.