the proboscis is the labium, which forms the sheath enclosing the rest of the mouthparts. when the mosquito first lands on a potential host, its mouthparts are enclosed entirely in this sheath, and it will touch the tip of the labium to the skin in various places. sometimes, it will begin to bite almost straight away, while other times, it will prod around, apparently looking for a suitable place. occasionally, it will wander for a considerable time, and eventually fly away without biting. presumably, this probing is a search for a place with easily accessible blood vessels, but the exact mechanism is not known. it is known that there are two taste receptors at the tip of the labium which may well play a role. the female mosquito does not insert its labium into the skin; it bends back into a bow when the mosquito begins to bite. the tip of the labium remains in contact with the skin of the host, acting as a guide for the other mouthparts. in total, there are six mouthparts besides the labium: two mandibles, two maxillae, the hypopharynx, and the labrum. the mandibles and the maxillae are used for piercing the skin. the mandibles are pointed, while the maxillae end in flat, toothed "blades". to force these into the skin, the mosquito moves its head backwards and forwards. on one movement, the maxillae are moved as far forward as possible. on the opposite movement, the mandibles are pushed deeper into the skin by levering against the maxillae. the maxillae do not slip back because the toothed blades grip the skin. the hypopharynx and the labrum are both hollow. saliva with anticoagulant is pumped down the hypopharynx to prevent clotting, and blood is drawn up the labrum. to understand the mosquito mouthparts, it is helpful to draw a comparison with an insect that chews food, such as a dragonfly. a dragonfly has two mandibles, which are used for chewing, and two maxillae, which are used to hold the food in place as it is chewed. the labium forms the floor of the dragonfly's mouth, the labrum forms the top, while the hypopharynx is inside the mouth and is used in swallowing. conceptually, then, the mosquito's proboscis is an adaptation of the mouthparts that occur in other insects. the labium still lies beneath the other mouthparts, but also enfolds them, and it has been extended into a proboscis. the maxillae still "grip" the "food" while the mandibles "bite" it. the top of the mouth, the labrum, has developed into a channeled blade the length of the proboscis, with a cross-section like an inverted "u". finally, the hypopharynx has extended into a tube that can deliver saliva at the end of the proboscis. its upper surface is somewhat flattened so, when the lower part of the hypopharynx is pressed against it, the labrum forms a closed tube for conveying blood from the host. saliva for the mosquito to obtain a blood meal, it must circumvent the vertebrate's physiological responses. the mosquito, as with all blood-feeding arthropods, has mechanisms to effectively block the hemostasis system with their saliva, which contains a mixture of secreted proteins. saglin is a protein produced by the salivary glands of mosquitoes. mosquito saliva acts to reduce vascular constriction, blood clotting, platelet aggregation, angiogenesis and immunity, and creates inflammation. universally, hematophagous arthropod saliva contains at least one anti-clotting, one anti-platelet, and one vasodilatory substance. mosquito saliva also contains enzymes that aid in sugar feeding, and antimicrobial agents to control bacterial growth in the sugar meal. the composition of mosquito saliva is relatively simple, as it usually contains fewer than 20 dominant proteins. as of the early 2000s, scientists still were unable to ascribe functions to more than half of the molecules found in arthropod saliva. one promising application of components of mosquito saliva is the development of anti-clotting drugs, such as clotting inhibitors and capillary dilators, that could be useful for managing cardiovascular disease. it is now well recognized that feeding ticks, sandflies, and, more recently, mosquitoes, have an ability to modulate the immune response of the animals (hosts) on which they feed. the presence of this activity in vector saliva is a reflection of the inherent overlapping and interconnected nature of the host hemostatic and inflammatory/immunological responses and the intrinsic need to prevent these host defenses from disrupting successful feeding. the mechanism for mosquito saliva-induced alteration of the host immune response is unclear, but the data have become increasingly convincing that such an effect occurs. early work described a factor in saliva that directly suppresses tnf-α release, but not antigen-induced histamine secretion, from activated mast cells. experiments by cross et al. (1994) demonstrated that the inclusion of ae. aegypti mosquito saliva into naïve cultures led to a suppression of interleukin (il)-2 and ifn-γ production, while the cytokines il-4 and il-5 are unaffected. cellular proliferation in response to il-2 is clearly reduced by prior treatment of cells with mosquito salivary gland extract. correspondingly, activated splenocytes isolated from mice fed upon by either ae. aegypti or cx. pipiens mosquitoes produce markedly higher levels of il-4 and il-10 concurrent with suppressed ifn-γ production. unexpectedly, this shift in cytokine expression is observed in splenocytes up to 10 days after mosquito exposure, suggesting natural feeding of mosquitoes can have a profound, enduring, and systemic effect on the immune response. t cell populations are decidedly susceptible to the suppressive effect of mosquito saliva, showing increased mortality and decreased division rates. parallel work by wasserman et al. (2004) demonstrated that t and b cell proliferation was inhibited in a dose dependent manner with concentrations as low as 1/7 of the saliva in a single mosquito. depinay et al. (2005) observed a suppression of antibody-specific t cell responses mediated by mosquito saliva and dependent on mast cells and il-10 expression. a 2006 study suggests mosquito saliva can also decrease expression of interferon−α/β during early mosquito-borne virus infection. the contribution of type i interferons (ifn) in recovery from infection with viruses has been demonstrated in vivo by the therapeutic and prophylactic effects of administration of ifn inducers or ifn itself, and different research suggests mosquito saliva exacerbates west nile virus infection, as well as other mosquito-transmitted viruses. studies in humanized mice bearing a reconstituted human immune system have suggested potential impact of mosquito saliva in humans. work published in 2018 from the baylor college of medicine using such humanized mice came to several conclusions, among them being that mosquito saliva led to an increase in natural killer t cells in peripheral blood; to an overall decrease in ex vivo cytokine production by peripheral blood mononuclear cells (pbmcs); changes to proportions of subsets of pbmcs; changes in the prevalence of t cell subtypes across organs; and changes to circulating levels of cytokines. egg development and blood digestion here an anopheles stephensi female is engorged with blood and beginning to pass unwanted liquid fractions of the blood to make room in its gut for more of the solid nutrients. most species of mosquito require a blood meal to begin the process of egg development. females with poor larval nutrition may need to ingest sugar or a preliminary blood meal before their ovarian follicles can reach their resting stage. once the follicles have reached the resting stage, digestion of a sufficiently large blood meal triggers a hormonal cascade that leads to egg development. upon completion of feeding, the mosquito withdraws her proboscis, and as the gut fills up, the stomach lining secretes a peritrophic membrane that surrounds the blood. this membrane keeps the blood separate from anything else in the stomach. like many hemiptera and other insects that survive on dilute liquid diets, many adult mosquitoes must excrete unwanted aqueous fractions even as they feed. (see the photograph of a feeding anopheles stephensi: note that the excreted droplet patently is not whole blood, being far more dilute). as long as they are not disturbed, this permits mosquitoes to continue feeding until they have accumulated a full meal of nutrient solids. as a result, a mosquito replete with blood can continue to absorb sugar, even as the blood meal is slowly digested over a period of several days. once blood is in the stomach, the midgut of the female synthesizes proteolytic enzymes that hydrolyze the blood proteins into free amino acids. these are used as building blocks for the synthesis of vitellogenin, which are the precursors for egg yolk protein. in the mosquito anopheles stephensi, trypsin activity is restricted entirely to the posterior midgut lumen. no trypsin activity occurs before the blood meal, but activity increases continuously up to 30 hours after feeding, and subsequently returns to baseline levels by 60 hours. aminopeptidase is active in the anterior and posterior midgut regions before and after feeding. in the whole midgut, activity rises from a baseline of approximately three enzyme units (eu) per midgut to a maximum of 12 eu at 30 hours after the blood meal, subsequently falling to baseline levels by 60 hours. a similar cycle of activity occurs in the posterior midgut and posterior midgut lumen, whereas aminopeptidase in the posterior midgut epithelium decreases in activity during digestion. aminopeptidase in the anterior midgut is maintained at a constant, low level, showing no significant variation with time after feeding. alpha-glucosidase is active in anterior and posterior midguts before and at all times after feeding. in whole midgut homogenates, alpha-glucosidase activity increases slowly up to 18 hours after the blood meal, then rises rapidly to a maximum at 30 hours after the blood meal, whereas the subsequent decline in activity is less predictable. all posterior midgut activity is restricted to the posterior midgut lumen. depending on the time after feeding, greater than 25% of the total midgut activity of alpha-glucosidase is located in the anterior midgut. after blood meal ingestion, proteases are active only in the posterior midgut. trypsin is the major primary hydrolytic protease and is secreted into the posterior midgut lumen without activation in the posterior midgut epithelium. aminopeptidase activity is also luminal in the posterior midgut, but cellular aminopeptidases are required for peptide processing in both anterior and posterior midguts. alpha-glucosidase activity is elevated in the posterior midgut after feeding in response to the blood meal, whereas activity in the anterior midgut is consistent with a nectar-processing role for this midgut region. ecology female ochlerotatus notoscriptus feeding on a human arm, tasmania, australia distribution mosquitoes are cosmopolitan (world-wide): they are in every land region except antarctica and a few islands with polar or subpolar climates. iceland is such an island, being essentially free of mosquitoes. the absence of mosquitoes in iceland and similar regions is probably because of quirks of their climate, which differs in some respects from mainland regions. at the start of the uninterrupted continental winter of greenland and the northern regions of eurasia and america, the pupa enters diapause under the ice that covers sufficiently deep water. the imago emerges only after the ice breaks in late spring. in iceland, the weather is less predictable. in mid-winter it frequently warms up suddenly, causing the ice to break, but then to freeze again after a few days. by that time the mosquitoes will have emerged from their pupae, but the new freeze sets in before they can complete their life cycle. any anautogenous adult mosquito would need a host to supply a blood meal before it could lay viable eggs; it would need time to mate, mature the eggs and oviposit in suitable wetlands. these requirements would not be realistic in iceland and in fact the absence of mosquitoes from such subpolar islands is in line with the islands' low insect biodiversity; iceland has fewer than 1,500 described species of insects, many of them probably accidentally introduced by human agency. in iceland most ectoparasitic insects live in sheltered conditions or actually on mammals; examples include lice, fleas and bedbugs, in whose living conditions freezing is no concern, and most of which were introduced inadvertently by humans. some other aquatic diptera, such as simuliidae, do survive in iceland, but their habits and adaptations differ from those of mosquitoes; simuliidae for example, though they, like mosquitoes, are bloodsuckers, generally inhabit stones under running water that does not readily freeze and which is totally unsuited to mosquitoes; mosquitoes are generally not