Transcript Plasmodium
Protozoans Protozoans include a wide diversity of taxa that do not form a monophyletic group but all are unicellular eukaryotes. Protozoa lack a cell wall, have at least one motile stage in their life cycle and most ingest their food. Protozoan cell is much larger and more complex than prokaryotic cell and contains a variety of organelles (e.g. Golgi apparatus, mitochondria, ribosomes, etc). Protozoans Eukaryotic cell was developed through endosymbiosis. In distant past aerobic bacteria appear to have been engulfed by anaerobic bacteria, but not digested. Ultimately, the two developed a symbiotic relationship with the engulfed aerobic bacteria becoming mitochondria and eukaryotic cells developed. In a similar fashion, ancestors of chloroplasts formed symbiotic union with other prokaryotes. Protozoans Protozoans include both autotrophs and heterotrophs. They include free-living and parasitic forms. Reproduction can be asexual by fission or budding or sexual by conjugation or syngamy (fusion of gametes). Protozoans The protozoa were once considered a single phylum, now at least 7 phyla are recognized. Were also once grouped with unicellular algae into the Protista, an even larger paraphyletic group. Figure 11.01 Movement in Protozoa Protozoa move mainly using cilia or flagella and by using pseudopodia Cilia also used for feeding in many small metazoans. Cilia and flagella No real morphological distinction between the two structures, but cilia are usually shorter and more abundant and flagella fewer and longer. Each flagellum or cilium is composed of 9 pairs of longitudinal microtubules arranged in a circle around a central pair. Cilia and flagella The collection of tubules is referred to as the axoneme and it is covered with a membrane continuous with the rest of the organism’s cell membrane. Axoneme anchors where it inserts into the main body of the cell with a basal body. Figure 11.09a Protein spoke Dynein motor Basal body Cilia and flagella The outer microtubules are connected to the central pair by protein spokes. Neighboring pairs of outer microtubules (doublets) are connected to each other by an elastic protein. Figure 11.09a Protein spoke Dynein motor Cilia and flagella Cilium is powered by dynein motors on the outer doublets. As these motors crawl up the adjacent doublet (movement is powered by ATP) they cause the entire axoneme to bend. The dynein motors do not cause the doublets to slide past each other because the doublets are attached to each other by the elastic proteins and the radial spokes and have little freedom of movement up and down. Instead the walking motion causes the doublets to bend. Flagella, “intelligent design” and irreducible complexity Oddly, the humble flagellum has been dragged into the evolution culture wars! Flagella, “intelligent design” and irreducible complexity The U.S. Supreme Court has prohibited the teaching of creationism in public schools as a violation of the “establishment of religion” clause of the constitution. Latest attempt to insert creationism into schools is the idea of “Intelligent Design.” Flagella, “intelligent design” and irreducible complexity The concept of “intelligent design” is outlined most clearly in Michael Behe’s book “Darwin’s Black Box.” The central idea in “intelligent design” is that some structures in the body are so complex that they could not possibly have evolved by a gradual process of natural selection. These structures are said to “irreducibly complex.” Flagella, “intelligent design” and irreducible complexity By “irreducibly complex” Behe means that a complex structure cannot be broken down into components that are themselves functional and that the structure must have come into existence in its complete form. Flagella, “intelligent design” and irreducible complexity If structures are “irreducibly complex” Behe claims that they cannot have evolved. Thus, their existence implies they must have been created by a designer (i.e. God, although the designer is not explicitly referred to as such). Flagella, “intelligent design” and irreducible complexity One of Behe’s main examples is flagella/cilia. Behe claims that because cilia are composed of at least half a dozen proteins, which combine to perform one task, and that all of the proteins must be present for a cilium to work and that cilia could not have evolved in a step-by step process of gradual improvement. Flagella, “intelligent design” and irreducible complexity The flagellum is not, in fact, irreducibly complex. For example, the flagellum in eel sperm lacks several of the components found in other flagella (including the central pair of microtubules, radial spokes, and outer row of dynein motors), yet the flagellum functions well. Flagella, “intelligent design” and irreducible complexity The whole “irreducible complexity” argument could in reality be recast as an argument of “personal incredulity.” “I personally cannot imagine a sequence of steps by which this complex structure could have evolved. Therefore, it must have been created.” Movement in Protozoa: Pseudopodia Pseudopodia are chief means of locomotion of amoebas but are also formed by other protozoa and amoeboid cells of many invertebrates. In amoeboid movement the organism extends a pseudopodium in the direction it wishes to travel and then flows into it. Pseudopodia Amoeboid movement involves endoplasm and ectoplasm. Endoplasm is more fluid than ectoplasm which is gel-like. When a pseudopodium forms, an extension of ectoplasm (the hyaline cap) appears and endoplasm flows into it and fountains to the periphery where it becomes ectoplasm. Thus, a tube of ectoplasm forms that the endoplasm flows through. The pseudopodium anchors to the substrate and the organism moves forward. Figure 11.10 Feeding in amebas Feeding in amoebas involves using pseudpodia to surround and engulf a particle in the process of phagocytosis. The particle is surrounded and a food vacuole forms into which digestive enzymes are poured and the digested remains are absorbed across the cell membrane. Phagocytosis Reproduction in protozoa The commonest form of reproduction is binary fission in which two essentially identical individuals result. In some ciliates budding occurs in which a smaller progeny cell is budded off which later grows to adult size. Binary fission in various taxa Sexual reproduction in protozoa All protozoa reproduce asexually, but sex is widespread in the protozoa too. In ciliates such as Paramecium, a type of sexual reproduction called conjugation takes place in which two Paramecia join together and exchange genetic material Figure 11.28 Diseases caused by protozoa Many diseases are caused by protozaon parasites These include: Malaria (caused by a sporozaon) Giardia, Sleeping sickness (caused by flagellates) Amoebic dysentry (caused by amoebae) Malaria Malaria is one of the most important diseases in the world. About 500 million cases and an estimated 700,000 to 2.7 million deaths occur worldwide each year (CDC). Malaria was well known to the Ancient Greeks and Romans. The Romans thought the disease was caused by bad air (in Latin mal-aria) from swamps, which they drained to prevent the disease. Malaria symptoms The severity of an infection may range from asymptomatic (no apparent sign of illness) to the classic symptoms of malaria (fever, chills, sweating, headaches, muscle pains), to severe complications (cerebral malaria, anemia, kidney failure) that can result in death. Factors such as the species of Plasmodium and the victims genetic background and acquired immunity affect the severity of symptoms. Malaria Despite humans long history with malaria its cause, a sporozoan parasite called Plasmodium, was not discovered until 1889 when Charles Louis Alphonse Laveran a French army physician identified it, a discovery for which he won the Nobel Prize in 1907. Malaria In 1897 an equally important discovery, the mode of transmission of malaria, was made by Ronald Ross. His identification of the Anopheles mosquito as the transmitting agent earned him the 1902 Nobel Prize and a knighthood in 1911. Plasmodium There are four species of Plasmodium: P. falciparum, P. vivax, P.ovale and P. malariae. P. falciparum causes severe often fatal malaria and is responsible for most deaths, with most victims being children. Plasmodium Both Plasmodium vivax and P. ovale can go dormant, hiding out in the liver. The parasites can reactivate and cause malaria months or years after the initial infection. P. malariae causes a long-lasting infection. If the infection is untreated it can persist asymptomatically for the lifetime of the host. Life cycle of malaria Plasmodium has two hosts: mosquitoes and humans. Sexual reproduction takes place in the mosquito and the parasite is transmitted to humans when the mosquito takes a blood meal. Life cycle of malaria: humans The mosquito injects Plasmodium into a human in the form of sporozoites. The sporozoites first invade liver cells and asexually reproduce to produce huge numbers of merozoites which spread to red blood cells where more merozoites are produced through more asexual reproduction. Some parasites transform into sexually reproducing gametocytes and these if ingested by a mosquito continue the cycle. Plasmodium gametocyte Life cycle of malaria: mosquitoes Gametocytes ingested by a mosquito combine in the mosquito’s stomach to produce zygotes. These zygotes develop into motile elongated ookinites. The ookinites invade the mosquito’s midgut wall where they ultimately produce sporozoites, which make their way to the salivary glands where they can be injected into a new human host. How Plasmodium enhances transmission rates The Plasmodium parasite engages in a number of manipulative behaviors to enhance its chances of being transmitted between hosts. Such manipulations are a common feature of parasite behavior, in general, as we will see throughout the semester. How Plasmodium enhances transmission rates Mosquitoes risk death when feeding and attempt to minimize risk and maximize reward when doing so. To obtain blood a mosquito must insert its proboscis through the skin and then locate a blood vessel. The longer this takes, the greater the risk. How Plasmodium enhances transmission rates As soon as the mosquito hits a blood vessel the host’s body responds by clotting the wound. Platelets clump around the proboscis and release chemicals which cause the platelets to clot together. How Plasmodium enhances transmission rates To slow clotting and speed feeding, mosquitoes inject anticoagulants including one called apyrase that unglues the platelets. They also inject other chemicals that expand the blood vessels. Plasmodium in the host helps the mosquito feed by releasing chemicals that also slow clotting. The parasite’s help increases the chances of the mosquito feeding successfully and sucking up the parasite. How Plasmodium enhances transmission rates Once in the mosquito Plasmodium needs about 10 days to produce sporozoites that are ready to be injected into a human. During this time, to reduce the chances of the mosquito dying, Plasmodium apparently discourages its host from eating. Although how the parasite does this is not clear, mosquitoes containing ookinites abandon feeding attempts sooner than parasite-free mosquitoes. How Plasmodium enhances transmission rates Once sporozoites are in the salivary glands, however, Plasmodium wants the mosquito to bite and bite often. In the salivary gland the parasite cuts off the mosquito’s anticoagulant apyrase supply. This makes it harder for the mosquito to feed so it is hungrier and bites more hosts. How Plasmodium enhances transmission rates As a result, an infected mosquito is twice as likely to bite two people in a single night as an uninfected mosquito is. As a result, the parasite is spread more widely. Behavior of Plasmodium in humans Plasmodium enters the blood stream through a mosquito bite. The parasite must avoid the host’s immune system. To do so while in the body it moves from one hiding place to another. The parasite moves first to the liver. Can get there in about 30 minutes, which is usually fast enough to avoid triggering the immune system. Behavior of Plasmodium in humans At the liver Plasmodium enters a liver cell. The cell responds by grabbing Plasmodium proteins and displaying the antigens on its cell surface in a special cup the major histocompatibility complex or MHC. Behavior of Plasmodium in humans The immune system recognizes the Plasmodium antigens and mounts an immune response. However, in a week before the immune system has mounted its full response the parasite has produced about 40,000 copies of itself and these burst out of the liver to seek red blood cells. Behavior of Plasmodium in humans The parasites leave the liver, reenter the bloodstream, and find a red blood cell to enter. Each parasite spends two days in a red blood cell consuming the hemoglobin and reproducing. Plasmodium in red blood cell Red blood cells Red blood cells (strictly red blood corpuscles) are a challenging environment to live in. They lack a nucleus and have little metabolic activity. As a result, they have few proteins for generating energy and also lack most of a normal cell’s channels for transporting fuel in and wastes out. Red blood cells Red blood cells are specialized to transport oxygen, which they carry by binding and wrapping in hemoglobin molecules. A red blood cell is pumped around the body by the heart and travels about 300 miles over its lifetime. Red blood cells Red blood cells are squeezed through slender capillaries and compressed to one fifth of their normal diameter before rebounding. To survive this squeezing, red blood cells have a network of proteins under their membrane that can fold like a concertina and allow the cell to stretch and squeeze as needed. Red blood cells Old red blood cells eventually lose their elasticity and become stiff. Those that show signs of such aging are filtered out as they pass through the spleen and destroyed. Behavior of Plasmodium in humans Plasmodium cannot swim but uses hooks to move along the blood vessels. At the parasite’s tip are sensors that respond only to young red blood cells and clasp on to proteins on the cell’s surface. Behavior of Plasmodium in humans The parasite uses a set of organelles concentrated at its apical end to gain entry. A suite of proteins are produced that cause the red blood cell’s membrane to open and let the parasite squeeze in. It takes only about 15 seconds for the parasite to get in. Figure 11.30 Plasmodium Sporozoite Behavior of Plasmodium in humans Inside in the red blood cell the Plasmodium consumes the hemoglobin. It takes in a small amount of hemoglobin, slices it apart with enzymes and harvests the energy released. The toxic core of the hemoglobin molecule is processed into an inert molecule called hemozoin. Behavior of Plasmodium in humans In order to reproduce, Plasmodium needs more than hemoglobin. It sets about modifying the red blood corpuscle so it can obtain amino acids and make proteins. The parasite builds a series of tubes that connect it to the surface of the cell and uses these to bring in materials from the blood steam and to pump out wastes. Behavior of Plasmodium in humans The parasite also produces proteins that help to maintain the red blood cell’s springiness for as long as possible so it is not eliminated by the spleen. After a few hours, however, the red blood cell has been too modified by the parasite to fool the spleen. The parasite now produces sticky latch proteins that glue the cell to blood vessel walls. Behavior of Plasmodium in humans Infected cells clump up in capillaries. After another day the contents of the cell have been used up. The cell ruptures and 16 new parasites burst out to infect other red blood cells. Some of these parasites transform into sexually reproducing gametocytes and, as mentioned previously, these if ingested by a mosquito will continue the cycle. Behavior of Plasmodium in humans While in the red blood cells Plasmodium is invisible to the immune system because the red blood cells have no MHC and cannot alert the immune system. The latch proteins however do stimulate the immune system. Behavior of Plasmodium in humans The latch protein is made by a single gene, but Plasmodium has over 100 such genes each of which produces a unique latch. In each generation some of the new parasites switch on a new latch gene and so the immune system is always playing catch up. Effects of malaria on human evolution The intense selection pressure imposed by malaria has resulted in a large number of mutations that provide protection against the parasite being selected for in humans. The best known is sickle cell anemia. Anti-malaria mutations: Sickle cell anemia Sickle cell anemia is a condition common in West Africans (and African Americans of West African ancestry). In sickle cell anemia red blood cells are sickle shaped as a result of a mutation which causes hemoglobin chains to stick together. Anti-malaria mutations: Sickle cell anemia People with the sickle cell allele are protected against Plasmodium because their hemoglobin under low oxygen conditions contracts into needle-shaped clumps. This contraction not only causes the sickling of the cell, but harms the parasite. Parasites are impaled on the clumps and the cell loses its ability to pump potassium, which the parasite needs. Anti-malaria mutations: Sickle cell allele People with two copies of the sickle cell allele usually die young, but heterozygotes are protected against malaria. As a result the geographic distribution of the allele and malaria in Africa match quite closely. Anti-malaria mutations: (G6PD) deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency. There are hundreds of alleles known and with more than 400 million people affected G6PD deficiency is the commonest enzyme deficiency known. Anti-malaria mutations: Thalassemia Geographic distribution suggests it protects against malaria and epidemiological evidence also supports this. People with G6PD-202A a reduced activity variant common in Africa have a significantly reduced risk of suffering severe malaria. Anti-malaria mutations: Thalassemia Thalassemia: People with thalassemia make the ingredients of hemoglobin in the wrong amounts. many or too few α or ß hemoglobin chains are produced and when they are assembled into hemoglobin molecules spare chains are left over. Too Other anti-malaria mutations: Thalassemia Extra chains clump together and cause major problems in the cell. These clumps grab oxygen, but don’t enclose it and the oxygen often escapes and because it is strongly charged, the oxygen damages other molecules in the cell. Severe thalassemia is fatal, but mild forms protect against malaria because the loose oxygen severely damages the parasite and renders it unable to invade new cells. Anti-malaria mutations: Ovalocytosis Ovalocytosis: Occurs in South east Asia and has same genetic rules and consequences as sickle cell anemia. People with ovalocytosis have blood cell walls that are so rigid they can’t slip through capillaries. The rigid cell walls make it hard for the parasite to enter the cell and the cell’s rigidity appears to prevent the parasite pumping in phosphates and sulphates it needs to survive. Anti-malaria mutations: One major advantage of these various antimalarial mutations appears to be that they provide a natural vaccination program for children. By slowing the development of the parasite these mutations give a child’s naïve immune system time to overcome Plasmodium’s attempts to elude the immune system and mount an immune response. Mild cases of malaria thus immunize children to malaria and allow them to survive to adulthood. Mosquito nets save lives www.nothingbutnets.net or www.nothingbutnets.org $10 gets a net to a family. 100% of your donation goes to purchase and distribute nets. Human African Trypanosomiasis (Sleeping sickness) Sleeping sickness is a protozoan disease, which like malaria is spread by an insect vector, the tsetse fly. The disease is endemic to sub-Saharan Africa and an estimated 300,000 people are infected annually with about 40,000 deaths. The disease organism is Trypanosoma brucei. Trypanosoma forms in blood smear from patient with African trypanosomiasis http://en.wikipedia.org/wiki/File:Trypanosoma_sp._PHIL_613_lores.jpg Sleeping Sickness Symptoms: Begins with fever, headaches, and joint pains. Lymph nodes may swell enormously and parasite numbers may be incredibly high. Greatly enlarged lymph nodes in the back of the neck are tell-tale signs of the disease. If untreated the parasite may cross the blood-brain barrier, which causes the characteristic symptoms the disease is named for. The patient becomes confused and the sleep cycle is disturbed with the patient alternating between manic periods and complete lethargy. Progressive mental deterioration is followed by coma and death. Sleeping Sickness Trypanosome levels in infected patients show a cycle of sharp peaks and valleys in parasite numbers of approximately a week in length. The cycle occurs because the immune system recognizes the glycoprotein in the trypanosomes coat and mounts an immune response to it, which eliminates parasites with that glycoprotein. Sleeping Sickness Trypanosomes, however, possess about 1,000 different coat-building genes and periodically a new one is turned on by a trypanosome that produces a different coat, which the immune system doesn’t recognize. Trypanosomes with this new coat reproduce undetected until the immune system can mount a response to the new coat. Sleeping Sickness If the first generation of trypanosomes to infect a host turned on their coat genes at random the immune system could learn to recognize the various possibilities quickly, remember them, and eliminate the parasite. Instead the coat-building genes are turned on in pre-set sequence. This means that the immune system every week or so is faced with a new coat that it has not seen before. Sleeping Sickness As a result of the sequential coat-switching, the immune system becomes chronically overstimulated and begins to attack the host’s body. The overstimulation of the immune system and the movement of parasites into the central nervous, where they escape the immune system altogether, eventually kills the patient.