Immunological Responses to Malaria

Immunological Responses to Malaria Our immune system is comprised of many specialised components, which work collectively to defend the body from harmful foreign bodies. Knowledge of the immune response elicited during malarial infections mainly comes from research using small animal models such as rodents; Plasmodium berghei and Plasmodium yoelii are species of rodent malaria commonly used in studies. Although an immune response is elicited against malaria, in many individuals the parasite is not effectively eliminated, allowing the parasite to multiply and induce clinical symptoms. Due to the morphological transformations occurring, a different group of immune components will be stimulated at different stages of the life cycle. Pre-erythrocytic stage Following immunisation of irradiated sporozoites, sterile protective immunity against malaria can be induced in all models studied, including humans (Nussenzweig et  al., 1967; Edelman et al., 1993; Doolan Hoffman, 2000). Rodent models have implicated antibodies as mediators of this protective immunity; Potocnjak et al. found that monoclonal antibodies against plasmodium berghei sporozoite proteins neutralised the parasite, blocking hepatocyte invasion and protecting mice from subsequent infection (Potocnjak et al., 1980). However, as discussed by Good Doolan, parasite elimination in humans by antibodies is unlikely, as high levels of pre-circulating specific antibody would be required at sporozoite inoculation to prevent hepatocyte infection (Good Doolan, 1999). In addition, studies have demonstrated that antibodies do not mediate protection and instead cell mediated responses are involved (Belnoue et al., 2004). Schofield et al. highlighted the significance of a group of T lymphocytes called cytotoxic CD8+ T cells and the cytokine interferon-gamma (IFN-ÃŽÂ ³). Mice immunised with attenuated sporozoites were not protected from malarial infection when depleted of CD8+ T cells, and when IFN-ÃŽÂ ³ was neutralised mice were no longer immune (Schofield et al, 1987). Other studies have reported similar conclusions, suggesting CD8+ T cells and IFN-ÃŽÂ ³ are important mediators of an immune response against pre-erythrocytic stages, as reviewed by Doolan Martinez-Alier (Doolan Martinez-Alier, 2006). However little is known of the activation or mechanism of CD8+ T cells in malarial infection. Rodent models have suggested naà ¯ve CD8+ T cells in the lymph nodes near the site of inoculation or in the liver become activated through coming into contact with antigen presenting cells called dendritic cells (DCs), which prime CD8+ T cells through cross presenting sporozoite antigens such as CSP. D Cs internalise, process and present antigens in association with MHC class I molecules to CD8+ T cells. After specific interaction and co-stimulatory molecule signals, CD8+ T cells become activated and migrate to, or stay in the liver, where they can eliminate parasitised hepatocytes (Jung et al, 2002; Amino et al., 2006). Usually CD8+ T cells kill via cytotoxic mechanisms; however immunity to P. berghei sporozoites in mice was found to be independent of cytotoxicity molecules fas and perforin, which suggests the cytokine secretion of CD8+ T cells, eliminates parasites (Renglli et al., 1997). Evidence also indicates IL-12 and natural killer (NK) cells are important for CD8+ T cells to carry out effector functions (Doolan Hoffman, 1999). CD4+ T cells are essential for CD8+ T cell effector responses and optimal functioning; IL-4 secreting CD4+ T cells are crucial (Carvalho et al., 2002; Doolan Martinez-Alier, 2006). Furthermore, CD4+ T cells have anti-parasitic functions; CD4+ T cells clones derived from mice immunised with irradiated sporozoites, provided protection against sporozoite infection in malaria-naà ¯ve mice (Tsuji et al., 1990). Belnoue et al. proved both CD4+ T cells and CD8+ T cells were important to eliminate pre-erythrocytic P. yoelii in mice; protection was mediated by IFN-ÃŽÂ ³ production and dependent upon nitric oxide (NO) (Belnoue et al., 2004). The toxic effects of NO, suggest it is a critical mediator of effectively eliminating malaria. The mechanisms remain undefined; studies have implicated many different immune components, which can singularly or collectively confer protection in rodent models, with parallel studies identifying different critical mediators. Erythrocytic stage Passive transfer studies provide evidence that antibodies are important in eliminating parasites; antibodies from malaria-immune individuals successfully treat individuals with malaria (Cohen S et al, 1961). Furthermore immunity in individuals living in malaria endemic areas may be mediated by high concentrations of antibody specific for a variety of erythrocyte stage parasitic antigens (Osier et al, 2008). As reviewed by Beeson et al., antibodies play a role and are likely to target merozoite proteins, such as MSP-1, to prevent erythrocyte invasion. Antibodies may also target parasitic ligands on the surface of PRBCs such as PfEMP-1. Antibody mechanisms may include inhibition of parasitic development or assist cell mediated destruction of PRBCs or merozoites through opsonisation or via the complement system (Beeson et al., 2008). As discussed by Engwerda, the spleen is a primary site of cell mediated immune responses against erythrocytic parasites (Engwerda et al., 2005). Murine models have highlighted the significance of CD4+ T cells in eliminating malaria and suggest they are important for gamma-delta T cell (ÃŽÂ ³ÃƒÅ½Ã‚ ´ T cell) expansion in the spleen during infection (van der Heyde et al.,1993). Research suggests that DCs internalise parasites, mature and migrate to the spleen, where they can present parasitic antigens in association with MHC class I molecules to naà ¯ve CD4+ T cells. The subsequent differentiation of CD4+ T cells, through IL-12 secretion from DCs, mediates protective immunity against erythrocytic malarial parasites. Th1 cells activate macrophages through the secretion of IFN-ÃŽÂ ³ and Th2 cells assist B cell maturation for the production of antibodies through IL-4, IL-6 and IL-10 secretion (Taylor-Robinson, 1998; Good Doolan 2010). The production of IL-12 is also believed to ac tivate natural killer (NK) cells, which secrete IFN-ÃŽÂ ³. Cytokine secretions from activated cells simulate a positive feedback loop, amplifying the immune response. Using mice, Couper et al. demonstrated that monocytes/macrophages are crucial to eliminate malaria; the infection got worse in mice depleted of these cells. Evidence suggested there are other pathways of activating macrophages other than T cells and IFN-ÃŽÂ ³ (Couper et al., 2007). Activated macrophages secrete TNF-ÃŽÂ ±, a mediator of inflammation, which is believed to participate in the pathogenesis of malaria. Macrophages destroy some PRBCs through phagocytosis and by the release of toxic free radicals such as NO (Good Doolan, 2010). Therefore antibodies, T cells, cytokines, macrophages and free radicals are likely to all play a role in the immune response against the symptomatic stage of the malaria life cycle.

Ted Bundy was a brutal serial killer Essay examples -- essays research

Works Cited â€Å"A Condemned Man’s Last Bequest†. People 6 February, 1989 p. 44-51. Gerdes, Louise. Serial Killers. San Diego: Greenhaven Press Inc.2000. Knappaman, Edward W. Great American Trials. Detroit: New England Publishing, Associates, Inc. 1994. Ted Bundy was a brutal serial killer. He was also very charming and handsome to the ladies, which made it easier to prey on them. He admitted to killing over twenty people just before his execution. Many families were relieved when he was finally executed. Ted Bundy thought of himself as very smart, because he was able to outsmart the authorities multiple times throughout the years of being a serial killer ( Gerdes 41). His victims of choice were young, college age, women ( Gerdes 128). He was in Colorado, on trial, for the brutal murder of a twenty-three year old woman. He used his intelligent mind to escape the prison. He went on and made his way to Florida for no apparent reason. He went to the Chi Omega House at Florida State University and unleashed his wrath on some of the students. He killed one student named Lisa Leavy. He also injured a couple other students severely. One and a half hours later, just after visiting the Chi Omega House, Ted killed another student just six blocks away. Later, the police were trying to pull him over for a minor traffic violation when he fled causing them to chase him. Shortly, they realized he was in a car stolen from near the Chi Omega House. Just days before he killed a twelve ye...

Summary and Personal Response: “on Becoming a Writer”

Summary and Personal Response: â€Å"On Becoming a Writer† Naomi Cranfield Prof. Denise Ogden ENG 115 28 October 2012 Summary and Personal Response: On Becoming a Writer Mr. Russell Baker is a professional writer whose writings have earned him the Pulitzer Prize on more than one occasion. The excerpt â€Å"On Becoming a Writer† came from his memoir â€Å"Growing Up† (Baker, 1982). In this section of his memoirs, Mr. Baker is explaining that pivotal moment in his life when he realized he wanted to become a writer.Russell (1982) says that he had â€Å"been bored by everything associated with English courses†. He had dreaded having to write compositions, and knew that they were not acceptable writings. He didn’t like having to read the classics and said that it was â€Å"as deadening as chloroform†. He had an English teacher, Mr. Fleagle, who at first seemed to be straitlaced and puritanical. From his first impression of this teacher, he expecte d yet another year of monotony and boredom. Then one day his class had been given an assignment to write an informal essay.Russell had been given a list of topics to choose from for writing his essay. He took home this list and ignored it until the night before it was due. The topic that Mr. Baker chose to write about was â€Å"The Art of Eating Spaghetti†. He chose this topic because it was the one that stood out the most to him. It reminded him of an occasion when his family was eating spaghetti and the comical opinions of how to do it were making everybody laugh. It was at that moment that he actually had an epiphany.There was something he really wanted to evoke into his writing, particularly for himself. He started writing with the intentions of rewriting another version for his teacher. However by the time he finished writing the original he had no time to â€Å"compose a proper, respectable essay† for class. Mr. Baker had to turn in the original essay. He was sur e that he was going to fail that lesson. When his English teacher had finished grading the class’s essays, he returned all but Mr. Baker’s. Young Russell Baker just knew that he was in trouble. All of sudden Mr.Fleagle caught the attention of Russell and the rest of the class and proceeded to read out loud Russell’s essay. Everybody was enthralled and pleasantly amused with the essay to include Mr. Fleagle. That was when Russell Baker knew he wanted to be a writer. I believe that the purpose of this writing is so that Mr. Baker can share his experiences with his audience and to inform them of how it came to be that he wanted to become a writer. The genre of Mr. Baker’s writing is a literacy narrative, because he is describing his thoughts on how he believed that he truly became a writer.I think that Mr. Baker’s audience could possibly student writers, English students, and maybe even followers of his columns. The tone that he uses in this writing m ight be one of satisfaction. He started out explaining his frustration with his English composition but then towards the end he was proud and satisfied with what he had accomplished. My response to this writing is, as a student who is currently taking an English composition class right now, I do get very easily frustrated with having to write.I find it difficult to find a topic that interests me to the point of wanting to just let my words flow. I have a desire to be able to write something that will catch the reader’s attention and keep it but I have such a hard time with it. I also can relate to Mr. Baker’s point of view that sometimes it takes something so simple as a family dinner to bring to mind a whole slew of interesting and amusing ideas. References: Baker, R. (1982) Growing up: On becoming a writer. New York, NY: Don Congdon Associates

Kurt Vonnegut s Slaughterhouse Five - 1246 Words

In Kurt Vonnegut’s Slaughterhouse-Five, Billy Pilgrim becomes â€Å"unstuck† in time. The question here is, why? The fact of the matter is that he does not actually begin to time-travel. Billy â€Å"becomes unstuck† as a coping mechanism to deal with his traumatic experiences during the war. Billy attempts to reorganize his life’s events and cope with a disorder known as post traumatic stress (PTSD). â€Å"Post traumatic stress disorder is a debilitating condition that follows a terrifying event† (Marilyn 8). It occurs when one has witnessed or experienced a traumatic event, such as war, child abuse, or other types of violence. Victims may claim to relive or re-experience events that were traumatic to them. They may even â€Å"feel† or â€Å"hear† things from the event. Other symptoms may include: â€Å"forgetfulness†¦amnesia, excessive fantasizing†¦trancelike states†¦imaginary companion, sleepwalking, and blackouts† (Putman 2). A lot of times, coping mechanisms fail and the following inner dissonance can lead to a multiplicity of upsetting emotional and physical symptoms (Robert Saperstein 2). Some children suffering from PTSD may show traumatic play. This refers to the reenactment of a traumatic experience. Usually, children will change the ending to make it happier. This is an extreme example of using the imagination as a way to escap e the terrible memories. Billy has all the symptoms associated with the disorder as he also used his imagination to escape his bad memories. When Billy Pilgrim goes toShow MoreRelatedKurt Vonnegut s Slaughterhouse Five 1490 Words   |  6 Pages4 April 2016 Vonnegut Reveals Suffering Through Billy Pilgrim Kurt Vonnegut was an American author who published a variety of works including novels, short stories, plays, and a few works of non-fiction. Kurt Vonnegut explains how war and the experiences that come with it can cause suffering to the minds of people that it affects. In his novel Slaughterhouse-Five, Kurt Vonnegut uses his novel to focus on his anti-war stance by showcasing humanity s suffering due to war. Vonnegut reveals this sufferingRead MoreKurt Vonnegut s Slaughterhouse Five902 Words   |  4 Pageswould do anything to avoid memories of trauma, including inventing an alternate planet. 2. Billy, the main character in Kurt Vonnegut’s novel Slaughterhouse-Five, experienced firsthand the trauma of war during the firebombing of Dresden. After this event, Billy created Tramfaladore, the planet where time does not exist. B. Summary 1. In Kurt Vonnegut s novel, Slaughterhouse-Five, he waves a story of destruction, war, mental health, and time travel to demonstrate the effects of posttraumatic wartimeRead MoreKurt Vonnegut s Slaughterhouse Five 1901 Words   |  8 PagesKurt Vonnegut developed his view of America through a history of personal loss and trauma that was largely endured at the same time by his characters. As a child, Kurt Vonnegut lived in Indianapolis, Indiana, which he would use in many of his later novels. His father was a prominent architect, while his mother came from the family of a wealthy brewer. After the depression hit, his father lost his business and gave up, his mother became addicted to alcohol and prescription drugs. In his teen yearsRead MoreKurt Vonnegut s Slaughterhouse Five1250 Words   |  5 PagesIrrational behavior is a huge part of Kurt Vonnegut’s Slaughterhouse-five because Billy Pilgrim’s character and the plot line are shaped by it throughout the book. The spastic ordering of his life story and the thorough belief that he was abducted by Tralfamadorian aliens are what shape this book’s story and Billy’s way of life. Although unreasonable, his behavior can be considered justified because of the time he spent in World War II. 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Vonnegut, as an author, received his essential voice by writing about his own experiences, using what would become his signature pessimistic yet humanist view. Vonnegut is described by Lindsay Clark as, â€Å"Worse than a pessimist†¦ he is an eternal optimist doomed to disappointment† (Clark, â€Å"Viewing Four Vonnegut NovelsRead MoreAnalysis Of Kurt Vonnegut s Slaughterhouse Five Essay2080 Words   |  9 PagesDraft Slaughterhouse-five War is a virus, a plagues our world and has experienced since the early ages of time. Once a war is cured a new strain begins stronger and more unforgiving as the last. Humans are creatures of habit which continue the violence. Kurt Vonnegut’s novel, slaughterhouse-five, is a deliberate and well developed statement against war as expressed through the tone, rhetoric, and characters, making anti war a prominent theme through the entirety of the novel. Slaughterhouse-fiveRead MoreKurt Vonnegut s Slaughterhouse Five Essay1905 Words   |  8 PagesKurt Vonnegut reflects his life during World War II as a German prisoner through his character Billy Pilgrim in the novel Slaughterhouse-Five. While enlisted in the US Army, Vonnegut had life threatening experiences that were inspiration for his writing. Vonnegut was a young boy during the Great Depression and was raised through the hardships of the time. As a child, Vonnegut’s father worked as an architect, but during the Gr eat Depression, the building industry was brought to a halt and Vonnegut’sRead MoreAnalysis Of Kurt Vonnegut s Slaughterhouse Five1134 Words   |  5 Pagesmoment, but that the same person is just fine in plenty of other moments. Now, when I myself hear that somebody is dead, I simply shrug and say what the Tralfamadorians say about dead people, which is so it goes. This quote, from Kurt Vonnegut s Slaughterhouse-five, has always stuck with me. Looking at the world through a softly tinted glass can brighten the edges. All the difficult and low stretches of life could be such a small fraction, if we would look at things from perspectives other thanRead MoreAnalysis Of Kurt Vonnegut s Slaughterhouse Five 1453 Words   |  6 Pagesbut the main traits of post-modernism are embracing skepticism and overturning conventions. With this in mind, Kurt Vonnegut explores war drawing parallels from his own past experience and depicts it through his character Billy Pilgrim allowing th e reader to see the dichotomy in reality and fiction, separating his novel from the normal layout of a linear novel. Also, Slaughterhouse-Five discusses the controversial military action as a post-modern novel, as it brings many perspectives to the bombing