Toll like receptors and their therapeutic potential Essay -- essays re

Cellular Basis Of Disease: Why has the discovery of Toll-like receptors revolutionised our understanding of how the innate immune system works, and what is the therapeutic potential? The body has two immune systems: the innate immune system and the adaptive immune system. Adaptive, or acquired, immunity refers to antigen-specific defence mechanisms that take several days to become protective and are designed to react with and remove a specific antigen. This is immunity develops throughout life. Innate immunity refers to antigen-nonspecific defence mechanisms that a host uses immediately or within several hours after exposure to an antigen. This is the immunity that you are born with, and is the initial response by the body to eliminate microbes and prevent infection. It is in the innate immune system that Toll-like receptors are important in helping our understanding. The most important role of the innate immune system is to react rapidly to infectious agents with the initiation an inflammatory response, and to shape the subsequent adaptive immune responses. There are currently two different models for immune system induction. The first model predicts the recognition of non-self determinants on pathogens, and the other, more controvertial, model predicts that there is recognition of damage or danger to self-tissues. In the first model, pathogens are recognised by either specific or general components of their structure. A system referring to the patterns that are recognised are the pathogen associated molecular patterns (PAMPs) and the receptors recognising them are pattern recognition receptors (PRRs). The second model, put forward by Matzinger, is that it is the danger itself that is sensed. It is argued that it is tissue damage or cellular debris from necrotic cells that sends the signal for the immune system to initiate a response. The presence of DNA or RNA, that shouldn't be outside of the cell, may cause an alarm signal. Heat shock proteins released from the cell, or mannose that is normally cleaved off, may also serve as an alarm signal. It is suggested that the PRRs are there to recognise these endogenous signals from ruptured cells, and not to recognise pathogens as proposed in the first model. It is the first model that is most widely accepted in the scientific community, and it is this model of events that I shall describe. Activation of the ... ...77(9):7059-65 9. Horng T. et al., 2002. The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature. 420(6913):329-33 Takatsuna H., et al. 2003. Identification of TIFA as an adapter protein that links TRAF6 to IRAK-1 in IL-1 receptor signaling. J Biol Chem. 2003 Yang L, Blumbergs PC, Jones NR, Manavis J, Sarvestani GT and Ghabriel MN (2004). Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury. Spine. 29: 966-71 Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases. O'Neill LA. Nat Rev Drug Discov. 2002 Oct;1(10):797-807 Role of toll-like receptors and their adaptors in adjuvant immunotherapy for cancer. Seya T, Akazawa T, Uehori J, Matsumoto M, Azuma I, Toyoshima K. Anticancer Res. 2003 Nov-Dec;23(6a):4369-76 Toll-like receptor signaling in anti-cancer immunity. Okamoto M, Sato M. J Med Invest. 2003 Feb;50(1-2):9-24 H. Hemmi, et al., "A toll-like receptor recognizes bacterial DNA," Nature, 408(6813):740-5, 7 December 2000. bst.portlandpress.com/ bst/031/0637/bst0310637.htm

Drinking Coffee Elsewhere

Drinking Coffee Elsewhere is a very interesting story that brings up a number of thought-provoking issues in a relatively short format. Among these are questions of race, identity, and stereotyping. The narrator of the story is a young woman named Dina who feels lonely and confused in her new surroundings. As a poor, African American female at Yale (which the narrator portrays as a rich, male, and subtlety racist institution) she has difficulty adapting to the expectations of the university. From the very beginning, her differences set her apart from her classmates, until, from her point of view, she becomes a pariah, invisible and despised by the community. Of course, one must view these complaints with some skepticism. The narrator deliberately isolates herself with off-hand comments and antisocial behavior. She seems to take pride in her jarring attitude toward authority and friendliness. Only on rare occasions do we see her treated poorly by the other characters. While her behavior is rude and obnoxious, they seem to be welcoming and sincere in their attempts to reconcile her depression. It soon becomes apparent that Dina finds comfort in her intentional isolation. She takes some satisfaction from stereotyping others unfairly and irrationally, since stereotypes provide a simple and lazy detour around human interaction. The narrator in Drinking Coffee Elsewhere has many problems with communication that prevent her from forming healthy relationships. During her sessions with the school psychiatrist, his probing questions provide a window into some of the difficulties she has. One of his most insightful statements is that Dina’s constant deceptions and dismissals have accustomed her to an offensive reaction. Whenever someone asks her a question her response belittles and mystifies them. Because she has set herself up for this attitude it is a natural custom. For example, in the first few pages, during an exercise designed for incoming freshman, the students choose an object they would like to be. The game inspires creativity and helps the freshmen get to know each other. Dina, disgusted by her classmate’s insipid choices, states that she would be a revolver. This response, obviously meant to shock and discomfort her peers, earns Dina her psychiatric evaluations. Many other examples occur throughout the story. In a meeting with the psychiatrist, the doctor asks Dina about her sexual history. This question create tension in different ways, such as sexuality, class, relationships, and shame. Typically, Dina invents a ridiculous story about losing her virginity spontaneously and foolishly. Because of her stereotyping attitude, Dina assumes that the white, male doctor would expect her, a poor, black girl, to do these sorts of things. She derails what could have been an important and intriguing discussion of Dina’s insecurities into what she thinks the doctor expects. Later, he calls this attitude her survival mechanism of a â€Å"black living in a white world. † It’s an interesting assertion, if not entirely fair to the people of all races who succeed without such pointless and insulting tactics. Ultimately, Drinking Coffee Elsewhere is a story of regret. At the end of the tale, Dina gives a heartfelt reminiscence of her college days, now long past, and the opportunities she missed and friendships she broke. One person in particular, Heidi, could have been a close and important friend. Instead, Dina’s harsh and unpleasant demeanor severed a deep connection. In fact, Dina’s quick and thoughtless speaking leads her to belittle the death of Heidi’s mother. This error draws attention to Dr. Raeburn’s original warning: that Dina’s tendency to speak nonsense would become an unfortunate habit. The warning applies to the reader as well, encouraging us to speak thoughtfully and honestly in all human interactions.

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