Othello And Racism Essay Research Paper Although free essay sample

Othello And Racism Essay, Research Paper Although there are tonss of things to propose this is a racialist drama I don # 8217 ; t believe that racism really dominates the drama, even though it has a racialist subject. There is a romantic brotherhood between black and white which gets destroyed because most people think the relationship is incorrect. At the clip the drama was written, 1604, even the Queen of England was racist so at that place must hold been a strong hatred of inkinesss around that clip. Most racist remarks in the drama are said by people that are angry or disquieted. For illustration, when Emilia found out that Othello had killed Desdemona she was highly huffy and she called Othello a Blacker Satan , this was the lone clip in the drama that she had said anything racialist about Othello. The chief characters that have racist attitudes are Iago, Brabantio, Roderigo and Emilia, with the hate of Othello as the footing for their racialist actions and remarks towards him. We will write a custom essay sample on Othello And Racism Essay Research Paper Although or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page Iago is the most racist character in the book as he has it in for Othello right from the start. What flickers off Iago # 8217 ; s hatred towards him is the fact that when Othello chose his lieutenant, it was Cassio who was chosen alternatively of Iago. What made Iago angry was the fact that Cassio had no experience in war when he did and Cassio was chosen alternatively of him. Iago does non state anything racialist to Othello # 8217 ; s face but he has a batch to state against him behind his dorsum. He schemes to destruct Othello and anything in his manner including Cassio and Desdemona. The first clip we hear one of his racialist remarks is when he # 8217 ; s speaking to Brabantio about Othello and Desdemona, Even now, really now, an old black random-access memory is tupping your white Ewe . Iago says this to seek and turn Brabantio against Othello. Iago utilizations racialist remarks all the manner through the drama, as he tries to turn people against Othello, for illustration naming him a Barbary Horse . He neer says anything racialist to Othello # 8217 ; s face because in his secret plan he had to be his best friend, so as non to do him leery that Iago was doing all the problem for him. Iago is covetous of Othello for many grounds, one being that Othello has higher ranking in the ground forces than him, and besides he has a good matrimony with Desdemona which Iago does non hold himself with Emilia. These are the chief causes of his hate for Othello and the ground he adopts such a racialist attitude. Roderigo is another 1 of the racialist characters in the drama, being so right from the start. He is Iago # 8217 ; s confederate and will make anything that Iago wants him to. I think he does this because of the manner Iago can writhe a state of affairs to do it sound as if Roderigo would acquire something good from it but in the terminal he doesn # 8217 ; t. One of the racialist names he calls Othello behind his dorsum is Thick-lips . He hates Othello because he # 8217 ; s covetous of him as he besides loves Desdemona but can non hold her. I don # 8217 ; t believe he views Othello in a really bad, racist manner but uses the racism against Othello because he # 8217 ; s covetous of him. Neither Roderigo or Iago would state anything racialist to Othello # 8217 ; s face as he is the general of the ground forces. Brabantio is besides a racialist character, and is enraged when he finds out that his girl, Desdemona, has been seeing the Moor behind his dorsum. Brabantio is so huffy he sends out his guards to catch Othello and put him in prison. Brabantio views Othello as a foul and dirty no good black, I think this racialist position of his is because he # 8217 ; s angry when he finds out that his girl has been seeing this Moor . Unlike Iago and Roderigo, Brabantio will openly do racialist remarks about Othello to his face such as, lewd Moor , Wheeling alien . Brabantio can make this because he is the Senator of Venice and is higher in rank than Othello. The other character who is racist towards Othello is Emilia, the lady in waiting to Desdemona. Emilia is disgusted with Othello when she finds out that Othello had killed Desdemona this is the clip she gets a opportunity to show her feelings about Othello, O, the more angel she, and you the blacker Satan! Although this is the lone clip she says what she thinks of him, I think that she was racist towards Othello all through the drama and did non approve of his relationship with Desdemona but merely could non demo it because she would acquire in problem with her Godhead . Because Shakespeare wrote a drama about a black and white brotherhood, which was later destroyed, I think it shows that he # 8217 ; s non racist. I think he feels that the brotherhood between the two is right, but the relationship would neer last in a racialist community at that clip. He portrayed the brotherhood between Othello and Desdemona as a good thing, and the people who destroyed it, chiefly Iago and Roderigo as immorality. This shows one time once more that he approves of a black and white relationship and therefore was non racist himself. Once before Shakespeare wrote a sonnet about his kept woman which says, for illustration, If snow be white, why so her chest be dun He writes about his kept woman being black when other poets of that clip wrote about how their kept womans were white. The other poets were the racialist 1s, they girlfriends were ever white and perfect, Shakespeare wrote about how his kept womans is black and non really beautiful. Although the drama has a strong racist subject against inkinesss I don # 8217 ; t think that the drama is racist. 32c

Japan Essays - Military Personnel, Asia, Japan, Empire Of Japan

Japan Essays - Military Personnel, Asia, Japan, Empire Of Japan Japan The occupation of Japan was, from start to finish, an American operation. General Douglans MacArthur, sole supreme commander of the Allied Power was in charge. The Americans had insufficient men to make a military government of Japan possible; so t hey decided to act through the existing Japanese gobernment. General Mac Arthur became, except in name, dictator of Japan. He imposed his will on Japan. Demilitarization was speedily carried out, demobilization of the former imperial forces was complet ed by early 1946. Japan was extensively fire bomded during the second world war. The stench of sewer gas, rotting garbage, and the acrid smell of ashes and scorched debris pervaded the air. The Japanese people had to live in the damp, and col d of the concrete buildings, because they were the only ones left. Little remained of the vulnerable wooden frame, tile roof dwelling lived in by most Japanese. When the first signs of winter set in, the occupation forces immediately took over all the s team-heated buildings. The Japanese were out in the cold in the first post war winter fuel was very hard to find, a family was considered lucky if they had a small barely glowing charcoal brazier to huddle around. That next summer in random spots new ho uses were built, each house was standardized at 216 square feet, and required 2400 board feet of material in order to be built. A master plan for a modernistic city had been drafted, but it was cast aside because of the lack of time before the next winte r. The thousands of people who lived in railroad stations and public parks needed housing. All the Japanese heard was democracy from the Americans. All they cared about was food. General MacAruther asked the government to send food, when they refus ed he sent another telegram that said, "Send me food, or send me bullets." American troops were forbidden to eat local food, as to keep from cutting from cutting into the sparse local supply. No food was was brought in expressly for the Japanese durning the first six months after the American presence there. Herbert Hoover, serving as chairman of a special presidential advisory committee, recommended minimum imports to Japan of 870,000 tons of food to be distributed in different urban areas. Fi sh, the source of so much of the protein in the Japanese diet, were no longer available in adequate quantities because the fishing fleet, particularly the large vessels, had been badly decimated by the war and because the U.S.S.R. closed off the fishing g rounds in the north. The most important aspect of the democratization policy was the adoption of a new constitution and its supporting legislation. When the Japanese government proved too confused or too reluctant to come up with a constitutional reform that satisfied MacArthur, he had his own staff draft a new constitution in February 1946. This, with only minor changes, was then adopted by the Japanese government in the form of an imperial amendment to the 1889 constitution and went into effect on May 3, 1947. The new Constitution was a perfection of the British parliamentary form of government that the Japanese had been moving toward in the 1920s. Supreme political power was assigned to the Diet. Cabinets were made responsible to the Diet by having the prime minister elected by the lower house. The House of Peers was replaced by an elected House of Councillors. The judicial system was made as independent of executive interference as possible, and a newly created supreme court was given the power to review the constitutionality of laws. Local governments were given greatly increased powers. The Emperor was reduced to being a symbol of the unity of the nation. Japanese began to see him in person. He went to hospitals, schools, mines, industrial plants; he broke ground for public buildings and snipped tape at the opening of gates and highways. He was steered here and there, shown things, and kept muttering, "Ah so, ah so." People started to call him "Ah-so-san." Suddenly the puybli c began to take this shy, ill-at-ease man to their hearts. They saw in him something of their own conqured selves, force

The Current Obama Administration Essay Example | Topics and Well Written Essays - 1000 words

The Current Obama Administration - Essay Example Alinksy believed that the people he was working with had no power in the community, but he sought to make that community heard. [Alinsky] believed that widespread poverty left America open to the influence of demagogues and that the only antidote was active, widespread participation in the political process†¦[he] envisioned an ‘organization of organizations,’ comprised of all sectors of the community...† In fact, many of the people he worked with felt like they had no say in their own lives, and as a result some turned to crime. â€Å"[Alinsky] realize[d] that criminal behavior was a symptom of poverty and powerlessness.† Alinsky believed in empowerment of the people, and the Have-Nots desperately needed someone who would step up to the plate for them and plead their case. â€Å"Alinsky considered himself a realist above all, the ultimate pragmatist†¦[he] had no qualms about assorted versions of morality in the pursuit of worldly power. He didn't coddle his radical acolytes or encourage their bourgeois distinctions between good and evil when it came to transferring power from the Haves to the Have-Nots.† Alinsky claimed that making the opposition live up to their own standards was something that would trip up the opposition every time, because the other could not live up to its promises in a political showdown. Saul Alinsky said, "Make the enemy live up to his/her own book of rules. You can kill them with this. They can no more obey their own rules than the Christian church can live up to Christianity." The Obama Administration would do well to fight fire with fire, especially on the topic of the health care reform debate. There are about 40 million Americans who have no say when it comes to facing big insurance companies, and therefore are uninsured. If Obama and his Administration held the Republicans' feet to the fire, and really extracted from them that what they did not want was tort reform-but for people to continue going on without health insurance-the dark underbelly of Republican politics would certainly be shown. The Republicans would then be beaten by their own game. The people Saul Alinsky chose to organize were people who had no relative value. "[Alinsky] recruited and guided indigenous leaders who identified common interests that brought together previously hostile ethnic groups of Serbs and Croatians, Czechs and Slovaks, Poles and Lithuanians into a large organization, the Back of The Yards Neighborhood Council."7 The Obama Administration, likewise, has done well to hire a bunch of people from different backgrounds. They should still continue this policy. Saul Alinsky commented, "One of the criteria for picking the target is the target's vulnerability ... the other important point in the choosing of a target is that it must be a personification, not something general and abstract."8 The Obama Administration must focus on the vulnerable points of the Republican Party. If one msut choose the topic of health care, the main sticking points that will keep the Democrats in power-as one is sure this is a factor Obama wants to have a successful presidency-is to expose the Republicans' "can't-do" attitude, obstructionist politics, and misguided, misinformed, and idiotic notions. "An organizer working in and for an open society is in an ideological dilemma to begin with, he does not have a fixed truth -- truth to him is relative

My Dilemma (acquisition, merger and initial public offer) Research Paper

My Dilemma (acquisition, merger and initial public offer) - Research Paper Example How the Dilemma came about One Monday morning when I got to the office, something strange and out of protocol happened. Hitherto, I rarely had any say on proposals for growth and expansion. I was more or less a passive observer who was around to learn from his superiors. This time round I was not even asked to give contributions towards a proposal to be sent to management but to select one of three choices management had taken on a long term growth and expansion move. Most of the time, proposals from my department to management were discarded but when proposals came from management to my department, it meant that the proposal was certainly going to be implemented. This means that the choice I made was going to be implemented. For a student on internship to decide the long term growth and expansion program for the multi million advertising company was indeed a herculean task. The dilemma was also with the fact that I had to choose among options given by management. The options were acquisition, merger and initial public offer. The company was considering either purchasing an events organization company or merging with the events organization company or putting its shares on public offer as a means of expanding the existing company. This was a dilemma because all three options had their own advantages and disadvantages. It was indeed difficult pointing out which of the options was going to be better than the either. Meaning of the three options Merger has been explained by Farlex (2011) to be â€Å"a combination of two or more companies in which the assets and liabilities of the selling firm(s) are absorbed by the buying firm.† It continues to posit that in the event of merger, there is a â€Å"decision by two companies to combine all operations, officers, structure, and other functions of business† (Farlex (2011). To this effect, it meant th at if I chose the option of merger, my company would have been tagged as the buying firm. It also meant that by merger, our company was going to combine all its operation, staff, structure and organizational culture with the selling firm. The new company that was going to be formed out of the merger was not going to be under the outright ownership of our firm but then ownership shared by the two companies in question. The Investopedia (2011) on the other hand explains that â€Å"when one company takes over another and clearly established itself as the new owner, the purchase is called an acquisition.† The implication of this definition is that if this choice was chosen by me, our company was

Outsourcing Plan Essay Example for Free

Outsourcing Plan Essay 1. Outsourcing has become a way to increase an organization’s flexibility to meet rapidly changing market conditions, focus on core competencies and develop competitive advantage. As a result, the need for SM has intensified and positioned Supply Managers as agents of strategic change critical to supply chain success. A. True 2. Outsourcing decreases an organization’s flexibility to meet rapidly changing market conditions, but it can usually reduce total costs in the long-term B. False 3. Early supply management involvement is an approach in supply management to bring the expertise and collaborative synergy of suppliers into the design process. A. True 4. The strategic sourcing plan should be developed in a collaborative environment that includes all relevant functional area representatives and supply chain members. A. True 5. Foreign governments never impose countertrade requirements. B. False 6. Statutory rates are full rates for tariffs. A. True 7. Which of the following is not a strategic issue in making the outsourcing decision? A. The issue of short-term vulnerabilities. 8. Which of the following is a consideration that favors buying a product? B. Multiple source policy 9. Which of the following is not one of the conditions demanding negotiation? C. Market must consist of adequate number of sellers.

Struggles Within the Middle East: United States Supplying Israel During

In October of 1973, a war between the Arabic states of Egypt and Syria and the state of Israel broke out known as the Yom Kippur War. Being vastly overwhelmed by the Arabic states in terms of sheer volume of troops and equipment, Israel turned toward its ally in the West, the United States. With profound diplomatic pressure from multiple Arabic states, the United States found itself in an increasingly difficult position. In an effort to create the best outcome for America in both the Middle East and the global theatre, the United States made the decision, knowing full well the possible consequences, to help supply Israel during the Yom Kippur War. On October 6th, 1973, during the Jewish holy day of atonement, Yom Kippur, a surprise attack transpired, catching Israel off-guard and potentially putting over sovereign nations in a precarious position pertaining to Middle Eastern foreign affairs. The governments of Egypt and Syria, knowing that Yom Kippur was the holiest Jewish day of prayer and fasting that the Jewish military actively participated in, knew that they would be able to catch the well-defended Israeli positions off-guard. By combining their military might, the Egyptian army created a combined force that totaled the forces of NATO in Western Europe, creating a potential security threat to first world nations. In Golan Heights, the Syrian tank force outmatched Israeli by nine to one, and in the Suez region the Egyptian forces outnumber the Israeli by a ratio of one-hundred and sixty to one. Both sides, willing to commit both their men and equipment, were willing to sacrifice in order to gain their necessary victory. W illing to sacrifice their equipment, all sides in the war were looking outward toward other nations in or... ...rael during the war. With a fear that failure to maintain the balance of power in the Middle East, while trying to drive Soviet influence out, could upset America’s interests and security in the Global theatre, United States officials made the decision that supplying Israel during the Yom Kippur War was in America’s best interest the long term. Works Cited U.S. State Department. Middle East Task Force. Situation Report #18. Washington, DC: Government Printing Office, 1981. U.S. State Department. Middle East Task Force. Situation Report #22. Washington, DC: Government Printing Office, 1981. U.S. State Department. Middle East Task Force. The Middle East Conflict and U.S. Oil Interests. Washington, DC: Government Printing Office, 1981. The White House. Memorandum of Conversation, October 9, 1973. Washington, DC: Government Printing Office, 1981.

Medical Immunology

MEDICAL IMMUNOLOGY & SEROLOGY Terence L. Eday, RMT, MT(ASCPi), MPH College of Medical Technology / Medical Laboratory Science University of Perpetual Help System DALTA Historical Perspective †¢ 1773, Voltaire reported on an ancient Chinese custom where dried and powdered small pox scabs were inhaled †¢ 1798, Edward Anthony Jenner, Smallpox vaccination †¢ 1862, Ernst Haekel, Recognition of phagocytosis 1877, Paul Erlich, recognition of mast cells Historical Perspective †¢ 1879, Louis Pasteur, Attennuated chicken cholera vaccine development †¢ 1883, Ellie Metchnikoff developed the cellular theory of immunity through phagocytosis; phagocytic theory; cellular theory of vaccination †¢ 1885, Pasteur discovered therapeutic vaccination; first report of live â€Å"attenuated† vaccine for rabies Historical Perspective 1888, Pierre Roux & Alexander Yersin, Bacterial toxins (Yersinia pestis) †¢ 1888, George Nuttall, Bactericidal action of blood †¢ 1 890, Emil von Behring and Kitasata introduced passive immunization into modern medicine; humoral theory of immunity †¢ 1891, Robert Koch demonstrated the cutaneous (delayed-type) hypersensitivity †¢ 1894, Richard Pfeiffer, Bacteriolysis Historical Perspective (1 of 6 ) 1895, Jules Bordet, Complement and antibody activity in bacteriolysis †¢ 1900, Paul Ehrlich, responsible for the antibody formation theory †¢ 1901, Karl Landsteiner, A, B, and O †¢ 1901-8, Carl Jensen & Leo Loeb, Transplantable tumors †¢ 1902, Paul Portier & Charles Richet, Anaphylaxis Historical Perspective (1 of 6 ) †¢ 1903, Nicolas Maurice Arthus, discovered the Arthus reaction of intermediate hypersensitivity †¢ 1903, Almroth Wright and Stewart Douglas observed the humoral component, opsonin †¢ 1906, Clemens von Pirquet, coined the word allergy †¢ 1907, Svante Arrhenius, coined the term immunochemistryHistorical Perspective †¢ 1910, Emil von Dungern, & Ludwik Hirszfeld, Inheritance of ABO blood groups †¢ 1910, Peyton Rous, Viral immunology theory †¢ 1914, Clarence Little, Genetics theory of tumor transplantation †¢ 1915-20, Leonll Strong & Clarence Little, Inbred mouse strains Historical Perspective †¢ 1917, Karl Landsteiner, Haptens †¢ 1921, Carl Prausnitz & Heinz Kustner, Cutaneous reactions †¢ 1924, L. Aschoff, Reticuloendothelial system †¢ 1926, Loyd Felton & GH Bailey, Isolation of pure antibody preparation †¢ 1938, John Marrack, Antigen-antibody binding hypothesis Historical Perspective 1936, Peter Gorer, Identification of the H2 antigen in mice †¢ 1940, Karl Landsteiner & Alexander Weiner, Identification of the Rh Antigens †¢ 1941, Albert Coons, Immunofluorescence technique †¢ 1942, Jules Freund & Katherine McDermott, Adjuvants †¢ 1942, Karl Landsteiner & Merill Chase, Cellular transfer of sensitivity in guinea pigs (anaphylaxis) Historical Perspective †¢ 1944, Peter Medwar, Immunological hypothesis of allograft rejection †¢ 1948, Astrid Fagraeus, Demonstration of antibody production in plasma B cells †¢ 1948, George Snell, Congenic mouse lines †¢ 1949, Macfarlane Burnet & Frank Fenner, Immunological tolerance hypothesisHistorical Perspective †¢ 1950, Richard Gershon and K Kondo, Discovery of supressor T cells †¢ 1952, Ogden and Bruton, discovery of agammaglobulinemia (antibody immunodeficiency) †¢ 1953, Morton Simonsen and WJ Dempster, Graft-versus-host reaction †¢ 1953, James Riley & Geoffrey West, Discovery of histamine in mast cells Historical Perspective †¢ 1953, Rupert Billingham, Leslie Brent, Peter Medwar, & Milan Hasek, Immunological tolerance hypothesis †¢ 1955-1959, Niels Jerne, David Talmage, Macfarlane Burnet, Clonal Selection Theory †¢ 1957, Ernest Witebsky et all. Induction of autoimmunity in animals †¢ 1957, Alik Isaacs & Jean Lindemann, Discovery of interferon (cytokine) Hi storical Perspective †¢ 1958-62, Jean Dausset et al. , Human leukocyte antigens †¢ 1959-62, Rodney Porter et al. , Discovery of antibody structure †¢ 1959, James Gowans, Lympocyte circulation †¢ 1961-62, Jaques Miller et al. , Discovery of thymus involvement in cellular immunity †¢ 1961-62, Noel Warner et al. , Disctinction of cellular and humoral immune response Historical Perspective †¢ 1963, Jacques Oudin et al. Antibody isotypes †¢ 1964-68, Anthony Davis et al. , T and B cell cooperation in immune response †¢ 1965, Thomas Tomasi et al. , Secretory immunoglobulin antibodies †¢ 1967, Kimishige Ishizaka et al. , Identification of IgE as the reaginic antibody Historical Perspective †¢ 1971, Donald Bailey, Recombinant inbred mouse strains †¢ 1972, Gerald M. Edelman & Rodney Porter, Identification of antibody molecule †¢ 1974, Rolf Zinkernagel & Peter Doherty, MHC restriction †¢ 1975, Kohler and Milstein, First monoclona l antibodies used in genetic analysisHistorical Perspective †¢ 1984, Robert Good, Failed treatment of severe combined immunodeficiency (SCID, David the bubble boy) by bone marrow grafting †¢ 1985, Tonegawa, Hood et al. , Identification of immunoglobulin genes †¢ 1985-1987, Leroy Hood et al. , Identification of genes for the T cell receptor †¢ 1986, Monoclonal hepatitis B vaccine Historical Perspective †¢ 1986, Mosmann, Th1 versus Th2 model of T-helper-cell function †¢ 1990, Yamamoto et al. Molecular differences between the genes for blood groups O and A and between those for A and B †¢ 1990, NIH team, Gene therapy for SCID using cultured T cells †¢ 1993, NIH team, Treatment of SCID using genetically altered umbilical cord cells Historical Perspective †¢ 1996-1998, Identification of toll-like receptors †¢ 2001, FOXP3, the gene directing regulatory-T-cell development †¢ 2005, Frazer, Development of human papilloma-virus vaccine Th e IMMUNE SYTEM What is Immunology? †¢ Study of the molecules, cells, organs, and systems responsible for the recognition and disposal of foreign (nonself) material †¢ †¦ ow body components respond and interact †¢ †¦desirable and undesirable consequences of immune interactions †¢ †¦ways in which the immune system can be advantageously manipulated to protect against or treat disease What is Immunity? †¢ Latin word â€Å"immunitas†, freedom from †¢ It refers to all mechanisms used by the body as protection against environmental agents that are foreign to the body. †¢ Can be either natural (innate or inborn) or acquired (adaptive) Function of the Immune System †¢ Recognize â€Å"self† from â€Å"nonself† †¢ Defend the body against nonself Physiologic function is to prevent infection and to eradicate established infections (sterilizing immunity) Key Characteristics of the Immune System †¢ Innate immunit y †¢ Primary response †¢ Secondary response and immunologic memory †¢ Immune response is highly specific †¢ Immune system is tolerant of self-antigens †¢ Immune responses against self-antigens can result in autoimmune diseases †¢ Immune responses against infectious agents do not always lead to elimination of the pathogen (HIV/AIDS) Major Principles of Immunity (immune response): Elimination of many microbial agents through the nonspecific protective mechanisms of the innate immune system. †¢ Cues from the innate immune system inform the cells of the adaptive immune system as to whether it is appropriate to make a response and what type of response to make. Major Principles of Immunity (immune response): †¢ Cells of the adaptive immune system display exquisitely specific recognition of foreign antigens and mobilize potent mechanisms for elimination of microbes bearing such antigens. The immune system displays memory of its previous responses. à ¢â‚¬ ¢ Tolerance of self-antigens. Cells of the Immune System †¢ Lymphocytes – occupy the central stage; determines the specificity of immunity †¢ Dendritic cells (DCs) & Langerhan cells †¢ Monocyte/macrophages †¢ Natural killer (NK) cells †¢ Neutrophils †¢ Mast cells & Basophils †¢ Eosinophils †¢ Epithelial and stromal cells – provides anatomic environment (secretion of critical factors that regulate migration, growth and homeostasis) Lymphoid Tissues and Organs Primary Lymphoid Organs Sites where pre-B and pre-T lymphocytes mature into naive T and B cells in the absence of foreign antigen; †¢ Fetal Liver, Adult bone marrow, and thymus The INNATE IMMUNE SYTEM INNATE IMMUNE SYSTEM †¢ relies on germ line-encoded receptors to detect a limited set of microbial structures that are uniquely associated with microbial infection †¢ not a function of a single defined physiologic system; rather, it is a product of multiple a nd diverse defense mechanisms Modules of the Innate Immune System †¢ Surface epithelium The phagocyte system – critical for the defense against both intracellular and extracellular bacteria as well as fungal pathogens; aided by opsonins †¢ Acute phase response and complement – variety of secreted proteins that function in the circulation and in tissue fluids; secreted by the hepatocytes in response to the inflammatory cytokines IL1 and IL-6 Modules of the Innate Immune System †¢ Natural killer (NK) cells are specialized in the elimination of infected host cells and in aiding defense against viral and other intracellular infections through production of cytokines(IFN-? ; regulated by type I interferons (IFN-? /? ) †¢ Mast cells, eosinophils, and basophils are specialized in defense against multicellular parasites, such as helminthes; regulated by several cytokines, including IL-4, IL-5, IL-9, and IL-13 Strategies of Innate Immune Recognition 1. Recog nition of microbial nonself – referred to as pattern recognition, based on the recognition of molecular structures that are unique to microorganisms and not produced by the host 2.Recognition of missing self – based on the recognition of molecules expressed only on normal, uninfected cells of the host Targets of Innate Immune Recognition †¢ PAMPs (pathogen-associated molecular patterns) – molecular structures produced by microbial pathogens, but not by the host organism †¢ PRRs (pattern recognition receptors) – receptors of the innate immune system and represents targets of the innate immune system Targets of Innate Immune Recognition Examples of PAMPs include: (1) LPS of gram-negative bacteria (2) LTA of gram-positive bacteria (3) Peptidoglycans (4) Lipoproteins of bacteria (cell wall) (5) Lipoarabinomannan of mycobacteria (6) dsRNA produced by virus during the infection cycle (7) ? -glucans and mannans found in fungal cell wall Receptors of th e Innate Immune System †¢ Broad categories of PRRs: (1) PRRs that signal the presence of infection; expressed on the cell surface or intracellularly Categories of gene products: a. proteins and peptides that have direct antimicrobial effector functions (antimicrobial peptides and lysozyme) b. nflammatory cytokines and chemokines (TNF, IL-1, IL-8) c. gene products that control activation of the adaptive immune response (MHC, CD80/CD86, IL-12) Receptors of the Innate Immune System †¢ Broad categories of PRRs: (2) Phagocytic (or endocytic) PRRs; expressed on the surface of macrophages, neutrophils, and dendritic cells(DCs) (3) Secreted PRRs (mannan-binding lectin and peptidoglycan-recognition proteins Function: a. activate complement b. opsonize microbials cells to facilitate their phagocytosis c. ccessory proteins for PAMP recognition by transmembrane receptors (TLR) Receptors of the Innate Immune System †¢ Toll-like Receptors – comprise a family of type 1 transm embrane receptors characterized by leucine rich repeats (LRRs) in the extracellular portion and an intracellular TIR (Toll/IL-1 receptor) domain; grouped into two classes: (1) TLRs 1, 2, 4, 5, and 6 are expressed on the plasma membrane and detect bacterial and fungal cell wall components; (2) TLRs 3, 7, and 9 are expressed in endosomal compartments and recognize viral nucleic acidsToll-like receptor 4 (TLR4) †¢ expressed predominantly in the cells of the immune system, including macrophages, DC, neutrophils, mast cells, and B cells †¢ also expressed on endothelial cells, fibroblasts, surface epithelial cells, and muscle cell †¢ Signal transducing receptor for LPS, heat sensitive protein associated with the cell walls of MTB †¢ Together with CD14 shown to mediate responsiveness to the fusion (F) protein of RSVToll-like receptor 2 (TLR2) †¢ Involved in recognition of LTA and peptidoglycan from gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprot ein, mycobacterial lipoarabinomannan, a phenol-soluble modulin from S. epidermidis, zymosan of yeast cell walls, and lipoglycosylphosphotidylinositol T. cruzi †¢ Also shown to recognize two kinds of atypical LPS: L. interrogans and Porphyromonas gingivitis Toll-like receptor 3 (TLR3) Receptor for dsRNA †¢ Can mediate responses to poly(IC) †¢ Expressed on DCs, macrophages, and surface epithelial cells, including instestinal epithelium †¢ Also expressed in CD8+ DCs Toll-like receptor 7 (TLR7) †¢ Involved in viral recognition and both detect nucleic acids together with TLR9 †¢ Recognizes viral ssRNA (derived from RNA viruses); TLR9 (unmethylated DNA derived from DNA viruses) †¢ Expressed primarily on plasmacytoid dendritic cells †¢ Activated by small antiviral compunds, e. g. imiquinoid †¢TLR7-mediated recognition takes place inside the late lysosomes Toll-like receptor 9 (TLR9) †¢ Involved in the antiviral host defense; especially on r ecognition of DNA viruses (HSV) †¢ Expressed in type-I INF-producing plasmacytoid DCs Phagocytic Receptors †¢ Scavenger receptors – cell-surface glycoproteins that are defined by their ability to bind to modified LDL †¢ Macrophage Mannose Receptor (MR) – type I transmembrane protein expressed primarily in macrophages; involved in phagocytosis of bacterial (MTB, P. eruginosa, K. pneumonia), fungal (S. cerevisae, C. albicans), and protozoan pathogens (P. carinii) Cells of the Innate Immune System †¢ Macrophages – most central and essential functions and have multiple roles in host defense (e. i. â€Å"housekeeping functions†); in red pulp of the spleen, it phagocytose and remove from circulation senescent RBCs †¢ Neutrophils †¢ Mast Cells – best known effectors of allergic response; protective role is by rapid production of TNF-? nd leukotriene B4 (neutrophil recruitement) Cells of the Innate Immune System †¢ Eosino phils – found primarily in the respiratory, intestinal, and genitourinary tracts; contains cationic effector proteins toxic to parasitic worms; poor phagocytes †¢ Dendritic Cells – immature DCs reside in peripheral tissues and are highly active in macropinocytosis and receptor-mediated endocytosis; expresses PRRs and TLRs; have roles in the initiation of adaptive immune response Cells of the Innate Immune System Suface Epithelium – lines the mucosal surfaces of the intestinal, respiratory, and genitourinary tracts provide an important physical barrier The Effector Mechanisms of the Innate Immune System The Major Categories of Antimicrobial Effector Enzymes that hydrolyze components of microbial cell walls Antimicrobial proteins and petides that disrupt the integrity of microbial cell walls †¢ Lysozyme †¢ Chitinases †¢ Phospholipase A2 †¢ †¢ †¢ †¢ †¢ BPI Defensins Cathelicidins Complement Eosinophil cationic protein Mi crobicidal serine proteasesProteins that sequester iron and zinc Enzymes that generate toxic oxygen and nitrogen derivatives †¢ Seprocidins †¢ Lactoferrin †¢ NRAMP †¢ calprotein †¢ Phagocytic oxidase †¢ Nitric oxide synthase †¢ myeloperoxidase The Effector Mechanisms of the Innate Immune System †¢ Lysozyme – a. k. a. muramidase; degrades the peptidoglycan of some gram(+) bacteria; highly concentrated in secretions such as tears and saliva †¢ Chitinases – enzymes that degrade chitin; secreted by activated macrophages and presumably play a role in antifungal defenseThe Effector Mechanisms of the Innate Immune System †¢ Defensins – cationic peptides with a broad spectrum of antimicrobial activities against gram(+) and gram(-) bacteria, fungi, parasites, and some envelope viruses; kill microorganisms by forming pores in the membranes; divided into ? – and ? defensins †¢ ? -defensins – presynthesize d and stored in granules of neutrophils and Paneth cells of the small intestine †¢ ? -defensins – produced by epithelial cells and not stored in cytoplasmic granulesThe Effector Mechanisms of the Innate Immune System †¢ Cathelicidins – active against gram(+) and gram(-) bacteria and fungi; produced in neutrophils and stored as inactive proproteins in the secondary granules †¢ Serprocedins – comprise a family of cationic serine proteases with antimicrobial activity (neutrophil elastase, proteinase 3, cathepsin G, and azurocidin); exert its antimicrobial activity by either perturbation of microbial membranes or by proteolysisThe Effector Mechanisms of the Innate Immune System †¢ Lactoferrin, NRAMP, and Calprotectin – antimicrobial activities are due to the ability to sequester iron and zinc †¢ Lactoferrin – found in the secondary granules of neutrophils, in epithelial secretions (e. i. breast milk), in the intestinal epitheli um of infants, and in airway fluids; bacteriostatic (iron sequestration) and bacteriocidal (perturbation of microbial membranes) The Effector Mechanisms of the Innate Immune System NRAMP (natural resistance-associated macrophage protein) – integral membrane protein that functions as an ion pump in the phagocytic vacuoles of macrophage and neutrophils †¢ Calprotectin – member of the family of calciumbinding proteins; microbial activity is by chelation and sequestration of zinc ion ACUTE PHASE REACTANTS †¢ Soluble factors which are normal constituents that increase or decrease rapidly as produ †¢ Not a function of a single defined physiologic system; rather, it is a product of multiple and diverse defense mechanisms