The Autoimmune Hemolytic Anemia Biology Essay

The Autoimmune Hemolytic Anemia Biology Essay Autoimmunity is a disorder in which an organism loses its ability to recognize the self and non-self antigen, which would further lead to immune response against its own cells and tissues. Diseases that results from such abnormal immune responses are termed as autoimmune diseases. Autoimmune hemolytic anemia (AIHA) is an autoimmune disorder in which endogenous antibodies are directed against the red blood cells and upregulated leading to erythrocyte death. This review article focuses on the types of AIHA based on the classification of the antibodies and the temperature at which they are active i.e warm AIHA, cold AIHA and mixed AIHA , based on the age of its occurance i.e adult or pediatric AIHA, causes, diagnostic techniques, diseases which may cause AIHA as a secondary disorder, treatment and its aftereffects, current and future prospectives of its studies. Abbreviations: AIHA Autoimmune hemolytic anemia, WAIHA Warm autoimmune hemolytic anemia, CAIHA Cold autoimmune hemolytic anemia, RBCs Red blood cells, DAT Direct antiglobin test. INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a disorder in which the auto-antibodies are directed against the persons own red blood cells (1). It is a relatively uncommon but not a rare disorder. It has an estimated incidence of 1 to 3 cases per 100,000 population per year (1). There are three types of AIHA based on the temperature of activity of the autoantibodies i.e warm AIHA, cold AIHA and mixed type AIHA of which warm AIHA has the most common occurance (more than 70%) followed by cold AIHA (about 20%) and mixed type has least occurance (2). Further AIHA is classified on the basis of age of the patient suffering from the disorder i.e pediatric AIHA and adult AIHA. Pediatric AIHA is from the age group of 1 to 16 (or 18) years and mostly has no underlying causes (2). Adult AIHA is from 18 years and above and is mostly associated with some underlying primary diseases. Sometimes AIHA is caused due to administration of some drugs and is called drug induced AIHA. AIHA may also be of secondary or idiopathic type. The further description of the different types of AIHA is explained below. TYPES OF AIHA: Based on the temperature at which the auto-antibodies are active: Warm autoimmune hemolytic anemia (WAIHA) It the most common type of AIHA. Warm auto-antibodies are usually IgG. It is called warm autoimmune hemolytic anemia because the antibodies have their peak activity at 370C. IgG effectively binds to the FC receptor of phagocytic cells. Hence the destruction of RBCs takes place mostly by phagocytosis. IgG may or may not fix complement. Hemolysis of RBCs also takes place in spleen. WAIHA may be idiopathic i.e when there is no primary infection causing the disorder or secondary to lymphoproliferative diseases, autoimmune diseases, viral infections, immune deficiency etc (1)(2)(3)(6). Cold autoimmune hemolytic anemia (CAIHA) Cold auto-antibodies are usually IgM antibodies. Rarely IgG or IgA antibodies can act as cold auto-antibodies. It is so called because the antibodies have their peak activity at temperature ranging from 0-40 C (1)(2)(3)(6). IgM antibodies are potent classical complement pathway activators. Hence causes complement mediated lysis of RBCs. Paraxysmal cold hemoglobinurea a form of CAIHA, is caused by cold active IgG hemolysin. It was usually associated with some underlying diseases like syphilis, measles, mumps or other viral diseases (1)(2)(6). Mixed autoimmune hemolytic anemia Both warm auto-antibodies and cold auto-antibodies are present the blood. It is more fatal than the WAIHA and CAIHA. Detection and diagnosis is also more difficult than the earlier types (1)(2)(3)(4)(6). Based on the age of the patient suffering from the disorder AIHA is classified as: Pediatric AIHA Affects the age group of 1-16 years, with a higher incidence of occurance in the first four years of life (1). It may spontaneously resolve on its own. It shows a good response to the steroid treatment. It has a severe onset and less morbity rate. Males are more prone to pediatric AIHA (2). Adult AIHA Affects the age group of 18 years and above. It is more often associated with the underlying lymphoproliferative, autoimmune and infectious diseases. Treatment is steroid therapy or spleenectomy. Has higher morbity rate compared to adult AIHA because of the difficulty or inability in treating the underlying disease (2). Based on the cause of its occurance, following are the types of AIHA: Secondary AIHA It is mainly caused due to some underlying diseases like bacterial, fungal or viral infections. The primary underlying diseases that may cause secondary AIHA are Sjogrens syndrome (10), lymphoproliferative and autoimmune diseases (2).Treatment of the secondary AIHA would also include the treatment of the underlying primary disease, for its complete remission (1). Idiopathic AIHA Has no particular underlying causes like infections or primary diseases for its occurance. Mortality rate is comparatively less than that of secondary AIHA (1). Drug induced AIHA Cause of occurance are drug molecules that binds to the surface of the RBC membrane, acts as non-self antigens, thus inducing the autoantibodies against the RBCs and further leads to hemolysis (2). Examples of the drugs that cause drug induced hemolytic anemia are Ibuprofen, Diclofenac, L-dopa, Procainamide (6). CAUSES In majority of the cases AIHA is caused due to some primary underlying diseases like lymphoproliferative, autoimmune and infectious diseases (2). For example, after the M.suis infection in pigs, warm IgG autoantibodies are directed against the RBCs and destroys it. In this case actin was the active component that played a vital role in inducing an autoimmune response. Actin acted as a target protein for the autoreactive antibody during the acute phase of the M.suis infection. The autoreactive antibody production is induced by a misguided upregulation of the naturally occurring B cells specific for self antigens, appearance of previously cryptic antigens, occurance of altered self antigens, tolerance to self antigens due to molecular mimicry. The autoimmune epitopes (in this case actin) on the RBCs may be due to contact with the proteolytic enzymes. Cytoskeleton of the RBCs gets modified by the attachment and invasion of the infectious agent. Also the infectious agent causes damage to the RBCs making the hidden cytoskeletal proteins of the RBCs accessible for the circulating antibodies. Due to all the above mentioned reasons the antibodies recognizes them as non-self and elicit an immune response (3). There are several other causes which may lead to AIHA other than due to a primary infections. For example higher incidence of occurance of AIHA after allogenic hematopoetic stem cell transplantation in adult patients. Further studies proved that the chances of development of AIHA is more in patients with HSCT from unrelated donors and also that they develop chronic extensive graft versus host disease (GVDH). In such cases it was observed that AIHA was never the primary cause of death, rather it was due to infection of GVDH (5). In some rare cases, liver transplantation or solid organ transplantation leads to the development of AIHA (11)(14)(15). DIAGNOSIS: The destruction or removal of red blood cells from the circulation before their normal life span of 120 days is called Hemolysis. Hemolysis manifests itself as acute or chronic anemia, reticulocytosis or jaundice. Intravascular hemolysis refers to the destruction of red blood cells in the blood with the release of contents into plasma. This is then followed by direct membrane degradation and cell destruction caused by mechanical trauma from a damaged endothelium, complement fixation and activation on the cell surface. On the other hand, extravascular hemolysis refers to the removal and destruction of red blood cells with membrane alterations by the macrophages of the spleen and liver. The hemolysis can be categorized broadly into the following types: HEMOLYTIC ANEMIA HEREDITARY (6) ACQUIRED (6) ( Due to infections (6) Microangiopathic (6) Autoimmune (6) Autoimmune (6) Alloimmune (6) Drug induced (2) (6) Paroxysmal (1)(2)(6) Mixed (1)(2)(3) (4)(6) Cold (1)(2) (3)(6) Warm (1)(2) (3)(6) Immune complex or Auto-antibody (6) Drug absorption (hapten induced) (6) Delayed transfusion reaction (6) Acute transfusion reaction (6) Flow chart 2: Broad classification of autoimmune hemolytic anemia. Since all the above said categories of hemolytic anemias have many similar symptoms and expressions, efficient diagnostic techniques should be developed to detect the correct category of hemolytic anemia for its appropriate treatment. DIAGNOSTIC TESTING Basic diagnosis for hemolysis on the basis of laboratory and peripheral smear findings: Hematologic tests Reticulocytosis which is the normal response of the bone marrow to the peripheral loss of blood cells is an important characteristic laboratory feature of hemolysis. Checking for the presence of reticulocytosis can be used for diagnosis of hemolysis. Review of the peripheral blood smear with an assessment for pathognomic red blood cell morphologies (spherocytes or schistocytes) along with examination of WBCs and platelets is very important for the evaluation of any anemia (6). Chemistry tests Increased unconjugated bilirubin, increased lactate dehydrogenase, and decreased haptoglobin levels are characteristic feature of the distruction of RBCs and thus can be used for diagnosis of hemolysis (6). c) In addition to the above tests, urinary tests are also be performed (6) After diagnosis of the basic hemolysis, its etiology is determined by performing further diagnostic tests. This review article focuses on the diagnostic techniques specific for AIHA. Microspherocyte on a peripheral smear and positive direct antiglobin test (DAT) is a characteristic feature of AIHA (1). The direct antiglobin test ,is also known as direct Coombs test (8). It demonstrates the presence of antibodies or complement on the surface of red blood cells which is the hallmark of autoimmune hemolysis (8). In this technique, the patients red blood cells are mixed with rabbit or mouse antibodies against human IgG or C3. The test would give a positive result if an agglutination reaction between the patients antibody or complement coated red blood cells by anti-IgG or C3 is observed. RBC agglutination with anti-IgG serum indicates warm AIHA and RBC agglutination with anti-C3 indicates the cold AIHA. However further efficient and very specific diagnostic techniques should be developed to distinguish mixed AIHA and paraxysomal cold hemoglobinuria from the other types. Also the present diagnostic techniques many a times failed to give an errorless distinction between these two types of AIHA (4). The three types of drug induced anemia based on their mechanism of their mechanism of action can be detected by a positive DAT and its type can be identified by the intravascular or extra-vascular hemolysis that it produces (6). TREATMENT: Treatment mainly depends upon the type of AIHA i.e warm antibody type, cold antibody type, mixed antibody type or paraxysomal cold hemoglobinuria and also on the secondary or the idiopathic forms. The following are the treatment options for AIHA. However each treatment stratergies has its own advantages and disadvavtages. Warm antibody autoimmune hemolytic anemia i) CORTICOSTEROIDS The initial therapeutic agent used for treatment of WAIHA patients are the corticosteroids. There is a rapid onset of response. This therapy is usually maintained for 1-3 weeks, however sudden ceasation of therapy may result in prompt relapse of hemolysis. The adverse effects of long term use of corticosteroids as a therapeutic agent would include pulmonary aspergellosis, central nervous system hemorrhage (2), osteoporosis, avascular necrosis, susceptibility to infection, abnormalities in glucose and lipid metabolism and growth suppression in children (7).The gluocorticoids may inhibit antimicrobial activity of macrophages thus showing side effects when treated with it (2). In cases of pediatric anemia, prednisolone along with folic acid supplementation was used for therapy which showed a positive response in 81% of the patients (8). ii) SPLENECTOMY Splenectomy is mainly considered in patients who donot respond to the corticosteroid therapy. The main advantage of splenectomy is that it has a potential for a complete and long term remission. The adverse effect of spelectomy would include overwhelming postspelectomy infection (OPSI) which may result in serious morbity or mortality in a small percentage of patients after spelectomy (2)(7)(8). iii) IMMUNOSUPPRESSIVE DRUGS This is the third therapeutic option after both corticosteroid therapy and spelectomy. Examples of the immuno-suppressive drugs would include azathioprine, cyclosporine (8), rituximab (9)(11) etc. iv) DANAZOLE It is an attenuated androgen with good responses and comparatively lesser side effects (2)(7). v) INTRAVENOUS IMMUNOGLOBIN In patients who doesnot respond to the corticosteroids, it is used as a second line therapy. However, intravenous immunotherapy is expensive (2)(7). vi) PLASMA EXCHANGE Used for acute reversal of severe hemolysis along with other therapeutic agents. Cold antibody autoimmune hemolytic anemia The simplest and the possible way for reducing the severity of CAIHA is avoidance of cold. Plasma exchange showed a temporary benefit in a small percentage of patients. Any other therapeutic options involved more potential risks than probable benefits. Paroxysmal cold hemoglobinuria In most of the cases hemolysis terminates spontaneously and hence only supportive care is required. Sometimes transfusion of RBCs and corticosteroid therapy may have a positive impact on the treatment. Atmost care should be taken in case of secondary autoimmune hemolytic anemia i.e the underlying diseases like chronic lymphocytic leukemia, systemic lupus erytromatous, lymphomas etc should be treated for complete remission from AIHA (7).Combinational therapy was used in some cases of AIHA as secondary infection. Example, a case in which AIHA was found in association with Plasmodium vivax infection was treated with chloroquine and primaquine (for P.vivax infection), prednisolone and transfusion of least incompatible RBCs (for AIHA) (12). CONLUSION This review article gives a very short explanation about autoimmunity as a disorder. It mainly focused on auto-immune hemolytic anemia which is a subset of autoimmunity. The types of AIHA, causes, diagnosis and possible treatment stratergies were discussed. The future area of research under this topic is in finding out more efficient and specific diagnostic techniques to detect mixed and paroxysmal cold hemoglobinuria and treatment options with maximum results and minimum side-effects. Drugs like Bortizomib (13), Alemtuzumab (humanized monoclonal antibody targeting CD52 antigen) etc are still under research for the treatment of hemolytic anemia (16).

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With the BRIC countries now boasting more than a quarter of the world’s land area and more than 40% of the world’s population, it’s now considered inevitable that, in terms of size, speed, and directional flow, the transfer of global wealth and economic power is shifting from West to East. While it’s true that the BRICs offer some of the best investment opportunities, in terms of companies on the Fortune Global 500, the dominance of the BRICs is still far from today’s reality. The BRICs account for 58 companies among the Fortune Global 500. China stands head and shoulders above its rivals, with 37 companies on the list — a gain of nine companies from only a year ago. India has seven companies on the list, while Brazil has six and Russia has eight among the top 500. As pundit David Rothkopf observed, â€Å"Without China, the BRICs are ust the BRI — a bland, soft cheese that is primarily known for the wine that goes with it. † That said, even the Chinese companies on the list are hardly world beaters. Most are state-owned behemoths — not known for savvy or innovation. China’s second-biggest company is the creatively named â€Å"State Grid,† which ranks (a shocking) #15 in the world. And in 2009, you can still win be ts at almost any U. S. bar by betting someone that she can’t name a Chinese brand. Most of the Chinese companies on the list are like a 7†² 5†³ basketball player who can barely dribble the ball. Sure, it’s hard to ignore that he is an intimidating presence on the basketball court. But that doesn’t mean that you’d want to put him on your All-Star team. And it’s hard not to notice that the largest BRIC companies outside of China are largely based on natural resources — that is, â€Å"trust fund† countries pumping wealth from the ground. Take away the oil and steel industries, and Russia, India and Brazil all suddenly rank alongside Denmark, Austria, Ireland and Finland, with two Fortune Global 500 companies each. In terms of heft, the BRICs are still distinctively minor league. Brazil has one company in the top 100, Russia has two, India has zero, and China has five, totaling eight companies from the BRIC countries in the top 100. By this measure, the combined BRICs beat Britain alone — but not France. The Fortune Global 500: The World’s Surprising Economic Superpower? With all eyes looking toward the inevitable rise of the BRICs, it’s easy to spurn â€Å"Old Europe† as a global economic force. I’m guilty of it and I’ve spent my entire adult life here. There may be a handful of contrarians willing to say that China may not be all that it’s cracked up to be. But in over 15 years of active investment reading, I can recall only a single book that ever viewed Europe’s prospects in a positive light. Taken together, Europe’s economy is not only bigger than the U. S. economy, but its companies also rival the United States for corporate oomph. The economy of Germany, with a population of 80 million people, is the size of China’s, and it both exports more and boasts more companies among the Fortune 500 than its Asian rival (39). Throw in France (40), the United Kingdom (26), Switzerland (15), the Netherlands (12), and Spain (12), and the top six European economies boast an impressive 155 companies among the Fortune Global 500. Not bad for a combined population of 266 million — substantially less than the United States. Include the Scandinavian countries of Sweden, Norway and Denmark (combined population 19 million) landing nine companies on the list, and you skew the list even further in Europe’s favor. And unlike the BRICs, the European companies are distinctly top-heavy. Germany has 15 companies in the top 100, France, 10; Britain, six; Italy, five; Spain, three; and Netherlands, two, for a total of 41. That far outpaces the United States’ collective 27 companies on the list of the world’s 100 largest. The Fortune Global 500: A Welcome Correction Parsing the Fortune Global 500 rankings offers an important correction to what you hear in the mainstream business press. First, on a country level, U. S companies still dominate the global economy. And Japan, for all of its widely publicized problems, is still a powerful economic force. Second, China plays a much smaller role in the real world than it does in your email inbox. Third, and perhaps most surprisingly, taken together, the European companies outrank the United States — both in the top 100 and top 500 of the Fortune Global 500. Think of Europe as a single country and you suddenly realize that it trounced both the United States and China in the Beijing Olympics. And it wasn’t even close. Yet, consider how likely it would be that you’d ever subscribe to an investment newsletter that focused solely on investment opportunities in Europe. The broader lesson is that distinctions on national lines are increasingly irrelevant. A good example is Arcelor Mittal, the world’s largest steel-maker, which grew its revenues faster than Google did over the past five years. Arcelor Mittal is technically a Luxembourg-based company, run by an Indian, who lives in London. And I’d be surprised if you even knew (or cared) that the world’s #1 company, Royal Dutch Shell, is actually based in the Netherlands. For true multinationals, country of origin is so yesterday. And that’s the way it should be for you in looking at your investments. How to cite The World’s Surprising Economic Superpower, Papers

Local Area Networks Essay Research Paper LANs free essay sample

Local Area Networks Essay, Research Paper Local area network: Local Area Networks Local Area Networks besides called LANs have been a major participant in industrialisation of computing machines. In the past 20 or so old ages the universes industry has be invaded with new computing machine engineering. It has made such an impact on the manner we do concern that it has become indispensable with an ever-growing demand for betterment. LANs give an employer the ability to portion information between computing machines with a simple comparatively cheap system of web cards and package. It besides lets the user or users portion hardware such as Printers and scanners. The velocity of entree between the computing machines is illuming fast because the information has a short distance to cover. In most instances a LAN merely occupies one or a group of edifices located following to each other. For larger country demand there are several other types of webs such as the Internet. We will write a custom essay sample on Local Area Networks Essay Research Paper LANs or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page LANs systems can be defined and connected in many different ways. This is the ground for the standardisation for every one can hold a common land to get down from. The LANs described Herein are distinguished from other types of informations webs in that they are optimized for a moderate size geographic country such as a individual office edifice, warehouse, or a campus. The IEEE 802 LAN is a shared medium peer-to-peer communications web that broadcasts information for all Stationss to have. As a effect, it does non inherently supply privateness. The LAN enables Stationss to pass on straight utilizing a common physical medium on a point-to-point footing without any intermediate shift node being required. There is ever need for an entree sublayer in order to intercede to entree to the shared medium. The web is by and large owned, used, and operated by a individual organisation. This is in contrast to Wide Area Networks ( WANs ) that interconnect communicating installations in different parts of a state or are used as a public public-service corporation. These LANs are besides different from webs, such as backplane coachs, that are optimized for the interconnectedness of devices on a desk top or constituents within a individual piece of equipment. ( IEEE 802 Standard 1990 ) That is the standard definition for LANs by Institute of Electrical and Electronics Engineer commission 802. They are the commission used to put the criterion in craft and operations for technicians that set-up and perform care on LANs systems. And through all the proficient words what they are seeking to state is a LAN is a little country web that distributes information among computing machine in a little work environment unlike WANs that distribute information across planetary countries. It is normally the instance that LAN is owned by the same organisation that owns the affiliated devices. For WANs, this is less frequently the instance, or at least a important fraction of the web assets are non owned. This has two deductions. First, attention must be taken in the pick of LAN, since there may be significant capital investing ( compared to dial-up or leased charges for wide-area webs ) for both purchase and care. Second, the web direction duty for a local web falls entirely on the user. ( Local and metropolitan country webs 1997 ) . The inquiry now is you have a criterion and you have a connexion now how make you pull off the system to run cleanly? Networks use protocols, or regulations, to interchange information though a individual shared connexion. These protocols prevent hits of informations caused by coincident transmittal between two or more computing machines. Computers on most LANs usage protocols known as Ethernet or Token Ring. An Ethernet-linked computing machine cheques if a shared connexion is used. If non, the computing machine transmits informations. Since computing machine can feel an idle connexion and direct informations at the same clip, conveying computing machines continue to supervise their shared connexion and halt transmission if a hit occurs. Token Ring protocols base on balls a particular message called a item through the web. A computing machine that receives the item is given permission to direct a package of information or, if the computing machine has no package to direct, it passed the item to the following computing machine. ( Local Area Network Microsoft 2000 ) I know that it is complicated to understand, but for the existent user the package takes attention of most all of the direction for you. There are seven things that a LANs can make that you can non with easiness do with non-networked stand-alone systems. First sharing files A LAN enables many user to portion a individual transcript of a file stored on a cardinal file waiter computing machine. ( Introduction to Networking 1992 ) Transfering files A LAN enables you to copy files from machine to machine without holding to interchange floppy discs. ( Understanding Data Communications 1993 ) Access information and files A LAN enables anyone to run the accounting package, for illustration, or other application package from any of the workstations ( Introduction to Networking 1992 ) Share applications A LAN enables two people to utilize the same transcript of the Microsoft Word word processing plan at the same time ( Introduction to Networking 1992 ) Simultaneously cardinal informations into an application. Printer sharing and electronic mail with in the system. In decision the LAN has become indispensable in the modern work environment. The ever-growing demand for promotion has become a really profitable industry in its ego and it will go on to turn for a long clip to come. For now we are hardly planing the possibilities and uses for this new networking engineering.