Research on Immunology in Pregnancy

Research on Immunology in Pregnancy Investigative Review Nichole Gale The systems controlling the implantation and acceptance of the genetically and immunologically foreign fetus within the maternal body have often been likened to that of an organ transplant, or the growth of a cancerous tumour. The fetus is ‘like a transplanted kidney’, in the way that it is ‘genetically different from the host’ and ‘must evade immune defences to avoid rejection’ (Quinn 1999). The fetus inherits ‘foreign paternally derived histocompatibility genes’, meaning that ‘there is close contact between two genetically disparate individuals’ within the maternal body (Warshaw 1983, p63). Thus, the fetus is often referred to as an allograft, an allograft being a ‘graft transplanted by an individual that is not genetically identical, but of the same species’ (Marieb 1998, p789). The subject of fetus acceptance and tolerance within the maternal body has triggered great interest and controversy, and the sy stems that allow the acceptance of the fetus are complex and varying. Internal gestation has involved ‘a wide range of adaptations of animals for retention of young within the body of the parent’ (Warshaw 1983, p63). The human immune system includes many ‘cellular patterns that constantly exchange information’ to provide the body with the ability to ‘recognise foreignness or â€Å"non-self† in the form of antigens that enter our body’ (Warshaw 1983, p200). The recognition of antigens spark the inflammatory response, which must act with ‘minimum damage to the host’, in order to ‘eliminate the intruder’ (Warshaw 1983, p200). ‘Antigens are expressed by early human embryonic tissue’ (Loke 1978, p5), so it could be expected that the early human embryo would trigger an inflammatory response to rid the mother’s body of the ‘foreign body’. The exposure to non-self paternal antigens on the fetus ‘requires the adaptation of the maternal immune system to prevent the rejection of the allogeneic fetus without compromising the ability of the mother to fend off infection’ (Koch Platt 2003). The immune system consists of an innate (humoral) and an adaptive (cellular) component, in order to combat potential pathogens. It has been suggested that the main immune response triggered by the fetus is the adaptive response, where there is antigen representation, followed by response instruction by Helper T cells (Quinn 1999). In normal pregnancy, progesterone suppresses the humoral response. This has been used to explain why some autoimmune diseases, such as rheumatoid arthritis that are under humoral effect, often improve during pregnancy (Quinn 1999). Early work on immunological tolerance, conducted by Medawar, has been the foundation of further studies regarding the paradox of pregnancy. Medawar proposed three mechanisms that might together act to allow immune protection of the fetus. Two of Medawar’s earlier suggested mechanisms have since been proved to not actually ‘pertain during pregnancy’ (Aluvihare, Kallikourdis Betz 2004). The first hypothesis was that there was ‘segregation of the fetal and maternal circulations’, or that ‘a barrier might form between the mother and fetus, preventing exposure of the maternal immune system to allogeneic antigens expressed on fetal tissue’, leading to immunological ignorance (Koch Platt 2003). Medwar’s second hypothesis referred to the immunological immaturity of fetal tissue, and this allogenic immaturity acting to suppress the ‘expression of antigens that the maternal immune system might recognise as foreign and target for dest ruction’ (Koch Platt 2003). More recent research has tended to focus on Medwar’s third hypothesis, ‘that the maternal immune system somehow ignores potentially immunogenic fetal tissue’ (Aluvihare, Kallikourdis Betz 2004). Leading from this, there has also been much focus on ‘the means of inducing immune tolerance, the emergence of T cell suppression in mediating peripheral tolerance, the mechanisms mediating matererno-fetal tolerance and the role played by regulatory T cells in mouse and human pregnancy’ (Aluvihare, Kallikourdis Betz 2005). Koch and Platt (2003) suggest overlapping mechanisms such as ‘the formation of an anatomical barrier between mother and fetus, lack of maternal immune responsiveness, and a lack of expression of allogenic molecules by the fetus’ to account for the lack of fetal rejection. These mechanisms can help in beginning to understand how rejection is avoided, yet do not ‘completely explain how the fetus evades the maternal immune system’ (Koch Platt 2003). Harding and Bocking (2001, p238) state that it was originally proposed that the maternal-fetal interface was perhaps ‘an immunologically privileged site’, or that there was a ‘generalised suppression of maternal immune response’. Recent studies have challenged earlier theories such as these, and it has since been found that not only is there actual recognition of fetal alloantigens by the mother’s immune system, but that her body also responds to them. Fetal cells can be detected in maternal circulation, and ‘fetal tissue expresses MHC class I and class II and is antigenically mature’ (Aluvihare, Kallikourdis Betz 2004). MHC are major histocompatibility complex proteins coded for by genes. Class I are found on virtually all body cells, whereas class II displayed only by cells that act in immune response (Marieb 1998). The understanding of the immune events and mechanisms occurring at the maternal-fetal interface are likely to help in the understanding of the ability of the fetus to survive within the maternal body. Since Medawar’s proposed hypotheses, much focus has continued on fetal immune evasion mechanisms. As well as the three mechanisms above, suggested by Medawar, Koch and Platt (2003) explore a fourth mechanism, site-specific suppression. This refers to ‘local suppression of maternal immune responses at the maternal-fetal interface’ (Koch Platt 2003). ‘Localised suppression at the maternal-fetal interface during pregnancy negates the need for systemic immunosuppression which could threaten the well-being of the mother’ (Koch Platt 2003). Earlier studies suggested that trophoblast acted simply as a barrier between the mother and fetus, but it now seems that perhaps that it could have ‘diverse immunoregulatory properties controlling immune recognition, activation, and effector functions’ (Koch Platt 2003). It has been proposed by various studies that T cells play a major role in sustaining pregnancy. T cells are lymphocytes that mediate cellular immunity. ‘T cells with regulatory functions are potent suppressors of T cell responses and can protect tissues from T cell mediated destruction’ (Mellor Munn 2004). Observations in experimental pregnant mice have shown that while pregnant, they tend to ‘overproduce a kind of T cell that reins in other immune cells that might target the fetus’ (Seppa 2004). In one study, conducted by immunologist Betz (Seppa 2004) it was found that ‘pregnant mice have double to triple the number of CD4+ CD25+ T cells, also called regulatory T cells, in their blood, spleen, and lymph tissue as do female mice that are not pregnant’. It has also been shown that in humans, levels of circulating CD4+ and CD25+ cells ‘increases progressively at each stage in human pregnancy starting from the first trimester’ (Mello r Munn 2004). It has been ‘demonstrated that Tregs (T regulator cells) have a key role in regulating maternal effector T cell responses to fetal alloantigens’ as maternal effector T cells seem to ‘pose a potentially lethal threat to the developing fetus in the absence of regulatory function mediated by maternal Tregs’ (Mellor Munn 2004). It has also been speculated ‘that hormonal changes during pregnancy might provide one explanation for enhanced maternal Treg development during fetal gestation because pregnancy-associated hormones, such as progesterones, promote immunosuppression’ (Mellor Munn 2004). In regard to the suppression of maternal immunity, it is still ‘unclear if Tregs directly or indirectly inhibit effector T cell responses to fetal alloantigens’ (Mellor Munn 2004). To further test the cells’ effect on pregnancy, 30 female mice were mated with males. 15 out of the 30 mice had fully functioning immune systems, whilst the other 15 mice lacked the regulatory T cells. While a slightly higher than normal number of healthy female mice became pregnant, none of the mice lacking T cells were able to become pregnant. It seems that the role of T cells remains unclear, but that further understanding ‘of the role of regulatory T cells might also lead to new treatments for suppressing rejection of transplanted organs and inhibiting autoimmune reactions, in which a persons immune cells attack his or her own tissues’ (Seppa 2004). Mellor and Munn (2004) also suggest that the revelation that ‘maternal Tregs might help protect the developing fetus’ will have various implications, not only the possibility of offering alternative therapies to suppress immunity, but also possibilities for ‘improving pregnancy success rates in p atients with problematic pregnancies’. Again, the effect of T cells on autoimmune diseases is referred to by Mellor and Munn (2004), ‘increased systemic Treg function might explain why some autoimmune syndromes, such as rheumatoid arthritis, go into remission during pregnancy’. There has also been some discussion on the role of macrophages as immunoregulators of pregnancy. It has been claimed that most attention has focused on immune tolerance to the invading trophoblast and fetus, but Mor and Abrahams (2003) suggest that it is also important to ‘consider the function of the maternal immune system in the promotion of implantation and maintenance of pregnancy’. During implantation, apoptosis is necessary for ‘tissue remodelling of the maternal decidua and invasion of the developing embryo’ (Mor Abrahams 2003). It has been sited that apoptosis is active in the ‘trophoblast layer of placentas from uncomplicated pregnancies throughout gestation, suggesting that there is a constant cell turnover at the site of implantation necessary for the appropriate growth and function of the placenta’ (Mor Abrahams 2003). During implantation and invasion, it appears that a large number of macrophages are present in the maternal decidu a and in tissues close in proximity to the placenta. Originally it was thought the large numbers of macrophages were ‘to represent an immune response against the invading trophoblast’. Mor and Abrahams (2003) propose that this may not be the case, and that ‘macrophage engulfment of apoptotic cells prevents the release of potentially pro-inflammatory and pro-immunogenic intracellular contents’. Trophoblast cells carry proteins that are antigenically foreign to the maternal immune system. If these proteins are released as a result of cell death, it could initiate or accelerate immunological responses, ‘with lethal consequences for the fetus’ (Mor Abrahams 2003). Therefore, the appropriate removal of the intracellular components by macrophages may be critical for the prevention of fetal rejection. Mor and Abrahams (2003) conclude that the ‘field of apoptotic cell clearance is beginning to flourish, and many questions remain unanswered’. There is not just one mechanism involved in the immune regulation of pregnancy, but ‘multiple, diverse mechanisms that are likely sequential during gestation’ (Koch Platt 2003). As humans have a much longer gestation period, and a more invasive placental anatomy, it is sometimes difficult to test in laboratory animals and apply results to humans, as there may be different mechanisms. But it is believed that mechanisms involved with the fetus can be utilised in the studies of rejection following transplantation. As Koch and Platt (2003) suggest, ‘knowledge of the immunoregulatory mechanisms of both the fetus and stem cells will help immunologists understand general mechanisms of tolerance and immune evasion, and will prove invaluable in the fields of organ and cellular transplantation’. It has been suggested that both studies in stem cells and fetal rejection can benefit each other and help in understanding of systems involved. Pregnancy has also been said to have overall effects on the mother’s immune system and maternal defence against organisms. According to Creasy and Resnik (2004, p103) ‘numerous reports indicate that pregnant women have increased susceptibility to a variety of infections’. It is said that ‘there appears to be a trend toward increased susceptibility to viral infections, consistent with suppressed cell-mediated immunity and a relative decrease in Th1 (humoral/innate) responses during pregnancy’ (Creasy Resnik 2004, p103). However, it also added that ‘more recent carefully analysed data do not indicate that maternal immunity is substantially impaired, and most pregnant women are able to adequately respond to most infectious diseases’ (Creasy Resnik 2004, p103). Harding and Bocking (2001, p238) also claim that most studies tend to suggest that ‘maternal cell-mediated immunity is unchanged during pregnancy’. According to some experts, infertility, recurrent miscarriage, premature delivery and preeclampsia may all be linked to immunological abnormalities. It could be that some of these problems are due to ‘defective generation of Tregs during pregnancy’ (Mellor Munn 2004). It is possible that methods involving in vitro expansion of Tregs could help in treating spontaneous immune disease syndromes. Koch and Platt (2003) also suggest that both adult and embryonic stem cells might use mechanisms similar to the fetus in avoiding rejection. ‘Future discoveries in the field of reproductive immunology will help us understand not only immune regulation during pregnancy, but also how immune responses towards organ and cellular transplants might be controlled’ (Koch Platt 2003). References: Aluvihare, V., Kallikourdis, M., and Betz, A. 2004 ‘Tolerance, suppression and the fetal allograft’. Journal of Molecular Medicine. [Online], vol. 83, no. 2, pp 88-96. Available from: Medline. [11 October 2005]. Creasy R. Resnik R. (ed.) 2004. Maternal-Fetal Medicine, 5th edn., Saunders, Philadelphia. Harding, R., Bocking, A., (ed.) 2001. Fetal Growth and Development, Cambridge University Press, Cambridge. Koch, C. Platt, J. 2003 ‘Natural Mechanisms for evading graft rejection: the fetus as an allograft’, Springer Seminars in Immunopathology, [Online], vol. 25, no. 2, pp 95-117. Available from SpringerLink. [7 October 2005]. Loke, Y., 1978. Immunology and Immunopathology of the Human Fetal-Maternal Interaction, Elsevier Horth-Holland Biomedical Press, New York. Marieb. E., 1998. Human Anatomy and Physiology, 4th edn., Addison Wesley Longman, California. Mellor, A. Munn, D. 2004 ‘Policing pregnancy: Tregs help keep the peace’, Trends in Immunology. [Online], vol. 25, no.11, pp 563-565. Available from: Medline. [10 October 2005]. Mor, G. Abrahams, V. 2003 ‘Potential role of macrophages as immunoregulators of pregnancy’, Reproductive Biology and Endocrinology. [Online], vol. 119, no.1. Available from Medline. [11 October 2005]. Quinn, T. (1999), Immunology in Pregnancy; The Fetal Allograft, [Online], SIU Medical Library. Available from: http://www.siumed.edu/lib/ref/ppt/immunpreg/> [20 September 2005]. Seppa, N. 2004 ‘Some T cells may be a fetus’ best friend’, Science News, [Online], vol. 165, no. 8, p125. Available from: Proquest. [11 October 2005]. Warshaw, J. (ed.) 1983, The Biological Basis of Reproductive and Developmental Medicine, Elsevier Science Publishing Co., New York.

James Arthur Baldwin :: Biography James Baldwin Writers Essays

James Arthur Baldwin James Arthur Baldwin was born the first of nine children during 1924 in Harlem. His father, David, was a clergyman and a factory worker, and was the source of all of James Baldwin's fears. Baldwin's mother, Berdis, was a homemaker. Baldwin first started writing around age fourteen as a way of seeking the love which he was missing from his family life. During this time Baldwin attended Frederick Douglas Junior High School and DeWitt Clinton High School. During his school years, Baldwin won several awards for his writings. The joy that he felt from having others praise his work was overshadowed, however, by his father's disapproval of his non-Christian-oriented writing. James Baldwin's father was a very religious Christian who forced the church on young James. For a few years (from ages fourteen through seventeen), Baldwin was even a preacher. It was the bittersweet beauty of the church which Baldwin said turned him into a writer. Those few years of lost herding opened James Baldwins' eyes to the fact that he was in need of soul searching. Those years would not be in vain; the cadences of black religious rituals sound throughout his writings. Baldwin was also known to credit his years at the pulpit for morphing him into the writer he was to become. In 1942 James Baldwin was fed up with his father, fed up with the church, and (at that point) fed up with his life. The brassy, young Baldwin went into a restaurant, which he knew was designated for whites only, and demanded that he be served. When the waitress informed him that they did not serve his "kind" in that restaurant Baldwin picked up a glass and hurled it at her with all his pent up spite for the world. (That was the last straw for James Baldwin, he knew that he needed to leave his home since childhood for new experiences, and did so that very same day.) With a high school diploma under his belt James Baldwin moved to New Jersey and began working as a railroad hand. After two years in New Jersey, Baldwin moved to Greenwich Village. There, he first met Richard Wright (an African-American author whose strong protests against racial prejudice made him one of his generation's most important spokespersons) and began his first novel, In My Father's House. It was not until four years later that James Baldwin began to receive recognition, such as awards and fellowships, for his writings.

“Review of AIDS and Stigma’ by Gregory M. Harek

The current literature as of 1999 is reviewed regarding the stigma that attaches to people with AIDS (PWA’s and people with HIV (PWHIVs).   Ã¢â‚¬Å"Stigma† refers to discrimination and prejudice directed at PWAs and PWHIVs as well as those people associated with them or caregivers for them.This stigma has resulted in firings, evictions, and other forms of prejudice to people with AIDS and HIV. The existence of stigma has had a bad effect on the response to the AIDS crisis and could have a continuing affect on the various policies designed to assist PWAs and PWHIVs.Surveys throughout the world and specifically in the United States have indicated a negative attitude towards PWAs and PWHIVs by a significant majority of people.There are several possible reasons for the stigma. Many people believe PWAs and PWHIVs got the disease by their own actions and behavior. Others fear contracting the disease from any contact with PWAs and PWHIVs.Then there is the stigma associated wit h any disease considered that cannot be cured followed by the fear of contracting a contagious disease. Finally is the stigma associated with diseases or conditions affecting the victims’ outward appearance and capability.The stigma of AIDS has an impact on a personal level and with society and public policy.   For example, many people with AIDS or HIV do not get tested for fear of the stigma attached to the disease.In society the negative attitude has and continues to have an effect on public policy and public health issues and legislation. However, the situation has changed over the years with education, and with continued education discrimination and prejudice towards PWAs and PWHIVs will further decrease.I like this article for several reasons. It is well written and organized. It is written in a style and manner which is easy to read for the average student.There is no specialized language or information presented. Additionally there are no graphs or tables of statisti cs or lengthy quotations or references to other work. There is no detectible bias in the article. It is a very relevant topic today as much as it was when written. It is very thought provoking and informative regarding a variety of issues.The issue of stigma can have a very strong affect on the individual reader, as it has had on me. Unfortunately AIDS has spread to the point where more and more people know of someone afflicted with the disease or know someone who has been directly affected by the disease.With this increase comes the awareness of the stigma associated with PWAs and PWHIV, and the likelihood that someone we know has suffered from discrimination or prejudice.There is an â€Å"association† effect as well, when there is a similar prejudice, discrimination or fear of people who take care of or are related to PWAs and PWHIVs. The information presented in the article cannot help but make the individual aware of the issue if he or she is not already familiar with the disease, and adds knowledge to those who are familiar with it.Additionally, it makes the individual, and me, question whether or not I harbor any prejudice or discrimination and if so how I exhibit it. This article is very good at making me look past myself to broader issues, as well as to look inside myself for attitudes I should question.I particularly like the method in which the causes of stigma are presented. It is particularly helpful in examining whether or not I believe in any of the reasons or use them as an excuse. It is also helpful in realizing the fallacy of many of the reasons.The first reason presented seems very irrelevant, as regardless of how someone contracted AIDS or any disease should have no bearing on attitude, although for many people religious belief may be a factor that cannot be easily ignored.The second reason, fear of contracting the disease, was a personal fear of mine until I became aware of the fact that it cannot be contracted by casual contact. Com mon sense tells us that we are probably around PWAs and PWHIVs daily without knowing it, and there has been no cases caused by casual contact.The third and fourth reasons are the ones that I have the most difficult time with, as I have always been uncomfortable around people with life-threatening or terminal diseases, or people who obviously show outward signs of the disease.I believe many people have this discomfort, and probably always will, as it can be very difficult to interact with such strong issues â€Å"in the background†. However, what is important is to keep the discomfort into becoming a prejudice or source of discrimination.I really liked the article because it is hopeful. It has taken a very difficult and depressing topic but presented it a manner which gives optimism to the issue. It does this by making the reader aware of the reasons, and on reflection, realizes all of the reasons can be lessened or removed with awareness and education.It has made me more awar e of a very significant issue in society today. It has also caused me to reflect on my personal attitude and actions. It has clearly presents a thesis and evidence in an easy-to-read manner.I like it because it stresses how common and damaging prejudice and discrimination is, and the role of education in overcoming prejudice, which is important not just for PWAs and PWHIVs but for everyone. Finally, it is an article I can use as reference to anyone who can benefit from the information or may be interested in the issue.Works CitedHarek, Gregory M. â€Å"AIDS and Stigma†. American Behavioral Scientist, Volume 42, No. 7, April 1999. 1102-1112.

Is Freedom Mere License or Wisdom to Choose What Is Right for Oneself - Free Essay Example

Sample details Pages: 3 Words: 985 Downloads: 6 Date added: 2017/09/14 Category Advertising Essay Did you like this example? Freedom is the right to make important decisions for yourself and your family without coercion or fear of retaliation. Freedom is the right to take advantage of the various opportunities out there in the world to better your life. Freedom is the right to express your opinion and fight for what you believe in, as long as you do not bring harm to anyone with an opposing point of view. â€Å"Man is born free but everywhere he is in chains† said Rousseau. This statement of his inspired the romantic poets like Shelley and Keats to glorify individual freedom. It also paved the way for French Revolution and the American War of Independence. Now the question is what actually freedom is? So to understand the true principles of freedom, one must understand the scope of the word. Freedom means capacity to exercise one’s own choice or free will and act upon it. It is nothing but the condition of being free of restraints and the right to unrestricted use or full access to many privileges which one is entitled to. Freedom is the right to make important decisions for yourself and your family without coercion or fear of retaliation. Don’t waste time! Our writers will create an original "Is Freedom Mere License or Wisdom to Choose What Is Right for Oneself?" essay for you Create order Freedom is the right to take advantage of the various opportunities out there in the world to better your life. Freedom is the right to express your opinion and fight for what you believe in, as long as you do not bring harm to anyone with an opposing point of view. The true meaning of freedom can be defined as the right given to an individual, when he has the right wisdom, to do what ever he wishes to do but with a care that he does not dominate the wishes and desires of other person. So freedom doesn’t mean that one can do anything he wants to do or have everything he wants to have. Freedom has its own limitations. A G Gardiner’s essay â€Å"On the Rule of the Road† clearly justifies this statement. A fat lady was moving in the middle of the road saying that she has the freedom to go as she likes. The bus driver said he would run his bus over her. This example shows that one’s freedom should not interfere without another freedom. Similarly, a child is free to go to lessons or play because that is his own affair. We cannot dictate him to do anything which he does not wish to do. He is at liberty to decide what to do and what not to do. But at the same time he has no right to blow a trumpet when others want to study or sleep. So freedom does not mean license for the child to interfere with others freedom. In other words, freedom is the ability to make choices, regardless of the consequences, as long as the consequences do not affect anyone around us. The dictum â€Å"Live and Let Live† contains a very sound advice. We must tolerate others, refrain from interfering with others and reconcile ourselves to the ways of living of others. One should not try to impose one’s own ideas and modes upon others. When we believe in freedom we should also believe in the freedom of others. Everyone has the right to decide how he should behave and lead his life. Every individual is different and hence we cannot expect uniformity in the modes of our lives. We should respect the way of life of our others just as we expect them to respect our own way of life. One cannot lay laws about freedom and license. License means excessive freedom or permit and free from restraint. So license is freedom to deviate deliberately from normally applicable rules or practices especially in behavior or speech. Freedom over-extended turns into license. When it comes to freedom and license there is no Bible or Encyclopedia to consult any final authority. The boundary of giving freedom and license has to be judged by the individual parent. For instance, though we believe in giving freedom to our children still we curb their freedom at times because never to say no is to bring up a spoiled child who will be incapable of facing the realities of life. Such a kid will grow up to expect the world to provide everything he wants. Freedom and the limitations on freedom are both needed to live peacefully. Freedom is synonym of license which means restrictions. Absolute freedom cannot be achieved because when you take away limitations you take away a freedom. But at the same time, without rules governing our society, people would be able to do what they want to each other with out fear of punishment. It is the fear of punishment which restricts or checks the crime rate and so absolute freedom should not be given to anyone in the interest of the society. So freedom with some restrictions is absolutely essential as freedom coupled with some limitations promotes development of an individual who will be enriched with wisdom. And wisdom is experience, knowledge and common sense together, along with the power of applying them. It is the ability to think and act wisely. Wisdom is not taught in school and it cannot be bought. So a person who has wisdom does not jump to rash conclusions, but makes an educated decision based on the information or intelligence provided. When freedom and wisdom are clubbed together it means freedom of choosing what is right for us. On the whole, it may be said that equating freedom with license is highly absurd. Freedom stands for creativity whereas license spells doom and disaster. Freedom leads to wisdom which stands for moral values of life. In short, freedom does not mean license, but the wisdom to choose what is right for one self which makes him a better responsible citizen. 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