The Recognition of the Death of Cells by Apoptosis - Dissertation Example

? BIOCHEMISTRY Task: Outline i. Introduction ii. iii. Apoptosis iv. Death of mature immune cells v. Apoptosis in clinical immunology vi. Conclusion References The biochemistry of apoptosis Introduction The recognition of the death of cells by apoptosis has existed for many years. The full explanation of the biochemistry of apoptosis, that has surfaced for years is nothing short of astonishing, and has changed our perceptions about diseases. Usually, the categorization of ailments has been in accordance of the organ system they affect. Nevertheless, it is useful for researchers to discover the system responsible for the diseases. In this respect, the simple reclassification according to whether ailments are connected with too little or more cell death is very enlightening. Abstract All multicellular animals experience the happening of apoptosis. The fading of cells is mainly seen in the growth and exclusion of redundant cells. It is an essential cellular defense against viral infectivity. Such death results during the action of cytotoxic T lymphocytes or tumor necrosis. Apoptosis furthermore plays an essential function in medical immunology. They play this part by deleting the cells that distinguish self-antigens during the maturation of the immune mechanism to remove purposely those cells that harm the organism by activating autoimmune and autoreactive systems. Apoptosis Apoptosis is distinguished by different morphological transformations plus membrane blebbing, nuclear compression, manifestation of apoptotic antibodies, and ologonucleosomal DNA (Sluyer, 2005, p 190). The inductions of apoptosis involve action of aspartate particular cysteine proteases or caspases, which can inactivate aimed substrates by proteolytic cleavage (Sluyer, 2005, p 190). The initiator caspases go through autocatalytic processing, and then cleavage and stimulate the downstream executioner caspases that coordinate cell removal. Other identified targets of caspapes are the polymerase and DNA relying protein kinase. The indication of the participation of caspase in apoptosis is seen in the baculovirus protein p35, which hinders cysteine proteases and obstruct activation of apoptosis. Genetic and biochemical facts show that apoptosis progresses by two main cell killing ways. The first one is the fundamental pathway, which entails mitochondrial membrane permeability (Sluyer, 2005, p 190). Besides, there is the production of some apoptogenic things like cytochrome-c. Secondly, an essential apoptotic signaling path arises mainly through caspase-8 stimulatuion (Sluyer, 2005, p 190). According to some researches, some drugs trigger apoptosis by mitochondria –dependant and mitochondria-independent way. Nevertheless, these indicators join to common downstream paths. The anti-MM agent usually causes the changes in mitochondrial transmembrane potential and the stimulation of caspases. Nonetheless, these agents stimulate differential upstream signaling paths. Additionally, some anti-MM agents down normalize signaling pathways interconnected with growth, anti-apoptosis, and angiogenesis. This suggest that the hindrance of apoptotic signaling is linked with the control of development and survival signaling, and that curative strategies merging two or more agents that concurrently aim these signaling pathways will have enhanced anti-MM actively (Figg & Folkman, 2008, p 34). There should be the consideration of the biochemistry of apoptosis from two angles. The initial one is the alteration of molecules, which can remove a cell or protect it from apoptosis. The second one is changes in the molecules, which occur in the cell throughout apoptosis. Knowing the dissimilarity between the two is usually difficult since the biochemical stage at which at which a cell is permanently committed to undergo apoptosis is not known (Gupta, 2009, p 12). Death of mature immune cells The numbers of mature immune cells change in accordance of the needs. The quantity of cells is influenced by the interaction of the entire mechanism of the immune system. Ordinary hemopoietic cells require cytokine viability factors, which comprise of the colony invigorating things and interleukins, and undergo apoptosis after being withdrawn. Researches have proved that, circulating T cells can endure for about 10 years, contributing to T cell memory, although most have shorter lifespan. Stimulation with bacteria surperantigens, divide ligation of CD4 and TCR molecules, or stimulation with cytokinase like IL-2 have been revealed to activate apoptosis in mature T cells under some conditions (kalden & Herrmann, 2006, p 6). After stimulation, the CD8 cells can start cytotoxicity in a number of aimed cells without becoming effete, although some die in the second encounter with the specific antigen. The need to finish a T cell reaction is done by the apoptosis of the IL-2 dependent stimulated CD8 cells, which are caused by the escalating level of IL-12. This is reflected in the apoptosis of lymphocytes from the patients who are affected by virus (kalden & Herrmann, 2006, p 6). When the adult humans produce more neutrophilis than monocytes, there is a sign of a continuous deletion of cells. The probable lifespan of polymorphonuclear neutrophilis is about one day. Unless there is the stimulation by things like bacterial products, they assume a senescent nature and experience apoptosis. Apoptosis causes the deletion of stimulated monocytes, unless the bacterial products or the proiflammatory cytokinase rescue them. Senescent megakaryotes too experience apoptosis. Therefore, cytokinase and other immune factors cause the regulation of the immune system by when the creation and segregation are stimulated. Moreover, the immune system is caused by the inflection of apoptosis (kalden & Herrmann, 2006, p 6). Apoptosis in clinical immunology Immune system affects a host of medical ailments. What is seen to be the ordinary immune action is considered in inflammation and graft elimination. Insufficient immune functions contribute to severe illnesses and cancer while over stimulation causes hypersensitivity and autoimmune ailment. Apoptosis occurring in, and stimulated by the resistance system is crucial in these disorders (Hoang-Xuan, Baudouin & Creuzot-Garccher, 2001, p 45). Resolution of inflammation shows the elegant function of apoptosis to limit the activities of neutrophilis. At the end of an inflammatory reaction, there is a decrease in pro-inflammatory lymphokinase and bacterial products, on which stimulated neutrophilis are reliant. Consequently, they experience apoptosis with concurrent membrane alterations, which identifies them to macrophages for phagocytosis before the lytic production of the toxic neutrophilis contents. If lytic production occurs, there will be the destruction of more tissues, which may result into unceasing inflammation and probably autoimmune ailment. One of the descriptions of apoptosis is the gradual necrosis, which is the feature of the active inflammation in persistent hepatitis of the autoimmune type. In such state, lymphocytes may be seen neighboring hepatocytes, and bodies are noticeably visible in the areas of gradual necrosis seen in stained biopsies (Hoang-Xuan, Baudouin & Creuzot-Garccher, 2001, p 45). The core purpose of the cellular immune system, certain T cells, is the control of viral contagions. Cells, which are affected with virus, are usually parts of viral proteins on the surface in connection with MHC molecules, which cause the occurrence of the CTL identification of the cell as unfamiliar. This is comes before the apoptosis and the removal of the infected cells (Griffin, 2005, p 224). There are some genes, which have directly resulted into the regulation of apoptosis of their host cell. The system is inclusive of Bcl-12 type activity of the Epstein Barr virus gene BHRF1, and hindrance of cystein proteases by the baculovirus gene p35 and the cowpox virus gene crmA. An extra family of viral proteins called apoptosis inhibitory proteins also restrains apoptosis possibly through hindering receptor signaling (Griffin, 2005, p 224). Hence, it emerges that viruses can control apoptosis to optimize viral reproduction. The HIV infectivity attacks the immune system by removing the CD4 aid cells (Griffin, 2005, p 224). Some mechanisms that relate to apoptosis are advanced. There is hope that the manipulation of apoptosis may hinder the immune insufficiency, if not eradicate the infection (Griffin, 2005, p 224). Tumor developments are cause by the overproduction of cells against the removal of cells. Many immune system malignancies are linked with the alteration in gene expression making the lymphoid and myeloid cells less vulnerable to apoptosis. The core function of the immune mechanism is to remove the outside attackers like infected cells, tumor cells and transplanted cells. This if followed by killing the foreign targets, usually by apoptosis, which results into a controlled environment friendly target cell death. Cytotoxic T cells stimulate apoptosis in their targets via an undefined mechanism, which may or may not engage membrane-lytic proteins like perforin. Other cytotoxic agents used by the immune mechanism like the killer cells, lymphokine stimulated killer cells, and cytokines like tumor necrosis factor stimulate apoptosis in their targets, while complement stimulates necrosis (Alvero, 2007, p 2). The many clinical circumstances in which the immune mechanism plays a major part, like viral infections, cancer, autoimmune ailment, and graft versus host illnesses, all involve the initiation of apoptosis. The role of apoptosis in immune function, and the authority of immune over infection, is presently inspiring the design of remedial interventions centered both on apoptosis regulation by the immune mechanism and on immune regulation by apoptosis (Alvero, 2007, p 2). Diseases connected with apoptosis The existing stability in the division and dying of cells usually influences the sustainability of liver homeostasis. If the stability is disturbed, the liver diseases can occur. For instance, extremely high cell removal may result into liver injury while very little cell death can make hepatocellular carcinoma to develop. Therefore, the sustainability of the steadiness between the division and the dying of cells is crucial. When the liver is injured, the hepatocytes, endothelial cells, and cholagiocytes are removed by apoptosis because of accumulation of cytokines like TNF and interferon. Deregulation of the apoptosis program is pathophysiologically involved in sharp and unceasing liver ailments, plus cholestasis, alcoholic, and non-alcoholic steatohepatitis. Fulminant hepatic failure is a liver illness, which is distinguished by the unregulated death of the hepatocytes, for instance, in people having serious Wilson disease. The interference with apoptosis can start the development cancer. Apoptosis can lead to unwanted cell removal, as with cells adjacent to neurons that have died from a stroke. The close cells that were deprived of oxygen die quickly, but the surrounding cells can dies at a slower pace due to apoptosis. The caspases are triggered by proteolisis of their undeveloped forms after their production in a dormant form called procaspases. Following the triggering, caspases start a chain of attacks against particular targets, making the cells to die. In some cancers, decreased apoptosis is the key cause of timorous developments, for instance early prostrate cancer. In such tumors, there is survival of cell, which should undergo apoptosis during the usual tissue homeostasis (Alvero, 2007, p 4). Apoptotic cells are also implicated in the commencement of autoimmunity. The gathering of cells in the late apoptosis is because of the poor apoptotic cells removal, and plays the central part in the development of systemic lupus erythematosus, rheumatoid arthritis and type I diabetes and in exacerbation of cystic fibrosis and chronic obstructive pulmonary disease. The escalation of the proportion between apoptotic cells and phagocytes can uphold inflammation and resistance (kalden & Herrmann, 2006, p 16). Neorodegeratide disorder like Parkinson’s illness, Alzheimer illness, and Huntington’s illness are typified by steady loss of various neurons. Some processes have been said to cause the cell removal in neurodegenerative ailments. The processes are accountable in the initiation of apoptosis (kalden & Herrmann, 2006, p 13). Systemic Lupus erythematosus is a common tissue disease that causes arthritis and immune complicated deposition in tissues. It is typified the growth of antinuclear antibodies, and also linked with a fault in apoptosis that cause intracellular components to be present to lymphocytes, as if they are foreign antigens, triggering the growth of antibodies against components of self cells (kalden & Herrmann, 2006, p 43). Peritonsis is a disease associated with apoptosis. The inhibition of caspase-1 accelerates the resolution of peritonitis that is triggered by the staphylococcus aureus. It is caused by the abnormal escalation of the speed of apoptosis of the peritoneal neutrophilis. Heart attack is also an illness that has connections with apoptosis. Apoptosis resulting from ischemia and reperfusion is the key contributing thing in various heart illnesses. Heart attack is cause by the high amount of cellular deaths (kalden & Herrmann, 2006, p 21-30). Conclusion The explanation of the cell biology and biochemistry of cell death has resulted into some of the vital breakthrough in the awareness of the autoimmunity in many years. Insight in the ways of cell death offers the understanding that can be translated into therapeutic action. There is possibility that additional basic discoveries in apoptosis will be uncovered, thus resulting into further insight and improved therapy of many human autoimmune problems (Carvaillon & Adrie 2008, p 209). Outline i. Introduction ii. Abstract iii. Toxins and poisons iv. How toxins and poisons work v. Toxicity vi. Acute toxicity vii. Chronic toxicity viii. Toxins and poisons in the environment ix. Sources of toxins and poisons x. Exposure routes of toxins and poisons xi. Symptoms of toxins and poisons xii. Effects of toxins and poisons xiii. Solutions to toxins and poisons xiv. Conclusion Toxins and Poisons Introduction Toxins and poisons are molecules, which can negatively affect living organisms. It is good to know that when any substance is in more than required concentration, it becomes harmful to a given living organism. Therefore, it is necessary to observe the dose level before administering substance or chemical is to a living organism because the dose is what determines the poison. Commonly, the words toxins and poisons are substance that can be detrimental to living organisms when given in small amounts; furthermore, a toxin has the same meaning as poison (Eiichiro 2011, p. 202). Their production can either natural or by artificial. The current society creates and utilizes thousands of substances, most of these substances being noxious implying that they are very harmful to living organisms; therefore, there should be regulation of its release to the atmosphere. Abstract Toxins and poisons are very unsafe to human body. This is so because they lead to disruption of different body functions, they can cause extreme complications to human body and lastly it can cause death in some living organisms. Additionally, toxins and poisons affect the speed of body organs by either slowing them or making them faster than their regular pace. In toxins and poisons, toxicity, acute toxicity and chronic toxicity plays a big role. In environment, toxins and poisons are either naturally formed or manmade. Other sources of these chemicals, which encompass; medicines, improperly cooked food, detergents equally exist. Toxins and poisons have three main ways through which they get themselves into human body. These methods are; ingestion, absorption and inhalation. When these chemicals access the body, they may result to some symptoms and sometimes results to death. Toxins and poisons These substances or chemicals may bring about death or illness in living organisms. Taking of these substances can lead to dysfunction in human body or any given living organism. Poisons are the same as toxins and these words are interchangeable. Toxins and poisons are naturally formed or be formed by man. Natural poisons includes fungi produced ones, bacteria, plants, animals etc. and the natural happening arsenic, lead, copper etc. while the man-made toxins and poisons includes elements manufactured in large industries by man. Toxicology is the investigation of poisons (Lyle, 2008, p.229). People respond in different manners to toxins and poisons, and it is seen that children can be more vulnerable compared to adults. When one is very sensitive to a given toxin or poison, he is oversensitive to that substance. Mostly, the introduction of people to these toxins and poisons can be through the daily intake of water, the food that they eat and it can be from the atmosphere. How toxins and poisons work When organisms take toxins and poisons, firstly it affects the speed of several body functions; mostly the speed increases e.g. the rate of heartbeat and sweating increases or decreases to a point whereby they become zero. For example, poison from parathion insecticide increases the sweating rate. This is so because when this poison gets into human body, the enzymes are inactivated. Immediately this process occurs, the cellular shape changes increasing the nerve activity and this leads to physiological effect bringing about signs of that toxin and poison. In my case, one can realize the resultant features in sweat glands (Kent, 2009, p. 251). Toxicity Every chemical can be poisonous, and the determination of this can be the quantity of dose intake. When the dose is more than the required, the chemical will cause complications to the organism (Reese, 2010, p. 13). Toxin and poison exposure can be through inhaling, result from skin absorption, and be through ingesting and finally injecting an organism. Contamination is the lesser contact to these chemicals whereas more contact is poisoning. When these substances are present in the environment, we refer to it as contamination. Acute Toxicity Peoples’ reaction when in contact with toxins and poisons varies from death, disruption of tissue, irritation or the general function of an organism is lost. When these reactions occur within a short period of contact with toxins and poisons of high dose, then this situation is acute toxicity (Reese, 2010, p. 13). An example is the LD50, which focuses on required toxins and poisons to exterminate given organisms within a short period. Chronic Toxicity When the toxin and poison effect appears after longer period of contact with lesser concentration compared to the one used in acute poisoning, it is chronic toxicity (Reese, 2010, p. 14). Chronic toxicity can have negative effects to human, e.g. it can culminate to the development of birth defects, unplanned abortions, cancer and damage to organs. Because of their slowness and taking time to develop, chronic toxicities diagnosis turns out to be a problem compared to acute toxicities. For children, there are many household chemicals, which can be sources of chronic toxicity for example detergents, cosmetics, art supplies and medication products. In the Environment Most of the toxins and poisons that are found in the environment e.g. metals are naturally formed and they are the main cause of environmental pollution (Shabecoff, 2010, p. 3). When these metals, for example lead, copper, arsenic etc. are highly concentrated, there is increased possibility of soils contamination in that area and this will lead to plant contamination. When there is plant infectivity with these elements, they pose dangers to the cattle’s that depend on them. In the environment, most of the toxins have their sources in either animals or plants. Animals produce toxins throughout their animal kingdom for defense purposes or enhancing their means of obtaining preys. Those animals that are proficient in producing poisons are in two groups, which include the venomous and poisonous animals. Venomous animals’ toxins are in extremely generalized secretory glands and when in contact with human being, it leads to being bitten or pricked. Poisonous animals contain dissimilar tissues with toxins, which are harmful to human beings. Example of the Venomous animals comprises of several types of snakes that can transfer hazardous poisons to human. Effects of snake poisons depend on the snake venom, these effects may contain permeability of blood vessel changing, blood cellular mechanisms changing, developing clotting complications and nervous systems failing to work. Plants also act as sources of poisonous which acts as defense mechanisms against predators. For the previous decades, individuals have been using the plant toxins for medicinal use and hunting. Plant poisons and toxins can negatively affect human organs, lead to vomiting, dehydration and bloody diarrhea’s. In home settings, various products can turn out to be poisonous; these include households’ products like furniture polish, oils and fresheners. Most of these products are not effective when in small volumes but high volumes lead to stomach and mouth irritation, vomiting and diarrhea. Secondly, existence of both recommendation and over-the-counter medicines can be poisons in homes. Over doses of these medicines can result to drowsiness, agitation and stomach upsets. Thirdly, different homes contain dissimilar environmental poisoning such as lead, mercury and sulfur whose exposures are through absorption, inhalation and ingestion. High volume exposure to these environmental poisons and toxins can result to death. Lastly, plants and mushrooms within homes and outdoors are mostly attractive to children but on ingestion results to difficulty in breathing. Toxins and poisons sources Today, toxins and poisons are more in comparison to countless years back. This is so because their sources have extremely increased making them more available. They include; medical drugs and some treatments like chemotherapy. Tests in hospitals like X-rays, contains poisonous rays that can result to cancer. Foods, sugar and salt have chemicals that affect the general health of a human body. Finally, wrongly prepared grains and legumes, genetically modified products, cosmetics, detergents, pesticides, building materials like paints and varnishes (Hardman, Limbird, Goodman et al, 2001, p. 187) Major exposure routes for toxins and poisons Toxins and poisons mostly get into human body in three ways, ingestion, breathing and absorption (Christson, 2008, p. 72) and this can be through the lungs, skin and gastrointestinal tract. Due to the skins large surface and directly exposed to the environment, it turns out to be the common route of toxins and poisons which can either be from spills. Lungs are also among the routes because they offer toxins and poisons direct way to the bloodstream. Gastrointestinal tract ingestion can also lead to ingestion of toxins and poisons therefore exposing one to these chemicals. Example of such toxins includes the inorganic arsenic, which is very highly poisonous, naturally forming, odorless and colorless grey metal. This metals forms when arsenic elements chain with oxygen, sulfur or chlorine. Arsenic gets into human body through breathing, ingestion or skin absorption and a lot of it can cause death. Symptoms of toxins and poisons Toxins and poisons come out with so many different symptoms making it a major task when it comes to categorization. For example, when taken, they may culminate in the enlargement of pupils whereas others reduce them. They may also lead to drooling but others lead to dryness of the mouth. There are those that increases the heartbeats but others lowers is and finally, breathing rate can be increased by some and others lower it, there are some which are more painful while others turn out to be painless (Christison, 2008, p. 75) Example of such toxins and poisons includes lead metals, which gets into human body when an individual absorbs, swallows and inhales it in any available forms. This metal has negatives effects to almost all human body organs. In addition, the metal can bring about high blood pressures, affecting pregnant women by damaging the fetus brain or causing miscarriages. In children, higher volumes of lead can contribute to chances of disabilities, delay in development and finally, it can cause death. Effects of toxins and poisons on an organism/ human body Most of the toxin and poison effects turn out to be reversible meaning that they lack permanent effect to an organism though it may take a long time for it to recover completely. Conversely, there are some toxins and poisons which are irreversible in that once they occur, they are permanent (Eiichiro, 2011, p. 201). Both toxins and poisons can be of effect to one organ or they may end up affecting several body organs. The affected parts include; the spinal cord and brain, this comes because of lead, alcohol and poorly done medications thus resulting to headache, being depressed and experiencing dizziness. Secondly, ingestion of specific poisons and toxins like periwinkle and oleander may leads to heart infections, racing heart and sometimes-experiencing dizziness. Thirdly, the lungs can be affected when poisons like detergents, car refuse and kerosene fumes are inhaled and these can lead to coughing, chest problems, difficulty in breathing, wheezing etc. fourthly, the kidneys can be affected from medical toxins and poisonous thus leading to back pains, problem when urinating. Fifthly, toxins and poisons can have an impact on liver, resulting to some liver pain probably leading to swelling of the liver. Sixthly, they have an effect on the stomach and this mainly results from excessive taking of alcohol, bleach and detergent. These make one to vomit; have abdominal pain and cramps. Lastly, intake of toxins and poisons can lead to death. Solutions to toxins and poisons In order for one to avoid infectious from these toxins and poisons, he or she should be able to identify common poisons. Label all medicine, the required dose intake and follow instructions before use. He should avoid direct contact with dangerous chemicals, poisonous fumes and lastly, improve room ventilations and avoid contamination of food at home. (Kent, 2009, p. 253) Toxins and poisons that require labeling in homes includes household cleaners, pesticides, paints, cosmetics and automotive products. These toxins can get into human body via inhalation, ingestion and absorption thus resulting skin irritations, lung cancers, slowing the rate of decomposition, damaging liver and lungs. It is very impossible to get rid of the dangerous products in homes therefore, it is vital to follow the above given guidelines in keeping home environments safe to everyone. Conclusion From the above discussion on toxins and poisons, I came to conclusion that these chemicals are present in the environment making us to encounter them in day-to-day chore. Therefore, it is upon us to ensure that we know the best shielding measures that can be in use to handle them. For example, medicines from hospitals for treatment can end up intoxicating us. Therefore, it is upon to us to be observant and carefully follow instructions before taking any substance. List of References Alvero, A, (2007) Apoptosis and cancer: methods and protocols, Washington: Springer, Carvaillon, J & Adrie, C, (2008) Sepsis and non-infectious systemic inflammation: from biology to critical care, New York: Wiley-VCH Christison, R. (2008) a treatise on poison: in relation to medical jurisprudence, physiology and the practice of physics, Washington DC: Black Eiichiro, O. (2011) Chemicals of life and living, Springer publishing Inc, Washington DC. 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Shabecoff, A and Shabecoff, P (2010), poisoned for profit: how toxins are making our children chronically ill. With new information on what we can do. Chelsea Green Publishing: Boston. Read More