The Roles of Immunology
Immunology is a very important branch of the medical and biological sciences. Many diseases in humans and animals are caused by infections and disorders of the immune system. Understanding Immunology is, therefore, key to developing treatments to help manage and reduce the debilitating effects disease brings. Immunology also helps in diagnosing disease, by providing the basic tools for identifying aberrant changes in the body.
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Vaccination and global welfare
Our understanding of the immune system and how it works has improved remarkably over recent decades. International efforts to eradicate disease, through collaboration and exchange of information, have enabled exciting breakthroughs to occur. Several infectious diseases including smallpox, measles, mumps, rubella, diphtheria, tetanus, whooping cough, tuberculosis and polio are no longer a threat in Europe. This is due to the successful development and application of medicinal preparations known as vaccines.
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A vaccine is a substance that teaches the body to recognise and defend itself against infections caused by dangerous microbes or 'pathogens' such as bacteria, viruses and parasites. Vaccines provide a sneak 'preview' of a specific pathogen, which stimulates the body's immune system to prepare itself in the event that infection occurs.
Vaccines contain a harmless part of the pathogen responsible for causing a particular infection. The immune system mounts an immune response to the pathogen component (or antigenic component) of the vaccine and produces molecules, known as 'antibodies'. During this primary response, cells responsive to the vaccine proliferate both in order to manufacture antibodies specific to the provoking agent, but also, and more importantly, to form what are known as 'memory cells'. When a 'secondary' response (produced by a subsequent encounter with the relevant pathogen) is provoked, these memory cells become active, and are then quickly able to deal with the threat by producing sufficient quantities of antibody. Pathogens inside the body are eventually destroyed, thereby thwarting further infection.
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Global eradication of disease
Eradicating diseases on a global scale requires a major public effort. Disease eradication is currently defined as the extinction of a particular pathogen in the human population. This does not necessarily refer also to its elimination in the environment. Therefore, it is vital that control measures like vaccination still continue.
Vaccination is particularly important for people from poorer regions of the world, who suffer from many types of infectious diseases, due to lack of basic healthcare resources and treatment. Many charity organisations, such as the Bill & Melinda Gates Foundation, provide financial aid to support the global fight against ongoing and emerging diseases.
Smallpox is currently the only infectious disease that has been completely eradicated as a result of a global vaccination programme. (However, stocks of the virus which causes smallpox are still held in two laboratories in the US and Russia. This is because the virus may be needed for research purposes, if smallpox is ever used for bioterrorism purposes.)
Polio is the only other disease that is close to being eliminated due to vaccination efforts. Polio is reported to be widespread in only four countries in the world: Nigeria, India, Pakistan and Afghanistan. The World Health organisation hopes to eradicate polio globally by 2007. However, there are several obstacles that threaten its complete eradication. These include:
- Competition for resources from other important diseases.
- Local cultural suspicions of vaccine programmes affecting uptake.
- Potential complications arising from the vaccine itself, since the viral component of the vaccine can mutate after excretion into a more virulent form capable of infecting people once more.
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Meeting emerging and ongoing healthcare challengesImmunology is a dynamic discipline. Immunologists are constantly pushed to discover ways of defending the public against new and ongoing healthcare challenges.
Respiratory virus infections, such as influenza or 'the flu', are a particular challenge for immunologists. 'Flu' causes illness and death each year, particularly among the young and old. This is because different strains of the flu virus constantly emerge as a result of the virus's ability to change its structure and escape an immune response.
Flu vaccines are available and prevent or reduce the effects of influenza. However, their effects are not long lasting due to the different strains that arise on an annual basis.
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Avian influenza or 'bird flu' presents a worrying disease scenario for both humans and animals. The current threat to humans presented by this infectious and largely fatal disease of birds, comes from a strain of the Influenza A virus, known as H5N1, which infects poultry and other animals.
In 2003, the H5N1 virus changed into a new strain capable of infecting humans from animals, but not able to pass between humans. Over half of the people infected died (about 100 dead in total); and the disease has spread to a number of countries in Asia and Europe. Public health officials are concerned that it could develop into a pandemic that affects the globe.
The last influenza pandemic occurred in 1918 and killed between 20-40 million people. The worry is that this could also happen with the H5N1 virus if it manages to change into a form that allows human-to-human transfer of infection. Prevention control strategies are therefore in place, with plans to develop vaccines and treat those infected with anti-viral drugs.
The main challenge for Immunology is to develop a vaccine against the pandemic version of the virus - which itself has yet to emerge. It is a gamble as the current production of Influenza A (H5) vaccine, is based on the hope that the pandemic flu virus resembles H5N1.
A further hurdle to overcome relates to the actual production of the vaccine, which is usually made using chicken egg embryos. The virus H5N1 is so virulent that it kills the eggs in which it is grown, which slows down the production rate.
It is also most likely that developing countries would be hardest hit and probably last in line for any vaccine produced.
The MMR vaccine
The MMR Vaccine was developed to protect children from three highly contagious, yet vaccine-preventable diseases (VPD), i.e. measles, mumps and rubella. These diseases can lead to severe health consequences, including disability and death.
In 1998, a report was published suggesting that there was a possible link between MMR vaccination and the development of inflammatory bowel disease and autism in children. This report sparked a major controversy in the UK over the use of the triple MMR vaccine. It received huge media coverage and caused many parents to decide against immunising their children with the MMR vaccine.
The MMR controversy presents a unique risk management and communication challenge for the immunological community. The Government has tried to dispel the fear and convince the general public that the risk of MMR-vaccinated children developing inflammatory bowel disease or autism is extremely low. Indeed, studies continue to show that there is no link, and find that the scientific evidence, which suggests that there is a link, is very weak.
The problem is partly due to there being a certain degree of public mistrust in the Government, due to the inaccurate and misleading statements made about the risks associated with consumption of contaminated beef products from animals infected with BSE in late 1980s.
The greatest fear for clinical immunologists is that a reduction in MMR uptake could lead to a reduction in local immunity. This could result in large-scale outbreaks for diseases that have been, up until recently, effectively controlled.
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The mechanism by which human immunodeficiency virus (HIV; the virus that causes AIDS) evades the immune system is far from being completely elucidated. HIV poses a unique challenge for Immunology, which is currently unable to keep up with HIV's profound ability to change its structure and protective coating (which it uses to help mask itself from any antibodies produced by the immune system).
Immunology is crucial to developing an understanding of how AIDS evolves, but it is also vital to help find an effective remedy for it. Many drugs have been developed to block HIV's ability to reproduce.
HIV, like other viruses, is unable to grow and reproduce outside living cells. HIV must attach itself to, and then invade, a cell before it can replicate. Newly created viruses then destroy the host cell and seek out other cells to continue replication.
The HIV/AIDS research community have for the most part shifted their attention away from anti-retroviral drug therapy towards producing effective vaccines against HIV.
The biggest challenge facing immunologists is developing a vaccine that can help the immune system recognise the different strains of HIV. Although information from the Human Genome Project should help, and several vaccines are currently undergoing trials in humans, most researchers have accepted that it is likely to take years before vaccines for use against HIV/AIDS become available. Moreover, any vaccine produced will be unlikely to block infection completely. A useful vaccine would most likely reduce the amount of HIV in the body, where it is hoped HIV levels remain low and not develop into full blown AIDS.
Research into microbicides has also been proposed as a novel way tackling the battle with HIV/AIDS. By applying these anti-microbial agents at external sexual sites of the body, HIV is immobilised before it gains entrance into the body.
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Malaria is a parasitic disease caused by infection with a microbe that is carried in mosquitoes. The parasite, which has several different strains, is transferred to people when an infected mosquito bites them. Malaria is particularly common in people who live in tropical and subtropical countries. Partial immunity is known to develop in previously infected individuals, although this can take several years. Malaria can be fatal in vulnerable groups such as children and in tourists lacking natural acquired immunity.
Three main strategies exist to prevent and control the disease. This includes treatment with anti-malarial drugs, mosquito control and post-eradication monitoring. Anti-malarial drugs can also be taken as a prophylactic (i.e. preventative treatment) in those not yet infected. Unfortunately, the parasite's resistance to anti-malarial drugs is increasing, and there is currently no vaccine available.
In addition to there being significant Immunological obstacles, efforts to produce malaria vaccines have been hampered by the lack of interest expressed by several governments and the private sector. However, despite this, there has been great progress in malaria vaccine research, and first generation vaccines are on the horizon, and are likely to be developed within a few decades. These vaccines will most likely give only partial protection due to the number of strains of the malaria parasite. They are also intended to supplement rather than replace current disease control efforts.
Scientists have also investigated ways of preventing the mosquitoes themselves from becoming infected with the parasite. By preventing infection in the mosquito this would also reduce the number of people subsequently infected. Researchers have used genetic engineering techniques to produce a mosquito that is resistant to malaria parasites. It is hoped this could lead to large malaria-resistant wild populations in the future.
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Allergy and asthma
Allergies are hypersensitivity disorders that occur when the body's immune system reacts against foreign substances that are actually harmless. This immune response causes damage to the body's own tissues. The most common types of allergies arise after eating certain types of food, such as shellfish, peanuts or eggs, or from inhaling airborne substances, such as pollen, or dust.
Almost any substance can cause allergies, i.e. function as an allergen. Most allergens contain protein; although non-protein allergens include drugs like penicillin, which only cause a reaction once they bind to proteins in the body. In allergic reactions, the body believes allergens are dangerous and immediately produces substances to attack them. This causes other cells of the immune system to release potent chemicals like histamine, which causes inflammation and many of the symptoms associated with allergies.
Immunology strives to understand what happens to the body during an allergic response and the factors responsible for causing them. This should lead to better methods of diagnosing, preventing and controlling allergic diseases. Researchers are currently looking into the possibility of developing vaccines against most forms of allergies. For example, by identifying the proteins in pollen or peanuts that are responsible for causing hay fever or peanut allergy, and converting them into harmless forms; scientists hope vaccines can be produced and used to dampen down the immune system's response to these allergens.
Many factors are known to provoke an allergic response. Genetic and environmental factors are believed to be involved. Therefore, researchers are also trying to identify and describe the genes that make a person particularly vulnerable to developing an allergic disease. Environmental monitoring of outdoor and indoor air also plays an important role in allergy research. Immunologists are constantly evaluating ways to control environmental exposures to these allergens and pollutants as preventative measures.
Asthma is a debilitating and sometimes fatal disease of the airways. It generally occurs when the immune system responds to inhaled particles from the air, and can lead to thickening of the airways in patients over time. It is a major cause of illness and is particularly prevalent in children living in inner-city environments. In some cases it has an allergic component, however in a number of cases the aetiology is more complex and poorly understood, with recent research suggesting that it could be a disease with a genetic component impinging upon the actual development of respiratory tissue; causing it to be more vulnerable to provoking substances, hence triggering the resultant immune response.
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Autoimmune diseases occur when the immune system attacks the body it is meant to protect. People suffering from autoimmune diseases have a defect that makes them unable to distinguish 'self' from 'foreign' molecules.
Autoimmune diseases may be described as idiopathic or 'primary' autoimmune diseases, e.g. Type-1 diabetes, which may be manifest from birth or during early life; or as 'secondary' autoimmune diseases, which manifest later in life due to various factors. Rheumatoid arthritis and multiple sclerosis are thought to belong to this type of autoimmunity.
The principles of Immunology have provided a wide range of laboratory tests for the detection of autoimmune diseases.
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Diabetes is a disease characterised in patients with high levels of sugar in their blood. There are different forms of diabetes, but it is Type-1 diabetes that has particular relevance to Immunology.
Type-1 diabetes is a primary autoimmune disease that occurs when the cells of the immune system attack and destroy those cells of the pancreas responsible for producing the hormone insulin. Insulin plays an important role in the conversion of sugar into energy, as it facilitates the transport of sugar from the blood into cells.
Complications arising from diabetes include kidney damage, blindness, heart disease, loss of limbs and coma. There is currently no known cure. Current interventions to treat and manage the disease include injecting insulin, which can lead to further problems with regard to reaching normal blood-glucose levels.
Immunology helps us understand precisely how the pancreatic cells are destroyed and also helps us to devise ways of preventing this autoimmune response from occurring.
Researchers have attempted to cure the disease by replacing the damaged parts of the pancreas (known as the Islets of Langerhans) with pancreatic cells transplanted from a donor. However, as these cells are in short supply and require the use of drugs to suppress the immune system in order to prevent rejection of the transplant, immunologists are investigating the possibility of producing pancreatic cells using 'stem cells', which have the potential to develop into any type of cell.
Rheumatoid arthritis (RA) is another type of debilitating autoimmune disease that causes pain, swelling, stiffness and loss of function in the joints of humans and animals. It often affects the joints of the wrist and finger joints closest to the hand. Unlike other types of arthritis, there is often inflammation and both hands or knee-joints are affected, including other parts of the body. Many sufferers can develop anaemia, fatigue and fevers.
RA is not thought to be a primary autoimmune disease as several genetic, environmental and hormonal factors are thought to cause the immune system to react against the surface of the joints. However, there is no strong evidence for one specific cause. Treatment is largely symptomatic and provides pain relief, reduces inflammation and slows down further damage to the joints. For those patients with more severe damage, surgery is often performed.
An understanding of Immunology is key to developing better ways of diagnosing the disease (which is particularly difficult to identify in the early stages), and producing therapeutic agents that permanently stop the ongoing immune response. Clinical immunologists, therefore, strive to diagnose the condition early, in order to treat patients with powerful drugs and reduce or prevent further damage.
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Multiple Sclerosis (MS) is a devastating autoimmune disease that affects the brain and spinal cord in people aged between 20 and 40 years. It is a chronic disease, and is characterised by the presence of multiple areas of damage and scarring (sclerosis) on the nerve fibres of the nervous system.
It is not known what triggers the immune system to attack the nerve fibres but the presence of viruses lying dormant in the nervous system has been suggested. Patients with MS lose the ability to make smooth, rapid and co-ordinated movements. The disease arises when the fatty material that insulates nerve fibres (known as myelin) is destroyed by cells of the immune system.
Myelin allows nerves to transmit electrical impulses extremly rapidly. MS sufferers often end up developing sensory disturbances, paralysis and, can ultimately, suffer a slow and painful death. Although, thankfully, not all forms of the disease are so severe.
At present, there is no cure, but symptomatic therapies do exist. Drugs that suppress the immune system have also been used to treat the disease.
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Improving transplant outcomes
Organ transplants are one of the most miraculous achievements of modern medicine. They provide the best possible treatment for people with organ failure. Since the mid-1950s, transplantation has moved from an experimental form of therapy (that was used almost exclusively for kidney failure) to an accepted treatment for people with end-stage diseases of the kidney, heart, liver, lung and diabetes. More recent successes have included a partial face transplant conducted in France; with permission for a full face transplant having recently been granted in the UK.
Organ transplantation involves the transfer of a whole organ, or parts of an organ or tissues from one body to another (or from one donor site on the patients own body to another). Transplantation is performed to replace the recipient's damaged or failing organ or tissues with functional organs or tissue from another donor individual.
Unfortunately, due to the normal functions of the immune system, the recipient's body often rejects any transplanted cells, tissues and organs (also known as organ or tissue grafts). This presents a key barrier for achieving a successful organ transplantation outcome.
Advances in transplantation immunology have led to the development of drugs capable of suppressing the immune response that causes a transplant to be rejected. However, although these drugs permit excellent short-term survival of the graft they do not provide any significant long-term survival. Furthermore, these immunosuppressant drugs are so powerful that they can prevent the immune system from generally protecting the body from infections and cancer.
Transplant immunological research is currently trying to develop ways of helping the immune system tolerate transplants without preventing the immune system from doing its main job of protecting the body from invading pathogens. Research has also found that some patients have a lower risk of rejecting transplants than others. Therefore, developing the means to identify these two groups remains a high priority.
Research using stem cells also provides an exciting prospect for organ transplantation. The possibility of creating cells that are genetically identical to the recipient, would overcome the many associated complications that arise from the use of donor organs, tissues and cells.
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Improving animal health
Veterinary immunology is a branch of Immunology dedicated to improving animal health. Only a small number of immunologists work in this field. However, the number of species and challenges faced are huge. Like humans, animals also suffer from diseases caused either when organisms try to invade their body, or when their immune system does not function properly. Wild, domestic and farm animals, are commonly exposed to a whole range of dangerous bacteria, viruses and parasites, which threaten their welfare.
The health of domestic animals is a particular concern for pet owners who enjoy the companionship having a pet brings. The prevention and treatment of infections via compulsory immunisations, together with the use of antibiotics to treat pets with bacterial infections, ensures that they live much longer and healthier lives. Although many bacterial diseases in animals can be treated with antibiotics, prevention is considered to be a better approach. The field of veterinary vaccinology is rapidly expanding, there being big public health, political and economic incentives to immunise animals against disease.
Interest in animal healthcare is not completely altruistic, as diseases in animals also impacts on humans. Various animal diseases are known to cross the species barrier and infect humans. For example, 'yellow fever' is spread from monkeys to humans after insects, such as mosquitoes, bite infected monkeys and then pass the disease on to humans. It is, therefore, extremely important that these types of diseases, known as 'zoonoses', are effectively controlled. These measures not only prevent any further transmission to other animals and humans, but also reduce any, potentially devastating, social and economic consequences.
Keeping track of diseases in wild animals is also critical because of our increasing colonisation of wilderness territories. By doing so, we are increasingly coming into closer contact with wild animals who could potentially be harbouring extremely dangerous pathogens.
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Health control of animals living in the wild is especially important, not only to keep wildlife populations healthy but also to control the transmission of disease between wild and farm animals. It is particularly important to control diseases in animals in developing countries as a greater percentage of people from these areas depend on their livestock as their main source of income/livelihood.
In developed countries, farm animals are often raised in relatively biosecure facilities to decrease their dependence on antibiotics and vaccines. Developing countries, however, lack the resources to immunise animals and prevent infections spreading to the human population. Therefore, it is critical that disease control efforts also extend to countries in the developing world.
Animal health policies/strategies
Governments across the world have worked together to develop various health strategies and policies to improve and control the spread of infectious animal diseases. Health policies to manage non-infectious diseases, which also threaten the quality of life and survival of animals, are likely to be developed at a local level. Animal health is also a major concern because many disease outbreaks are extremely costly. And there are various ethical issues related to the mass slaughter of animals when controlling a disease outbreak.
The implementation of animal health policies helps facilitate trade in animals and their products. It also supports projects that aim to conserve the more diverse and endangered animal species becoming extinct.
Ecological concerns with wild animals
Healthcare in wild animals is important because a particular animal species reduced by disease can upset the ecological balance of an area. Wild animals also form part of a country's heritage, so it is vital they achieve optimal survival to prevent their extinction and those of other more rare animals.
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Immunology and biotechnology
Biotechnology is a term used to describe any technique that uses living organisms (or parts of a living organism) to make products used in agriculture, food science and medicine. Immunotechnology is a term used to describe the branch of biotechnology concerned with the production of immunological agents in living organisms. Advances in immunotechnology have made it possible to produce immunological agents that protect people and animals against many types of diseases. Many organisms have been designed specifically to produce antibiotics or vaccines. Also, chicken embryos are commonly used in the production of vaccines.
A new approach, hailed as 'the third vaccine revolution' uses what are called 'DNA vaccines' as a basis for protecting against infection. The technique involves introducing a specific part of DNA from a pathogen into a living host. The cells of the host then make proteins normally produced by the invading pathogen, which leads to an immune response that would protect the individual against possible infection if exposed to the real pathogen. Other advances within this field include the application of genetic engineering to produce edible vaccines. The genetic material of plants is altered to enable them to synthesise vaccines in the edible part of a food plant, i.e. fruit. This is particularly beneficial to countries lacking adequate storage facilities or staff to administer vaccines to its public.
Therapeutic substances called 'biologics' have also provided new effective treatments for auto-immune diseases such as rheumatoid arthritis. Modified human antibodies and the cell receptors that they bind to, are used to specifically target the substance responsible for causing joint destruction
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