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Biology – The Search for Better Health Section 5: The Immune Response Identify the components of immune response: T cells, B cells Antibodies If foreign particles are successful in penetrating the barriers of the first line of defence, and then survive the non-specific responses of the second line of defence, the body will then instigate the third line of defence. The third line of defence is called the immune response and is a specific response. It involves the production of two different types of lymphocytes, B cells and T cells, which are specific to the invading particle. These lymphocytes work together and launch an intensive attack to try and rid the body of this foreign material. In the process, cells that remember the specific antigens are also produced, so that the next time these antigens enter the body they are destroyed as soon as they are recognised. This ability to remember is called acquired immunity and develops during lifetime of an individual. T-cells T cells are lymphocytes that are produced in the bone marrow and mature in the thymus gland, which is situated in the thoracic (chest) cavity. After they mature, the T cells are released into the blood, spleen, tonsils and lymph nodes. Each T cell has a particular surface receptor protein that can recognise a specific antigen. When T cells encounter the antigen in the body that matches their receptor protein, they become activated and produce many clones of cytotoxic (killer) T cells specific to that antigen. These then move to the site of the infection and release chemicals that destroy the infected cell. T cells control cell-mediated immunity, which is effective in defending the body against: - bacteria and viruses that are inside the cells. - Protozoa, fungi, flatworms and roundworms - Cancerous cells and transplanted foreign tissue. B-Cells B cells are also lymphocytes that are produced and mature in the bone marrow. After they have matured they are also released into the blood, spleen, tonsils and lymph nodes. On its surface, each mature B cell has a different antibody that will only respond to a specific antigen. B cells only live for a few days and if they encounter their antigen they will become activated; if not, they will die. When a B cell becomes activated, it makes many copies of itself of these and each cells form plasma cells that produce antibodies specific to that particular antigen. These antibodies will then move to the site of the infection and combine with the antigen to form an antigen-antibody complex, which deactivates the antigen. B cells control the antibody- mediated (humoral) immunity, which defends the body against: bacteria and viruses outside the cells and toxins produced by bacteria. Antibodies Antibodies are proteins, known as immunoglobulins, which are produced in response to the presence of an antigen in the body. When the appropriate B cells are activated they form plasma cells that produce antibodies, the antigen binding sites of which match the shape of the antigen they are specific for. These antibodies then seek out the antigen and bind to a part of it, forming the antigen-antibody complex, which causes the deactivation of the antigen. There are a number of ways in which the antigen can be destroyed including immobilising it, blocking and neutralising the active binding site of the antigen, or elimination via phagocytosis (note: clumping together of antibody-antigen complex makes this process significantly easier). Describe and explain the immune response The immune response has two major pathways that are used to destroy invading foreign material. These are processes of cell-mediated immunity and antibodymediated (or humoral) immunity. Each of these responses is specific to the type of antigen present. Each type of response uses a different type of lymphocyte (T cells or B cells) and relies on the interaction of these two types of cells to successfully defend the body against infection. Much of the interaction between the different types of cells involved in the immune response is regulated by the secretion of chemicals known generally as cytokines. A specific type of cytokine chemical, interleukin is responsible for many of the processes involved in the immune response. There are four main types of T lymphocytes: 1) Helper T cells (Th cells): on its surface each of these cells has a receptor protein that will recognise only one type of antigen. When a Th cell is activated by the presence of a particular antigen, it releases a cytokine chemical that activates the cytotoxic T cells and B cells specific for antigen. Other cytokine chemicals that stimulate the activity of macrophages are released. 2) Cytotoxic T cells (Tc Cells): These cells are stimulated to produce many copies (clones) of themselves when activated by the helper T cells and also when they detect cells that have displayed on their surface antigens that match their own surface receptor protein. This army of identical cells bind with the infected cells and release chemicals that destroy it. 3) Memory T cells: These cells are produced at the same time as the Tc cells are multiplying and remain in the body so that the body can respond more quickly to future invasions by the same antigen 4) Suppressor T cells: These cells are responsible for the stopping of the immune response when the infection has been defeated. Interaction between B and T lymphocytes When a macrophage encounters a foreign particle with an antigen attached to its surface, it surrounds and engulfs it in the process of phagocytosis. In the course of destroying the foreign material, the antigen that was present on its surface is moved to the surface of the macrophage which then transports it to lymph nodes. The antigen-presenting macrophage is then presented to helper T cells that activate them. When a B cell encounters the antigen it binds these antigens to antibodies. It processes the antigen, attaches it to its surface molecules and presents this to the helper T cells that have the matching T cell receptors. Chemical signals in the form of cytokines are then secreted by the helper T cells and this activates the production of clones of the B cells that are specific to the antigen. When the immune response has successfully defeated the infection suppressor T cells are responsible for suppressing the activity of the B cells and cytotoxic T cells. Mechanisms for Interaction To help the B and T cells interact successfully, there is a system that allows these cells to identify that they both belong to the body and prevents them from attacking each other. On the surface of cells there are glycoprotein molecules (composed of a carbohydrate molecule and a protein molecule) that are called MHC molecules. These molecules allow the recognition of cells from the body. MHC molecules allow the recognition of cells from the body. MHC molecules also allow the identification of cells that are foreign. Foreign cells will have a different MHC molecule on their surface and this will identify them as not part of the body. There are two types of MHC molecules: 1) MCHI molecules are present on all cells that have a nucleus and are involved in the recognition of antigens by T cells. The infected cell holds the antigen on its MHCI molecule on the surface so that the cytotoxic T cell can identify it and destroy it. 2) MHCII molecules are present only on B cells and macrophages and are involved in the recognition of antigens on macrophages and B cells by Th cells. The macrophage holds the antigen on its MHCII molecule on the surface and is recognised by the Th cell that as the same antigen receptor. The helper T cell then activates the appropriate B and T cells. Interaction between B and T cells is also helped by their close proximity to each other and the regulation of their activities by the secretion of chemicals called cytokines by the helper T cells. Extra: Cell Mediated Immunity The process of cell mediated immunity is carried out by T cells, and is as follows - Foreign material is engulfed by macrophages which then display the antigen attached on their surface. - The antigen presenting macrophages move to the lymph node where they are inspected by the helper T cells that have the T cell receptor that corresponds to the antigen being presented. - These helper T cells then activate the cloning of millions of cytotoxic T cells and memory T cells that are specific for this antigen by secreting interleukin-2 - These then release chemicals that destroy the cell and any pathogens - These chemicals also increase inflammation, attracting more macrophages to carry out phagocytosis to help destroy the pathogens and clean debris - Once the infection has been defeated the suppressor T cells release other chemicals to stop the production and action of cytotoxic T cells. - The memory T cells that are produced at the time are specific for that antigen and remain in the body in the lymph nodes. Antibody-mediated immunity: - Antigen-presenting B cells or macrophages move to the lymph nodes. - They are inspected by the helper T cells that have the antigen receptor that corresponds to the antigen being presented. - These helper T cells stimulate the cloning of millions of B cells that are specific to the antigen by secreting interleukin-2. At the same time millions of memory B cells are produced The activated B cells produced plasma cells that remain in the lymph nodes These plasma cells secrete antigen specific antibodies that then move via the blood and lymph to the infected areas. The antibodies then combine with the antigen to form the antigen-antibody complex that inactivates the pathogen The pathogen is then destroyed. An inflammation response follows, attracting more phagocytes. The memory B cells produced can lead to immunity. Outline the reasons for the suppression of the immune response in organ transplant patients. When a patient receives a donor organ, this organ will have, on its surface, ‘marker’ molecules on the cells in the recipient’s body. These ‘marker’ molecules on the donor organ act as antigens that identify the organ as foreign material, and the immune response is initiated. The cytotoxic T cells are activated and move to the transplanted organ to attack and destroy the cells. This causes the rejection of the transplanted organ. In order to reduce the severity of the immune response, the tissue of the donor and recipient are matched as closely as possible (this is known as ‘tissue typing’). Perfect matches will occur only between identical twins. Drugs such as cyclosporine are given in order to suppress the immune system so the risk of rejection is lowered. These drugs act to reduce the activity of the T cells as these are the principal cells that attack the transplanted organ. This has the advantage that the whole of the immune system is not suppressed and can still act to defend the body against other disease. These anti-rejection drugs must be taken for the rest of the recipient’s life and are needed in large doses at first, but over time the immune response lessens and lower doses are needed. Outline the way in which vaccinations prevent infection When an antigen is first encountered by the immune system the time taken to fight the infection is quite long. This is because once the antigen has been identified, the appropriate T cells and B cells have to be activated and then it takes time to build clones. Time is also needed for the cytotoxic T cells to kill the infected cells and for the B cells to produce plasma cells that then secrete antibodies and bind with the antigen to neutralise it. If sufficient antibodies are made to destroy all the infecting agents, the person recovers completely. This is known as the primary response. At the same time, memory T cells and memory B cells specific to the antigen are produced and remain in the body. If the same antigen were to re-enter the body in the future, the response, known as the secondary response, is much quicker. After identification of the antigen, the memory cells will activate the production of the cytotoxic T cells and B cells. A very large number of B cells will then form many plasma cells which will destroy the invading antigens before their numbers are large enough to cause any symptoms. The secondary response is more rapid and requires fewer antigens to initiate it. It produces a much greater quantity of antibodies and it lasts for a longer period of time. This type of immunity is called active acquired immunity. It is naturally induced as the body has to undergo the immune response and suffer the symptoms of the disease in order to develop immunity. Vaccines contain cultures of micro-organisms, which may be either: -Living but attenuated (weakened) and therefore harmless (eg rabies) -Dead (eg. Thypoid) Vaccines are all harmless to the body and will not cause the disease that they are specific for, but still contain the antigens that cause the body to undergo an immune response and produce memory cells for that particular antigen. If the body is exposed to that antigen in the future, the secondary response will be activated and the antigen will be destroyed before any symptoms of the disease are experienced. The immunity formed in this way is usually life-long. Each vaccine is specific for only one type of antigen, and therefore will give immunity to only one type of disease. Immunisation is the process in which the body reacts the vaccine by going through the immune response that produces memory cells for the antigen and confers immunity to the body so that if the antigen enters the body in the future, the secondary response will occur and the body will not suffer any symptoms of the disease. For a vaccine to be effective, a series of vaccines should be given over a number of years. Each time the vaccine is introduced into the body, a small response is produced. Over a series of vaccinations the lymphocytes will more rapidly recognise the antigen and the numbers of memory cells produced will be enough to give immunity for a long time. Another way vaccines can prevent infection is via passive acquired immunity. This involves the introduction of antibodies (immunoglobins) to the body to prevent a disease from developing. These antibodies have been produced by another organism. This immunity however, will only last for a few months as no memory cells have been produced. Evaluate the effectiveness of vaccination in preventing the spread and occurrence of once common diseases including smallpox, diphtheria, polio. Before much was known about the cause, treatment and prevention of disease, many people including large numbers of children lost their lives to diseases that today have been eradicated or the incidence of which is very low. Vaccination has been recognised as one of the most successful public health programs used to prevent disease. In 1974, WHO increased the percentage of world’s infants immunised against diphtheria, tetanus, whooping cough, polio, measles and TB, from 5% to 80% in 1997. This prevented an estimated 3 million deaths each year. Mass immunisation programs not only prevent the occurrence of the disease in individuals, but also help the spread of disease throughout the population. If the majority of the population is immunised against a disease, the chance of an infected individual coming into contact with an unprotected person is extremely low and the transmission of the disease is effectively stopped. This is known as the principle of ‘herd immunity.’ Despite the success of vaccination programs there has recently been an increase in the number of cases of disease such as whooping cough. This is because a number of people are neglecting to get themselves or their children immunised. The reasons for this may be: - People are becoming complacent and thinking they will not contract the disease because of the low incidence in the population. - Individuals may refuse to have themselves or their children immunised because they feel the risks of side effects are too great. Smallpox, diphtheria and polio are three diseases that were very common in the world until implementation of vaccination programs to try to prevent their spread and occurrence. Smallpox is caused by a virus that may be airborne or spread through direct contact. It enters the throat and lungs, causing a high fever and rash that spreads all over the body. It is often fatal. Smallpox has killed more people than any other infectious disease and was responsible for one-tenth of deaths in Europe in the 19th Century. As vaccinations were developed, the instance of smallpox only slightly declined. This is because of many people not bothering to get themselves vaccinated. However, as WHO committed itself to a worldwide mass immunisation program in order to eradicate the disease, the instance of smallpox dramatically declined. The program initiated by WHO led to its declaration in 1979 that it had ‘eliminated the virus from the world population and eradicated the smallpox disease.’ Hence, the vaccination program to help control the spread and occurrence of the smallpox virus has been very successful. Diphtheria is caused by highly contagious and fast-acting bacteria, often killing within a week of the start symptoms. It is transmitted by close contact with respiratory droplets. It begins with a sore throat, fever and rapid pulse and then the destruction of the lining of the throat and the formation of a leathery membrane across the throat. This can lead to death by suffocation – but death can also occur through toxins released by the bacteria which can cause brain/cardiovascular damage. Before the implementation of a vaccine program, the deaths due to diphtheria were almost more than 200 000 in the US alone. However, as vaccination programs were implemented, this number of deaths in children rapidly declined. Polio is a viral disease transmitted by inhaling infected droplets and by direct contact. It causes fever and paralysis. Death occurs in 50 % of cases, while 50% of cases suffer paralysis. Due to immunisation programs, the occurrence of polio has declined dramatically. Furthermore, the spread of the polio virus has decreased. Previously there were up to 125 countries with polio endemics, whereas at the end of 2006, there were only 4. This shows the effectiveness of vaccination programs in eradicating the occurrence and spread of diseases such as polio. The vaccination programs for diphtheria and polio are as follows. Note: a smallpox vaccination is now not needed as the virus has been eradicated from the world population. Diphtheria: 2, 4, 6, 18 months. Then at 4 and 17 years. And then every 10 years. The number of cases in Australia in Australia over the past 80 years have decreased by almost 99.95% Polio: 2,4,6 months then 4 and 17 years. There have been no cases of polio following mass immunisation in Australia. Biology – The Search for Better Health Section 6: Epidemiological studies Identify and describe the main features of epidemiology using lung cancer as an example. Epidemiological studies play a major role in indentifying patterns in the occurrence of disease, identifying the possible cause of disease that would be most effective in controlling disease in the population. They are scientific studies of patterns of occurrence of disease in human populations and the factors that effect these patterns. It describes, statistically analyses and hypothesises as to the cause of the disease in the population. Epidemiology can be used to study both infectious and non-infectious diseases as well as events such as suicides or car accidents. There are three major types of epidemiological studies: 1) Descriptive 2) Analytical 3) Intervention Descriptive studies are usually the first type of study completed when investigating the cause of a disease. These provide information about the patterns of the disease, including the frequency of the disease, which section of the population and the geographical location. In early studies launched to determine the cause of lung cancer, data was collected about the age, sex, smoking habits, diet, occupation and drinking habits of both smokers and non-smokers. Analytical studies now follow, which are used to collect more data which is statistically analysed to develop hypothesis as to the likely causes of the disease. The morbidity (number of causes of the disease) and the mortality (percentage of population that dies from the disease) are two indicators in this study. Data about the incidence, the prevalence are also compiled. When conducting analytical studies, there are two methods: 1) Case Control Studies: These compare people with the disease (case) to people without the disease (control) and look for differences in exposure to the possible causes of the disease. For lung cancer, patients with lung cancer were compared to patients with other conditions. Information about many factors about their life, including their smoking habits. This showed that most of the individuals with lung cancer were smokers and suggested a link btw smoking/lung cancer. 2) Cohort Studies: These involve studying two or more similar groups of people who are free from the disease. These groups differ in one main factor, being their exposure to the potential cause of the disease. These groups are followed over a long period of time to compare the resulting incidence of disease that is being studied. For example, a cohort study was set up following the discovery of the link between lung cancer and smoking through case controlled studies. At the end of this study it was found that the group that was smoking had a much higher incidence of lung cancer than the group that did not. This study also revealed that the greater the number of cigarettes smoked daily, the greater the chance of dying from lung cancer. Intervention studies are used to test the effectiveness of a treatment or the effectiveness of a public health campaign to change the behaviour of the population as a whole in order to decrease the incidence of disease. For example, the effectiveness of campaigns such as the ‘Quit.’ There a few criteria that a good epidemiological study should adhere to: - Study should be over a long time frame - Study should have a very large sample - A broad range of lifestyles and societies should be represented - Control groups should be used. - Data should be collected on incidence, prevalence, mortality and morbidity - Possible causes of the disease and any risk factors should be identified. - An evaluation of the effectiveness of control/treatment programs should be done. Identify the cause and effect relationship between smoking and lung cancer There have been many epidemiological studies carried out to determine the cause of lung cancer. These studies have involved collecting data from millions of people over a long period of time. The findings have universally demonstrated a clear link between smoking and the increased incidence of lung cancer. They have also shown that there is a clear link between cigarette smoking and reduced life expectancy. A 1960 in the US comparing smokers and nonsmokers showed that smokers have a 10 times greater chance than non-smokers of dying from lung cancer. Further studies have shown that the more cigarettes smoked each day, the greater the incidence of lung cancer. It has also been shown that the longer a person smokes, the greater the chance of developing lung cancer. More recent studies have also shown a greater risk of developing lung cancer due to passive smoking. The incidence of lung cancer has changed for both males and females since the 1900s. Very few women smoked early in the 20th century and the majority of cases of lung cancer affected men. As it became more socially acceptable and the number of females smoking increased, the incidence of lung cancer in women increased. By the 1990s the number of male smokers had decreased, as had the incidence of lung cancer in males. The number of female smokers had increased, as had the incidence of lung cancer in females. Smoking is the main cause of lung cancer and accounts for about 85% of cases in men and 75% of cases in women. Identify causes of non-infection disease using an example from each of the following categories: inherited diseases, nutritional diseases, environmental diseases. Inherited Disease: Cystic Fibrosis Cause: Cystic Fibrosis is a genetic disorder caused by a recessive gene. The recessive gene lacks the DNA sequence that codes for one amino acid, phenylamine, in an important protein. This protein normally controls the movement of ions across the cell membranes. The autosomal recessive gene is located on chromosome 7. It was shown that the gene is responsible for a trans-membrane chloride channel called the Cystic Fibrosis Trans-membrane Conductance Regulator (CFTR). This CFTR protein plays an important role in transported Cl- across cell membranes. As this cause is a genetic mutation, it can be inherited from one individual to their offspring. Effect on Body: CF affects the endocrine glands with secrete bodily fluids such as sweat, mucus and enzymes. CF involves a change in the nature of the mucus and other body secretions. The mucus secreting glands produce abnormally concentrated secretions which most seriously affect the lungs and pancreas. In the lungs the abnormally thick mucus makes it harder for the cilia to move the mucus towards the throat. This generally results in the slower resolution of infections. Tissue damage to the airway lining can occur, also resulting in infections taking longer to be fought and cleared. In turn this can impair cilia function, thus leading to an accumulation of mucus in the airways which makes it difficult to breath. Nutritional Disease: Scurvy Cause: Scurvy is caused by a lack of vitamin C in the daily diet. Vitamin C (ascorbic acid) is important in many biological functions in body, especially substances required for connective tissue, bones and dentin. A deficiency in vitamin C weakens the blood capillary wall, leading to bleeding and bruising. Effect on Body: Symptoms of scurvy include: pain and tenderness in the legs, swelling of the long bones, swollen, purplish and spongy gums. If prolonged it can lead to gangrene and the re-opening of old wounds. Environmental Disease: Mesothelioma Cause: Mesothelioma is a cancer of the mesothelial cells that occur in the pleura membrane on the outside of the lung. Mesothelioma grows in the pleural space surrounding the lungs and the tumour may eventually surround the entire lung. The initial stage in the development of cancer involves a mutation to a gene that is involved with the normal process of cell division. Currently, it is believed that exposure to asbestos causes this mutation leading to the development of the cancer. When asbestos fibres are inhaled, most of them stick to the mucus inside the respiratory passages and are coughed up or swallowed. The long thin fibres of asbestos are not easily cleared like this and may reach the ends of the small airways and penetrate the pleural lining. It is these fibres that damage the cells and cause the mutation and hence uncontrolled mitosis – and thus tumour forms. Effect on Body: The symptoms of Mesothelioma include a shortness in breath caused by the tumour squashing the lungs, chest pain and, in the later stages of the disease, weight loss, loss of appetite, fatigue, night sweats and anaemia. Incurable. Biology – The Search for Better Health Section 7: Prevention and control of disease Explain how public health programs have controlled or prevented disease. Public health programs There are a number of different types of public health programs in place to help prevent disease: - Government regulations ensure that standardised procedures are in place and are to be followed when handling, cooking and storing food. Strict guidelines must also be followed in hospitals, surgeries and clinics when sterilising equipment and when health workers move from patient to patient. By following these guidelines and procedures, the spread of pathogens is prevented: this in turn prevents the occurrence of diseases such as hepatitis. - Government regulations are also in place to ensure that garbage is disposed of correctly, drinking water is treated effectively and sewage is removed and treated. If these sanitation procedures are followed correctly, the spread of pathogens is prevented and hence the occurrence of disease is prevented. - The law requires that certain diseases are reported to authorities if they are detected. This allows the early detection of these diseases and allows appropriate strategies to be implemented to control the spread of these diseases through the community. Some examples of notifiable diseases are measles, cholera and malaria. - Public health programs encourage regular screening for certain diseases are also in place. Women are encouraged to regularly check their breasts for the presence of any unusual lumps and to have regular mammograms between the ages of 50-70 years. Regular pap tests for the early detection of cervical cancer are suggested. - Public health programs, such as the childhood immunisation programs that are in place for diphtheria, tetanus and measles prevent diseases from occurring. Mass immunisation programs for the human population leads to the prevention of disease, and the control of its occurrence. - Public education programs are another strategy that aims to help prevent disease. For many years there have been programs aimed at increasing public awareness of life-style related risk factors. These programs aim to change the life-style of individuals in order to prevent the occurrence of disease. Quit is an education program that has been in existence for many years. Its purpose is to raise awareness of the effects of smoking. It reduces the number of people smoking and in turn, reduces the incidence of diseases that are associated with smoking. Discuss the changing methods of dealing with plant and animal diseases, including a shift in emphasis from treatment and control to management or prevention of disease. 150 years ago, there was little understanding as to the causes of disease. When disease occurred in individuals, attempts were made to treat them. This was often unsuccessful and the death rate due to disease was very high, with many children in particular not surviving to adulthood. With the many breakthroughs in understanding of disease came the knowledge that allowed more successful treatments to be developed and used. The treatment of disease involves strategies employed to either cure the disease or relieve its symptoms once an organism has the disease. Control of the disease involves reducing its spread through the population of organisms once it is already present. Prevention of disease involves the use of strategies that help stop the occurrence of disease in other organisms. Management of disease is defined as programs that improve the outcomes of long-lasting conditions and improve the quality of life of sufferers. A number of years ago, when drugs such as penicillin and chloro-quine were discovered, the emphasis when dealing with diseases was on their treatment and control. As problems such as antibiotic resistance developed, the emphasis shifted towards prevention and management. This change in emphasis was made possible only by our increased understanding of the functioning of the immune system as the accompanying development of more advanced technologies. These preventative measures were further expanded with our increasing understanding of genetics and our ability to manipulate genetic information. Diseases can be treated using increasingly toxic antibiotics. However, these produce undesirable sideeffects for the patient as well produce more strain on the financial system due to their increased cost. As a result the quality of life is compromised; this is avoidable if the disease had been prevented in the first place. Hence, it is solely due to health and economical reasons that the shift has been observed. Also, with continuing treatment, the bacterium responsible for the disease continues developing resistance. This makes the disease much more difficult to eradicate, especially in poorer regions of the world, where the increased medicine cannot be afforded my much of the population, hence increasing the occurrence of the disease. As this is undesirable, there has been a change from treatment to prevention. In order to prevent the disease, a number of procedures can be implemented including quarantine to prevent the entry of the disease into a country, vaccination to provide induced immunity within the population, hence decreasing the chance for an unvaccinated individual to contract the disease through direct contact, and also the use of public health programs, genetic engineering and the use of pesticides to eliminate disease vectors. This reduces the incidence of disease in the population hence increasing the general standard of health and quality of life in society. Furthermore, less money needs to be spent on health and less drug and pesticide resistance would occur, hence preventing the generation of superbugs and superweeds.