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Immunology is the study of methods of how the body defends itself from infections and foreign substances in the environment. The immune system is an adaptable and complex system which has evolved in humans to protect the body against invading pathogenic micro-organisms. An infectious organism which can cause a disease is known as a pathogen and the person or animal infected is called the host. The immune system needs to eliminate a pathogen without damaging the host which makes the task very complicated and as a result it is able to generate a huge variety of cells and molecules which are able to recognise an enormous range and variety of foreign invaders, as well as being able to distinguish and destroy abnormal cells.
The immune system is split into two parts, the non-specific system and specific system.
NON SPECIFIC IMMUNE SYSTEM
The non specific system is a way of combating infection. The skin is an effective outer barrier to most micro organisms as sweat has high ion levels which make bacterial growth difficult. The skin also has sebum which has an antiseptic chemical, as well as containing a fatty acid that stops bacterial growth.
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The alimentary tract and gaseous exchange surfaces are major pathways which micro organisms can enter the body. They collect in mucus in the cilia lining and then beat to move the mucus to the respiratory tract and throat. This is an effective barrier as they are swallowed and then killed by hydrochloric acid in the stomach. Coughing and sneezing help to expel foreign bodies but areas of the body not covered by skin such as the eyes, nose and mouth are particularly vulnerable to invasion bacteria.
An enzyme (lysozyme) in tears, saliva and other body fluids can destroy some bacteria as it bursts it by slitting molecules in the bacterial cell wall. A major cause of infection is through wounds which can be cut down by the clotting of blood which prevents excessive bleeding and blocks the entry of micro organisms.
Phagocytosis is carried out by white blood cells called phagocytes (Macrophages, neutrophils). The process is in steps when certain cells engulf micro-organisms, other cells or foreign particles. The diagram below shows the stages of the process.
It is phagocytosis that a cause swelling in the infected area. The inflammation is caused by mast cells releasing substances such as histamine which dilute blood vessels and make them leaky which can form pus or a boil. Phagocytosis does not act against viruses as they reproduce inside the body’s own cells where they are protected from attack.
SPECIFIC IMMUNE SYSTEM
The specific immune system is a second line of defence when different types of cells can distinguish between the types of micro organisms. It also has a memory system which enables its cells to reproduce a response so the same type of micro organism.
Acquired immunity results from the actions of antibodies which are proteins produced in the lymph nodes in response to antigens to provide active immunity. The substance which triggers an active immune response is called an antigen. Antigens are mainly proteins or protein fragments called glycoprotein that are on the surface of the cell membrane, cell wall or a virus. These are recognised as non-self by the immune system and this creates a response. Self antigens are found in the membranes of our body cells. Organ donation and blood transfusion are ways in which antigens can be introduced to someone else. A particular antibody will only react with one type of antigen and therefore the body needs to distinguish between different types of antigen so that the immune system can function effectively. Antigens stimulate lymphocytes to create an immune response.
Lymphocytes originate in bone marrow from stem cells, move to the lymph nodes and then mature and reproduce in large numbers throughout life. The two types of lymphocyte are calls T-cells and B-cells. T-cells are processed in the thymus gland before moving to the lymph nodes and B-cells are processed in the bone marrow and in the blood. Approximately 80% are T-cells and the remainder are B-cells. The two types of cells have distinctive mechanisms called the humoral and cellular responses.
Cell Mediated Immunity
T cells are responsible for cell mediated immunity where they have to make contact with antigens which are on the surface of the body cells. There are special receptors on the surface which make them able to recognise the correct antigen. Below are the main types of T-lymphocyte and there specific functions:
- T helper cells are there to help other cells in the immune system. They help to stimulate and activate B cells into antibody producing cells. If T helper cells are not present the B cells cannot go into action. Another role is to enhance the action of phagocytes. In HIV the T cells are invaded which is why there are other infections with AIDS.
- T suppressor cells suppress the action of phagocytes and stop production of antibodies by the B cells.
- Memory T cells are able to recognise and respond to a pathogen when it invades and can give long lasting immunity.
- T Killer cells destroy body cells infected with a virus before it can time to spread. They release lymphotoxins, which cause lysis leading to the cell bursting. They also attack cells from other individuals which is why there are rejection problems with transplant surgery.
This type of immunity is caused by the production of antibodies from B lymphocytes. Humoral is the blood and the lymph where the antibodies circulate. In this system the body can react to specific antigens which were not previously in the body. It can be weakened if there is a huge dose of the virus as antibodies cannot be produced quickly enough. When a pathogenic micro organism enter the body and the lymph nodes, the B cells divide by mitosis and then swell to become plasma cells which produce antibodies which are specific to the antigen which triggered the response. Each antibody molecule consists of four polypeptide chains; two are heavy and two light. There are two binding sites on the molecule each linking with the antigen molecule and each region that blinds together have matching shapes like a jigsaw. When the antibodies enter the body they circulate as immunoglobulins and form the gamma globulin fraction of plasma proteins.
Some of the activated B cells do not develop into plasma cells and remain in the lymph nodes as memory B cells. As a result of an infection these memory B cells develop and can survive years, so that if the disease returns they can develop into antibody producing cells. Antibody can be built up very quickly so that no symptoms appear which is how the body becomes immune to a disease.
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In the 1975 Cesar Milstein and George Kohler successfully fused antibody secreting cells with tumour cells resulting in hybridomas which secrete antibodies and are immortal. These can be cultured as a pure clone and their antibodies collected. The antibodies produced and the cells that produced them are called monoclonal antibodies.
The antibodies are produced by using mice. The mouse is injected with antigens to stimulate the formation of antibody producing cells. They are then removed from the spleen and cultured. Tumour cells from another mouse and cultured and then fused with the antibody producing cells. The hybridoma cells contain properties from both parents and then each cell is isolated separately. Each culture contains cells secreting a single antibody which can then be used for large scale production of monoclonal antibodies.
Monoclonal means just one type and the antibody is produced in a laboratory from a single copy of a human antibody. They can be used for injecting a large amount into the body to overcome a particular disease. It is also used in finding the amount of a substance in a mixture (drug tests). In transplant surgery if there is rejection monoclonal antibodies can be used to stop specific T cells from functioning.
In cancer research monoclonal antibodies are used to find abnormal proteins on cancer cells and each antibody recognises one protein and therefore different antibodies can be produced to target different types of cancer. The research is making it possible to kill cancer cells without harming other body cells. Although cancer cells are abnormal they develop from normal cells, which is why it is difficult for the immune system to spot them. Some monoclonal antibodies can attach to cancer cells making it easier for the immune system to find them. Some monoclonal antibodies can seek out cells with too much growth and then block the cells receptors so that the cell cannot grow any further. Monoclonal antibodies can also have drugs or radiation attached so that they can attach to a specific cell.
Rabies and the immune system
According to the World Health Organisation more than 55,000 people die of rabies each year and about 95% of human deaths are in Asia of Africa. The majority of deaths happen after a bite from an infected dog and between 30% and 60% of the victims are children under 15 years old. Immunizations given as soon after the infection as possible, prevents the onset of rabies in 100% of exposures. Once the disease starts to show there is no treatment and it is almost always fatal. The best way of containing the disease is by eliminating rabies in dogs through animal vaccinations. In developed countries rabies is carried mainly through wild animals and in the past few years the disease has become a health problem in Americas and Europe.
The virus is a zoonotic disease (passed from animals to humans) and is transmitted through bites and scratches. The first symptoms are flu-like such as a fever and headache. The disease then goes to the respiratory system, gastrointestinal and/or central nervous system and eventually leads to hyperactivity or paralysis and then to a coma and death in all cases, usually due to breathing failure. Death usually happens in the first seven days of the illness.
The virus likes to attack nerves and can get there by going through a mucous membrane when the nerves are close to the surface; these are areas such as the nose, lips and eyes. The non specific immune system can prevent this transmission a lot of the time, but generally the disease is passed through animal bites. The virus likes to live in the saliva and with makes it thick and foamy in the animal carrying the virus. The disease takes a while to find a nerve to attack, this is called the incubation period and sometimes the human will never get sick. When rabies does attack it travels up the nerves to the spinal cord and then to the brain although sometimes the virus hides from the immune system until it is too late. The virus knows nerves are usually not checked for germs by the immune system and therefore it may not be recognised straight away. It tricks the immune system by hiding and by the time the enemy is there it is too late, which is why any bite from an animal needs to be check out straight away. Once the virus reaches the brain it multiplies and can make the infected person or animal crazy. It then travels through other nerves to come out the saliva glands.
Wound cleansing and immunizations after contact with an infected animal can prevent the onset of the disease in all cases. Rabies can be treated by immunoglobulin vaccines, or antibody which is used in category III cases where there have been one or more bites, scratches, licks on broken skin or other contacts that break the skin. The WHO states that vaccines are expensive and are in short supply in many developing countries.
Immunity can be active natural (contact with infection), which is long term and antigen specific. Artificial (immunization), which develops slowly and can last for years. Passive natural (transplacental), which develops immediately and is temporary. Passive artificial (injection) which develops immediately and is temporary.
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