Immune system a level

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can sometimes attack tissues and or organs that are transplanted into it as it identifies them as non-self, therefore usually the transplants cell recognition and immune system 1 are as closely matched to the patient and immunosuppressants are sometimes used and administered. How can lymphocytes recognise cells belonging to the body? In the foetus the lymphocytes constantly collide with other cells, with the body's own material, and some of them have receptors that exactly fit those of the body's own cells, and they die or are suppressed. The ones that remain are only the ones that fit foreign material and so only respond to it. This is why lymphocytes that are produced in the bone marrow usually counter self-antigens, when they show an immune response against them, they undergo apoptosis (programmed cell death) before they can differentiate into mature ones, and no more clones are formed, leaving only ones that might respond to non-self antigens. Phagocytosis There are two types of white blood cells: • Phagocytes: they ingest and destroy the pathogen with phagocytosis. • Lymphocytes: involved in immune responses Phagocytosis is when particles are engulfed by cells in the vesicles formed from the cell-surface membrane. Chemical products of pathogens or dead cells act as attractants, attracting the phagocyte, which have several receptors that attach to the chemicals on the surface of the pathogen, which is then engulfed to form a vesicle called a phagosome. Lysosomes then move towards the vesicle and fuse with it, they release enzymes called lysozymes which destroy the pathogen by hydrolysis of their cell walls. The products are then absorbed into the cytoplasm of the phagocyte. T-lymphocytes and cell-mediated immunity Antigens are any part of an organism or substance that is recognised as non-self by the immune system and causes a response. They are usually proteins on the cell-surface membrane, or cell walls. Its presence triggers the production of an antibody to counter it. Cell mediated immunity is when the T cells react to only antigens that are presented on a body cell, it is a process that does not involve antibodies, instead only phagocytes, and CD8 T cells. Lymphocytes are produced by stem cells in the bone marrow and there are two types: cell recognition and immune system 2 • B lymphocytes (B cells): they mature in the bone marrow and are in the immunity that involves antibodies that are present in body fluidity, humoral immunity. • T lymphocytes (T cells): they mature in the thymus gland and are associated with cell-mediated immunity, involving body cells. Lymphocytes respond to an organism's own cells that were infected by non-self- material, e.g., viruses, and they also respond to other cells of the same species as they are genetically different. however only to ones that are presented on the body cell and not the ones that are within the body fluids. Lymphocytes can distinguish phagocytes as they usually have some of the pathogen's antigens on their own cell-membrane and body cells that were invaded by viruses as they usually have some of the viral antigens on their own cell-surface membrane. They can also identify transplanted cells from normal cells and cancer cells as they have both different antigens. Antigen-presenting cells are cells that display foreign antigens on their surface such as phagocytes. The receptor on each T cell responds to a single antigen as follows: • Pathogens invade the body cells or are taken in by phagocytosis. • The phagocyte has the pathogen's antigens on its surface. (antigen presenting cell) • Receptors on a helper T cell, or CD4 T cells, fit exactly on these antigens. • This attachment activates the T cell to divide rapidly by mitosis. ● The cloned t cells: o Become memory cells. o Stimulate B cells to divide. o Stimulate phagocytosis. o Activate cytotoxic T cells. Cytotoxic T cells, or CD8 T cells, kill abnormal cells and cells that are infected by a pathogen by producing a protein called perforin which makes holes in the cell-surface membrane and allows it to become freely permeable to all substances, causing the cell to die, which is most effective against viruses, preventing them from multiplying. The CD8 T cells then form memory CD8 T cells, waiting for action again. B-lymphocytes and humoral immunity cell recognition and immune system 3 A B cell with the complementary antibody identifies the offending antigen in the bodily fluids, it attaches, and the antigen enters the B cell by endocytosis. Helper T cells then bind and stimulate the B cell to divide, called clonal selection, and are called monoclonal antibodies as each form only one specific antibody. The clones then develop into two different types: • Plasma cells that secrete antibodies into the blood plasma. • Memory cells that are responsible for the secondary immune response. The previous response was the primary immune response. They divide and form plasma cells and memory cells and circulate. Overall: pathogen antigen-presenting cell, e.g., phagocyte antigen from pathogen cloning by mitosis cell recognition and immune system T cell helper T cell's receptor that fits the particular antigen T cell Becomes a memory cell that circulates in the blood and tissue fluid in readiness to respond to a future infection by the same pathogen Stimulates B cells to divide Stimulates phagocytosis by phagocytes Activates cytotoxic T cells (Tc cells) to kill infected cells by making holes in their cell-surface membranes Antibodies Antibodies are proteins with specific binding sites synthesised by B cells. They have two identical binding sites and are complementary to a specific antigen, forming an antigen- antibody complex in the binding site, the variable region. An antibody is made of four polypeptide chains, two being heavy chains and are long, and two being light chains and are shorter. The rest of the antibody other than the variable region is called the constant region. When the pathogen is a bacteria cell, the antibodies cause agglutination where clumps of the bacteria cells are formed as the antibodies pull the antigens together, which is possible as each antibody has two antigen binding sites, making the bacteria easier to 4 locate as they are less spread out, the antibodies then act as markers for the phagocytes. Monoclonal antibodies can be used to target specific substances as they have a particular antibody. The most successful use of monoclonal antibodies involves treating cancer: • The monoclonal antibody attatched to the cancer cells • They block the chemical signals that stimulate the uncontrolled growth of the cells. The cell then undergoes apoptosis The monoclonal antibodies are not toxic and therefore the treatment has fewer side effects. Indirect monoclonal antibody therapy can also be used where a drug is attatched to the monoclonal antibody which then attaches to the cancer cells, killing them, this is cheaper as the doses are smaller and reduces the side effects. Monoclonal antibodies are also used for medical diagnosis (hepatitis, chlamydia, and influenza as an e.g.) they can also diagnose prostrate cancer as men have high levels of prostate specific antigen in their blood and monoclonal antibodies can detect that. Monoclonal antibodies can also be used for pregnancy testing, due to the fact that a hormone called human chorionic gonadatrophin (hCG) is released by the placenta and is found in the urine. The monoclonal antibodies with coloured particles attached to them, bind to hCG and are trapped by a different antibody, creating a coloured line (two lines if pregnant, one if not) Ethical issues regarding monoclonal antibodies: • Monoclonal antibodies involve deliberately inducing cancer in mice, which is a problem for some people due to animal treatment, there are guidelines however regarding minimal suffering. • There are still risks as there have been some deaths treating sclerosis and so both risks and benefits should be mentioned to the patient. • In one of the tests, six healthy volunteers suffered organ failurs after monoclonal antibody use and this raised an issue about the conduct of drug trials. Process as to how monoclonal antibodies are produced: Mouse exposed to non self material which requires an opposing antibody • B cells produce the antibodies which are taken from the spleen cell recognition and immune system 5 They are mixed with cells from a cancer tumour to enable them to divide Detergent is added to break down the cell membrane and fuse the cells together, forming hybridoma cells • Each cell is then cultured to form a clone and they are tested seperately to see if they produce the required antibody antigen-binding sites light chain heavy chain receptor binding site cell recognition and immune system variable region (different in different antibodies) constant region Vaccination There are two types of immunity: • Passive immunity: introduction of antibodies into individuals from an outside source. No pathogen presence and no lasting immunity. • Active immunity: this is when the body's immune system stimulates the production of an antibody, there are two types, and it is a long-lasting process: o Natural active immunity: body produces own antibodies. o Artificial active immunity: immune response due to vaccination, without suffering symptoms. 6 Vaccination is when a vaccine is introduced to the body to stimulate an immune response, which is smaller than usual, and memory cells are produced, which remain in the blood. This then results in a rapid antibody production when in contact with the pathogen again. The success of a vaccination programme depends on a few factors: • Must be economically available in sufficient quantities. • Unpleasant side-effects may discourage individuals in the population from being vaccinated. • Means of producing, storing and transporting the vaccine must be available. • Means of administering the vaccine properly at the appropriate time must be available. • Must be possible to vaccinate majority for herd immunity. Herd immunity is when a large population is immune to a disease due to vaccination that the pathogen cannot spread, this is important as it is impossible to vaccinate all the population however it still results in the protection of non-vaccinated individuals. To achieve it, it is most ideal for everyone to be vaccinated at one time. It can still be extremely difficult to eliminate a disease for the following: • For some people it might fail to make them immune. • Individual might catch the disease directly after the vaccine when immunity levels are not high enough, and they could reinfect others. • The pathogen may mutate, causing the vaccine to become ineffective. This antigenic variability commonly happens with influenza. • There may be many variables of a pathogen. • Some pathogens hide from the immune system such as cholera and therefore the vaccine does not work. • There may be objections against vaccination due to religious, ethical or medical reasons. Ethics: cell recognition and immune system 7 • Production and development involve animal use, is this acceptable, and how acceptable? • How can the risk of side-effects be balanced against the risk of developing a disease that causes even greater harm? • Who should the vaccines be tested on, trials etc.? • It is okay to trial a new vaccine in a country with the targeted disease if the benefits outweigh the negatives? • Should costly vaccine programs continue even if the disease is almost eradicated? • How can health risks be balanced against the advantages of controlling a disease for the benefit of the population at large? The human immunodeficiency virus (HIV) The structure of the human immunodeficiency virus • A lipid envelope is found on the outside and contains attachment proteins. • A protein layer called the capsid is found inside the envelope and encloses two strands of RNA and some enzymes (one being reverse transcriptase which catalyses the production of DNA from RNA, this means HIV belongs to a group of viruses called retroviruses) HIV uses its genetic material to instruct the host cell to produce the materials needed to make new HIV. First, HIV enters the bloodstream and circulates around the body, a protein on the HIV binds to a protein called CD4, this usually happens on T-helper cells. The capsid fuses with the cell membrane and the RNA and enzymes of the HIV enter the cell. Reverse transcriptase then converts the virus' RNA to DNA which moves to the T-helper cell's nucleus and enters the cell's DNA. It creates mRNA, using the cells enzymes, which contains instruction to make a viral protein and make the RNA go into the new HIV. The mRNA then leaves the nucleus and makes HIV particles using the cells mechanisms. The HIV particle then leaves the cell, taking a small section of the cell-surface membrane which forms a lipid envelope. HIV interferes with the function of the T-helper cells, and lowers the volume available, this results in a lack of B cells or cytotoxic T cells. Memory cells can also be infected cell recognition and immune system 8 and destroyed and therefore the body's immune response becomes greatly weakened, allowing diseases to become more deadly as they are unable to be countered. The ELISA test (enzyme linked immunosorbent assay) uses antibodies to detect the presence and quantity of a protein. An antibody that is specific to the antigen we are trying to detect is added, allowing them to bind together, and the excess antibodies are then washed off. A second antibody containing an enzyme then binds with the first and the colourless substrate of the enzyme is added, which changes it into a coloured product, and the amount of the antigen present is determined by the intensity of the colour. This technique is used to detect HIV and other pathogens such as tuberculosis and hepatitis, it is also used when testing for drugs and the amount present. Antibiotics inhibit certain enzymes required for the synthesis and assembly of the peptide cross-linkages in bacterial cell walls, which weakens the walls and makes them unable to withstand pressure, which causes the bacteria to die. Viruses however rely on the host cells and don't have their own metabolic pathways and cell structures; therefore, antibiotics are ineffective against them. Furthermore, they have a protein coat rather than a murein cell wall and therefore do not have sites where antibiotics can work. Also the antibiotics can't reach them. cell recognition and immune system 9