The immune system IMMUNE SYSTEM NON-SPECIFIC BODY DEFENCES PHAGOCYTES SPECIFIC CELL MEDIATED RESPONSE T LYMPHOCYTES HUMOURAL RESPONSE B LYMPHOCYTES Antigens are molecules (usually proteins) found on the surface of cells which are used by the immune system to identify: Pathogens Non-self cells Toxins Abnormal body cells (such as cancer) This is important so that the immune system does not destroy the organism’s own tissues. Phagocytes Once the pathogen has entered the body, the first line of defence is phagocytosis. A phagocyte (e.g. a macrophage) is a type of white blood cell that carries out phagocytosis, they are found in the blood and in tissues. A phagocyte recognises the foreign antigens on a pathogen The cytoplasm of the phagocyte moves round the pathogen, engulfing it A lysosome fuses with the phagocytic vacuole, the lysozymes break down the pathogen The phagocytes then present the pathogen’s antigens (antigens stick to surface to activate other immune system cells) Lymphocytes T lymphocytes (T cells) are so called because they mature in the thymus gland. They are associated with cell-mediated immunity (involving body cells) T lymphocytes will only respond to antigens that are presented on a body cell (they can also respond to cancer cells and transplanted cells.) The receptors on each T cell respond to a single antigen, therefore there are millions of T cells each responding to a different antigen. The response of T lymphocytes to infection: Phagocyte places antigens from pathogen on its cell surface membrane Receptors on a specific T helper cell (TH cell) fit exactly onto these antigens This activates the T cell to divide rapidly by mitosis, the T cells: o Develop into memory cells that enable rapid response to future infections of the same pathogen o Stimulate phagocytes o Activate cytotoxic T cells (TC cells) o Stimulate B cells to divide (which secrete antibodies) Cytotoxic T cells kill cells that are infected by pathogens by producing a protein called perforin, which makes holes in the cell-surface membrane. This causes the cell membrane to become freely permeable to all substances and the cell dies. B lymphocytes (B cells) are so called because they mature in bone marrow. They are associated with humoral immunity (antibodies in body fluids). B cells are covered with specific antibodies which bind to antigens in the blood or tissue fluid in the body Each B cell has a different shaped antibody, and responds to a single antibody therefore there are millions of different B cells Role of B cells in humoral immunity: Surface antigens of a pathogen are taken up by the B cell by endocytosis and are processed and presented on its surface Helper T cells attach to the presented antigens, activating the B cell The B cell then divides by mitosis to form a clone of identical B cells (called plasma cells) this is clonal selection The cloned plasma cells all produce and secrete identical specific antibodies that exactly fit the antigens on the pathogen The antibody attaches to the pathogen and destroys it o Some B cells develop into specific memory cells, which can respond to future infections of the same pathogen by dividing into plasma cells which produce antibodies Antibodies Antibodies are large Y shaped proteins which are produced by plasma cells. The specificity of an antibody depends on its variable regions, which form the antigen binding sites Each antibody has a variable region with a unique tertiary structure, that’s complementary to one specific antigen Antibodies bind to the antigens on the surface of pathogens to form lots of antigenantibody complexes. Antibody has two binding sites, so binds to two pathogens at the same time o This causes the pathogens to clump together agglutination making it easier for phagocytes to locate them They then act as markers to stimulate phagocytosis of the pathogen they are attached to Primary immune response When antigen enters body for first time Primary response is slow because not many B-cells to make antibody Eventually body produces enough antibodies Memory T-cells remember specific antigen Memory B-cells remember specific antibodies Secondary immune response If same antigen enters body again, there is a faster response Clonal selection happens faster, memory B-cells divide into plasma cells, which produce lots of antibodies Destroys pathogen before you show symptoms Vaccination Vaccines contain antigens which cause a primary immune response without causing disease Antigens may be free, or attached to attenuated pathogen (weakened) This produces memory cells against pathogen Allows for secondary immune response next time Herd immunity Provide vaccination to all population at risk Once enough people are immune, the disease will stop spreading Active and passive immunity Immunity Natural active Natural passive Artificial active Artificial passive Example Direct contact with pathogen Antibodies through breast milk Vaccination Injection of antibodies Antigen Variability Due to genetic mutation some pathogens change their surface antigens (antigen drift) Therefore memory cells from first infection will not recognise the pathogen This means there is no secondary immune response E.g. influenza virus – memory cells from vaccination do not recognise new strain Human immunodeficiency virus (HIV) HIV is a virus which affects the immune system, it leads to acquired immune deficiency syndrome. HIV infects and kills T helper cells. A core that contains genetic material (RNA) and reverse transcriptase This is enclosed by a protein layer called a capsid Lipid envelope, with lots of attachment proteins HIV can only replicate inside T helper cells: Attachment protein attaches to a receptor molecule on the T helper cell Capsid is released into the cell, where it uncoats, RNA enters cell Reverse transcriptase converts the RNA into DNA This DNA is inserted into the human DNA Host cell is used to make viral proteins and RNA The viral proteins are assembled into new viruses, which use a piece of the T helper cell’s membrane as the lipid envelope During initial infection, HIV replicates rapidly and the infected person may experience flu like symptoms. However the replication of HIV often goes into dormancy, and the infected person will not experience any symptoms (can last for years). HIV reduces the number of T helper cells in the blood. T helper cells are important in cell mediated immunity, with a reduced number of T helper cells, the immune system is unable to stimulate B cells or cytotoxic T cells. Therefore AIDS sufferers are much more susceptible to infections and disease. HIV does not cause death directly, it weakens the immune system so that it is less able to respond to other pathogens. These infections can cause death Antibiotics are ineffective against viruses Antibiotics kill bacteria by interfering with their metabolic activities E.g. penicillin interferes with cell wall production Viruses rely on host cells, and so don’t have their own enzymes and ribosomes Antibiotics can’t inhibit them because they don’t target human processes Monoclonal antibodies Monoclonal antibodies are antibodies produced from a single group of genetically identical B-cells. They have a number of useful functions in science and medicine Targeting drugs to a particular type of cell e.g. cancer Monoclonal antibodies are produced which are specific to antigens on cancer cells You can attach anti-cancer drugs to these antibodies Once given to a patient, they attach to the surface of their cancer cells The drug only accumulates where there is cancer Because the antibodies are highly specific, it leads to less side effects. Use in medical diagnosis e.g. pregnancy testing The placenta produces human chorionic gonadotrophin (hCG), found in the mother’s urine Monoclonal antibodies are linked to coloured particles If hCG is present in urine, it binds to these antibodies forming an antigen-antibody complex The urine moves up the test strip, carrying the coloured particles, creating a coloured line Enzyme-linked immunosorbent assay (ELISA) test The ELISA test uses antibodies to detect the presence and quantity of an antigen/ antibody: Apply sample to surface e.g. a slide, to which all sample antigens will attach Wash the surface to remove unattached antigens Add the specific antibody that is complementary to the antigen Wash the surface to remove excess antibodies Add a detection antibody with an enzyme attached, this binds to the first antibody Add the colourless substrate of the enzyme, the enzyme will digest and cause colour change The amount of antigen present is relative to intensity of colour This can be used to test for HIV by binding HIV antigens and adding a patient’s blood plasma. Ethics Use of animals to produce vaccines Vaccines may have unknown side effects, how should human trials be carried out? Should everyone be forced to be vaccinated?