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Animations… • http://highered.mheducation.com/sites/007 2507470/student_view0/chapter22/animatio n__the_immune_response.html • • http://www.sbs.utexas.edu/psaxena/Microbi ologyAnimations/Animations/HumoralImmu nity/micro_humoral.swf What is a cytotoxic T cell? Differences between humoral and cell mediated immunity Humoral Immunity Main blood cells involved Where are the cells produced and mature? Production of antibodies? How are pathogens identified? How are pathogens killed? How do cells divide once they are stimulated? Cell mediated immunity Differences between humoral and cell mediated immunity Humoral Immunity Cell mediated immunity Main blood cells involved B lymphocytes T lymphocytes Where are cells produced and mature? Produced and mature in the Produced in the bone marrow, bone marrow mature in the thymus gland Production of antibodies? Involves production of antibodies Does not involve production of antibodies How are pathogens identified? Via antigens in the blood/ tissue fluid Via antigens on the surface of infected cells. How are pathogens killed? By antibodies By specialised ‘cytotoxic T cells’ How do cells divide once they are stimulated? cells divide into either plasma cells or memory cells cells divide into different types of specialist T cells Antibodies Learning Objective: In order to be successful in this lesson you must be able to: The formation of antigen-antibody complexes and the subsequent destruction of pathogens. The definition of an antibody. The structure of an antibody. PROGRESS The formation of antigen-antibody complexes and the subsequent destruction of pathogens. Today we are covering from the specification: Pages 109 - 111 of your text book Why? Antibodies • Antibodies are proteins synthesised by B cells that recognise and bind to specific antigens • Antigens are foreign substances that stimulate the production of antibodies • Many of the molecules on the surface of viruses and bacteria are antigens Antibody Structure The specificity of the antibody depends on its variable regions Antigen Variable regions (red) The constant regions are the same for all antibodies Light chain Hinge region Disulphide bridges Heavy chain Constant regions (blue) Each antibody has a different shaped variable region (Due to different amino acid sequences) that is complementary to one specific antigen Agglutination Antibodies can cause microbes to stick together This makes it easier for phagocytes to engulf them How do antibodies function? Neutralisation Some pathogens make us ill by producing toxins Some antibodies work by neutralising these toxins Opsinisation or the Complement Cascade The binding of an antibody to the surface of a pathogen can set of a chain reaction with blood proteins, which... ... causes the pathogen to swell up an burst. Viruses have proteins on their surface which recognise and bind to receptors on the surface of the host cell This is how many viruses enter their host cell Antibodies can bind to viruses and stop them attaching to their host cells Antibodies • The remarkable specificity of antibodies makes them promising agents for human therapy. But there are problems… • What is needed is a way to make "monoclonal antibodies" – The response of the immune system to any antigen, even the simplest, is polyclonal. That is, the system manufactures antibodies of a great range of structures. – Even if one were to isolate a single antibody-secreting cell, and place it in culture, it would die out after a few generations because of the limited growth potential of all normal somatic cells. What is needed is a way to make "monoclonal antibodies" Monoclonal antibodies • This problem was solved for mice in 1975 with a technique devised by Köhler and Milstein (for which they were awarded a Nobel Prize). • An antibody-secreting B cell, like any other cell, can become cancerous. The unchecked proliferation of such a cell is called a myeloma. • Köhler and Milstein found a way to combine – the unlimited growth potential of myeloma cells with – the predetermined antibody specificity of normal immune spleen cells. • They did this by literally fusing myeloma cells with antibody-secreting cells from an immunized mouse. The technique is called somatic cell hybridization. The result is a hybridoma. What are the monoclonal antibodies used for? • • • • Separation of a chemical from a mixture Immunoassay Cancer treatment Transplant surgery http://www.biotopics.co.uk/microbes/a ntbod.html Ethical production and use of monoclonal antibodies • The development of monoclonal antibodies has provided society with the power to treat diseases in a whole new way. • However with this power and opportunity comes great responsibility. • The use of monoclonal antibodies raises some ethical issues Ethical issues Concerns for animal welfare: • Production involves the use of mice (to produce antibodies and cancer cells). Religious beliefs and Natural Law (based on the principle that God designed the world): • To eliminate the need for humanisation of the antibody, transgenic mice can be used (genetic engineering). Dangers to Humans: • There have been some deaths associated with the use of monoclonal antibodies for the treatment of multiple sclerosis. • Testing for the safety of new drugs presents dangers e.g. monoclonal antibody (TGN1412) induced multiple organ failure in 6 healthy volunteers in London in March 2006. Ethical issues We must balance the advantages that a new medicine provides with the dangers that its production might bring. Then we can make decisions at an individual, local, national and global level about the ethical use of drugs such as monoclonal anitibodies. Learning outcomes Student should be able to understand the following: • Antibody structure and the formation of an antigenantibody complex • The use of monoclonal antibodies in enabling the targeting of specific substances and cells. Candidates should be able to – evaluate methodology, evidence and data relating to the use of monoclonal antibodies – discuss ethical issues associated with the use of monoclonal antibodies – explain the role of the scientific community in validating new knowledge about monoclonal antibodies, thus ensuring integrity – discuss the ways in which society uses scientific knowledge relating to monoclonal antibodies to inform decisionmaking. Plenary: True or False? 1) Antibodies have a variable region specific to a pathogens antigens. 2) Antibodies contain a sulphide bridge. 3) A antigen-antibody complex is formed when an antibody binds to a pathogen’s antigens. 4) Agglutination makes it easier for phagocytes to engulf pathogens. 5) Neutralisation only occurs with viruses. 6) Opsonisation causes phagocytes to swell and burst. 7) Antibodies can stop viruses entering host cells. 8) The primary immune response produces memory cells. 9) The secondary immune response is caused by vaccination. 10) The secondary immune response is quicker. Primary – establishes immunological memory 24 Primary and secondary responses Annotate your graph of the primary and secondary responses by adding the following labels: - First dose of antigen - Second dose of antigen - Time between 1st and second exposure - Primary response - Secondary response Questions: 1) Compare the primary and secondary responses in terms of time taken, decline of antibodies and antibodies produced. 2) Memory cells are produced in the primary response, how else could these be produced without the person being infected? Extra challenge: What causes the secondary response to occur more rapidly? LO: Antibody Concentration – Primary and Secondary Response Primary Response 1. Infection (Ag) 2. Lag phase 3 Antibodies produced 4 Antibody level rises to combat infection 5 Ag dealt with 6 Ab level declines – short lived Secondary Response After the primary response, Antibodies do not stay in blood – the level declines If the body is infected by the same Antigen a second time Antibodies must be made again Re-infection causes much more rapid and a stronger immune response – concentration of Antibodies rises sooner- reaches a higher concentration – more plasma cells than in primary response – more cells to respond to Antigen; less time to produce same number of plasma cells –hence, a greater [Antibody] compared to primary response; increased affinity of Antibody for Antigen. This is due to the presence of memory cells (made during the primary response) – no need for antigen presentation and clonal selection Long-lived; basis of vaccination 27