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Antibodies Learning Objective: In order to be successful in this lesson you must be able to: Apply your knowledge of antibodies to explain how monoclonal antibodies are used to target specific substances and cells. Learning Outcomes: Describe the structure and function of antibodies. In order to Apply your knowledge of •Describe the nature of antibodies to explain how a monoclonal antibody monoclonal antibodies and how they are they be successful in this lesson you are must able specific to: usedbe to target produced. substances and cells. Key Words: Antibody, antigen, mononoclonal, polyclonal What are Antibodies? Antibodies are also known as immunoglobulins. Antibodies are proteins synthesised by B lymphocytes (there may be as many as 10 million different B cells each making it’s own antibody which responds to one specific antigen.) Antibodies are very specific, each antigen has it’s own antibody. Antibodies have a binding site that fits very precisely onto the antigen to form an antigen-antibody complex. Task 1 (10 mins) Label the different regions of an antibody using the labels provided. Annotate the diagram giving as much information as you can about each label. Support: Text books – Page 111 Extra challenges: 1) Explain the importance of the variable regions. 2) Explain the structure of antibodies in terms of the hierarchy of protein structure. 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 form a 3D shape) that is complementary to one specific antigen Antibody exam question Antibody exam question answer M2. (a) Has more than one / four polypeptide chains / made up of polypeptide chains; 1 (b) 1. Antibody / variable region has specific amino acid sequence / primary structure; 2. The shape / tertiary structure of the binding site; Do not accept active site for this point. 3. Complementary to / fits / binds with these antigens; Accept active site for this point. 4. Forms complex between antigen and antibody; 3 max [4] How do antibodies function? Agglutination Antibodies can cause microbes to stick together This makes it easier for phagocytes to engulf them Learning Objective: In order to be successful in this lesson you must be able to: Apply your knowledge of antibodies to explain how monoclonal antibodies are used to target specific substances and cells. Monoclonal antibodies- what are they? A micro organism such as a bacterium has hundreds of different antigens on its surface. Each antigen will induce a different B cell to multiply and form a clone of itself. Each clone will produce a different antibody. It is useful to medicine if we can produce antibodies outside the body and even more useful if a single type of antibody can be isolated and cloned. Work to do Task 2 Read through the textbook pages 112-114 making sure that you understand the content of each subheading as you go through it. Use your partner’s knowledge and information on the blog to help you understand the basic concepts. (10 minutes). Task 3 Research the task allocated to you and prepare one slide to help you teach your section to the rest of the group. (15 minutes) Task 4 Use your slide to teach your individual section (15 minutes) Group Tasks to present at the end of the lesson Warren Monoclonal antibodies and medical diagnosis Stijn Monoclonal antibodies and medical diagnosis (the direct and indirect ELISA test) p120 Maarya Monoclonal antibodies and pregnancy testing Tytus Ethics of using monoclonal antibodies Joseph Targeting medication to specific cell types using monoclonal antibodies. Huw Monoclonal antibodies and how they are produced. Producing monoclonal antibodies The response of the immune system to any antigen, even the simplest, is polyclonal. That is, the system manufactures antibodies for a great range of proteins found on the cell surface membrane. • Even if you 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" Producing 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. Monoclonal antibody production How monoclonal antibodies work to treat cancer Targeting medication to specific cell types by attaching a therapeutic drug to an antibody is one way to treat cancer. There are however many more. Ways Monoclonal antibodies can be used to treat cancer How monoclonal antibodies work to treat cancer Antibody specificity Though there are lots of proteins (antigens) present on this cancer cell, only the one that is different to ordinary body cells is chosen to be a target for the monoclonal antibody. Why? Using monoclonal antibodies in medical diagnosis Monoclonal antibodies are an invaluable tool for diagnosing disease (over 100 diagnostic products based on them) Examples of infections diagnosed are influenza, hepatitis, and chlamydia. They are also important in diagnosing certain cancers such as prostate cancer in men. Men with prostate cancer often produce more of a protein called prostate specific antigen (PSA) leading to high levels in the blood. By using a monoclonal antibody specific to PSA you can identify the levels of PSA in the blood – not a diagnosis in itself however raised levels can be an early warning sign. Pregnancy testing Can you describe how this test works? 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 Production involves the use of mice (to produce antibodies and cancer cells). To eliminate the need for humanisation of the antibody, transgenic mice can be used (genetic engineering). 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. Learning Objective: In order to be successful in this lesson you must be able to: Apply your knowledge of antibodies to explain how monoclonal antibodies are used to target specific substances and cells. Learning Outcomes: Describe the structure and function of antibodies. In order to Apply your knowledge of •Describe the nature of antibodies to explain how a monoclonal antibody monoclonal antibodies and how they are they be successful in this lesson you are must able specific to: usedbe to target produced. substances and cells. Key Words: Antibody, antigen, mononoclonal, polyclonal