The shape of the lesson
By the end of the lesson, learners can
- Structure that fits function: With the structure chip on, click each part of the antibody: the heavy chains (blue), light chains (green), variable regions (orange), constant region, hinge and disulfide bonds.
- Making one antibody in bulk: Step through the chips 1 immunise, 2 fuse, 3 screen and 4 clone.
- Variable region: antigen-binding site, complementary, two per antibody.
- Constant region: binds phagocytes; hinge: flexibility; disulfide bonds: hold chains.
- Hybridoma = B cell + myeloma: immunise, fuse, screen, clone.
- Diagnosis: detect one antigen; treatment: target one cell type.
One picture every idea returns to
An antibody is a globular glycoprotein made by plasma cells. It has four polypeptide chains, two long heavy chains and two short light chains, held together by disulfide bonds. The tips form two variable regions whose antigen-binding sites are complementary to one specific antigen; the constant region is the same for a class of antibodies and binds to receptors on phagocytes; a hinge region gives flexibility. Antibodies cause agglutination, neutralise toxins and viruses and mark pathogens for phagocytosis (opsonisation). Monoclonal antibodies, identical antibodies from one clone, are made by the hybridoma method: B cells from an immunised mouse are fused with myeloma cells, and the hybridoma making the wanted antibody is selected and cloned. Because they bind one antigen, they are used to diagnose disease (pregnancy tests, locating cancers) and to treat it (targeting cancer cells).
Forty-five minutes, phase by phase
| Time | Phase | What happens in the room | Grouping |
|---|---|---|---|
| 0 to 5 min | Hook: predict | Open with the question in the title, A protein shaped like a Y, built to fit.. Every antibody has the same basic shape, but the tips of its two arms differ from one antibody to the next. Put the figure on the board: it is the one picture every idea in the lesson returns to. | Whole class, then pairs |
| 5 to 17 min | Teach and check: Structure that fits function | With the structure chip on, click each part of the antibody: the heavy chains (blue), light chains (green), variable regions (orange), constant region, hinge and disulfide bonds. Project tab 5 of the lab (Immunity lab, antibody structure and function) and let a student drive it while the class predicts. | Whole class, then pairs |
| 17 to 30 min | Teach and check: Making one antibody in bulk | Step through the chips 1 immunise, 2 fuse, 3 screen and 4 clone. Project tab 6 of the lab (Immunity lab, monoclonal antibodies) and let a student drive it while the class predicts. | Mix-Pair-Share |
| 30 to 36 min | Check | The four Stage 1 questions from the student lesson, answered on mini whiteboards or by show of fingers. Re-teach the one most get wrong. | Individual, then whole class |
| 36 to 43 min | Plenary | The exam-style questions from Stage 2, one at a time: thirty seconds alone, then a random call. The feedback lines in the key give the examiner's wording. | Individual, random call |
| 43 to 45 min | Exit and homework | Set the worksheet below (6 questions, 19 marks). Learners self-assess against the objectives before they leave. | Individual |
Protect the parts that carry the learning
The sequence carries about fifty minutes of material, so the lab is driven by one student while the class predicts rather than explored freely. Times are a guide.
Protected: the check at 30 minutes. It is the only individual read on whether the key idea landed, and it is not cut.
Cut first if the build overruns: the last check in Making one antibody in bulk, never the check or the plenary.
In a 60 minute block: run worksheet questions 1 to 3 in class as a Rally Coach set and model both the hardest worked example and its check live.
Mix-Pair-Share
Students mix around the room until you call pair; they pair with the nearest classmate, discuss the prompt, then mix again. Three prompts of rising difficulty, three different partners.
The full structure, with its variations and the other twelve, is on the cooperative-learning page.
What to head off, and how
| Trap learners fall into | Teaching move that pre-empts it |
|---|---|
| The antigen-binding site is in the variable region, made by both a heavy and a light chain. | Do not put the binding site on the constant region, and do not call the variable region the "active site": that term is for enzymes. |
| A hybridoma is a fusion of a B-lymphocyte (or plasma cell) with a myeloma cell. | Answers that fuse "a B cell with a T cell" or "two plasma cells" lose the mark. |
Antibodies and monoclonal antibodies: worksheet
6 questions, 19 marks. Written in the style of the papers; no past paper question is reproduced.
Relate the structure of an antibody molecule to its function.
Describe three ways in which antibodies help to destroy or disable pathogens.
Outline the hybridoma method for producing monoclonal antibodies.
Explain how a pregnancy test strip uses monoclonal antibodies to detect the hormone hCG in urine.
Some breast cancer cells have large numbers of a particular receptor protein on their surface. Suggest how a monoclonal antibody could be used to treat this cancer.
Monoclonal antibodies made in mice can cause an immune response when given to patients. Explain why, and suggest how this problem is reduced.
Answer key and marking notes
- Variable regions have a specific shape that is complementary to one antigen, so the antibody binds only that antigen.
- There are two antigen-binding sites, so one antibody can bind two antigens and cause agglutination.
- The hinge region gives flexibility, so the antibody can bind antigens different distances apart.
- Disulfide bonds hold the four polypeptide chains together; the constant region binds receptors on phagocytes (opsonisation).
- Agglutination: antibodies clump pathogens together, so they cannot spread and are easier for phagocytes to engulf.
- Neutralisation: antibodies bind to toxins or to the attachment sites of viruses, so they cannot affect or enter host cells.
- Opsonisation: antibodies coat pathogens, marking them so phagocytes recognise and engulf them faster.
- A mouse is injected with the antigen, and B-lymphocytes making the antibody are taken from its spleen.
- The B cells are fused with myeloma (cancer) cells to form hybridoma cells.
- Hybridomas are grown separately and screened to find those making the required antibody.
- The selected hybridoma is cloned and grown in culture; the identical (monoclonal) antibodies are collected and purified.
- Mobile monoclonal antibodies with a coloured marker bind to hCG in the urine.
- The hCG-antibody complex moves along the strip and binds to fixed antibodies at the test line, so a coloured line forms.
- Unbound labelled antibodies are trapped at the control line, which shows the test has worked.
- A monoclonal antibody complementary to the receptor binds only to the cancer cells.
- It can block the receptor so growth signals cannot bind, slowing division of the cancer cells.
- It may also mark the cells for destruction by the immune system or carry an attached drug to them, so healthy cells are less affected.
- Mouse antibodies are proteins with non-self antigens, so the patient's immune system makes antibodies against them.
- Humanised antibodies are made, in which most of the molecule (except the binding sites) is human, so they are less likely to be recognised as non-self.
8 multiple-choice questions on this lesson
From the topic question bank. Assign them in the app for a marked score in your gradebook, or run the topic as a class game.
The diagram shows an antibody molecule. Which labelled part binds to a specific antigen?
- A1
- B2
- C3
- D4
Which type of bond holds the heavy and light chains of an antibody together?
- Adisulfide bonds
- Bpeptide bonds
- Cglycosidic bonds
- Dphosphodiester bonds
Antibodies produced against a toxin bind to the toxin and stop it affecting body cells. What is this action called?
- Aneutralisation
- Bagglutination
- Copsonisation
- Dphagocytosis
In the hybridoma method, which two cell types are fused?
- Aa B-lymphocyte from an immunised mouse and a myeloma cell
- Ba T-helper cell and a myeloma cell
- Ca B-lymphocyte and a macrophage
- Dtwo plasma cells from the same mouse
A doctor wants to find the exact position of a tumour in a patient's body. Which use of monoclonal antibodies would help?
- Aantibodies against a tumour antigen, labelled with a radioactive marker, are injected and detected by a scanner
- Bantibodies against the tumour are injected and the patient is tested for a fever
- Cantibodies from the patient's blood are mixed with tumour cells in a test tube
- Da vaccine containing tumour antibodies is given and memory cells are counted
A pregnancy test strip contains mobile antibodies with coloured markers that bind hCG, fixed antibodies at the test line that bind hCG, and fixed antibodies at the control line that bind the mobile antibodies. After use, a strip shows a coloured test line but no control line. What should be concluded?
- Athe result is invalid because the strip has not worked correctly
- Bthe woman is pregnant, because the test line is coloured
- Cthe woman is not pregnant, because the control line is missing
- Dthe urine contained no hCG but contained other antibodies
A monoclonal antibody used to treat a cancer binds to growth-factor receptors on the cancer cells. Which statement explains why it has fewer side effects than a drug that kills all dividing cells?
- Ait binds only to cells that carry the specific receptor shape, so most healthy cells are unaffected
- Bit kills cancer cells faster, so the drug leaves the body sooner
- Cit is a protein, so it cannot cause any immune response
- Dit stimulates memory cells that destroy the cancer permanently
Antibody molecules were treated with an enzyme that cuts them at the hinge region, separating the two arms from the constant region. The separated arms still bound to a virus but no longer caused clumping, and phagocytes did not engulf the coated virus faster. Which explanation fits all these results?
- Aeach arm has one antigen-binding site, so it cannot link two viruses, and without the constant region phagocyte receptors cannot bind
- Bthe enzyme destroyed the variable regions, so the arms bound to the virus non-specifically
- Cthe hinge region is the antigen-binding site, so the virus was no longer recognised
- Dthe constant region is needed for binding to the virus, so the arms bound weakly
Quiz key
Part 1 is the tip of an arm, the variable region, which forms the antigen-binding site. Part 2 is the constant region at the base, which binds to receptors on phagocytes. Part 3 is the hinge region, which gives flexibility. Part 4 is a light chain in the middle of an arm; it contributes to the binding site only at its tip, not along its length.
Disulfide bonds between cysteine R groups link the four polypeptide chains. Peptide bonds join amino acids within each chain, not the chains to each other. Glycosidic bonds link sugars, and phosphodiester bonds link nucleotides; neither joins polypeptides.
Antitoxins neutralise a toxin by binding to it and blocking the part that acts on cells. Agglutination is the clumping of pathogens by antibodies with two binding sites. Opsonisation is coating a pathogen so phagocytes engulf it faster. Phagocytosis is the engulfing itself, carried out by phagocytes, not antibodies.
A B-lymphocyte from the spleen of an immunised mouse makes the wanted antibody but does not divide in culture; a myeloma (cancer) cell divides indefinitely. The hybridoma does both. T-helper cells and macrophages do not make antibodies. Fusing two plasma cells would give a cell that still cannot divide indefinitely.
Monoclonal antibodies bind only to the specific antigen on the tumour cells, and an attached radioactive label shows where they have collected. A fever is not specific to the tumour. Mixing the patient's own antibodies with tumour cells in a test tube tells nothing about where the tumour is. Vaccines contain antigens, not antibodies, and counting memory cells would not locate anything.
Mobile antibodies should always reach and be trapped at the control line, so it must appear in every working test. If it is missing, the urine may not have flowed or the antibodies may be faulty, so no result can be trusted. Reading the test line alone ignores this check. The missing control line says nothing about hCG either way, and urine is not the source of the antibodies on the strip.
The variable region is complementary to one antigen, so the antibody targets cells carrying that receptor and leaves most healthy dividing cells (for example in the bone marrow and gut lining) alone. Speed of killing is not the reason for fewer side effects. Proteins can cause an immune response, which is why antibodies are humanised. Injected antibodies give passive protection and do not produce memory cells.
The arms keep their variable regions, so they still bind specifically. Agglutination needs two binding sites on one molecule to link two particles; a single arm has only one. Phagocytes recognise the constant region, which has been removed, so opsonisation fails. The variable regions were not destroyed, since binding continued. The hinge is not the binding site, and the constant region is not needed for antigen binding.
What to project
The student lesson embeds these tabs. Open them full screen on the projector; every slider has a drag handle on the stage.
Slides for this lesson
A projectable deck for every pack is on the way. Until then, present the student lesson full screen: its sections, figure and lab tabs follow the same order as the plan above.