Antibodies and vaccination

1. Overview

An antibody is a Y-shaped glycoprotein made by plasma cells that binds to a specific antigen and helps destroy it. Its molecular structure - two heavy chains and two light chains with variable and constant regions - is directly linked to how it works. Monoclonal antibodies are identical antibodies produced from a single clone of cells using the hybridoma method, and they are used in the diagnosis and treatment of disease. This topic also covers the four types of immunity (active/passive and natural/artificial), how vaccines contain antigens that trigger long-term immunity, and how vaccination programmes control infectious disease through herd immunity.

Key Definitions

• Antibody: a glycoprotein (immunoglobulin) made by plasma cells that binds specifically to a particular antigen and helps to destroy it.
• Antigen: a molecule, usually a protein or glycoprotein on a cell surface, that the immune system recognises as foreign and that stimulates an immune response.
• Agglutination: the clumping together of pathogens when antibodies bind to several of them at once, making them easier for phagocytes to engulf.
• Opsonin: an antibody (or other molecule) that coats a pathogen and tags it for recognition and engulfment by phagocytes.
• Monoclonal antibody: a population of identical antibody molecules produced by a single clone of plasma cells, all specific to one antigen.
• Hybridoma: a cell formed by fusing an antibody-producing plasma cell (B-lymphocyte) with a cancerous myeloma cell, which divides repeatedly and secretes one type of antibody.
• Active immunity: immunity gained when the body makes its own antibodies and memory cells after exposure to an antigen.
• Passive immunity: immunity gained when antibodies made by another individual are introduced into the body, giving immediate but short-term protection.
• Natural immunity: immunity gained through everyday processes such as infection or the transfer of antibodies from mother to child.
• Artificial immunity: immunity gained through medical intervention such as vaccination or the injection of antibodies.
• Vaccine: a preparation containing antigens that stimulates an active immune response and the formation of memory cells without causing the disease.
• Herd immunity: the protection of unvaccinated individuals that occurs when a high proportion of a population is immune, so transmission of the pathogen is greatly reduced.

Content

Antibody structure and how it relates to function

An antibody molecule is made of four polypeptide chains held together by disulfide bonds: two longer heavy chains and two shorter light chains, arranged in a Y shape. This is the quaternary structure of the protein. Each chain has a variable region at the tip of the arms and a constant region forming the rest.

Two terms describe what antibodies do once they have bound a pathogen:

• Agglutination - one antibody binds two pathogens at once, so many pathogens become clumped together.
• Opsonisation - the antibody coats a pathogen and acts as an opsonin, tagging it so that phagocytes recognise and engulf it.

Structure links to function in several ways:

• The variable region differs between antibodies and forms two identical antigen-binding sites. The shape of each site is complementary to one specific antigen, so binding is highly specific - this is why one antibody recognises only one antigen.
• Having two binding sites allows one antibody to bind two pathogens at once, causing agglutination (clumping), which makes them easier for phagocytes to engulf.
• The constant region has the same shape in all antibodies of a class. It allows phagocytes to bind to the antibody (the antibody acts as an opsonin, marking the pathogen for destruction) and can activate other defence proteins.
• The hinge region between the arms gives flexibility, so the binding sites can move to attach to antigens that are different distances apart.

In summary, antibodies destroy pathogens by agglutination, by acting as opsonins that tag pathogens for phagocytosis, by neutralising toxins, and by preventing pathogens from binding to and entering host cells.

The hybridoma method for making monoclonal antibodies

A monoclonal antibody is a single, pure type of antibody made by a clone of identical cells. Plasma cells make exactly the antibody we want but die after a few days in culture, so they are fused with myeloma (cancer) cells, which divide indefinitely. The fused cell is a hybridoma, combining both useful properties.

The outline steps are:

1. Inject a mouse (or other mammal) with the antigen so that its B-lymphocytes are stimulated to make the required antibody.
2. Remove B-lymphocytes (plasma cells) from the animal's spleen.
3. Fuse these plasma cells with myeloma cells to form hybridomas.
4. Select and screen the hybridomas to find those producing the required antibody.
5. Allow the chosen hybridoma to divide repeatedly (clone it), so it forms a large population of identical cells secreting the same monoclonal antibody.
6. Extract and purify the monoclonal antibody from the culture medium.

Using monoclonal antibodies in diagnosis and treatment

Because each monoclonal antibody binds to one specific antigen, it can be used to detect or target that molecule precisely.

In diagnosis - antibodies are used to find a particular molecule:

• They can be attached to a coloured dye, fluorescent marker or enzyme and used to detect a specific antigen in a sample. Pregnancy tests, for example, use monoclonal antibodies that bind to a hormone present in the urine of a pregnant person.
• They are used to locate specific molecules, such as antigens on cancer cells, and to identify blood groups or pathogens.

In treatment - there are two distinct strategies, so be clear about which one you mean:

• Targeted delivery (the "magic bullet"). An antibody that binds only to antigens on cancer cells is linked to a drug or radioactive substance. The antibody carries the treatment straight to the diseased cells, so healthy tissue is largely spared.
• Blocking action. A different monoclonal antibody simply binds to and blocks a specific receptor or signalling molecule involved in disease, for example damping down inflammation in autoimmune conditions. Here the antibody is the treatment itself - nothing is delivered.

Types of immunity: active vs passive and natural vs artificial

Immunity can be classified in two ways at once.

Feature	Active immunity	Passive immunity
Source of antibodies	the body makes its own in response to an antigen	ready-made antibodies from another source are introduced
Memory cells formed?	Yes	No
Speed of protection	slower to develop	immediate
How long it lasts	long-lasting	short-term (antibodies are gradually broken down)

Each of these can in turn be natural or artificial:

	Natural	Artificial
Active	antibodies and memory cells made after catching an infection	antibodies and memory cells made after a vaccination
Passive	antibodies passed from mother to baby across the placenta or in breast milk	antibodies injected into the body, e.g. anti-venom or anti-tetanus antibodies

How vaccines provide long-term immunity

A vaccine contains antigens from a pathogen - these may be a weakened or dead pathogen, a part of the pathogen, an inactivated toxin, or a harmless molecule carrying the antigen. The antigens are recognised as foreign and trigger the primary immune response: specific B-lymphocytes are activated, divide, and form plasma cells that secrete antibodies, plus memory cells. The vaccine does this without causing the disease.

The key to long-term immunity is the memory cells that remain in the body. If the real pathogen later enters, these memory cells trigger the secondary immune response, which is faster and produces more antibodies for longer, so the pathogen is destroyed before symptoms appear. Booster vaccinations give the body further exposures to the antigen, increasing the number of memory cells and so strengthening and prolonging immunity.

The graph below illustrates the shape of this pattern: compared with the first exposure, the second exposure to the same antigen produces a response that rises sooner, climbs to a much higher antibody concentration, and stays raised for longer. (The axes are not to scale - the figure shows the contrast in shape, not exact concentrations or times.)

Worked example

Exam-style question: A child catches measles and recovers. Their younger sibling is given the measles vaccine. Explain why both children are now protected against measles, and state which type of immunity each has. [4]

Model answer:

• Both children have made their own antibodies and formed memory cells against the measles antigen, so each has active immunity.
• The child who caught the infection acquired immunity through natural exposure to the pathogen, so this is active natural immunity.
• The sibling was given a vaccine containing antigens through medical intervention, so this is active artificial immunity.
• In both, if measles antigens enter again, memory cells trigger a faster, larger secondary response, destroying the pathogen before symptoms develop.

How vaccination programmes control infectious disease

Vaccination programmes reduce the spread of disease in a population, not just in individuals:

• A vaccinated person who later meets the pathogen mounts a rapid secondary response, so they are unlikely to develop the disease or pass the pathogen on.
• When a high proportion of the population is immune, there are too few susceptible people for the pathogen to spread easily. This is herd immunity, and it protects vulnerable individuals who cannot be vaccinated (such as very young babies or people with weakened immune systems).
• Ring vaccination (vaccinating everyone around a new case) and large-scale programmes can stop outbreaks and, in some cases, lead to a disease being eradicated.

Some pathogens are harder to control with vaccines. Pathogens such as influenza viruses show antigenic variation: changes in the shape of their surface antigens mean existing memory cells and antibodies no longer match, so the vaccine must be updated for new strains. This is a change in antigen shape, not a "resistance" to antibodies.

Worked example

Exam-style question: A graph shows the antibody concentration in a person's blood after a first injection of a vaccine and, some weeks later, a second (booster) injection of the same vaccine. Compare the two responses shown and explain the difference. [4]

Model answer:

• After the first injection there is a delay before antibodies appear, and the concentration rises to only a low peak - this is the primary response.
• After the second injection the antibody concentration rises much sooner, reaches a far higher peak, and stays raised for longer - this is the secondary response.
• The first exposure caused B-lymphocytes to form memory cells as well as plasma cells.
• On the second exposure these memory cells recognise the same antigen and rapidly divide into many plasma cells, so antibodies are produced faster and in greater quantity.

Worked example

Exam-style question: To stop a disease spreading, about 92% of a population must be immune. A town vaccinates 85% of its people. Explain whether an outbreak of the disease could still occur. [3]

Model answer:

• $85\%$ is below the $\sim 92\%$ threshold needed to break transmission, so herd immunity is not achieved.
• Enough susceptible (non-immune) people remain for the pathogen to be passed from person to person, so an outbreak can still occur and spread.
• The unvaccinated and vulnerable individuals (e.g. those who cannot be vaccinated) are at risk of catching the disease.

Key Equations

This is a qualitative topic, so there are no equations to learn; focus instead on precise terminology and the sequence of events in each immune response.

Common Mistakes to Avoid

• Mixing up the cell-mediated (T-lymphocyte) and humoral (B-lymphocyte) responses. If a question asks about T-cells, write about antigen presentation, killer (cytotoxic) T-cells and cytokines; if it asks about antibody production, write about B-lymphocytes and plasma cells. Read which one is wanted.
• Calling antibody chains "alpha and beta chains". Those terms belong to haemoglobin. Antibodies are built from heavy chains and light chains only.
• Saying antibodies "disappear" from the blood. They are gradually broken down (degraded) by enzymes - use precise wording.
• Confusing "immunity" with "resistance". Humans (and other organisms) develop immunity to pathogens; bacteria develop antibiotic resistance. Antibiotics act on bacteria, not on human cells, so people never become "immune to antibiotics".
• Saying a virus becomes "resistant" to antibodies. A new vaccine or antibody is needed because the shape of the viral antigens changes (antigenic variation), so existing antibodies no longer fit - this is not resistance.
• Treating "HIV" and "AIDS" as the same thing. HIV is the virus that is transmitted; AIDS is the condition that develops when the immune system has been severely damaged.
• Confusing active and passive immunity. Active = the body makes antibodies (slow but long-lasting, with memory cells); passive = antibodies are received ready-made (immediate but short-lived, no memory cells).
• Saying a vaccine "contains antibodies". A vaccine contains antigens; the body then produces its own antibodies in response.

Exam Tips

• When explaining antibody structure, always link each feature to a function (e.g. "the variable region forms a binding site complementary to one antigen, so binding is specific") - description alone earns fewer marks.
• For the hybridoma method, give the steps in the correct order and name the myeloma cell and the hybridoma specifically.
• For "type of immunity" questions, give both labels - state whether it is active or passive and natural or artificial.
• For "suggest/outline one use of a monoclonal antibody", name the specific antigen targeted and what the antibody is linked to or blocks - e.g. "the antibody binds hCG in urine, producing a coloured line" for a pregnancy test. Vague answers like "they detect disease" are not credited without a named target molecule and mechanism.
• Always credit memory cells when explaining long-term immunity and the faster, larger secondary response.
• When reading a primary-vs-secondary response graph, quote three differences - the secondary response is faster, larger and longer-lasting - and explain each in terms of memory cells.
• For herd immunity, explain that a high enough proportion must be immune to break transmission, and note that this protects people who cannot be vaccinated.
• Use exact terms throughout: antigen vs antibody, plasma cells, complementary, agglutination, degraded - precise vocabulary is rewarded.