Antigens and Cell Recognition

Cells carry characteristic molecules on their surfaces, including proteins. The immune system can recognise differences between these surface molecules, helping it distinguish the body’s own cells from foreign or abnormal material.

An antigen is a molecule or molecular structure recognised by a specific antibody or lymphocyte receptor. Antigens differ in their molecular structures, so a particular antibody or receptor recognises some antigens but not others. This provides a basis for specific recognition.

Antigens on cells and other material

Surface molecules can identify pathogens, cells from another organism of the same species, and abnormal body cells. Their antigens may differ from those normally found on the body’s own cells, allowing the immune system to recognise them as foreign or abnormal.

Antigens are not restricted to cells. For example, toxins are not cells, but they can also be recognised as foreign. Antigens on cells and other foreign material can initiate an immune response.

Antigen Variability

Antigens are structures that the immune system can recognise. Different variants of the same pathogen can have different antigens, and a pathogen’s antigens can also change over time. This is called antigen variability.

Immune recognition is specific to antigen structure. After an infection, the immune system produces antibodies and memory cells that recognise particular antigens. If a later variant has different antigens, the existing antibodies may bind less effectively and the memory cells may recognise it less well. The immune response may therefore be less effective, allowing the person to develop the disease again.

Antigen variability also makes disease prevention more difficult. A vaccine produces protection against the antigens it presents to the immune system, but that protection may not recognise every variant equally well. If the pathogen’s antigens change over time, the protection produced by the vaccine may become less effective.

Phagocytosis of Pathogens

Some white blood cells protect the body by surrounding and digesting pathogens. These cells are called phagocytes, and the process is called phagocytosis.

A phagocyte recognises a pathogen and extends its cell membrane around it. The membrane closes, engulfing the pathogen and enclosing it in a small membrane-bound sac called a vesicle inside the cell.

Structures called lysosomes then fuse with the vesicle and release digestive enzymes called lysozymes. These enzymes break down and destroy the enclosed pathogen.

Phagocytosis is a non-specific defence: a phagocyte can engulf different kinds of pathogen rather than responding to only one specific antigen.

B-Cell Clonal Selection

Each B lymphocyte, or B cell, has surface receptors that bind a particular antigen. When a foreign antigen enters the body, it binds to a B cell whose receptors have a complementary shape. This selects the B cell that can respond to that antigen.

With stimulation from a helper T cell, the selected B cell becomes activated. It divides repeatedly by mitosis, producing a clone: a group of cells with the same antigen-binding specificity as the original B cell.

Fates of the B-cell clone

Some cells in the clone differentiate into plasma cells. These secrete large quantities of antibodies that bind specifically to the antigen. Antibodies produced by one clone have the same specificity and are described as monoclonal.

Other cloned cells become memory B cells. These remain in the body and provide the basis for a faster response if the same antigen is encountered again.

Antibody Structure and Action

An antibody is a protein that binds specifically to an antigen. An antigen is a substance or feature that an antibody can recognise, such as a molecule on the surface of a bacterial cell.

Antibody structure

An antibody molecule has a roughly Y-shaped structure made from two heavy chains and two light chains. The chains are joined by disulfide bonds.

At the tips of the Y are antigen-binding sites formed by the antibody’s variable regions. Their shapes are complementary to a particular antigen, allowing the antibody to bind to it. Different antibodies have differently shaped variable regions and therefore bind different antigens. The constant regions have a more similar structure between antibodies.

Antibody binding and agglutination

When an antibody binds to an antigen, it forms an antigen-antibody complex. An antibody has more than one antigen-binding site, so it can bind to antigens on different bacterial cells. Antibodies can therefore link bacteria together into clumps, a process called agglutination.

The clumped bacteria are more readily engulfed and destroyed by phagocytes.

Primary and Secondary Immune Responses

When an antigen enters the body for the first time, the immune system takes time to produce a substantial amount of antibody against it. During this primary immune response, B cells that recognise the antigen are selected and divide. Some of their descendants become plasma cells, which produce antibodies specific to that antigen.

The primary response develops gradually because the selected B cells must first divide and produce plasma cells. Some activated B cells also become long-lived memory cells. These remain in the body after the primary response.

The secondary response to the same antigen

If the same antigen enters the body again, the memory cells recognise it and respond rapidly. They divide and produce many plasma cells, which produce antibodies against the antigen.

During this secondary immune response, antibody concentration rises more quickly and generally reaches a higher level than during the primary response. The faster response can control the pathogen before significant symptoms develop.

Vaccination and Herd Immunity

Vaccination prepares the immune system to respond to a pathogen before the person encounters it. A vaccine introduces antigens—substances that the immune system can recognise—in a form intended to stimulate an immune response without causing the disease.

The response produces immunological memory. If the vaccinated person is later exposed to the pathogen, their immune system can respond faster and more strongly. This reduces the likelihood that they will develop the disease or can make the disease less severe. Vaccination does not necessarily prevent every infection or illness.

How herd immunity reduces transmission

A susceptible person is someone who is not sufficiently immune to a pathogen and can become infected. When a sufficiently large proportion of a population is immune, an infected person is less likely to encounter someone susceptible. The pathogen therefore has fewer opportunities to spread, and transmission is reduced. This population-level protection is called herd immunity.

Reduced transmission can indirectly protect susceptible people, including some who cannot be vaccinated: they are less likely to encounter the pathogen because it is spreading less in the population. Herd immunity does not make these individuals immune themselves.

The effectiveness of herd immunity depends on how much immunity is present and how it is distributed, as well as how readily the pathogen spreads. For example, transmission may continue in a group where many people are susceptible, even if immunity is high across the wider population.

Active and Passive Immunity

Immunity can be gained either by making an immune response to an antigen or by receiving antibodies made by another individual. The difference determines how quickly protection begins and how long it can last.

Active immunity

Active immunity develops when a person’s own immune system responds to an antigen, a substance recognised by the immune system. The response produces antibodies specific to that antigen and forms memory cells. This can happen after an infection or vaccination.

The initial response takes time to develop. If the same antigen is encountered again, the memory cells enable a faster, stronger secondary response. Because memory cells remain after the initial response, active immunity can provide long-lasting protection.

Passive immunity

Passive immunity results from receiving antibodies made by another individual. The transferred antibodies can provide protection immediately because they are already available to act against their target.

Receiving these antibodies does not itself produce memory cells against their target. As the transferred antibodies are gradually broken down, protection is lost. Passive immunity is therefore temporary.

HIV Structure and Replication

HIV is an enveloped virus that infects helper T cells, a type of immune cell. It carries RNA as its genetic material and uses an infected cell to make new virus particles.

HIV structure

HIV has an outer envelope with attachment proteins on its surface. Inside the envelope is a protein coat called the capsid. The capsid contains viral RNA and enzymes, including reverse transcriptase.

The attachment proteins bind to receptors on the surface of a helper T cell. This binding allows HIV to enter the cell.

HIV replication in a helper T cell

Once HIV has entered the cell, reverse transcriptase uses the viral RNA as a template to make viral DNA. The viral DNA then becomes integrated into the helper T cell’s DNA.

The infected cell’s machinery uses the integrated viral DNA to produce viral RNA and proteins. These components are assembled into new virus particles, which are released from the cell. The released particles can then infect further helper T cells.

HIV, AIDS and Antibiotics

HIV is a virus that infects helper T cells, which help coordinate immune responses by stimulating other immune cells. Over time, HIV reduces both the number of helper T cells and how well they function. As a result, other immune cells receive less stimulation, and the body's immune responses become weaker.

AIDS is the advanced stage of HIV infection. At this stage, the immune system is severely weakened, allowing opportunistic infections and other illnesses to cause serious symptoms. Opportunistic infections take advantage of the weakened immune system; they may be controlled more effectively when the immune system is functioning normally.

Why antibiotics do not treat HIV

Antibiotics act against bacterial structures or processes. Viruses do not have the bacterial targets on which antibiotics act, and they reproduce using the machinery of host cells. Antibiotics therefore do not treat HIV or other viral infections.

A person with AIDS can nevertheless develop a bacterial infection. Antibiotics may be used to treat that bacterial infection, but they do not treat the underlying HIV infection.

Medical Applications of Monoclonal Antibodies

An antibody is a protein that binds to a specific target called an antigen. Monoclonal antibodies are produced by a single clone of antibody-producing cells, so they all have the same antigen specificity: they bind to the same antigen.

This specificity allows monoclonal antibodies to target particular cells in treatment or detect particular substances in diagnosis.

Monoclonal antibodies in treatment

A therapeutic drug can be attached to a monoclonal antibody that binds to an antigen on the target cells. The antibody binds to cells carrying that antigen, directing the attached drug towards them. The antigen therefore acts as a target that helps deliver the drug to the cells where it is needed.

Monoclonal antibodies in diagnosis

A monoclonal antibody can be used to test a sample for a particular antigen. If the antigen is present, the antibody binds to it. A detectable label attached to the antibody, or a reaction that produces a detectable signal, can then reveal that the target is present.

ELISA

An enzyme-linked immunosorbent assay (ELISA) detects a particular antigen or antibody in a sample. It relies on the specific binding between an antibody and its antigen. An enzyme-linked antibody then makes the binding visible by producing a colour change.

In an ELISA, either the target or a molecule that can bind it is immobilised—fixed to a surface, such as the inside of a test well. This keeps bound material on the surface when the well is washed.

ELISA: Detecting the target

The arrangement depends on whether the target is an antigen or an antibody. For example:

• To detect an antigen: an immobilised antibody captures the antigen from the sample. An enzyme-linked antibody then binds to the captured antigen.
• To detect an antibody: an immobilised antigen binds the matching antibody from the sample. An enzyme-linked antibody then binds to that antibody.

The well is washed to remove unbound material. If the target is present and has been bound, the enzyme-linked antibody remains attached to the surface. A substrate is then added: the attached enzyme acts on it to produce a detectable colour change.

ELISA: Interpreting the colour

The appropriate colour change indicates a positive result. Controls provide a basis for interpreting it: a positive control shows the expected response when the target is present, while a negative control shows the response when it is absent.

In an ELISA designed for quantitative measurement, the amount of colour can also be used to estimate the amount of target. The colour produced by the sample is compared with the colours produced by standards containing known amounts of the target.

Ethics of Vaccines and Monoclonal Antibodies

Ethical decisions about vaccines and monoclonal antibodies involve more than deciding whether they can work. They require the potential benefits to be weighed against possible harms, while considering the interests of everyone affected.

An informed decision depends on a person receiving understandable information about the expected benefits, possible adverse effects and remaining uncertainties. They can then decide whether to consent to treatment. Fair access also matters: a treatment’s benefits cannot be shared fairly if some people cannot obtain it.

Vaccination: individual choice and benefits to others

A vaccine can protect the vaccinated person from disease, but it can also affect other people. When vaccination reduces transmission, fewer people may be exposed to the infection, including people who are vulnerable to serious illness. The extent of this benefit depends on how well the particular vaccine reduces transmission.

A vaccination decision can therefore involve competing interests. Respecting individual autonomy means recognising a person’s choice about what happens to their body. At the same time, vaccination may benefit others, while adverse effects may harm the person vaccinated. An ethical judgement must consider both the individual’s interests and the potential effects on population health.

Monoclonal antibodies: treatment and research

Monoclonal antibodies are treatments made using identical antibodies that bind to a specific target. Their possible benefits must be weighed against potential harms to the person receiving them, including adverse effects. The person needs information about these risks and benefits to make an informed decision.

Some monoclonal antibody treatments are costly. This raises questions about fair access: people who could benefit may be unable to obtain treatment, and funding it may compete with other uses of limited resources.

Animals may also be used in research or production of monoclonal antibodies. An ethical assessment should consider possible harm to the animals alongside the potential benefits of the work, including whether suitable alternatives are available.

Making an ethical judgement

A reasoned judgement should state whose interests are affected, explain why particular benefits or harms carry weight, and acknowledge competing interests. It should also recognise uncertainty: the size of a benefit, the likelihood of an adverse effect or the effect on others may not be known precisely. Different judgements can follow when people give different weight to these considerations.

Evaluating Evidence on Vaccines and Monoclonal Antibodies

A study may report that a vaccine or monoclonal antibody has a particular effect, but the strength of that conclusion depends on how the evidence was collected. Evaluation asks whether the method allows the observed result to be attributed to the treatment and whether the result applies beyond the people or samples studied.

Comparison and study design

A comparison group provides a reference against which to judge the effect. Depending on the question, it might receive a placebo, an existing treatment or no treatment. For example, if a group receiving a monoclonal antibody improves, a comparison group helps show whether that improvement differs from what would have happened without the antibody or with another treatment.

The groups should be as similar as possible apart from the treatment being investigated. Otherwise, a confounding variable could help explain the difference in results. For example, if a vaccinated group is younger than an unvaccinated group, age as well as vaccination may affect the risk of severe illness.

Random allocation assigns participants to treatment groups by chance. It reduces systematic differences between groups, although it does not guarantee that the groups will be identical. Blinding, where appropriate, prevents participants, researchers or both from knowing who received which treatment during the study. This can reduce bias in how outcomes are reported or assessed.

Sample, measurements and repeatability

A larger sample generally gives a more precise estimate of an effect and is more likely to reveal uncommon adverse effects than a small sample. Size alone is not enough: how participants or samples were selected also matters. A large group drawn from a narrow population may not represent the wider population to which a conclusion is being applied.

Measurement methods should assess outcomes reliably and consistently across groups. For example, a difference may be less convincing if illness is measured in different ways in the treatment and comparison groups. Results that can be repeated in further studies increase confidence, particularly when those studies use suitable methods and produce similar findings.

Interpreting benefits and adverse effects

Evaluate evidence for both benefits and adverse effects. Consider the size of each observed effect, not just whether an effect was reported. A small benefit or a rare adverse effect may require a large study to estimate reliably. The length of follow-up also matters: a study can only detect effects that occur and are measured during the period observed.

Every estimate has uncertainty. A result based on a small sample, for example, may be compatible with a range of possible true effects. Consider that uncertainty before treating the observed size as exact.

A sound conclusion states what the results show for the population studied, then identifies limitations. If the participants were all from one age group, the findings do not by themselves establish the same effect in other age groups. Similarly, an observed difference between groups does not prove that the treatment caused it if confounding variables offer another plausible explanation.