What you'll learn
Immunity and disease covers how pathogens cause illness and how the body defends itself. At CAPE level the detail extends well beyond the naming of white blood cells: you are expected to describe the cellular and humoral responses separately, explain the structure of an antibody in relation to its function, distinguish the four types of immunity, explain the basis of the secondary response and of vaccination, and discuss monoclonal antibodies and antibiotic resistance. By the end of this topic you should be able to classify pathogens and modes of transmission, describe non-specific and specific defences in sequence, explain antibody structure and action, distinguish active from passive and natural from artificial immunity, explain vaccination and herd immunity, and evaluate monoclonal antibody applications.
Key terms and definitions
Pathogen — a microorganism that causes disease
Antigen — a molecule, usually a protein or glycoprotein on a cell surface, recognised as foreign and triggering an immune response
Antibody — a protein produced by plasma cells that binds specifically to one antigen
Phagocytosis — the engulfing and digestion of a pathogen by a phagocyte
Lysosome — the organelle supplying hydrolytic enzymes to digest an engulfed pathogen
Antigen-presenting cell — a cell displaying antigens from a pathogen on its surface
Cell-mediated response — the branch of specific immunity involving T lymphocytes
Humoral response — the branch of specific immunity involving B lymphocytes and antibodies
Clonal selection — the selection and activation of the lymphocyte whose receptor matches the antigen
Plasma cell — a differentiated B lymphocyte that secretes large quantities of antibody
Memory cell — a long-lived lymphocyte enabling a rapid secondary response
Herd immunity — protection of unvaccinated individuals when a large proportion of the population is immune
Monoclonal antibody — an antibody produced by a single clone of cells, all identical and specific to one antigen
Autoimmune disease — a condition in which the immune system attacks the body's own tissues
Core concepts
Pathogens and transmission
Pathogens fall into four groups. Bacteria cause tuberculosis, cholera and tetanus, and generally damage tissue by releasing toxins. Viruses cause influenza, HIV infection, measles and dengue, and damage cells by reproducing inside them and causing them to burst. Fungi cause ringworm and athlete's foot. Protoctists cause malaria and amoebic dysentery.
Transmission occurs by droplet infection through air; by direct contact including sexual contact; by contaminated food and water; by vectors, as mosquitoes transmit malaria and dengue, which is of particular significance in the Caribbean; and by exchange of body fluids.
Bacteria and viruses differ importantly in how they cause harm, and this difference explains why antibiotics work against one and not the other. Antibiotics target structures and processes unique to bacteria, such as peptidoglycan cell wall synthesis or 70S ribosomes. Viruses have no cell wall and no ribosomes of their own, using the host cell's machinery instead, so a drug able to disrupt viral reproduction would also damage the host cell.
Non-specific defences
The first line of defence prevents entry. The skin forms a physical barrier and its surface is slightly acidic. Mucous membranes trap pathogens in the respiratory and digestive tracts, and ciliated epithelium wafts the mucus away from the lungs. Stomach acid at about pH 2 kills most ingested pathogens. Lysozyme in tears and saliva hydrolyses bacterial cell walls. Blood clotting seals wounds.
If a pathogen enters, phagocytosis is the principal non-specific response and its stages should be known in order.
The phagocyte is attracted to the pathogen by chemicals it releases, moving towards the higher concentration by chemotaxis.
The phagocyte recognises the pathogen as foreign by its surface antigens and binds to it.
The cell surface membrane engulfs the pathogen, enclosing it in a vesicle called a phagosome.
Lysosomes fuse with the phagosome and release hydrolytic enzymes, which digest the pathogen.
The soluble products are absorbed, and the phagocyte displays some of the pathogen's antigens on its own surface, becoming an antigen-presenting cell. This step is what links the non-specific to the specific response, and it is frequently the mark candidates miss.
Inflammation also occurs, with histamine released by mast cells causing vasodilation and increased capillary permeability, which brings more blood, phagocytes and antibodies to the site.
The cell-mediated response
Specific immunity has two branches that operate together.
In the cell-mediated response, a T lymphocyte with a receptor complementary to the presented antigen binds to the antigen-presenting cell. This is clonal selection: the antigen selects the lymphocyte that already has the matching receptor, rather than inducing the cell to make one.
The selected T lymphocyte is activated and divides rapidly by mitosis, producing a clone of identical cells that differentiate into several types.
Helper T cells release chemical signals called cytokines, which stimulate phagocytes, activate B lymphocytes, and stimulate other T cells to divide. They are central coordinators, which is why HIV, which destroys helper T cells, is so devastating to immunity as a whole.
Cytotoxic T cells destroy cells displaying the foreign antigen, including virus-infected body cells and cancer cells, by releasing a protein that perforates their membranes.
Memory T cells persist and allow a rapid response on re-exposure.
The humoral response
In the humoral response, a B lymphocyte with a complementary antibody on its surface binds the antigen, is stimulated by cytokines from helper T cells, and divides by mitosis to form a clone.
Most of the clone differentiate into plasma cells, which secrete large quantities of the specific antibody. Plasma cells are short-lived, surviving only days, but produce antibody at an extraordinary rate.
The remainder become memory B cells, which are long-lived and remain in the body, providing the basis of long-term immunity.
The distinction between the two responses is worth stating plainly: the cell-mediated response acts against the body's own infected cells, while the humoral response acts against pathogens and toxins circulating in body fluids.
Antibody structure and action
An antibody is a Y-shaped glycoprotein made of four polypeptide chains: two identical heavy chains and two identical light chains, held together by disulfide bridges.
Each arm of the Y ends in a variable region, whose amino acid sequence differs between antibodies and gives each its specificity. The variable regions form two antigen-binding sites with a shape complementary to one particular antigen.
The remainder is the constant region, which is the same in all antibodies of a class and allows binding to phagocytes.
The hinge region gives flexibility, allowing the two binding sites to attach to antigens at varying distances apart.
Antibodies act in several ways. Agglutination clumps pathogens together, since each antibody has two binding sites and can bridge two pathogens; clumped pathogens cannot enter cells and are more easily engulfed by phagocytes. Neutralisation blocks the binding sites pathogens use to attach to host cells, and inactivates toxins. Opsonisation marks the pathogen for phagocytosis, since phagocytes have receptors for the constant region.
An antibody does not itself destroy a pathogen, which is a point examiners test; it marks, immobilises or neutralises it so that other mechanisms can act.
Primary and secondary responses
The primary response, on first exposure, is slow. Only a few lymphocytes have the matching receptor, and clonal expansion and differentiation take time, so there is a lag of several days before antibody appears. The concentration reached is relatively low and falls away afterwards. The person may become ill during this delay.
The secondary response, on re-exposure to the same antigen, is much faster and much greater. Memory cells are already present in far larger numbers than the original lymphocytes, and they divide and differentiate into plasma cells rapidly. Antibody appears within hours rather than days, reaches a much higher concentration, and persists longer. The pathogen is destroyed before it can multiply enough to cause symptoms, so the person does not become ill.
Comparing the two curves on a graph is a standard question, and three differences should be given: shorter lag, higher peak concentration, and longer persistence.
Types of immunity
Four types are distinguished by two criteria: whether the individual produces their own antibodies, and whether exposure was deliberate.
Natural active immunity results from catching the disease and mounting a response. It is long-lasting because memory cells are produced.
Artificial active immunity results from vaccination. It is also long-lasting, for the same reason.
Natural passive immunity results from receiving antibodies from another individual naturally, as a foetus does across the placenta and an infant does in breast milk. It is short-lived, because no memory cells are produced and the received antibodies are gradually broken down.
Artificial passive immunity results from an injection of antibodies, for example antivenom after a snake bite or anti-tetanus serum. It acts immediately, which is its advantage in an emergency, but is short-lived for the same reason as natural passive immunity.
The general rule worth memorising: active immunity is slow to develop but long-lasting because memory cells form; passive immunity is immediate but temporary because they do not.
Vaccination and herd immunity
A vaccine contains antigens from a pathogen, presented in a form that cannot cause the disease: a killed pathogen, an attenuated live strain, an isolated antigen, or a harmless toxoid.
The antigens trigger a primary response, producing memory cells without the person becoming ill. On later exposure to the live pathogen, a rapid secondary response destroys it before symptoms develop.
Booster doses are given because antibody concentration falls over time; a booster triggers another secondary response, raising memory cell numbers further.
Herd immunity arises when a sufficiently large proportion of the population is immune. The pathogen cannot readily find susceptible hosts, so transmission is interrupted and even unvaccinated individuals are protected. This matters for those who cannot be vaccinated, such as very young infants and the immunocompromised.
Vaccination fails to eliminate some diseases for identifiable reasons: the pathogen may mutate so that its antigens change, a process called antigenic variation, which is why influenza vaccines must be reformulated annually; some pathogens have many strains; some hide inside host cells; and practical barriers include cost, storage requiring refrigeration, and public refusal.
Monoclonal antibodies
Monoclonal antibodies are identical antibodies produced by a single clone of cells, all specific to one antigen.
They are produced by fusing a plasma cell producing the desired antibody with a tumour cell, which divides indefinitely. The resulting hybridoma both produces the antibody and divides without limit, and is cultured to yield large quantities.
Applications include targeted drug delivery, in which a drug is attached to an antibody specific to an antigen on cancer cells so that the drug accumulates at the tumour and damage to healthy tissue is reduced; diagnosis, including pregnancy testing, which detects a hormone in urine using monoclonal antibodies on a test strip; and identifying the antigens on cells for tissue typing before transplantation.
Ethical considerations include the use of animals in production and the deaths that occurred during early clinical trials, which led to changes in trial protocols.
Worked examples
Example 1: Comparing primary and secondary responses (5 marks)
A graph shows antibody concentration after a first and a second exposure to the same antigen. Describe and explain three differences.
The lag before antibody appears is much shorter after the second exposure. On first exposure only a few B lymphocytes carry the complementary receptor, and clonal selection, mitosis and differentiation into plasma cells take several days. After the first exposure, memory cells specific to that antigen are already present in large numbers and differentiate rapidly into plasma cells.
The peak antibody concentration is much higher after the second exposure, because far more memory cells are available to divide, producing a far greater number of plasma cells and therefore much more antibody.
The antibody concentration remains high for longer after the second exposure, because the larger population of memory and plasma cells sustains production. As a result the pathogen is destroyed before it multiplies sufficiently to cause symptoms, so the individual does not become ill.
Example 2: Explaining passive immunity (4 marks)
Explain why a baby receives antibodies in breast milk, and why this protection does not last.
The baby's own immune system is immature and has encountered few antigens, so it produces antibodies slowly and in small quantities. Antibodies in breast milk provide immediate protection against pathogens the mother has encountered, covering the period during which the baby is most vulnerable.
This is natural passive immunity. The baby has not produced the antibodies itself and has not been exposed to the antigens, so no clonal selection occurs and no memory cells are formed.
The received antibodies are proteins and are gradually broken down and not replaced, so the protection declines over a few months. Long-lasting immunity requires the baby's own active response, through infection or vaccination.
Example 3: Explaining a monoclonal antibody application (5 marks)
Explain how monoclonal antibodies can be used to deliver a drug specifically to cancer cells, and why this is an advantage.
Cancer cells carry antigens on their cell surface membranes that differ from those on normal body cells. A monoclonal antibody is produced whose variable region has a binding site with a shape complementary to one of these antigens.
The antibody is produced by fusing a plasma cell making that antibody with a tumour cell, forming a hybridoma that both secretes the antibody and divides indefinitely, so large quantities of identical antibody can be obtained.
A cytotoxic drug is attached to the antibody. When administered, the antibody circulates and binds specifically to the antigens on cancer cells, so the drug accumulates at the tumour.
The advantage is that the drug is concentrated where it is needed rather than distributed throughout the body. Healthy cells, which lack the antigen, are not targeted, so a smaller dose can be used and the side effects associated with conventional chemotherapy are reduced.
Common mistakes and how to avoid them
The most frequent error is stating that antibodies kill pathogens. They agglutinate, neutralise and mark pathogens so that phagocytes can destroy them.
Students often confuse antigens with antibodies. The antigen is on the pathogen; the antibody is produced by plasma cells.
Another common slip is describing clonal selection as the antigen causing a lymphocyte to produce a new receptor. The lymphocyte already has the receptor; the antigen selects it.
Many candidates omit the antigen-presenting step in phagocytosis, which is the link to the specific response and is regularly worth a mark.
In immunity type questions, answers frequently confuse passive with artificial. The two criteria are independent: whose antibodies, and whether exposure was deliberate.
Finally, candidates often say vaccines contain a weakened disease. They contain antigens, in the form of a dead or attenuated pathogen, an isolated antigen or a toxoid.
Exam technique for "Immunity and disease"
Describe phagocytosis and the specific response as numbered sequences, since marks follow the stages. Include chemotaxis and antigen presentation, which are commonly omitted.
Keep the cell-mediated and humoral responses distinct, and state which cell type acts in each.
For antibody structure, relate each region to its function: variable regions for specificity, constant region for phagocyte binding, hinge for flexibility.
When comparing primary and secondary responses, give three quantitative differences rather than a general statement that the second is faster.
For immunity types, name both criteria explicitly, and state whether memory cells are produced, since that determines duration.
Quick revision summary
Pathogens are bacteria, viruses, fungi and protoctists, transmitted by droplets, contact, food and water, vectors and body fluids; antibiotics target bacterial structures and cannot act against viruses. Non-specific defences include skin, mucus and cilia, stomach acid, lysozyme and blood clotting, and phagocytosis proceeds by chemotaxis, recognition, engulfment into a phagosome, lysosomal digestion and antigen presentation. In the cell-mediated response, clonal selection activates T lymphocytes that form helper T cells releasing cytokines, cytotoxic T cells destroying infected cells, and memory T cells. In the humoral response, B lymphocytes form plasma cells secreting antibody and memory B cells. Antibodies are Y-shaped glycoproteins with variable regions giving specificity, a constant region binding phagocytes and a flexible hinge, acting by agglutination, neutralisation and opsonisation. The secondary response is faster, larger and longer-lasting because memory cells are already present. Active immunity is slow but lasting because memory cells form, passive is immediate but temporary because they do not. Vaccination produces memory cells without illness, and herd immunity protects those who cannot be vaccinated. Monoclonal antibodies from hybridomas are used in targeted drug delivery, diagnosis and tissue typing.