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AS 11

Immunity

AS Level · Topic 11 · Papers 1 and 2

🎯What you need to be able to do

  • Describe the mode of action of phagocytes — macrophages and neutrophils.
  • Explain what an antigen is and distinguish self from non-self antigens.
  • Describe the primary immune response, including the roles of macrophages, B-lymphocytes and plasma cells, and T-helper and T-killer cells.
  • Explain the role of memory cells in the secondary response and long-term immunity.
  • Relate the molecular structure of antibodies to their functions.
  • Outline the hybridoma method for producing monoclonal antibodies and their use in diagnosis and treatment.
  • Distinguish active from passive and natural from artificial immunity, and explain how vaccines and vaccination programmes work.

📚The biology

Antigens: self and non-self

An antigen is a molecule — usually a glycoprotein or glycolipid on a cell surface — that the immune system recognises and that stimulates an immune response. Self antigens are those on the body’s own cells, and the immune system does not respond to them. Non-self antigens are those on pathogens, transplanted tissue or cancer cells, and these do provoke a response. The cell surface antigens you met in Topic 4 are exactly what is being recognised here.

Phagocytosis — fast, and non-specific

Neutrophils (multi-lobed nucleus, short-lived, first on the scene) and macrophages (developed from monocytes, long-lived) are phagocytes.

  1. The phagocyte is attracted to the pathogen by chemicals it releases — chemotaxis.
  2. It attaches to antigens on the pathogen surface.
  3. The membrane engulfs it by endocytosis, enclosing it in a phagosome (vacuole).
  4. Lysosomes fuse with the vacuole and release hydrolytic enzymes that digest the pathogen.
  5. Harmless products are absorbed; a macrophage then displays antigens from the pathogen on its own surface, becoming an antigen-presenting cell.

That last step is the hinge of the whole topic: it connects the fast non-specific response to the slow specific one.

The primary immune response

  1. A macrophage presents the pathogen’s antigen on its surface.
  2. A T-helper cell with a complementary receptor binds to it, is activated and divides, releasing chemicals that stimulate other cells.
  3. B-lymphocytes with a complementary receptor are activated by antigen and by T-helper cells. They divide rapidly by mitosis — clonal selection followed by clonal expansion — and differentiate into:
    • plasma cells, which secrete large quantities of a single specific antibody;
    • memory B cells, which persist.
  4. T-killer cells destroy the body’s own cells that are infected, by attaching to them and releasing substances that make holes in their membranes. Memory T cells also form.

This takes days to weeks, which is why you feel ill during a first infection: the pathogen multiplies while the specific response is still being assembled.

The secondary response and memory cells

Memory cells remain in the body, often for life. On a second exposure to the same antigen they are already present in large numbers and are activated directly, without waiting for the whole antigen-presentation sequence. The secondary response is therefore:

  • faster — antibody appears within hours or a day or two rather than weeks;
  • greater — a much higher concentration of antibody is produced;
  • longer lasting.

The pathogen is destroyed before it can multiply enough to cause symptoms, so the person is immune. Because memory cells and their receptors are specific to one antigen, immunity to one pathogen gives none to another — and a pathogen that changes its antigens, as influenza and HIV do, escapes the memory that was built against the old form.

Antibody structure and function

An antibody is a globular glycoprotein (an immunoglobulin) made of four polypeptide chains — two heavy, two light — held together by disulfide bonds in a Y shape.

  • The variable region at the tips of the two arms differs between antibodies and forms the antigen-binding sites. Its specific shape is complementary to one antigen, exactly as an active site is to a substrate. There are two binding sites per antibody.
  • The constant region is the same within a class of antibody and is what phagocytes bind to, so the antibody links pathogen to phagocyte.
  • The hinge region allows flexibility so the two arms can bind antigens at different angles.

Functions follow from that structure: agglutination (two binding sites let one antibody link two pathogens, clumping them so they cannot enter cells and are easily engulfed), neutralisation of toxins and of viral attachment proteins, and opsonisation — marking the pathogen so that phagocytes recognise and engulf it.

Monoclonal antibodies

A single plasma cell makes one antibody, but plasma cells do not divide in culture. The hybridoma method solves this:

  1. Inject a mouse with the chosen antigen.
  2. Extract B-lymphocytes (plasma cells) from its spleen.
  3. Fuse each with a myeloma (tumour) cell, which divides indefinitely.
  4. The resulting hybridoma both secretes the antibody and divides indefinitely.
  5. Select the hybridoma making the antibody you want, clone it, and harvest the antibody.

Because every cell in the clone descends from one B cell, every antibody molecule is identical and binds one antigen — that is what “monoclonal” means.

  • Diagnosis — pregnancy tests (binding hCG), detecting antigens specific to a pathogen or a cancer, blood typing, and locating tumours by attaching a radioactive or fluorescent marker to the antibody.
  • Treatment — targeting cancer cells directly, or as “magic bullets”: attach a cytotoxic drug to the antibody so it is delivered only to cells carrying that antigen, greatly reducing damage to healthy tissue.

The four kinds of immunity

Two questions decide the label. Did the body make the antibodies itself? If yes, active; if they were given ready-made, passive. Did it happen through ordinary life or by deliberate medical intervention? Natural or artificial.

  • Natural active — you catch the disease and recover. Memory cells form, so it is long-lasting.
  • Artificial active — vaccination. Memory cells form, so it is long-lasting.
  • Natural passive — antibodies cross the placenta or are received in breast milk. No memory cells, so it is temporary.
  • Artificial passive — an injection of antibodies (antivenom, or anti-tetanus immunoglobulin). Immediate but temporary, because no memory cells form.

Passive immunity acts immediately but does not last, because the antibodies are gradually broken down and there are no memory cells to make more. Active immunity takes time to develop but lasts. That trade-off decides which is used: antivenom must work now; a vaccine must work for years.

Vaccination

A vaccine contains antigens — from a dead, weakened (attenuated) or harmless-fragment form of the pathogen, or a toxoid. These provoke a primary immune response without causing the disease, so memory cells are produced. On subsequent exposure to the real pathogen, the rapid, large secondary response destroys it before symptoms develop.

A programme controls a disease at population level through herd immunity: if a high enough proportion of the population is immune, an infected individual is unlikely to meet a susceptible one, so transmission chains break and even the unvaccinated — the very young, the immunosuppressed — are protected. Successful programmes need high coverage, effective storage and transport at low temperature (the cold chain), and public confidence. Programmes fail where a pathogen has an animal reservoir, where its antigens change frequently (influenza needs a new vaccine each year), or where coverage falls below the threshold.

Vaccines do not contain antibodies. They contain antigens, and the point is to make the recipient produce their own antibodies and memory cells. Writing that a vaccine “gives you antibodies” describes artificial passive immunity and contradicts everything else you will say about memory cells and long-term protection.

✏️Worked example

A person was injected with antigen X on day 0 and again on day 28. The concentration of antibody against X in the blood was: day 0, zero; day 7, low; day 14, peak of 8 arbitrary units; day 21, falling; day 28, near zero; day 31, 45 units; day 35, peak of 120 units. (a) Describe three differences between the two responses. (b) Explain the differences in terms of the cells involved. (c) The person is later injected with a different antigen, Y, and shows only a small slow response. Explain why.

(a) The second response is:

  • faster — antibody is already at 45 units by day 31, three days after the second injection, whereas the first response took 14 days to reach its peak;
  • greater — the peak is 120 units against 8, fifteen times higher;
  • longer lasting — the first response fell to near zero within a fortnight of its peak, while the second is sustained.

(b) In the primary response, no cell specific to antigen X was present in quantity. A macrophage had first to engulf the antigen and present it; T-helper cells and the few B-lymphocytes with a complementary receptor then had to be selected and to divide repeatedly by mitosis before differentiating into plasma cells. All of that takes days, and the number of plasma cells finally produced is modest — hence a slow, small response.

The primary response also produced memory B cells specific to X, and these persisted after the antibody concentration fell. On the second exposure these memory cells were already present in large numbers and were activated directly by the antigen, dividing and differentiating into plasma cells immediately without the delay of antigen presentation and initial clonal selection. Many more plasma cells are produced, and each secretes antibody, so the response is faster, larger and more sustained.

(c) Memory cells and the receptors on B-lymphocytes are specific: the receptor and the antibody it gives rise to have a shape complementary to one antigen only. The memory cells produced against X cannot bind antigen Y, so they are not activated by it. The response to Y must therefore start from the beginning as a primary response, with its own antigen presentation, clonal selection and clonal expansion — so it is small and slow. Immunity to one pathogen confers none to another.

Check it. The shape of the two curves should match the biology before you look at any number: a primary response is a low, late, transient hump; a secondary response is a tall, early, sustained peak. Quote figures from the data rather than describing the shape in words alone — ‘120 units against 8’ and ‘peak at day 35 against day 14’ are what earn the marks. And check the timing is measured from the relevant injection, not from day 0: the second response took three days, not thirty-one.
Saying the memory cells ‘remember’ the antigen, and treating them as antibody stores. Memory cells do not secrete antibody and do not store it; they are a large standing population of lymphocytes already specific to that antigen, which can divide and differentiate into plasma cells at once. The saving is in time to produce plasma cells, which is what makes the response fast. Also note that the antibody concentration falling to near zero by day 28 does not mean immunity has been lost — the memory cells are still there, which is precisely what the data go on to demonstrate.

📝Practise

Work through these, then reveal the answer. Each question targets a different objective from the list above.

1. Describe the sequence of events in phagocytosis by a macrophage, and state what makes the final step important.
The macrophage is attracted to the pathogen by chemicals it releases (chemotaxis) and attaches to antigens on the pathogen surface. Its cell surface membrane engulfs the pathogen by endocytosis, enclosing it in a vacuole called a phagosome. Lysosomes fuse with the phagosome and release hydrolytic enzymes, which digest the pathogen. Soluble products are absorbed into the cytoplasm. Finally, the macrophage displays antigens from the pathogen on its own cell surface membrane, becoming an antigen-presenting cell. That last step is important because it is what activates T-helper cells and so initiates the specific immune response — it is the link between the fast, non-specific defence and the slow, specific one that produces antibodies and memory cells.
2. Explain how the structure of an antibody allows it to cause agglutination and to be recognised by a phagocyte.
An antibody has two identical antigen-binding sites, formed by the variable regions at the tips of the two arms of the Y. Because there are two, a single antibody molecule can bind two separate pathogens at once; with many antibodies doing this, pathogens are cross-linked into clumps. This is agglutination: clumped pathogens cannot enter host cells and are too large to disperse, and a phagocyte can engulf many at once. The variable region’s shape is complementary to one specific antigen, which is why the binding is specific. The constant region at the stem of the Y is the same in all antibodies of a class, and phagocytes have receptors that bind to it, so a coated pathogen is readily recognised and engulfed — opsonisation. The hinge region gives the arms flexibility to bind antigens at different angles.
3. Distinguish between active and passive immunity, and give one example of each of the four combinations.
Active immunity means the person’s own immune system is stimulated to produce antibodies and memory cells; it takes days or weeks to develop but is long-lasting. Passive immunity means ready-made antibodies are received from another source; protection is immediate but temporary, because the antibodies are broken down and no memory cells are produced. Natural active — recovering from measles. Artificial active — being vaccinated against measles. Natural passive — a fetus receiving antibodies across the placenta, or a baby receiving them in breast milk. Artificial passive — an injection of antivenom after a snake bite, or anti-tetanus immunoglobulin after a wound.
4. Outline the hybridoma method and explain why a myeloma cell is used.
A mouse is injected with the chosen antigen, provoking an immune response. B-lymphocytes producing the required antibody are extracted from its spleen. Each is fused with a myeloma (tumour) cell to form a hybridoma. The hybridomas are screened and the one producing the desired antibody is selected, then cloned and cultured, and the antibody harvested. The myeloma cell is necessary because plasma cells do not divide in culture — they secrete antibody but have a short life, so a culture of them would die out and yield very little. Myeloma cells are cancerous and therefore divide indefinitely. Fusing the two combines the useful properties of each: the antibody specificity of the B cell and the unlimited division of the tumour cell. Because every cell in the resulting clone descends from one B cell, every antibody molecule produced is identical — monoclonal.
5. Explain how a vaccination programme can protect people who have not themselves been vaccinated.
This is herd immunity. A vaccine contains antigens that provoke a primary immune response without causing disease, so vaccinated individuals produce memory cells and mount a rapid secondary response on real exposure, destroying the pathogen before symptoms develop and before they transmit it. If a high enough proportion of the population is immune, an infected person is unlikely to encounter a susceptible one, so chains of transmission are broken and the pathogen cannot spread through the population. Unvaccinated individuals — babies too young to be vaccinated, people who are immunosuppressed or allergic to a vaccine component — are therefore unlikely ever to meet the pathogen. The protection fails if coverage drops below the threshold, which is why falling uptake causes outbreaks in populations that had been free of a disease for years.
6. Influenza vaccines must be reformulated most years, whereas one course of measles vaccine gives lifelong protection. Explain.
Immunity depends on memory cells whose receptors are complementary to a specific antigen. The measles virus has stable surface antigens that change very little between strains and over time, so memory cells produced by vaccination will recognise the virus a person meets decades later, and the rapid secondary response destroys it. The influenza virus, by contrast, mutates frequently, so its surface antigens change — a process of antigenic change. Memory cells produced against last year’s antigens have receptors that are no longer complementary to this year’s, so they are not activated and the person must mount a slow primary response to the new strain. The vaccine must therefore be reformulated to contain the antigens of the strains predicted to circulate. The same problem, in a more extreme form, is one reason no effective HIV vaccine exists: HIV mutates extremely rapidly and, in addition, destroys the T-helper cells the response depends on.

🔗Go deeper — other people’s work

These are external resources, not mine. If one stops working, tell me and everything above it on this page still stands.

  • Nature Immunology and the British Society for Immunology — accessible summaries of the primary and secondary responses aimed at students rather than researchers
  • Any animation of clonal selection and clonal expansion — watching one B cell divide into a clone makes the primary/secondary distinction obvious
  • History of Vaccines (College of Physicians of Philadelphia) — good material on herd immunity thresholds and on why some diseases have been eradicated and others have not