The immune system

1. Overview

The immune system defends the body against pathogens by distinguishing the body's own cells from foreign material. It works in two linked ways. First, phagocytes (macrophages and neutrophils) engulf and destroy pathogens in a non-specific response that does not depend on which pathogen is present. Second, a specific response is coordinated by macrophages, T-lymphocytes and B-lymphocytes, which together recognise particular antigens and destroy the pathogen carrying them. After the first exposure, memory cells remain in the body so that any later infection by the same pathogen is dealt with faster and more strongly, giving long-term immunity.

Key Definitions

• Antigen: a molecule, usually a protein or glycoprotein on a cell surface, that the immune system recognises as foreign and that triggers a specific immune response.
• Self antigen: an antigen produced by the body's own cells that the immune system does not normally react against.
• Non-self antigen: an antigen from a foreign source, such as a pathogen or transplanted tissue, that triggers an immune response.
• Phagocyte: a white blood cell, such as a macrophage or neutrophil, that engulfs and digests pathogens by phagocytosis.
• Phagocytosis: the process by which a phagocyte engulfs a pathogen into a vesicle and digests it using hydrolytic enzymes.
• B-lymphocyte: a white blood cell that matures in the bone marrow and, when activated, divides to form plasma cells and memory cells.
• Plasma cell: an activated B-lymphocyte that secretes large numbers of antibodies specific to one antigen.
• T-lymphocyte: a white blood cell that matures in the thymus; includes T-helper cells that activate other immune cells and T-killer cells that destroy infected cells.
• Memory cell: a long-lived lymphocyte produced after a primary response that enables a rapid, larger secondary response on re-exposure to the same antigen.

Content

Antigens: self and non-self

An antigen is a molecule — typically a protein or glycoprotein on the surface of a cell — that the immune system can recognise and respond to. The key idea is recognition of self versus non-self.

• Self antigens are the molecules on the surface of an organism's own cells. The immune system normally does not react against them, so the body's healthy cells are left alone.
• Non-self antigens are foreign molecules, for example those on the surface of bacteria, viruses, fungi or cells in transplanted tissue. They are recognised as foreign and trigger a specific immune response.

Because each pathogen carries its own distinctive surface antigens, the immune system can mount a response that is specific to that particular pathogen. The shape of an antigen is complementary to receptors on lymphocytes, and this is how the correct lymphocyte is selected.

The mode of action of phagocytes

Phagocytes are white blood cells that carry out phagocytosis, a non-specific response that destroys pathogens regardless of their identity. There are two main types:

Phagocyte	Lifespan and origin	Key feature
Neutrophil	Short-lived; made in the bone marrow; first to arrive in large numbers	Dies after dealing with a few pathogens
Macrophage	Longer-lived; develops from monocytes made in the bone marrow that mature in the tissues	Presents antigens afterwards (acts as an APC)

The sequence of phagocytosis is:

1. Chemicals released by pathogens, and chemical signals from infected tissue, attract phagocytes to the site of infection by chemotaxis.
2. The phagocyte recognises the non-self antigens on the pathogen. Recognition is helped when the pathogen is coated with antibodies or other proteins (such as complement), a process called opsonisation.
3. The phagocyte's cell surface membrane surrounds the pathogen and engulfs it by endocytosis, enclosing it in a vesicle called a phagosome (phagocytic vacuole).
4. Lysosomes fuse with the phagosome and release hydrolytic enzymes (such as proteases and lipases, alongside the enzyme lysozyme) that digest the pathogen.
5. Soluble products are absorbed by the phagocyte; in the case of neutrophils the cell usually dies after dealing with a few pathogens.

A crucial extra role distinguishes the macrophage: after digesting a pathogen it displays the pathogen's antigens on its own cell surface membrane, becoming an antigen-presenting cell (APC). This presentation links the non-specific response to the specific response described below.

The primary immune response

The primary immune response is the response the first time the body meets a particular non-self antigen. It develops over several days and involves macrophages, T-lymphocytes and B-lymphocytes acting in sequence.

Before reading the detailed steps, use this chain as a quick map of who does what:

Cell	What it does	Main product / outcome
Macrophage	Engulfs pathogen, then presents its antigens (APC)	Activates a matching T-helper cell
T-helper cell	Binds the presented antigen and divides	Releases cytokines that stimulate other cells
B-lymphocyte → plasma cell	Selected and cloned, then differentiates	Secretes antibodies
T-killer cell	Activated by cytokines, then divides	Destroys body cells that are infected
Memory cells	Survive after the infection clears	Give a fast secondary response

The full sequence is:

1. A macrophage engulfs the pathogen, digests it, and presents its antigens on its surface as an antigen-presenting cell.
2. A T-helper cell with a receptor complementary to that antigen binds to the presented antigen. This activates the T-helper cell, which divides by mitosis to form a clone and releases signalling molecules called cytokines.
3. The cytokines stimulate the appropriate B-lymphocytes and other immune cells. Only the B-lymphocyte whose receptor (antibody) is complementary to the antigen is selected and activated — this is clonal selection.
4. The selected B-lymphocyte divides by mitosis (clonal expansion) to form a clone of identical cells. This single clone differentiates into two different cell types: most become short-lived plasma cells, which secrete large quantities of antibodies specific to the antigen (these antibodies bind the antigen and lead to the pathogen's destruction), while the rest become memory B-lymphocytes that survive long after the infection clears.
5. Cytokines from T-helper cells also activate T-killer cells. These divide, then recognise and destroy body cells that are infected (for example, virus-infected cells) by attaching to them and releasing substances that make the cells die.
6. As noted in step 4, part of the B-lymphocyte clone becomes memory B-lymphocytes rather than plasma cells; in the same way some activated T-lymphocytes become memory T-cells rather than killer cells. These memory cells remain in the body to give future protection.

Note the division of labour:

• The B-lymphocyte (humoral) response produces antibodies via plasma cells.
• The T-lymphocyte (cell-mediated) response includes T-helper cells that coordinate the response and T-killer cells that destroy infected cells.

Memory cells, the secondary response and long-term immunity

Memory cells are long-lived lymphocytes formed during the primary response. They remain in the blood and lymphatic system, sometimes for years, after the pathogen has been removed.

If the same non-self antigen enters the body again, the secondary immune response occurs. Compared with the primary response, the secondary response is:

Feature	Primary response	Secondary response
Speed	Slow; antibodies appear after a delay of several days	Fast; antibodies appear after a much shorter delay
Size	Lower antibody concentration	Much higher antibody concentration
Duration	Shorter	Lasts longer

This difference is shown clearly when antibody concentration in the blood is plotted against time — as the graph below shows, the second exposure produces a curve that rises sooner and reaches a far greater height than the first.

Memory B-lymphocytes rapidly divide and differentiate into plasma cells, while memory T-cells quickly generate active T-helper and T-killer cells. As a result the pathogen is usually destroyed before it can cause symptoms, so the person appears immune. This is the basis of long-term immunity, and it explains why vaccination — which generates memory cells without causing disease — gives lasting protection.

Worked example

Exam-style question: A child catches chickenpox and recovers after about two weeks. Years later the same person is exposed to the chickenpox virus again but shows no symptoms. Using your knowledge of memory cells, explain why the second exposure does not cause illness. [3]

Model answer:

• During the first infection (the primary response), activated lymphocytes produced memory cells specific to the chickenpox antigens, and these remained in the body after recovery.
• On the second exposure the memory cells trigger a secondary response that is faster and produces a higher concentration of antibodies (and active T-killer cells) than the primary response.
• The pathogen is therefore destroyed before it can reproduce enough to cause symptoms, so the person is immune.

Worked example

Exam-style question: A person is exposed to the same antigen twice, once at day 0 and once at day 40, and the concentration of a specific antibody in the blood is measured over time. The peak after the first exposure reached about 10 arbitrary units around day 14, while the peak after the second exposure reached about 80 arbitrary units around day 45. (a) State which exposure produced the secondary immune response. (b) Using the values given, describe two differences between the two responses. (c) Explain, in terms of memory cells, why these differences occur. [5]

Model answer:

• (a) The second exposure (at day 40) produced the secondary response.
• (b) The secondary response reached a much higher peak antibody concentration (about 80 units compared with about 10 units, roughly eight times higher). It also rose faster, peaking about 5 days after exposure compared with about 14 days for the first exposure.
• (c) After the first exposure, memory cells specific to the antigen were formed and remained in the body. On the second exposure these memory cells are already present, so they divide and differentiate into plasma cells rapidly, producing antibodies sooner and in far greater quantity than the primary response, which had to begin with antigen presentation and clonal selection from a small number of cells.

Key Equations

This topic is qualitative; there are no equations to apply.

Common Mistakes to Avoid

• Confusing the T-lymphocyte and B-lymphocyte responses. If a question asks for the cell-mediated (T-cell) response, write about T-helper cells, cytokines, antigen presentation and T-killer cells destroying infected cells — not just antibody production by plasma cells, which is the B-lymphocyte (humoral) response.
• Saying lysosomes release only "lysozyme". Lysosomes release a range of hydrolytic enzymes (proteases, lipases and so on) to digest the pathogen; lysozyme is just one such enzyme, so do not let it stand in for the whole group.
• Mixing up immunity and resistance. Immunity is the body's ability to defend itself against a pathogen; resistance usually refers to a pathogen (for example bacteria) being able to survive a drug such as an antibiotic. These are different ideas.
• Treating a pathogen and the disease it causes as the same thing. A pathogen and the illness it causes are distinct — be precise about which one is transmitted and which one is the resulting condition. HIV/AIDS is the classic example: HIV is the virus that is passed from person to person, while AIDS is the condition that can develop later once the virus has destroyed enough T-helper cells to leave the immune system unable to cope. You catch the virus, not the condition.
• Vague antigen definitions. Do not just call an antigen "something foreign". State that it is a molecule (often a protein/glycoprotein) on a cell surface that is recognised as non-self and triggers a specific immune response, and contrast self with non-self antigens.
• Forgetting the macrophage's presenting role. Many answers stop at "the macrophage engulfs the pathogen". Add that it then presents the antigens as an antigen-presenting cell, linking the non-specific response to the specific one.

Exam Tips

• Learn the primary-response sequence as an ordered chain — macrophage (antigen presentation) → T-helper cell → B-lymphocyte/plasma cells and T-killer cells → memory cells — and write the steps in order for "describe the sequence" questions.
• Use the precise cell names and their jobs: plasma cells secrete antibodies, T-killer cells destroy infected cells, T-helper cells release cytokines to coordinate the response, memory cells give the faster secondary response.
• For "why is someone immune?" questions, always credit memory cells with making the secondary response faster, larger and longer-lasting than the primary response.
• When reading an antibody-against-time graph, compare the two curves directly: quote the higher peak and the shorter delay of the secondary response, and use the numbers on the axes to support your description.
• When describing phagocytosis, name the structures involved — phagosome, lysosome, hydrolytic enzymes — rather than just saying the cell "eats" the pathogen.
• Use the words complementary and specific when explaining how lymphocytes recognise a particular antigen.
• Watch the command word. "Describe the primary response" means list the ordered events; "explain why the secondary response is faster" (or "explain the role of memory cells") means give the cause — memory cells specific to the antigen are already present, so there is no delay for antigen presentation and clonal selection, which is why the response is faster and larger.