Immune system

What the exam asks

The two items you will meet most are an antibody-against-time graph with a first and second exposure marked, and a scenario about vaccination or population coverage. For the graph, the questions are why the first curve lags, why the second is steeper and higher, and what happens if the second exposure is a different antigen: expect a distractor where the second exposure is to a new pathogen and the curve is drawn as a secondary response anyway. The trap in the whole topic is treating memory as though the immune system learned to build a better antibody. It did not build anything; it kept the cells that already worked and made more of them, and every feature of the secondary response falls out of that starting population being large instead of rare. For herd immunity, the trap is reading it as protection conferred on the unvaccinated by the vaccinated. Nothing is conferred: the unvaccinated are protected because the pathogen runs out of routes to reach them.

The immune system is responsible for distinguishing self from not-self and destroying the not-self. It does the job with two arms that differ in a way worth stating precisely, because every question in the topic uses the distinction. The innate arm is fast, acts on general features shared by whole classes of pathogen, and responds identically no matter how many times it meets the same one. The adaptive arm is slow the first time, targets one specific molecular feature, and is permanently changed by the encounter.

The adaptive arm's central idea is clonal selection, and it is the one candidates most often have backwards. The body generates an enormous variety of lymphocytes at random before meeting any pathogen at all, each committed to one target. An antigen does not instruct a cell to make a matching antibody; it finds the few cells that already happen to fit and drives them to divide. Everything else in the topic follows from that: why the first response is slow, why the second is fast, and why immunity to one virus is worth nothing against another.

Within the adaptive arm, antibodies handle what is outside cells and cytotoxic T cells handle what is inside them, because an antibody cannot reach a virus hiding in a cell's cytoplasm. Vaccination and herd immunity are then applications, not new biology: a vaccine buys a primary response without the disease, and herd immunity is what happens to chains of transmission when enough people have already had one.

What to hold

• Innate defences act within minutes to hours on features common to many pathogens, and respond the same way to a millionth exposure as to the first.
• Adaptive responses are specific to one antigen and leave memory, which is the only part of the system that improves with experience.
• The lymphocyte repertoire is generated at random before exposure, so the antigen selects a cell that already fits rather than instructing any cell to fit it.
• Helper T cells orchestrate: they license B cells to make good antibody and activate macrophages, which is why losing them cripples responses that appear to have nothing to do with T cells.
• Cytotoxic T cells kill the body's own infected cells, which is the only way to reach a pathogen that has got inside one.
• An antibody has two identical binding sites made by its variable regions, and a constant region that determines its class and which effector mechanism it recruits.
• Antibodies rarely destroy anything themselves: they neutralise, clump, and tag targets for phagocytes and complement, which do the destroying.
• The primary response lags for days because the specific clone starts out rare and must be found, activated and expanded before enough antibody exists to matter.
• The secondary response is faster and larger because memory cells for that antigen are already numerous, already class-switched, and already selected for tight binding, so it begins from where the first response finished.
• A vaccine works by causing a primary response to something that cannot cause the disease, so that a real encounter is met by a secondary response.
• Memory is specific to the antigen it was made against, so a pathogen that changes its surface meets an immune system that does not recognise it.
• Passive immunity means receiving antibodies rather than making them: it protects immediately, fades as the antibody degrades, and leaves no memory.
• Herd immunity is an effect on transmission, not on individuals: once enough of a population is immune, an average infection passes to fewer than one other person and chains die out.
• The more transmissible a pathogen, the larger the immune fraction needed before chains fail, so the threshold is a property of the pathogen and not a fixed percentage.