Primary and secondary immune responses

Primary response. After first exposure there is a lag (latent) phase of ≈ 4–7 days while rare naive clones are activated, expanded and differentiated. Antibody then rises exponentially, initially IgM (peaking at roughly 7–10 days), followed by a smaller amount of IgG as class switching begins; peak titres are modest and antibody affinity is relatively low. T-cell responses peak at about 1–2 weeks. Levels then decline as the antigen is cleared.

Secondary (anamnestic) response. On re-exposure, memory B and T cells — present at far higher frequency, with lower activation thresholds — respond within ≈ 1–3 days. Antibody levels rise to a much higher peak (often 10–100-fold or more above the primary peak) and persist longer; the antibody is predominantly IgG (or IgA/IgE at mucosal or allergic sites) and of higher affinity because of affinity maturation in germinal centres. Smaller doses of antigen suffice. Each subsequent exposure can further increase affinity and the size of the memory pool — the rationale for booster doses.

These kinetics underpin serological diagnosis: specific IgM suggests recent (primary) infection; IgG alone suggests past infection or immunity; a four-fold rise in IgG titre between acute and convalescent samples confirms current infection; and IgG avidity testing distinguishes recent (low-avidity) from older (high-avidity) infection — useful for toxoplasmosis or CMV in pregnancy.