CorpusHuman Anatomy

Adaptive Immune Response

From antigen capture to antibodies and cytotoxic killing

A schematic of the primary adaptive immune response, from infection to effector function. On the left is the infected tissue; on the right is the draining lymph node. A dendritic cell takes up antigen in the tissue, matures, and migrates in afferent lymph to the node. There it presents pathogen peptides on MHC class II to a naive CD4⁺ helper T cell and on MHC class I (cross-presentation) to a naive CD8⁺ T cell. T-cell activation needs signal 1 (peptide–MHC + TCR with CD4 or CD8) and signal 2 (B7–CD28 co-stimulation), shown in the synapse inset, plus cytokines (signal 3).

The activated helper T cell gives help to a B cell that has bound the same antigen (CD40L–CD40, IL-4, IL-21). The B cell undergoes clonal expansion and differentiates into plasma cells, which secrete antibodies, and memory B cells. The antibodies travel back to the tissue to neutralise and opsonise the bacteria. In parallel, CD8⁺ T cells expand into effector cytotoxic T lymphocytes that home to the tissue and kill virus-infected cells displaying peptide–MHC I, using perforin and granzymes. Memory T and B cells persist to give a faster, larger secondary response.

Step-by-step

  1. Infection and antigen capture

    Microbes breach the epithelium. Immature dendritic cells in the tissue sense them with pattern-recognition receptors (e.g. TLRs) and take up antigen by phagocytosis, macropinocytosis and receptor-mediated endocytosis.

  2. Migration to the lymph node

    The activated dendritic cell matures as it travels. It up-regulates CCR7, MHC molecules and B7 co-stimulators and migrates in afferent lymph to the T-cell zone (paracortex) of the draining lymph node, where naive T cells continually circulate.

  3. Presentation to a CD4⁺ T helper

    Exogenous antigen is processed in endosomes and loaded onto MHC class II. A naive CD4⁺ T cell whose TCR fits the peptide–MHC II (signal 1, CD4 binding MHC II) and receives B7–CD28 co-stimulation (signal 2) is activated. It makes IL-2, proliferates, and differentiates into an effector subset (Th1, Th2, Th17, Tfh) depending on the cytokines present (signal 3). Signal 1 without signal 2 causes anergy.

  4. T-cell help for the B cell

    A B cell binds native antigen through its BCR (surface IgM/IgD), internalises it and presents peptides on MHC II. The helper T cell (Tfh) that recognises the same antigen delivers CD40L–CD40 contact and cytokines (IL-4, IL-21). This is linked recognition: T and B cells recognise the same antigen, though often different epitopes.

  5. Clonal expansion and plasma cells

    Only clones with a matching receptor are selected (clonal selection). They proliferate and, in germinal centres, undergo somatic hypermutation, affinity maturation and class switching. Some differentiate into antibody-secreting plasma cells and others into long-lived memory B cells. The primary response peaks about 7–14 days after exposure and is dominated by IgM.

  6. Antibodies act in the tissue

    Secreted antibody reaches the tissue in efferent lymph and blood. It neutralises toxins and microbes, opsonises them for phagocytes (Fc receptors) and activates the classical complement pathway (IgM and IgG).

  7. CD8⁺ T-cell activation

    Dendritic cells cross-present captured antigen on MHC class I to naive CD8⁺ T cells. With co-stimulation, and often CD4⁺ help through DC licensing and IL-2, the CD8⁺ clone expands into effector cytotoxic T lymphocytes and memory T cells.

  8. CTL kills the infected cell

    Effector CTLs home to the infected tissue and recognise viral peptide on MHC class I, which all nucleated cells express. They release perforin and granzymes into the synapse, inducing apoptosis of the infected cell without damaging neighbouring cells. Fas ligand–Fas is a second killing pathway.

  9. Memory

    Once the antigen is cleared, most effector cells die (contraction), but memory B and T cells persist for years. On re-exposure, the secondary response is faster (2–3 days), larger and of higher affinity, and it is dominated by IgG. This is the basis of vaccination.

Labelled parts