Figure 1.

Immune response triggered by vaccination. Primary immune response triggered by vaccine administration is influenced by several factors, such as the vaccine formulation (including delivery systems and/or adjuvants), the nature and the dose of the antigen, and the route of immunization. (A) After vaccine administration, DCs mature and migrate to the T cell zone of draining LNs. DCs express vaccine epitopes on their MHC class II molecules, thus engaging naïve antigen-specific CD4⁺ T cells and inducing their proliferation and differentiation into effector T-helper cells (1). The local environment deeply influences the T cell priming event and the polarization of distinct effector T cell subsets (2). Effector T cells differentiate into subpopulations, such as Th1, Th2, Th17, Treg that mainly exert their function outside the LN. Some primed CD4⁺ T cells differentiate into Tfh that relocate to B-T cell borders. Cognate contact between Tfh cells and antigen-primed B cells in the extra-follicular regions of the lymph nodes is required for clonal expansion and antibody class switching (without affinity maturation) of short-lived plasma cells. GC-Tfh drives the GC reaction, in which B cells undergo clonal expansion, isotype switching, affinity maturation, and differentiate into long-lived plasma cells. (B) Low-affinity IgM and IgG antibodies produced by short-lived plasma cells during the extra-follicular reaction, appear at low levels in the serum within a few days after immunization (3). Effector Th1, Th2, and Th17 subpopulations exit the LN and through the blood disseminate toward other LNs and toward the inflamed tissue (in this context, the site of vaccine inoculation) where exert their effector function (4). (C) The long-lived plasma cells exit the LN at the end of the GC reaction and migrate to survival niches mostly located in the bone marrow (BM) where they survive through signals provided by supporting stromal cells and continue to release hypermutated antibodies (5). Another fraction of B cells, matured during the GC reaction, develop a memory phenotype and disseminate into the extra-follicular areas of the LN where they persist as resting cells until booster immunization or pathogen encounter (6). Memory T cells traffic through T cell areas of secondary LNs and BM (Tcm) (6), or localize within tissue (Tem) (7). Booster immunization induces a rapid reactivation of memory B and T cells, with proliferation and differentiation into effector cells. Memory B cells mature into plasma cells secreting large amounts of high-affinity antibodies that may be detected in serum within a few days after boosting.