Figure 1

Current understanding of immunology of vaccines containing alum adjuvants in vivo. Alum immunization leads to recruitment of neutrophil, natural killer cell, macrophage, eosinophil, and immature DC at the injection site. Immature DCs take up soluble Ag released from alum or particulate Ags mixed in alum in the subcutaneous areas and migrate towards draining lymph node (DLN). Soluble Ag can reach to DLN without help of DCs. In T cell area (paracortex), soluble Ags leaked out of conduits are taken up by resident DCs. DCs present Ag to the naïve T cells or transfer Ag to the resident DCs that present Ag to those T cells. In addition, B cells are capable of binding to this Ag with their surface immunoglobulins. B cells undergo activation, produce effector B cells (eB cells), and rapidly differentiate in plasma cells (PCs). Plasma cells produce low-affinity antibodies (LAb). B cells also migrate to B cell follicle. On the other hand, as a result of CD8 and CD4 T cell activation, effector CD8 (eCD8) T cells and effector CD4 (eCD4) T cells are produced. The eCD4 polarizes into T helper (Th) 1, 2, 17 or T follicular helper (Tfh) cells though alum induces development of mostly Th2 and Tfh cells. Tfh or Th2 may reach to the border of B cell follicle to activate B cells that produce eB cells and then PCs. The PCs consequently produce and secrete high-affinity antibody (HAb). Few alum-fed DCs and eCD4 may travel to efferent lymph vessels to reach into the distant LN in vivo. Ag: antigen, HEV: high endothelial venule, PVS: perivenular space (see text for explanation).