English: Eliciting humoral and cellular responses through vaccination. Vaccine immunogens prompt antigen-specific responses from B cells and T cells in draining lymph nodes. B cells are blue, CD8+ T cells are gold and CD4+ T cells are green. Some of the key molecular interactions between different cell types that are needed for optimal humoral and cellular defense are shown in boxes. For optimal humoral responses, antigen-specific B cells must interact with pre-TFH cells (“pTFH”) to initiate germinal center reactions. Within germinal centers, B cells proliferate and undergo somatic mutation, in which mutations are introduced into the genes encoding the B cell receptor, thereby enhancing or diminishing affinity for antigen. B cells bearing receptors that have acquired affinity through mutation interact with TFH cells to receive survival signals and re-enter the cycle of proliferation and mutation. Germinal centers produce long-lived plasma cells, which secrete high affinity antibody and memory B cells, which differentiate into plasma cells upon re-encounter of antigen. For protection from HIV, the goal of vaccination is to induce broadly neutralizing antibodies (“bnAb”), which serve as a first layer of defense by preventing HIV virions from infecting cells. For optimal induction of cellular immune responses, CD8+ T cells, dendritic cells and CD4+ helper cells are required. CD4+ T cells “license” dendritic cells to activate peptide-specific naïve CD8+ T cells, which receive co-stimulatory signals from both dendritic cells and CD4+ T cells to proliferate and differentiate into Cytotoxic T Lymphocytes (CTLs). For protection from HIV, a second goal of vaccination is to elicit a pool of HIV-specific memory CTLs to serve as a secondary layer of defense, killing host cells that become infected by virions that escape neutralization by bnAbs. Abbreviations: Ag: antigen; CTL: Cytotoxic T Lymphocyte; DC: Dendritic cell; FDC: Follicular Dendritic cell; GC TFH: Germinal Center T follicular Helper cell; pTFH: Pre-T Follicular Helper cell; TFR: T Follicular Regulatory cell.