Figure 1. Natural immunity to an intracellular pathogen.

Infected and stressed host cells (top left) release PAMP/DAMPs, activating APCs, like DCs. Activated DCs mature, upregulating phagocytosis, antigen presentation and co-stimulatory molecules, and migrate to a draining lymph node (dLN); lymph drainage also transports local antigens to the dLN. The activated DCs present MHCII restricted peptides to CD4⁺ T cells, which can in turn license DCs (including via CD40L:CD40 signals; see Inset A) to cross-present antigen on MHCI and activate CD8⁺ T cells. Cytokines from DCs also shape CD4⁺ Helper T cell differentiation. DCs, via p:MHCI stimulation of TCR and co-stimulatory signals (Inset B) activate CD8 cells to respond, produce IL2 and IL-12 (for autocrine signaling) and differentiate into cytotoxic T lymphocytes (CTLs). CD4⁺ T cells potentiate CTL differentiation via IL2, maintain CTL effector function in viral infection via IL21 and induce CD8⁺ resident memory differentiation via IFNγ (Inset C). CD4⁺ T cells that recognize cognate p:MHCII on B cells, can provide co-stimulation (Inset D) to support affinity maturation, antibody class switching and plasma cell differentiation. Abbreviations: Pathogen- /Damage- associated molecular pattern (PAMP/DAMP), Dendritic cell (DC), T4 (CD4⁺ Helper T cell), T8 (CD8⁺ T cell), CTL (Cytotoxic T lymphocyte), B (B cell), p:MHC (peptide bound multi-histocompatibility complex), TCR (T Cell Receptor).