Introduction to Infection and Immunity

The immune system operates through two broad arms that collaborate to protect the host against microbial invasion. The first line of defence consists of physical and chemical barriers: intact skin, mucosal surfaces lined with ciliated epithelium, and secretions such as mucus, saliva, and gastric acid. When pathogens breach these exterior defences, the innate immune system responds within minutes to hours through pattern recognition receptors (PRRs), most notably Toll-like receptors (TLRs). These receptors detect pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide on gram-negative bacteria, and danger-associated molecular patterns (DAMPs) released from damaged host cells including extracellular DNA, ATP, and uric acid.

Tissue-resident phagocytes—macrophages, dendritic cells, and mast cells—engulf pathogens via phagocytosis. The phagosome fuses with lysosomes to form a phagolysosome, an organelle with a hostile low-pH environment enriched with reactive oxygen intermediates and proteolytic enzymes. Activation of these phagocytes drives release of inflammatory cytokines, chemokines, and lipid mediators, collectively triggering the acute inflammatory response. Histamine from mast cells causes vasodilation and increased vascular permeability, enabling neutrophil extravasation into infected tissue.

The innate response bridges to adaptive immunity through dendritic cells. After capturing antigen, activated dendritic cells migrate via lymphatics to draining lymph nodes, where they present peptide epitopes on MHC class II molecules to naïve CD4 T cells. Three signals are required for full T-cell activation: MHC–peptide engagement with the T-cell receptor, co-stimulatory receptor ligation, and cytokine signalling. CD4 helper T cells subsequently assist B cells in producing class-switched, high-affinity antibodies and activate CD8 cytotoxic T cells.

B cells recognise native antigen through surface-bound immunoglobulin (the B-cell receptor), phagocytose the antigen, and present processed peptides on MHC class II to CD4 T cells. With T-cell help, B cells differentiate into plasma cells that secrete large quantities of antibody and into long-lived memory B cells. CD8 cytotoxic T cells recognise peptide–MHC class I complexes displayed on all nucleated cells and kill infected or cancerous cells by inducing apoptosis. Antibody diversity arises through VDJ recombination of immunoglobulin gene segments, and different isotypes (IgM, IgG, IgA, IgE) are encoded by different heavy-chain constant regions, conferring distinct effector functions while sharing the same antigen-binding specificity.