Figure 1. Human immune system is a multilayered network of various defence mechanisms. Each cell in a human body has various means to fight pathogens. Basic cellular mechanisms such as ubiquitination, RNAi and apoptosis contribute to immune defence. Specialized immune cells such as B cells and macrophages and humoral systems such as complement work autonomously but in communication with other mechanisms. All responses are coordinated at the body level by various mediators. Skin and epithelial barriers of the body are protected by secretion of antimicrobial substances.

Figure 2. Coevolution of humans and Staphylococcus aureus. FcaR1, a receptor for IgA-Fc, expressed on myeloid cells mediates phagocytosis of IgA-coated pathogens. S. aureus produces a bacterial decoy SSL7 that binds IgA-Fc region preventing FcaR1 binding and phagocytosis. Immunoglobulin duplication and diversification took place in primates (step 1). FcaR1 was positively selected for binding with the new IgA (step 2). Bacterial decoy proteins developed high affinity to this IgA (step 3). Next, IgA forms with low binding to the bacterial decoy were selected (step 4). Now, FcaR1 needs to change again to bind the new IgA (step 5) and so on. If FcaR1 fails to keep up, it may be lost from the genome.

Figure 3. IgG4 is a regulatory antibody inhibiting the formation of immune complexes, inflammation and allergy. It is under the dual selection pressure. Pressure from pathogens requiring stronger immune response can lead to loss of G4, whereas pressure from inflammatory/allergic diseases can lead to its duplication.