In addition, M. tuberculosis is able to down-regulate the expression of antibacterial immune effectors, such as nitric oxide, by infected macrophages.

The intestinal Gram-negative pathogen Salmonella enterica is able to modify its LPS into a form that is less identifiable by TLR4. Impairment of the LPS/TLR4 interaction reduces early activation of the innate immune response and hence allows Salmonella to better survive and proliferate within the host’s intestinal cells. Viruses such as cytomegalovirus (CMV) also have highly evolved host avoidance strategies. This member of the herpesvirus family has evolved multiple genes for the manipulation of host immunity, including those whose products prevent the display of viral proteins Buparlisib in association with MHC class I molecules (hence

avoiding triggering or being targets of specific CD8+ cytotoxic T cells) by both diverting viral products out of the degradation pathway and by suppressing expression of MHC class I molecules. Ordinarily, this would attract selleckchem the attention of NK cells, which are activated by nucleated cells lacking surface expression of MHC class I molecules. However, CMV possesses genes encoding MHC class I mimics, which are expressed on the surface of infected cells and are able to bind to receptors which switch off the cytotoxic activity of circulating NK cells. Parasites present a challenge to vaccine design because the parasite life cycle comprises distinct phases within

a single host, during which it will reside in different anatomical locations and, most importantly, express different surface antigens. Thus, parasites represent an immunological ‘moving target’. In addition, the immune response to parasites is very complex and may be modulated by the parasite itself, and host–parasite interactions are often poorly defined. There are currently no available vaccines for parasitic diseases of humans, although one vaccine for malaria is currently in Phase III clinical trials (see Chapter 6 – Vaccines of the future). Other important considerations in vaccine immunology include GNA12 the phenomena of immune tolerance and immunological/antigenic interference, which can suppress or prevent development of adequate immune responses following vaccination. Immune tolerance refers to the induction of immunological non-responsiveness by repeated exposure to similar antigens, such as polysaccharide antigens; this effect is dose-dependent and may be limited in time as increasing the interval between subsequent doses can partially restore responsiveness. Immunological/antigenic interference occurs when previous or concomitant exposure to another antigen prevents the development of adequate responses to the vaccine antigen, which may be due to previous or concurrent vaccinations.