Antigenic variation
Antigenic variation refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters its surface proteins in order to avoid a host immune response. It is related to phase variation. Immune evasion is particularly important for organisms that target long-lived hosts, repeatedly infect a single host and are easily transmittable. Antigenic variation not only enables immune evasion by the pathogen, but also allows the microbes to cause re-infection, as their antigens are no longer recognized by the host's immune system. When an organism is exposed to a particular antigen (i.e. a protein on the surface of a bacterium) an immune response is stimulated and antibodies are generated to target that specific antigen. The immune system will then "remember" that particular antigen, and defenses aimed at that antigen become part of the immune system’s acquired immune response. If the same pathogen tries to re-infect the same host the antibodies will act rapidly to target the pathogen for destruction. However, if the pathogen can alter its surface antigens, it can evade the host's acquired immune system. This will allow the pathogen to re-infect the host while the immune system generates new antibodies to target the newly identified antigen. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. There are many molecular mechanisms behind antigenic variation, including gene conversion, site-specific DNA inversions, hypermutation, as well as recombination of sequence cassettes. In all cases, antigenic variation and phase variation result in a heterogenic phenotype of a clonal population. Individual cells either express the phase-variable protein(s) or express one of multiple antigenic forms of the protein. This form of regulation has been identified mainly, but not exclusively, for a wide variety of surface structures in pathogens and is implicated as a virulence strategy.
Cancer immunoprevention
Two main protective mechanisms elicited by cancer immunoprevention in various mouse models were cytokines released by T cells, in particular gamma-interferon, and cytotoxic antibodies against the target antigen. This is at variance with cancer immunotherapy administered to cure existing tumors, which is mainly based on cytotoxic T lymphocytes (CTL). The lack of a relevant CTL response in long-term immunoprevention is thought to be an advantage, because chronic CTL activation is severely toxic for the host. In contrast circulating antibodies provide long-term protection without toxic side effects. A similar situation happens in viral immunity, acute infections are resolved by CTL, whereas long term immunity from reinfection is provided by antibodies.
Both gamma-interferon and antibodies prevent tumor growth in multiple ways. Gamma-interferon activates T, natural killer and B cells, inhibits angiogenesis and tumor invasiveness, stimulates major histocompatibility complex expression in tumor cells and inhibits cell proliferation. Antibodies binding to antigens on the surface of cells trigger lytic mechanisms mediated by the complement system (complement-mediated cytotoxicity) or by leukocytes carrying Fc receptors (antibody-dependent cell-mediated cytotoxicity, ADCC). Moreover, antibody binding interferes with the cellular functions of the target antigen, causing its internalization or hampering molecular interactions, eventually blocking downstream signaling. If the target antigen controls cell growth (e.g. if it is the product of an oncogene), then a block of signaling can disrupt the carcinogenic process. Surface antigens causally involved in carcinogenesis are called oncoantigens.