Antigenic escape occurs when the immune system is unable to respond to an infectious agent. This process can occur in a number of different mechanism of both genetic and environmental nature.[1] Such mechanisms include homologous recombination, and manipulation and resistance of the host's immune responses[2].
Different antigens are able to escape through a variety of mechanisms. For example, the African Trypanosome parasites are able to clear the host's antibodies, as well as resist lysis and inhibit parts of the innate immune response[3]. Another bacteria, Bordetella pertussis, is able to escape the immune response by inhibiting neutrophils and macrophages from invading the infection site early on.[4] One cause of Antigenic escape is that a pathogen's epitopes (the binding sites for immune cells) become too similar to a patient's naturally occurring MHC-1 epitopes. The immune system becomes unable to distinguish the infection from self-cells.
Antigenic escape is not only crucial for resistance of a host's natural immune response, but also for the resistance against vaccinations. The problem of antigenic escape has greatly deterred the process of creating new vaccines. Because vaccines generally cover a small ratio of pathogenic strains, the recombination of antigenic DNA that lead to diverse pathogens allows these invaders to resist even newly developed vaccinations[5]. Some antigens may even target pathways different than those particular to the vaccine[4]. Recent research on many vaccines, including the malaria vaccine, has focused on how to anticipate this diversity and create vaccinations that can cover a broader spectrum of antigenic variation[5].
Mechanisms of Evasion
editHelicobacter pylori and Homologous Recombination
editThe most common of antigenic escape mechanisms, homologous recombination, can be seen in a wide variety of bacterial pathogens, including Helicobacter pylori, a bacterium that infects the human stomach. While a host's homologous recombination can act as a defense mechanisms for fixing DNA double stranded breaks (DSBs), it can also create changes in antigenic DNA that allows the antigen to escape recognition by the host's immune response. Through the recombination of H. pylori's outer membrane proteins, immunoglobulins can no longer recognize these new structures and, therefore, cannot attack the antigen as part of the normal immune response.[2]
African Trypanosomes
editAfrican Trypanosomes are parasites that are able to escape the immune responses of its host animal through a variety of mechanisms. Its most prevalent of mechanisms is its ability to evade recognition by antibodies through antigenic variation. This is achieved through the switching of its variant surface glycoprotein or VSG, a substance that coats the entire antigen. When this coat is recognized by an antibody, the parasite can be cleared. However, variation of this coat can lead to antibodies being unable to recognize and clear the antigen. In addition to this, the VSG coat is able to clear the antibodies themselves to escape their clearing function.
Trypanosomes are also able to achieve evasion through the mediation of the host's immune response. Through the conversion of ATP to cAMP by adenylate cyclase, TNF-α production by liver myeloid cells is inhibited. In addition, Trypanosomes are able to weaken the immune system by inducing B cell apoptosis and the degredation of B cell iymphopoiesis. They are also able to induce suppressor molecules that can inhibit T cell reproduction.[3]
Tumor Escape
editMany head and neck cancers are able to escape immune responses by a variety of mechanisms. Once such mechanism is through the production of pro-inflammatory and immunosuppressive cytokines. This can be achieved when the tumor recruits immunosuppressive cell subset into the tumor's environment. Such cells include pro-tumor M2 macrophages, myeloid-derived suppressor cells (MDSC's), Th-2 polarized CD4 T-lymphocytes, and regulatory T-lymphocytes. These cells can then limit the responses of T cells through the production of cytokines and by releasing immune-modulating enzymes.[1]
Escape from Vaccination
editConsequences of Recent Vaccines
editWhile vaccines are created to strengthen the immune response to pathogens, in many cases these vaccines are not able to cover the wide variety of strains a pathogen may have. Instead they may only protect against one or two strains, leading to the escape of strains not covered by the vaccine.[5] This results in the pathogens displaying different targets of the immune system than the targets formulated in the vaccination.[4] This parasitic antigen diversity is particularly troublesome for the development of the malaria vaccines.[5]
Solutions to Escape of Vaccination
editIn order to fix this problem, vaccines must be able to cover the wide variety of strains within a bacterial population. In recent research of Neisseria meningitidis, the possibility of such broad coverage may be achieved through the combination of multi-component polysaccharide conjugate vaccines. However, in order to further improve upon broadening the scope of vaccinations, epidemiological surveillance must be conducted to better detect the variation of escape mutants and their spread.[4]
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- ^ a b Allen, Clint; Clavijo, Paul; Waes, Carter; Chen, Zhong (2015). "Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches". Cancers.
- ^ a b Hanada, Katsuhiro; Yamaoka, Yoshio (2014). "Genetic Battle between Helicobacter pylori and humans. The Mechanism Underlying Homologous Recombination in Bacteria, Which Can Infect Human Cells". Microbes and Infection.
- ^ a b Cnops, Jennifer; Magez, Stefan; De Trez, Carl (2015). "Escape Mechanisms of African Trypanosomes: Why Trypanosomosis Is Keeping Us Awake". Parisitology.
- ^ a b c d Barnett, Timothy; Lim, Jin; Soderholm, Amelia; Rivera-Hernandes, Tania; West, Nicholas; Walker, Mark (2015). "Host-Pathogen Interaction During Bacterial Vaccination". Current Opinion in Immunology.
- ^ a b c d Barry, Alyssa; Arnott, Alicia (2014). "Strategies for Designing and Monitoring Malaria Vaccines Targeting Diverse Antigens". Frontiers in Immunology.