An Introduction to the Immune Evasion Strategies Website
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| Classic intranuclear inclusion formed by a cytomegalovirus, the subject of our immune evasion case study. Source: The World of Human Cytomegalovirus. |
Why did these evasion strategies evolve?
The host-microbe interaction demonstrates the dynamic nature of the evolutionary process. In studying this interplay, one gains access to an historical dialogue between the immune system and the infectious agent. The two participants have sustained this dialogue for millions of years—exchanging blows, revising tactics, striving for the upper hand. One researcher described the host-microbe relationship as "life at immunity’s edge." (Ploegh, 1998)
As invaders and parasites, pathogens initiate the relationship with host species to bolster their own chances for survival, proliferation, and subsequent dissemination. A stable interaction, from their perspective, consists of a high prevalence rate among the host population and lifelong persistence with minimal symptoms of disease. Achieving such goals would guarantee ample time for reproduction and passage to new hosts. The host immune system, however, mobilizes its molecular arsenal to thwart multiplication and eliminate the infectious agent. Pathogens, in response, have evolved various strategies to deal with the threat of the host immune system.
What are the basic types of evasion strategies?
Viruses, such as herpes simplex virus, enter a state of latency in which viral protein production is drastically downregulated. Other microbes reside in so-called privileged tissues (salivary glands, neurons) in which factors of the immune response are not active. Some pathogens exhibit antigenic variation to prevent the immune system from preparing for reinfection. Acting as a physical barrier to the immune response or as oxygen radical-scavenging units that interfere with immune recognition, microbial structural components offer the means for passive evasion. (Kotwal, 1998)
Host-specific and highly subversive, active strategies often involve the production of pathogenic immunomodulatory proteins which alter normal host protein function and general immune function. The three immune targets for modulation discussed in this website fall under this category.
Microbes, like HIV and the measles virus, infect cells essential for immune function (T and B lymphocytes, monocytes), thereby causing immunosuppression.
How did these evasion strategies evolve?
The flatworm Platyhelminthes is found at the stem position in the evolution of other metazoan animals, including other parasitic flatworms and their vertebrate hosts. In other words, "we are parasitized by our ancestors." At the particular point of evolutionary divergence represented by the flatworm, the basic rules of biochemistry and organization had already been well-established; therefore, genes were thereupon conserved through evolutionary history. Pathogenic immunomodulatory proteins are actually shared molecular keepsakes. (Damian, 1997)
In all probability, molecular mimicry is also the result of convergent evolution through extensive historical interaction between microbe and host. Not surprisingly, distinguishing between conservation and convergence is difficult.
The horizontal transfer of DNA between pathogen and host has also been identified as a source of immunomodulatory proteins. Retroviruses are the probable agents of such gene capture.
Why is the study of evasion strategies important?
The implications of studying immune evasion strategies are, not surprisingly, interrelated:
What is the focus of this website?
The website focuses on an important triad of active evasion mechanisms:
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