How parasites can affect normal immune function

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How do parasites affect the immune system? Parasites become invisible! Parasites such as protozoa, fungi, helminthes and arthropods are known as eukaryote pathogens, which have a life cycle that orientate throughout a hosts organism. Given that a parasite must live within a host, it must have strategies to survive against the highly complicated immune system of their hosts. These strategies consist of avoiding immune detection, suppressing cellular immunity and deflecting immune attack mechanisms. In humans, evidence worldwide show that parasitic infections clinically go unnoticed due to these mechanisms of immune evasion. The human immune response to parasitic infection is the innate immune system characterized by a range of molecules known as pattern recognition receptors consisting of serum proteins, intracellular and cell surface receptors. In the presence of parasite infection, these receptors send out macrophages and granulocytes that have antimicrobial proteins and reactive metabolites. Dendritic cells are also released in parasitic infection that activates lymphocytes of the adaptive immune system. This induces proliferation of T-cells and antibody B-cells that have variable receptors that recognize the parasite. Parasite survival is dependent on its ability to survive the innate immune response by evading the adaptive immune response. This is achieved by producing antigenic variants of surface molecules to avoid immune detection or regulating of immune cell components by the use of specialized immunomodulators [3] [4].

The process of antigenic variation is the process a parasitic organism alters its surface proteins in order to evade a host immune response. The process of antigenic variation not only enables immune evasion but can allow infection to reoccur due to the immune system not being able to recognize the infection. When a parasite is exposed to an antigen, immune responses are generated to the specific antigen. Immunological memory is established in order to deal with the future infection of microorganism to protect the host. Parasites change this antigen to counteract this recognition system. Parasites using antigenic variation have an advantage as it allows them to cross species barrier effectively and insures persisted infections to occur in their hosts. Protozoa such as plasmodium (malaria) and trypanosomes (changas disease)and T. brucei gambiense and T. brucei Rhodesians (African sleeping sickness) are known to facilitate antigenic variation effectively making up a majority of problematic parasitic infections worldwide. Many different groups of parasites use this mechanism evident that parallel evolution exist between them, one example is trypanosomes and fungi use equivalent signals to target their host using similar methods in delivery of molecules that manipulate the immune defense of the host.[6][2]

The concept of immunomodulation covers a wide range of mechanisms: including suppression, diversion and conversion of host immune response. A largely researched and best example of immune regulation by a parasite is the helminths. Helminths are a broad range of microorganisms that include intestinal parasitic worms, (roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura), or hookworms (Necator americanus and Ancylostoma duodenale) are associated with pathological complications such as granulomatous disease and organ failure [1]. Most micro parasites avoid immune response by antigenic variation or hide in Sequestrated niches, helminthes tend to proliferate in exposed intracellular locations such as the in the bloodstream ,lymphatics and in the gastrointestinal tract, this is achieved by their ability to regulate their environment using immunomodulators such as cytokine homologs(variations of signal molecules produced by the parasite in to evade response, unmodified examples IL-10, IL-12, TNF-a etc),proteases, protease inhibitors(molecules that inhibit the function of proteases) ,venom allergen homologues(types of modified allergens), glycoltic enzymes and lectins in immune suppression[3]. The characteristic among host cells that are affected is the dominance of the T-helper 2 cell (Th2) phenotype and selective losses of effector activity against a environment of regulatory T cells, alternatively activated macrophages, and Th2-inducing dendritic cells [1].Evidence has also been found that helminths regulate other innate cells, such as mast cells and eosinphils. The overall effect of changes made on these cells immune components of the host is to create a favorable environment for the parasite, free of inflammation, which help prevent immune response and clinical detection for the parasite.

The methods that parasites deploy in general when avoiding the immune system change during the time of infection. These changes are dependent on the mechanisms of the immune response involved over a given time of infection; these stages are the innate immune response, early immune response, adaptive immune response and protective immune response stages. During the innate stage of immune response during the time of infection parasites block macrophages, avoid phagocytosis, block complementation and manipulate cell surfaces in order to avoid recognition. During the stages of early induced response parasites can deploy methods by which they can block inflammation, interfere with signaling, and degrade antimicrobial peptides manipulate cell vacuoles and cytoskeletons and interfere with RNAj, at this stage this can give a parasite a strong foothold in the host. The next step to extended survival of a parasite in a host is to evade the adaptive immune response. The methods in which parasites can do this is by interfering with cell maturation, interfere with receptors and signaling, interfere with antigen and processing and the release of super antigens. This process can help the parasite avoid detection for days to months.The final stage for a parasite to remain undetected are avoiding protective immunity responses by means of antigenic and phase variation. Overall the success of a parasite depends on the ability to achieve these processes, the more interference strategies used the longer they can survive in a host, which can lead to severe conditions if not detected [2].

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