Animal-parasitic nematodes have evolved a mutiplicity of evasive strategies to survive in immunologically competent host. The parasite's ability to exist for long periods of time in their host, has been attributed to a rapid turnover of their cuticle surface, shedding of surface antigens and membrane rigidity, which are likely to render the parasite less susceptible to immune attack (Simpson et al. 1984; Kusel and Gordon 1989). The mechanisms underlying surface antigen switching mechanisms are presently unknown but nematodes can alter their SC protein compositions at the moults between developmental stages or in response to host/ environmental changes. As a rapid change in the surface lipophilicity of various animal-parasitic nematodes occurs during their transition from pre- to post-parasitic forms, these surface alterations may enable parasitic nematodes to evade host immune defenses during the course of infection (Jungery et al. 1983). Intracellular signalling and second messenger pathways involving cyclic nucleotides, calcium and intracellular alkalinisation participate in bringing about these surface changes (Modha et al. 1995, 1997).
Disguise of the parasite cuticle surface with the acquisition of host derived antigens (Smithers and Doenhoff 1982) and the action of parasite surface proteases that can cleave the Fc region of Immunoglobulins (Auriault et al. 1981) are some other mechanisms that may also help parasites to evade the host immune response by inhibiting important cellular functions.
Evasion of host immunity by Toxocara canis infective larvae is mediated by the nematode SC, as this nematode is able to shed the entire SC in response to binding antibodies or eosinophils, thus permitting parasites to physically escape immune attack (Maizels and Loukas 2001a). The major constituent of the SC of this nematode is the O-linked TES-120 (Toxocara excretory/secretory) glycopro-teins series, which has a typical mucin domain and may explain a generally non-adhesive property of this parasite. Membrane associated mucins are closely concerned with the adhesion status of cells through electrostatic charge and due to steric effects of long chains protruding from the surface. It has been shown that the inhibition of T-cell adhesion can interfere with the ability of eosinophils to bind to the surface cuticle and kill schistosome parasites in in vitro tests (Hayes et al. 1990). TES-120 is secreted in internal excretory glands and ducted to the surface via the oesophagus and excretory pore and it is also released from Toxocara surface. The overexpression of some membrane-associated mucins suggests a possible model for the role of SC in immune evasion by parasitic nema-todes, through changing the nematode surface cuticle adherence to defence cells and/or by releasing soluble mucins that might interact with host cells and blocks defence responses (Gems and Maizels 1996). Toxocara canis also secretes large quantities of a C-type lectin thought to compete with host innate immune system receptors (Loukas and Maizels 2000).
Another important group of surface proteins which may act to promote immune evasion in B. malayi are the anti-oxidant products glutathione peroxidase and superoxide dismutase. Bm-GPX-1 is the major 29 kDa surface glycoprotein of adult Brugia (Cookson et al. 1992; Maizels et al. 1989), which is believed to act as a lipid hydroperoxidase, protecting parasite membranes from peroxidation caused by free-oxygen radicals (Tang et al. 1996). A minor surface-associated protein of similar molecular weight is a superoxide dismutase, allowing the parasite to detoxify superoxide radicals (Tang et al. 1994). Many other surface-associated molecules may contribute to immune escape in a less obvious manner. For example, the polyprotein antigen (variously named gp15/400 or Bm-NPA-1) has a very high affinity for fatty acids (Kennedy et al. 1995; Smith et al. 1998) which could sequester substrate required for host leukotriene synthesis. Non-protein filarial products are also likely to play a significant role: a novel lipid found in the cuticle of B. malayi acts as a sink absorbing oxidative attack, perhaps protecting essential membrane lipids and proteins from degradation (Smith et al. 1998). A further component prominently expressed by B. malayi is phosphorylcholine (PC). Not only has this been suggested as an immunosuppressive moiety in lymphatic filariasis (Lal et al. 1990), but it has been possible to demonstrate direct down-regulation of both B (Deehan et al. 1998) and T cell (Harnett et al. 1998) function by a PC-bearing protein secreted from the filarial parasite Acanthocheilonema viteae.
A proteinase inhibitors member of the cystatin (cysteine protease inhibitor) family located on the surface of both L3 and adult B. malayi, and secreted by these parasites in vitro blocks conventional cysteine proteases but also the aspariginyl endopeptidase involved in the Class II antigen processing pathway in human B cells (Maizels et al. 2001b)
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