IMMUNO REGULATION IN PARASITIC INFECTION: A dominant theme with chronic parasitcs infections is the necessity for the host to modulate its immune response appropriately. Evidence suggest that a response dominated by the production of TH2 cytokins, such as IL-10, may play a crucial role in reducing the severity of acute disease and allowing survival. Despite evidence that IL-13 plays a central role in the development of fibrosis during infection with S. mansoni, the absence of IL-4 (a cytokine most commonly coproduced with IL-13 by Th2 cells)
allows the development of a severe, lethal inflammatory condition in which mice become cachectic prior to death (Peaarce et al., 1997).
The absence of IL-10 exacerbates this condition (Rickard et al., 1989). In this model, pathologic changes that Occur in the absence of IL-4 appear to be related to the dysregulation of No production during infection and subsequent production of damaging levels of peroxynitrate. Thus, while Th2 responses are clearly implicated in immnopathology during parasitic infections.
They can also permit survival in the face of continuing infection while simultaneously protecting against super infection. An additional facet of immuno regulation during filarial as well as schistosome infections is that the marked T-Cell responsiveness that follows initial infections is, in the majority of patients, dampened as the infection becomes chronic, (Yazdanbakhsh et al., 1999), this diminution of responsiveness is believed to be in the best interest of the host, as it is not apparent in infected individuals exhibiting the most severe forms of disease (Allen et al., 1999).
For example, peripheral blood mononuclear cells taken from microfilaramic individuals fail to proliferate to filarial antigen in vitro but are still able to respond in an Ag-specific manner as measured by cytokine production. Conversely, individuals with chronic lymphatic pathology, who rarely exhibit blood microfilaremia, generally mount stronger filarial specific cellular poriferative responses.
The underlying mechanisms behind down-regulation of cellular proliferative responses during parasitic infection remain unknown, although recent studies have suggested that host macrophages may be alternatively activated by the parasite to effect suppression via a contact dependent mechanisms (Allen et al., 1998), Via the production of No in response to parasitic glycoconjugates (Hara et al., 2001) or through /L-10 (Nutman et al., 1996) indeed, it is clear that /L-10 plays a major role in the regulation of the intensity of both Th1 and TH2 responses during parasitic infections and in so doing plays a principal role in minimizing immuno-pathology and in suppressing the expression of the allergic like symptoms that mighty otherwise be expected in parasitic infected individuals who are producing large amounts of lgE; (Yazdambakhsh et al., 2000). There is an important additional role for idiotypic regulation of immune responsiveness in disease severity in schistosomiasis.
COINFECTION, AUTOIMMUNITY, AND ALLERGY IN PARASITIC INFECTION
Since so many people are infectected with parasites, there is little doubt that many individuals become exposed to non parasite pathogens while harboring chronic parasitic infections.
How the presence of an underlying TH2 response-inducing infections affects the host ability to mount an appropriate immune response to the new infection is a subject of growing interest (Abel et al., 1991). It is clear from existing reports that parasitic infection can make mice far more. Susceptible to certain pathogen against which TH1 response are protective (eg Toxoplasma gond) (Adreason et al., 2001).
And more resistant which TH2 responses are protective (eg I. Muris) (Adreason et al., 1991). Ongoing studies are examining the impact of schistosomiasis and other parasitic infections; on the outcome of human immunodeficiency virus infection.
Another important issue is that of how the presence of ongoing parasitic infection affects likelihood of the development of immunological disorders, such as autoimmunity and allergy. Data from studies addressing the issue of autoimmunity are still descriptive but nevertheless tantalizing.
Wein stock and colleagues have argued that a failure to acquire parasites predisposes one to Crohn’s disease and correlated increased hygiene in westernized countries with the decreased prevalence of parasites and the increased prevalence of autoimmune intestinal diseases and other forms of autoimmunity (Grencis et al., 1994).
The relationship between immune responsiveness to allergens and/or allergic symptoms and parasitic infections is fascinating and has puzzled immunologists for decades, parasitic infections induce strong IgE responses, which in combination with high Ag levels would be expected to lead to allergic symptoms and possible anaphyslaxis (Bauman et al., 2001). However, parasites-infected individuals rarely have allergic reactions to these parasites and, moreover, appear to suffer less from allergic disorders in generally.
There are several possible explanations for this paradox, including the production of IgG antibodies that block access of allergenic Ag [to specific IgE (Nafeh et al., 1996). but in an exciting recent development, studies have correlated. Increased IL-10 levels resulting from chronic parasitic infection disease.