Antibody‐dependent cell‐mediated immune reactions to <i>Loa loa microfilariae</i> in amicrofilaraemic subjects

Pinder, Margaret; Leclerc, A.; Everaere, S.

doi:10.1111/j.1365-3024.1992.tb00027.x

Cited by 26 publications

(20 citation statements)

References 28 publications

(12 reference statements)

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“…Both the alternative and the classical pathways of complement activation have been shown to occur on the surface S. stercoralis L3 in vitro (7), and it was previously shown that complement activation was also required for IgM to effect larval killing in mice (4). In vitro studies have also shown a requirement for complement activation in killing the helminths T. spiralis (38), Loa loa (30), Angiostrongylus cantonensis (34), Nippostrongylus brasiliensis (8), and Schistosoma mansoni (2) and in the control of S. mansoni in vivo (10,39).…”

Section: Discussionmentioning

confidence: 99%

Specificity and Mechanism of Immunoglobulin M (IgM)-and IgG-Dependent Protective Immunity to LarvalStrongyloides stercoralisinMice

et al. 2003

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Protective immunity in mice to the infective third-stage larvae (L3) of Strongyloides stercoralis was shown to be dependent on immunoglobulin M (IgM), complement activation, and granulocytes. The objectives of the present study were to determine whether IgG was also a protective antibody isotype and to define the specificity and the mechanism by which IgG functions. Purified IgG recovered from mice 3 weeks after a booster immunization with live L3 was shown to transfer high levels of protective immunity to naïve mice. IgG transferred into mice treated to block complement activation or to eliminate granulocytes failed to kill the challenge larvae. Transfer of immune IgG into IL-5 knockout (KO) mice, which are deficient in eosinophils, resulted in larval attrition, while transfer into FcR␥ KO mice did not result in larval killing. These findings suggest that IgG from mice immunized with live L3 requires complement activation and neutrophils for killing of L3 through an antibody-dependent cellular cytotoxicity (ADCC) mechanism. This is in contrast to the results of investigations using IgM from mice immunized with live L3 and IgG from mice immunized with larval antigens soluble in deoxycholate in which protective immunity was shown to be ADCC independent. Western blot analyses with immune IgM and IgG identified few antigens recognized by all protective antibody isotypes. Results from immunoelectron microscopy demonstrated that the protective antibodies bound to different regions in the L3. It was therefore concluded that while IgM and IgG antibodies are both protective against larval S. stercoralis, they recognize different antigens and utilize different killing mechanisms.Large multicellular organisms like Strongyloides stercoralis present a significant challenge to the immune system, and the mechanisms by which this parasite is controlled and eliminated by the immune response remain poorly defined. In humans with severe strongyloidiasis, a significant decrease in the immunoglobulin M (IgM) and IgG levels was observed compared to the levels found in people with asymptomatic and mildly symptomatic infections. Eosinophil levels were also lower in people with severe strongyloidiasis than in individuals with asymptomatic or symptomatic infections. These findings suggest that antibody and eosinophils play a role in protective immunity to larval S. stercoralis in humans (5). In Erythrocebus patas monkeys and dogs infected with S. stercoralis, elevated anti-larval IgG titers were observed; however, it was not determined whether the elevated antibody titers were related to decreases in parasite survival (9, 12). Jirds can also support the complete S. stercoralis life cycle. It was determined that after a single primary infection, jirds eliminated the challenge infection within 24 h via a mechanism dependent on cell contact and a factor found in serum (27).To gain an understanding of how the immune response eliminates the larval stages of S. stercoralis, a mouse model was developed. In this model it was demonstrated that i...

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Section: Discussionmentioning

confidence: 99%

Specificity and Mechanism of Immunoglobulin M (IgM)-and IgG-Dependent Protective Immunity to LarvalStrongyloides stercoralisinMice

et al. 2003

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“…Antibodies to the sheath of L. loa are commonly seen in amicrofilaremic humans from areas with endemic loiasis. 30 When the time course of infection was followed in a mandrill/L. loa model, antibodies to the mf sheath were detected in the prepatent period only, and subsequently disappeared shortly before the onset of patency.…”

Section: Discussionmentioning

confidence: 99%

Bancroftian filariasis in Tanzania: specific antibody responses in relation to long-term observations on microfilaremia.

Simonsen¹,

Meyrowitsch²

1998

Am J Trop Med Hyg

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Abstract. Following a 16-year clinical and parasitologic follow-up survey for Bancroftian filariasis in three endemic communities in northeastern Tanzania, serum antibody responses were analyzed in selected individuals in relation to the long-term observations on microfilaremia. Comparison of responses in three categories of adults (microfilaria [mf] positive at both surveys, mf positive at first but mf negative at the second survey, and mf negative at both surveys, respectively) indicated no significant differences between the mean levels of filarial-specific IgG1, IgG2, IgG3, IgG4, or IgE (measured by ELISA). However, specific IgG2 to the sheath of Wuchereria bancrofti mf (measured by an indirect fluorescence antibody test [IFAT]) was detected only in the third category. Comparison of responses in two categories of children born around the time of the first survey (to mf-positive and mf-negative mothers, respectively) showed a significantly higher mean level of filarial-specific IgG4 in the first than in the latter category, whereas the mean levels of filarial-specific IgG1, IgG2, IgG3, and IgE, and the prevalences of IgG2 IFAT positivity were similar. The overall prevalence of IgG2 IFAT positivity was considerably higher in the child study population (45.5%) than in the adult study population (16.7%). In both populations, however, a clear association between IgG2 IFAT positivity and a negative microfilarial status and negative specific circulating antigen status was seen. The study suggests that specific anti-sheath-antibodies are associated with an immunologic resistance mechanism that in the endemic community is expressed with highest prevalence in young individuals before development of patent microfilaremia.Despite the widespread occurrence of Wuchereria bancrofti infections in tropical areas, many aspects of the natural history of infection and disease in Bancroftian filariasis remain poorly understood. Basic knowledge on determinants related to host susceptibility, the longevity of infection and development of resistance, being of utmost importance for understanding the epidemiology of Bancroftian filariasis and for planning and implementation of control programs, is lacking. 1-3 A major reason for this is a scarcity of longitudinal studies.In an attempt to clarify some of these aspects, a 16-year follow-up study was carried out on Bancroftian filariasis in three endemic communities in northeastern Tanzania. All individuals were examined for microfilariae and clinical manifestations in 1975 4 and again in late 1991, 5 and as many as possible of the individuals examined in the first surveys were re-identified in the second surveys. Analyses of the parasitologic and clinical findings have already been presented. 5,6 Briefly, with respect to microfilaremia, the study showed that only few individuals had changed from a microfilaria (mf)-positive to -negative status over the 16-year period, despite the fact that the average life span of adult worms has been estimated to be much shorter. 1 In the 1991 survey...

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“…1 In an endemic area, two-thirds of the infected subjects do not have circulating microfilariae (occult loiasis). 2 Microscopy is universally used for both epidemiologic data collection and medical diagnosis of human loiasis, but this method is unable to detect occult infections. Various antibody-based assays have been used to measure host antibodies in L. loa-exposed or -infected individuals.…”

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confidence: 99%

Human occult loiasis: improvement in diagnostic sensitivity by the use of a nested polymerase chain reaction.

Touré

Kassambara²,

Williams³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. The development of control strategies for loiasis is of crucial importance in endemic areas and depends heavily on the accurate identification of occult-infected individuals. A polymerase chain reaction (PCR) and nested polymerase chain reaction (nested PCR) were developed and based on sequences of the repeat 3 region (15r3) of the gene encoding a Loa loa 15-kD protein. The assays was performed on 20 blood samples from occult-infected subjects and 30 from field-collected amicrofilaremic individuals. The size of the initial PCR product was 396 basepairs (bp). When this initial amplification using primers 15r3 1 and 15r3 2 was carried out for 30 cycles, the PCR products from three of the 20 occult-infected and five of the 30 amicrofilaremic individuals were visualized after electrophoresis by staining the gel with ethidium bromide. Subsequent Southern blotting and hybridization with the specific probe revealed hybridization in 19 of 20 occult-infected and 23 of 30 amicrofilaremic samples but only after two days of exposure of the blot to the x-ray film. When the nested PCR was carried out (product size ϭ 366 bp, primers 15r3 3 and 15r3 4 ), 19 of 20 occult-infected and 23 of 30 amicrofilaremic samples that were positive by Southern hybridization of the initial PCR products were strongly positive by staining with ethidium bromide. Qualitative Southern blotting of the nested PCR products using the same probe previously described confirmed the ethidium bromide staining results after a very short exposure time of 4 hr. These results demonstrate that the nested PCR amplification product is specific and that its sensitivity in detecting occult loiasis is 95%. This approach has significant promise for the screening of large human populations for active loiasis without the requirement for blotting and hybridization of the PCR products.The filarial parasite Loa loa is transmitted by Chrysops dimidiala and C. silacea (family Tabanidae). This parasite has been estimated to cause chronic infection in as many as 13 million people in west and central Africa. The major clinical presentations are calabar angioedema and pruritus, although the majority of individuals with heavy microfilarial loads are asymptomatic. In exceptional cases, serious sequelae such as endomyocardial fibrosis, renal complications, and encephalitis have been reported. 1 In an endemic area, two-thirds of the infected subjects do not have circulating microfilariae (occult loiasis). 2 Microscopy is universally used for both epidemiologic data collection and medical diagnosis of human loiasis, but this method is unable to detect occult infections. Various antibody-based assays have been used to measure host antibodies in L. loa-exposed or -infected individuals. However, the major limitation of serologic tests for filarial infections, such as loiasis, is their low specificity due to the cross-reactivity among filarial antigens. Furthermore, these antibody-based assays cannot always distinguish between past and current infections, nor can they be used t...

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Antibody‐dependent cell‐mediated immune reactions to Loa loa microfilariae in amicrofilaraemic subjects

Cited by 26 publications

References 28 publications

Specificity and Mechanism of Immunoglobulin M (IgM)-and IgG-Dependent Protective Immunity to LarvalStrongyloides stercoralisinMice

Specificity and Mechanism of Immunoglobulin M (IgM)-and IgG-Dependent Protective Immunity to LarvalStrongyloides stercoralisinMice

Bancroftian filariasis in Tanzania: specific antibody responses in relation to long-term observations on microfilaremia.

Human occult loiasis: improvement in diagnostic sensitivity by the use of a nested polymerase chain reaction.

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