Although it is difficult to draw any sweeping conclusions that would be applicable to all helminth infections, the main features that are emphasized in this review may be summarized briefly. Pathogenic helminths, although extremely diverse in structure and behaviour, have one common feature, namely that they present to the host's defenses large, non-phagocytosable surfaces. Because of this, they are susceptible to a range of effector mechanisms differing either quantitatively or qualitatively from those that are active against other parasites or against normal or abnormal host cells. As an extreme example, the various types of cytotoxic lymphocyte, with one interesting exception, are inactive against helminths. Instead, helminth infections are characterized by high IgE responses and increased numbers of circulating eosinophils. Such eosinophils are activated, and show a marked capacity to kill a variety of target helminths in vitro. Further activation may occur in response to mast cell mediators released as a result of IgE-dependent degranulation; and IgE, as well as IgG and complement, can mediate eosinophil attachment and killing. It may therefore be suggested that the eosinophil/IgE/mast cell axis represents a powerful host defense against helminth infections. IgE can also mediate macrophage-dependent killing of several helminths, a process which involves a functional change in the macrophage, resembling activation. Although eosinophil-mediated and IgE-dependent macrophage-mediated effects are particularly potent, other effector cells are not excluded: in certain circumstances, neutrophils and conventionally activated macrophages may be equally or more effective. Neutrophils appear to act solely by oxidative killing mechanisms, whereas degranulation and the release of toxic granule contents is equally or more important in eosinophil-mediated damage. Different stages of different helminths vary in their degree of susceptibility to different mechanisms. Eosinophils appear to be somewhat less active than neutrophils against ensheathed nematodes, whereas trematodes and exsheathed nematodes are highly susceptible to eosinophil attack. In many experimental helminth infections, studies in vivo suggest a role for antibody-dependent cell-mediated immune effector mechanisms. The identity of the effector cell is difficult to establish because of a lack of techniques for specific manipulation of individual cell types, but histological studies frequently point to a strong eosinophil or macrophage involvement. The development and analysis of in vitro assays allows the study of immune effector mechanisms in man.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell-mediated damage to helminths.

Publisher Summary This chapter discusses the evasion of immunity by nematode parasites causing chronic infections. Human nematode infections are long-lasting (chronic), and people living in endemic areas may become infected in early childhood and carry worms for the remainder of their lives. This chapter considers those aspects of the immunological relationship between host and parasite, in field and laboratory studies, that are pertinent to an understanding of the mechanisms by which immunity is avoided and thus, chronicity of infection achieved. Human parasite epidemiologists, veterinary parasitologists, parasite biologists, and immunologists all have an interest in the strategies employed by parasites to evade host immune responses and also in control measures aimed at breaking the transmission of these important pathogens. Much remains to be accomplished in this challenging area of parasite immunology, and a closer liaison between all research groups interested in chronic nematode parasites ensures rapid progress in the near future.

Evasion of immunity by nematode parasites causing chronic infections.

SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models.

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

The purpose of this study was to assess the MR lymphographic potential of AMI-227 to reduce the signal intensity of hyperplastic inflammatory lymph nodes by using ferrets with filariasis as the animal model. Both interstitial and IV modes of administration were studied.Twelve ferrets were infected with the filaria Brugia malayi and six control ferrets were injected with super-paramagnetic iron oxide AMI-227, either interstitially or IV. Signal intensities of the left popliteal lymph node, left hamstring muscle, and left inguinal fat were measured before, 48 hr after, and up to 138 days after contrast injection with the use of both spin-echo and gradient-echo techniques. The signal intensity data were statistically analyzed. The lymph nodes, liver, spleen, and lungs were studied with light and electron microscopy.Forty-eight hours after the interstitial injection of AMI-227, the signal intensities of the ipsilateral popliteal nodes of the infected and control ferrets were significantly reduced (p less than...

https://www.ajronline.org/doi/pdfplus/10.2214/ajr.159.4.1529857

MR lymphography with iron oxide compound AMI-227: studies in ferrets with filariasis.

The roles of antibodies (Ab) and Fc receptors (FcR) in clearance of Brugia malayi microfilariae (Mf) in vivo have not been previously elucidated. Different background strainsof mice clear Mf at different rates and we established that there were no major differences in Ab production between three particular strains. However, genetic immunodeficiencies in B cell and Ab production on each of these background strains significantly enhanced Mf survival. B cell-deficient μMT (C57BL/6) mice injected with B. malayi Mf i.v. retained significant numbers of live Mf in comparison to wild-type mice. Treatment of μMT mice with hyperimmune whole sera in the first week of infection significantly reduced the number of Mf surviving in the cardiac blood at 135 days p.i. Mf survival in FcRγ-deficient (Sv129×C57BL/6) mice was also dramatically increased in the cardiac blood compared to wild-type mice, indicating that Ab itself is involved in Mf clearance most likely via a mechanism involving ADCC. These data indicate that Ab plays an important role in vivo in Mf killing in mice and this role is mediated via the FcR.

A role for antibody and Fc receptor in the clearance of Brugia malayi microfilariae.

Ferrets inoculated subcutaneously with 150--200 infective larvae of Brugia malayi (subperiodic strain) usually developed patent infection during the 3rd month post inoculation. Microfilaremia was transient, and most animals became amicrofilaremic after the 6th month of infection. Ferrets developed a persistent eosinophilia at the time of patency. At necropsy, 5--8 months post infection, adult worms were recovered principally from lymphatic vessels and recovery ranged from 0.5--13% of the inoculated larvae. The inflammatory response of ferrets to microfilariae was characterized by nodules 1--5 mm in diameter in the liver, lungs, spleen, and submucosa of the gastrointestinal tract. The center of these lesions contained a degenerated microfilaria or the cast of a microfilaria embedded in Splendore-Hoeppli substance. The Splendore-Hoeppli substance was surrounded by eosinophils and/or foreign body giant cells. Identical lesions were observed in ferrets experimentally infected with Brugia pahangi. Sera from ferrets infected with B. malayi demonstrated a 3- to 5-fold increase in IgG by the 4th month of infection and these sera produced 2--3 precipitin bands in double gel diffusion assays with an extract of B. malayi microfilarial antigen. Skin tests with B. malayi microfilarial antigen showed that the majority of the infected ferrets had immediate hypersensitivity responses, but none had Arthus or delayed hypersensitivity responses.

Neilson Jt

Papers

The ferret (Mustela putorius furo) as an experimental host for Brugia malayi and Brugia pahangi.

Serum immunoglobulin and antibody levels and the passive transfer of resistance in hamsters infected with Dipetalonema viteae.

Antibody responses to experimental Brugia malayi infections in patas and rhesus monkeys.

Evaluation of inbred strains of hamsters as hosts for Brugia malayi