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Parasite immunity: Workshop summary
Veterinary
ELSEVIER
Veterinaty immunology and immunopathology
Immunology and Immunopathology 54(1996)351-353
Parasite Immunity: Workshop Summary Will Goff USDA / ARS, Washington Stute Uniuersity, Pullman, WA, USA
1. Introduction The purpose of the discussion workshop was to provide a forum for an informal dialog among those symposium participants who have an interest in parasite immunology and/or are actively investigating this aspect of the host-parasite interaction. The intention was to discuss major issues in this area within a broad context, using specific examples as evidence for conceptual arguments. The topics were chosen in an effort to acknowledge as many areas of activity as were evident from the 24 poster presentations associated with this workshop. Thus, questions for discussion covered issues pertinent to immune responses to helminths, protozoa, and ectoparasites. The summaries that follow, are not meant to touch on all points raised during the discussions, but rather to highlight the central points, and conclusions if any were stated.
2. Immune
responses
induced by nematode
gut-associated
antigens
Worm gut-associated antigens were discussed in relation to other antigens associated with gastrointestinal nematode infections. These nematode infections usually require development to the adult worm stage before a significant antibody response is detected, and one of the better antigenic preparations used as an immunogen in terms of the antibody response are the excretory/secretory (E/S) antigens. While inducing a more limited antibody response in terms of the number of antigens recognized, E/S antigens from ascarids are considered to induce a better antibody response than extract antigens in terms of titer and correlation with protection. The importance of E/S antigens was also suggested by a study involving Hemonchous conforms, where antibodies from animals rendered immune by an infection and treatment method and confirmed by challenge, recognized E/S antigens, and whose lymphocytes responded to E/S antigen in vitro. It was also suggested that E/S antigens from other than gastrointestinal nematodes may be important in the immune response, such as secreted acetylcholinesterases from the lung worm Dictyocaulus uiuiparous. 0165-2427/96/$15.00 Copyright PII SO1 65-2427(96)05673-5
0 1996 Elsevier Science B.V. All rights reserved.
Recently, it has been proposed that since proteins associated with blood feeding worm gut surface are not a part of the worm-host interface, and thus may not be subject to evolutionary pressure, they may serve as protective antigens. It was argued however. that since these antigens are concealed. and as such. will not be recognized by naturally infected animals, there is little chance for a memory response. making them inadequate immunogens. It was pointed out that one such antigen from Hemonchus conforms (H-l l), has been shown to induce both an antibody response and confer a degree of protection in both adult sheep and lambs. Other gut antigens have also been evaluated, and the question of their concealed nature has been raised. It has been suggested that some of these proteins may, in fact be excreted or secreted and therefore naturally exposed to the immune system. The arguments will remain until better methods of detection are adopted, and studies conducted to assess the memory response.
3. Source of leukocytes to helminth, protozoal,
and associated cellular products for assessment and ectoparasite infections
of response
This discussion dealt with regional versus systemic indicators of the immune response to parasitic infections. It has been recognized that blood cells and associated soluble products taken from the peripheral circulation may not provide an entire picture of the immune response and therefore, activity within regional lymphoid tissue associated with parasite replication and/or lesions are important to a complete characterization of the immune response. The importance of evaluating the local response rather than just a systemic assessment has been known for some time in infections involving larval migration and schistosomiasis, and examples of differences in the kinetics and magnitude of antigen-specific proliferative responses between PBLs and regional lymph node-derived lymphocytes were also cited in other helminth (Osferfugia and Dictyocaulus) and protozoa] (Theilerial infections. There is also evidence for functional differences between spleen macrophages and blood monocytes and monocyte-derived macrophages in response to hemoprotozoal infection. There was also discussion concerning differences in antibody recognition depending on the source. For example, evidence was presented for a more restricted antigen recognition of B-cells taken from local draining lymph nodes, and those antigens recognized were those that had been demonstrated to induce some degree of protection. Finally, there was agreement that both qualitative and quantitative differences in cytokine expression occurred when evaluating cells from peripheral blood versus local sites of immune activity. The importance of characterizing the local area of immune response was also clearly apparent when considering the response to ectoparasite infestations such as ticks and skin penetrating fly larvae. Studies are revealing the predominant cells involved at the local bite site and in the regional lymph node associated with the skin lesion. This is important both regarding efforts to induce rejection of the tick, and in considering novel methods for possible control of the disease agents they transmit. Examples presented here, showed evidence of inflammatory cell followed shortly by immune cell infiltration into the bite site. and that the immune cells had been activated in the node before infiltrating to the skin lesion. Among these cells were dendritic cells and y6T-cells. The
W. GoJ’/
importance transmitted
Vererinury
Immunology
and tmmunopurholo~y
of these cells in the immune has yet to be determined.
4. Parasitism
in livestock:
T-helper
response
cell dichotomy
54 (1996)
351-353
to the infectious
in immune
353
agent
being
responses
In rodent models, there is a generous amount of evidence suggesting that, with few exceptions, CD4 + , Th2, IL-Cdependent immune mechanisms predominate in response to gastrointestinal nematode infections, while CD4 + , Thl , IFN-y-dependent mechanisms are more important against protozoa1 (at least intracellular) infections. As investigations continue in this regard with livestock, it is becoming clear that similar responses do occur against similar infectious agents. However, there are some important differences both between livestock and rodents, and among different species of livestock. For example, current evidence suggests that ruminant CD4 + T-cell subset phenotypes more closely resemble that of humans, where a ThO phenotype capable of producing IFN-y and IL-10 exists. Also, both ruminant Thl and Th2 cells produce both IFN-y and IL-IO. Despite these differences, there is evidence from bovine studies that IL-12 upregulates and IL-IO downregulates IFN-y production. Furthermore, a Thl -like or Th2-like response can be induced in ruminants depending on the parasitic infection. For the most part, the intracellular protozoa1 infections induce a Thl-like response associated with protection, where nematode infections may or may not result in IFN-y production, but where high levels are induced, there is no correlation with expulsion or protection. It was suggested that with helminth infections, it was more difficult to make generalizations, and that each species had to be taken individually. This is apparent when evaluating differences between helminths whose life-cycles involve tissue migration versus a direct gastrointestinal existence. These differences are important also when considering the best target for immune intervention; the larval or adult stages. An example was that when ascarid E/S antigens were delivered with alum versus Freund’s adjuvant, a response more characteristic of a Th2 occurred and better protection realized. This also pointed out the importance of the delivery system. When the best target for immune intervention is determined, and antigens chosen that inherently induce the preferred response, it is important that the adjuvant not interfere, but rather enhance the response.
ELSEVIER
Veterinaty immunology and immunopathology
Immunology and Immunopathology 54(1996)351-353
Parasite Immunity: Workshop Summary Will Goff USDA / ARS, Washington Stute Uniuersity, Pullman, WA, USA
1. Introduction The purpose of the discussion workshop was to provide a forum for an informal dialog among those symposium participants who have an interest in parasite immunology and/or are actively investigating this aspect of the host-parasite interaction. The intention was to discuss major issues in this area within a broad context, using specific examples as evidence for conceptual arguments. The topics were chosen in an effort to acknowledge as many areas of activity as were evident from the 24 poster presentations associated with this workshop. Thus, questions for discussion covered issues pertinent to immune responses to helminths, protozoa, and ectoparasites. The summaries that follow, are not meant to touch on all points raised during the discussions, but rather to highlight the central points, and conclusions if any were stated.
2. Immune
responses
induced by nematode
gut-associated
antigens
Worm gut-associated antigens were discussed in relation to other antigens associated with gastrointestinal nematode infections. These nematode infections usually require development to the adult worm stage before a significant antibody response is detected, and one of the better antigenic preparations used as an immunogen in terms of the antibody response are the excretory/secretory (E/S) antigens. While inducing a more limited antibody response in terms of the number of antigens recognized, E/S antigens from ascarids are considered to induce a better antibody response than extract antigens in terms of titer and correlation with protection. The importance of E/S antigens was also suggested by a study involving Hemonchous conforms, where antibodies from animals rendered immune by an infection and treatment method and confirmed by challenge, recognized E/S antigens, and whose lymphocytes responded to E/S antigen in vitro. It was also suggested that E/S antigens from other than gastrointestinal nematodes may be important in the immune response, such as secreted acetylcholinesterases from the lung worm Dictyocaulus uiuiparous. 0165-2427/96/$15.00 Copyright PII SO1 65-2427(96)05673-5
0 1996 Elsevier Science B.V. All rights reserved.
Recently, it has been proposed that since proteins associated with blood feeding worm gut surface are not a part of the worm-host interface, and thus may not be subject to evolutionary pressure, they may serve as protective antigens. It was argued however. that since these antigens are concealed. and as such. will not be recognized by naturally infected animals, there is little chance for a memory response. making them inadequate immunogens. It was pointed out that one such antigen from Hemonchus conforms (H-l l), has been shown to induce both an antibody response and confer a degree of protection in both adult sheep and lambs. Other gut antigens have also been evaluated, and the question of their concealed nature has been raised. It has been suggested that some of these proteins may, in fact be excreted or secreted and therefore naturally exposed to the immune system. The arguments will remain until better methods of detection are adopted, and studies conducted to assess the memory response.
3. Source of leukocytes to helminth, protozoal,
and associated cellular products for assessment and ectoparasite infections
of response
This discussion dealt with regional versus systemic indicators of the immune response to parasitic infections. It has been recognized that blood cells and associated soluble products taken from the peripheral circulation may not provide an entire picture of the immune response and therefore, activity within regional lymphoid tissue associated with parasite replication and/or lesions are important to a complete characterization of the immune response. The importance of evaluating the local response rather than just a systemic assessment has been known for some time in infections involving larval migration and schistosomiasis, and examples of differences in the kinetics and magnitude of antigen-specific proliferative responses between PBLs and regional lymph node-derived lymphocytes were also cited in other helminth (Osferfugia and Dictyocaulus) and protozoa] (Theilerial infections. There is also evidence for functional differences between spleen macrophages and blood monocytes and monocyte-derived macrophages in response to hemoprotozoal infection. There was also discussion concerning differences in antibody recognition depending on the source. For example, evidence was presented for a more restricted antigen recognition of B-cells taken from local draining lymph nodes, and those antigens recognized were those that had been demonstrated to induce some degree of protection. Finally, there was agreement that both qualitative and quantitative differences in cytokine expression occurred when evaluating cells from peripheral blood versus local sites of immune activity. The importance of characterizing the local area of immune response was also clearly apparent when considering the response to ectoparasite infestations such as ticks and skin penetrating fly larvae. Studies are revealing the predominant cells involved at the local bite site and in the regional lymph node associated with the skin lesion. This is important both regarding efforts to induce rejection of the tick, and in considering novel methods for possible control of the disease agents they transmit. Examples presented here, showed evidence of inflammatory cell followed shortly by immune cell infiltration into the bite site. and that the immune cells had been activated in the node before infiltrating to the skin lesion. Among these cells were dendritic cells and y6T-cells. The
W. GoJ’/
importance transmitted
Vererinury
Immunology
and tmmunopurholo~y
of these cells in the immune has yet to be determined.
4. Parasitism
in livestock:
T-helper
response
cell dichotomy
54 (1996)
351-353
to the infectious
in immune
353
agent
being
responses
In rodent models, there is a generous amount of evidence suggesting that, with few exceptions, CD4 + , Th2, IL-Cdependent immune mechanisms predominate in response to gastrointestinal nematode infections, while CD4 + , Thl , IFN-y-dependent mechanisms are more important against protozoa1 (at least intracellular) infections. As investigations continue in this regard with livestock, it is becoming clear that similar responses do occur against similar infectious agents. However, there are some important differences both between livestock and rodents, and among different species of livestock. For example, current evidence suggests that ruminant CD4 + T-cell subset phenotypes more closely resemble that of humans, where a ThO phenotype capable of producing IFN-y and IL-10 exists. Also, both ruminant Thl and Th2 cells produce both IFN-y and IL-IO. Despite these differences, there is evidence from bovine studies that IL-12 upregulates and IL-IO downregulates IFN-y production. Furthermore, a Thl -like or Th2-like response can be induced in ruminants depending on the parasitic infection. For the most part, the intracellular protozoa1 infections induce a Thl-like response associated with protection, where nematode infections may or may not result in IFN-y production, but where high levels are induced, there is no correlation with expulsion or protection. It was suggested that with helminth infections, it was more difficult to make generalizations, and that each species had to be taken individually. This is apparent when evaluating differences between helminths whose life-cycles involve tissue migration versus a direct gastrointestinal existence. These differences are important also when considering the best target for immune intervention; the larval or adult stages. An example was that when ascarid E/S antigens were delivered with alum versus Freund’s adjuvant, a response more characteristic of a Th2 occurred and better protection realized. This also pointed out the importance of the delivery system. When the best target for immune intervention is determined, and antigens chosen that inherently induce the preferred response, it is important that the adjuvant not interfere, but rather enhance the response.