Immunology Today vol. 3, .No. 1 1982
directed to tetal antigens may be regulated locally, at the maternal-fetal interface. Clark (Hamilton, Canada) presented evidence for non-specific suppressive activity among cells from lymph ~aodes draining the pregnant uterus and for a soluble suppressor activity in the draining lymph nodes in allogeneic pregnancies. But W. Jones (Bedford Park, Australia) and P. Matangkasombut (Bangkok, Thailand) have found little evidence for generalized non-specific suppression during human pregnancy which could affect the survival of the fetus. The complex mechanisms involved in the success of pregnancy are still largely obscure and effects seen at the 'wholeanimal' level must be distinguished from the p e r h a p s more crucial mechanisms active at local level which allow fetal survival. Regulation of fertility The natural consequences of both natural and induced immune responses against spermatozoa, ova and proteins associated with pregnancy are abortion and autoimmune disorders of the reproductive system. Induced immunity is intended to regulate fertility without inducing autoimmunity. K. Tung (Albuquerque) discussed various models of autoimmunity involving the testis and con-
cluded that multiple pathogenic mechanisms are operating in testicular autoimmunity in infertile black mink, A-line beagles and W18 backcross mice. The production of antisperm antibodies after vasectomy is genetically controlled. He suggested that vaccination against pregnancy in a population might increase the reproductive capacity of those individuals who are low responders to the vaccine. The consequences of autoi m m u n i t y after vasectomy were discussed in greater detail by N. Alexander (Beaverton, Oregon). She described the presence of antisperm autoantibodies in vasectomised monkeys and arterial damage presumably due to immune complex formation and deposition on vascular tissues. Human chorionic gonadotropin (hCG), a protein hormone necessary for the maintenance of pregnancy in its earliest stage, has been a candidate pregnancy vaccine for some years. G. Talwar (New Delhi, India) has used the beta chain of hCG as a vaccine in animals and in women and he reviewed some of the difficulties associated with its poor immunogenicity in certain individuals. He also described other potential approaches for fertility regulation, including the use of luteinising hormone-releasing hormone and the use of intrates-
ticular iI!jections of BCG vaccine. V. Stevens (Columbus, Ohio) presented a detailed immunochemicaI study of the C terminal peptide of the beta chain of hCG and his efforts to make it i m m u n o g e n i c e n o u g h to inhibit fertility. E. Goldberg (Evanston, Illinois) presented data on the structure and immunochemistry of a sperm-specific antigen, LDH-X, a variant of the enzyme lactate dehydrogenase. Immunization of baboons against this sperm-specific isozyme reduces their fertility. Antibodies to a synthetic peptide fragment of LDH-X can bind to the native enzyme on spermatozoa, and this might be a usefial way to block fertilization. Antigens on the zona pellucida can also be used to immunize against fertility (N. Dunbar, New York) and recent methods for the preparation of individual zonal glycoproteins should refine this approach in the near future. The abstracts of papers presented at this meeting have been published (o7. Repro& [ramun. 1981 (suppl.) S1-$46). The complete proceedings will appear in Reproduetzve Immunology Eds. T. G. Wegmann and T. J. Gill), Oxford University Press, New York 1982. Bhagirath Singh and Phillip I. Gambel are in the Deparlment of Immunology and MRC Group on hnmunoregulation, Universily of Alberta, Edmonton, Alberta, Canada T6G 2117
)
X]
The state of transfer factor Myer R. Salaman Department of Immunology, St. Mary's Hospital Medical School, London W2 1PG, U . K
T h e condition of transfer factor (TF) has been giving cause for c o n c e r n for some years now. H e r e is an immunological p h e n o m e n o n , first r e p o r t e d in 1954, w h i c h seems straightforward e n o u g h a n d has received a great deal of attention. Yet in 1982 we are still arguing about it at a most basic level. H a p p i l y , a recent c o n t r i b u t i o n fi'om Borkowsky a n d L a w r e n c e l offers a way forward fi'om this impasse. Skin reactions of the delayed type (peaking at 24-48 h) are d e p e n d e n t on circulating T l y m p h o c y t e s of the a p p r o p r i a t e sub-set that are sensitive to the test antigen a n d the capacity to r e s p o n d can thus be transferred in a suitable animal system by injection of © Elsevi~i giomedicM Press 1982
0167-4919/82/0000-0000/$275
viable blood leucocytes. T h e challenge of T F has been the claim that, in man, transfer of delayed hypersensitivity from sensitive d o n o r to negative recipient can be b r o u g h t about by a dialysable extract of these cells. But is sensitivity really t r a n s f e r r e d specifically by a factor in the extract? A n alternative view is that in the recipient the extract m a y amplify a pre-existing low-level sensitivity in a m a n n e r u n r e l a t e d to the sensitivities of the donor. Some w o u l d c o n c e d e neither of these attributes ! This curious state of affairs is not h a r d to explain. Because no bt-vivo animal model or irt-~ilro system yields the striking results r e p o r t e d in man, it has been
hnmunology T~)dayvol. 3, No. 1 1982
necessary until recently to continue to use h u m a n volunteers as donors a n d recipients of TF. T h e n there are the vagaries of the delayed hypersensitivity test the difficulties of measurement, the fluctuations in the magnitude of the response from m o n t h to m o n t h and the occasional conversion of a negative reactor by skin test alone. Apparently negative T F recipients may indeed have been primed at a low level on previous environmental contact with the c o m m o n microbiological antigens. It is thus not surprising that thc many reports supporting the concept of an antigenspecific TF, viewed separately or together, are not entirely convincing. In reaction to this situation a credibility gap has opened up around the subject as a whole. Doubts about specificity have been fanned by continuing reports that T F preparations can [email protected] anqplify delayed reactions in the guinea-pig 2,3 and in m a n 4. Work in my laboratory suggests that the level of such non-specific activity may vary in different donors in line with their capacity to react to tubercular antigen, a type of relationship which could give an illusion of specificity s. Specific and nonspecific activity could co-exist in TF. T h e dialysate is extremely heterogeneous, containing the small molecules of cells together with the breakdown products of their macromolecules, principally polynuclcotides and polypeptides. T h e nature of the active components is unknown, and in the case of a specific factor a difficulty i~ posed by the low molecular size (
directed to tetal antigens may be regulated locally, at the maternal-fetal interface. Clark (Hamilton, Canada) presented evidence for non-specific suppressive activity among cells from lymph ~aodes draining the pregnant uterus and for a soluble suppressor activity in the draining lymph nodes in allogeneic pregnancies. But W. Jones (Bedford Park, Australia) and P. Matangkasombut (Bangkok, Thailand) have found little evidence for generalized non-specific suppression during human pregnancy which could affect the survival of the fetus. The complex mechanisms involved in the success of pregnancy are still largely obscure and effects seen at the 'wholeanimal' level must be distinguished from the p e r h a p s more crucial mechanisms active at local level which allow fetal survival. Regulation of fertility The natural consequences of both natural and induced immune responses against spermatozoa, ova and proteins associated with pregnancy are abortion and autoimmune disorders of the reproductive system. Induced immunity is intended to regulate fertility without inducing autoimmunity. K. Tung (Albuquerque) discussed various models of autoimmunity involving the testis and con-
cluded that multiple pathogenic mechanisms are operating in testicular autoimmunity in infertile black mink, A-line beagles and W18 backcross mice. The production of antisperm antibodies after vasectomy is genetically controlled. He suggested that vaccination against pregnancy in a population might increase the reproductive capacity of those individuals who are low responders to the vaccine. The consequences of autoi m m u n i t y after vasectomy were discussed in greater detail by N. Alexander (Beaverton, Oregon). She described the presence of antisperm autoantibodies in vasectomised monkeys and arterial damage presumably due to immune complex formation and deposition on vascular tissues. Human chorionic gonadotropin (hCG), a protein hormone necessary for the maintenance of pregnancy in its earliest stage, has been a candidate pregnancy vaccine for some years. G. Talwar (New Delhi, India) has used the beta chain of hCG as a vaccine in animals and in women and he reviewed some of the difficulties associated with its poor immunogenicity in certain individuals. He also described other potential approaches for fertility regulation, including the use of luteinising hormone-releasing hormone and the use of intrates-
ticular iI!jections of BCG vaccine. V. Stevens (Columbus, Ohio) presented a detailed immunochemicaI study of the C terminal peptide of the beta chain of hCG and his efforts to make it i m m u n o g e n i c e n o u g h to inhibit fertility. E. Goldberg (Evanston, Illinois) presented data on the structure and immunochemistry of a sperm-specific antigen, LDH-X, a variant of the enzyme lactate dehydrogenase. Immunization of baboons against this sperm-specific isozyme reduces their fertility. Antibodies to a synthetic peptide fragment of LDH-X can bind to the native enzyme on spermatozoa, and this might be a usefial way to block fertilization. Antigens on the zona pellucida can also be used to immunize against fertility (N. Dunbar, New York) and recent methods for the preparation of individual zonal glycoproteins should refine this approach in the near future. The abstracts of papers presented at this meeting have been published (o7. Repro& [ramun. 1981 (suppl.) S1-$46). The complete proceedings will appear in Reproduetzve Immunology Eds. T. G. Wegmann and T. J. Gill), Oxford University Press, New York 1982. Bhagirath Singh and Phillip I. Gambel are in the Deparlment of Immunology and MRC Group on hnmunoregulation, Universily of Alberta, Edmonton, Alberta, Canada T6G 2117
)
X]
The state of transfer factor Myer R. Salaman Department of Immunology, St. Mary's Hospital Medical School, London W2 1PG, U . K
T h e condition of transfer factor (TF) has been giving cause for c o n c e r n for some years now. H e r e is an immunological p h e n o m e n o n , first r e p o r t e d in 1954, w h i c h seems straightforward e n o u g h a n d has received a great deal of attention. Yet in 1982 we are still arguing about it at a most basic level. H a p p i l y , a recent c o n t r i b u t i o n fi'om Borkowsky a n d L a w r e n c e l offers a way forward fi'om this impasse. Skin reactions of the delayed type (peaking at 24-48 h) are d e p e n d e n t on circulating T l y m p h o c y t e s of the a p p r o p r i a t e sub-set that are sensitive to the test antigen a n d the capacity to r e s p o n d can thus be transferred in a suitable animal system by injection of © Elsevi~i giomedicM Press 1982
0167-4919/82/0000-0000/$275
viable blood leucocytes. T h e challenge of T F has been the claim that, in man, transfer of delayed hypersensitivity from sensitive d o n o r to negative recipient can be b r o u g h t about by a dialysable extract of these cells. But is sensitivity really t r a n s f e r r e d specifically by a factor in the extract? A n alternative view is that in the recipient the extract m a y amplify a pre-existing low-level sensitivity in a m a n n e r u n r e l a t e d to the sensitivities of the donor. Some w o u l d c o n c e d e neither of these attributes ! This curious state of affairs is not h a r d to explain. Because no bt-vivo animal model or irt-~ilro system yields the striking results r e p o r t e d in man, it has been
hnmunology T~)dayvol. 3, No. 1 1982
necessary until recently to continue to use h u m a n volunteers as donors a n d recipients of TF. T h e n there are the vagaries of the delayed hypersensitivity test the difficulties of measurement, the fluctuations in the magnitude of the response from m o n t h to m o n t h and the occasional conversion of a negative reactor by skin test alone. Apparently negative T F recipients may indeed have been primed at a low level on previous environmental contact with the c o m m o n microbiological antigens. It is thus not surprising that thc many reports supporting the concept of an antigenspecific TF, viewed separately or together, are not entirely convincing. In reaction to this situation a credibility gap has opened up around the subject as a whole. Doubts about specificity have been fanned by continuing reports that T F preparations can [email protected] anqplify delayed reactions in the guinea-pig 2,3 and in m a n 4. Work in my laboratory suggests that the level of such non-specific activity may vary in different donors in line with their capacity to react to tubercular antigen, a type of relationship which could give an illusion of specificity s. Specific and nonspecific activity could co-exist in TF. T h e dialysate is extremely heterogeneous, containing the small molecules of cells together with the breakdown products of their macromolecules, principally polynuclcotides and polypeptides. T h e nature of the active components is unknown, and in the case of a specific factor a difficulty i~ posed by the low molecular size (
