Autoantibodies and circulating immune complexes are common associated findings in inflammatory disease of unknown aetiology. In most circumstances, however, it is far from easy to demonstrate their pathogenic significance. Sometimes pathological events can be linked clearly with the presence of autoantibodies. These include antibodies found in autoimmune haemolytic anaemia and myasthenia gravis. On the other hand, in a host of other diseases the precise mechanism of tissue injury and inflammation is understood only in the vaguest conceptual terms. For this reason it is important to consider the mechanism of action of cytotoxic chemotherapeutic agents that have beneficial effects in these diseases.
{"title":"Therapeutic aspects. Immunosuppression in established humoral responses.","authors":"R F Gagnon, I C MacLennan","doi":"10.1136/jcp.s3-13.1.126","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.126","url":null,"abstract":"Autoantibodies and circulating immune complexes are common associated findings in inflammatory disease of unknown aetiology. In most circumstances, however, it is far from easy to demonstrate their pathogenic significance. Sometimes pathological events can be linked clearly with the presence of autoantibodies. These include antibodies found in autoimmune haemolytic anaemia and myasthenia gravis. On the other hand, in a host of other diseases the precise mechanism of tissue injury and inflammation is understood only in the vaguest conceptual terms. For this reason it is important to consider the mechanism of action of cytotoxic chemotherapeutic agents that have beneficial effects in these diseases.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"126-9"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11379035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G L Asherson, S Johnson, T A Platts-Mills, A D Webster
mitogen and IgM measured seven days later in g±g/ml. To assess suppressor cells equal numbers (6 x 10') of normal T cells or T cells from a patient with thymoma were added. The data show that the patient's T cells, whether treated (Tmito) or untreated (T) with mitomycin C, suppressed immunoglobulin production while normal T cells caused an increase. This experiment was repeated with similar results (de Gast et al., 1979a).
{"title":"Pathogenesis of hypogammaglobulinaemia with thymoma and late-onset hypogammaglobulinaemia.","authors":"G L Asherson, S Johnson, T A Platts-Mills, A D Webster","doi":"10.1136/jcp.s3-13.1.5","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.5","url":null,"abstract":"mitogen and IgM measured seven days later in g±g/ml. To assess suppressor cells equal numbers (6 x 10') of normal T cells or T cells from a patient with thymoma were added. The data show that the patient's T cells, whether treated (Tmito) or untreated (T) with mitomycin C, suppressed immunoglobulin production while normal T cells caused an increase. This experiment was repeated with similar results (de Gast et al., 1979a).","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"5-9"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11530511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I will concentrate on recent work that has improved our understanding of the earliest phases of lymphocyte maturation, since this work provides a basis for the analysis of various forms of immunodeficiency. However, the reasons for interest in primary lymphocyte differentiation extend beyond a consideration of immunodeficiency. According to the clonal selection theory, which has received considerable support from experimental work, the broad range of foreign antigens which may enter the body are recognised by a repertoire of lymphocytes, each specific for a particular antigen. There is evidence that this repertoire of lymphocytes is acquired during the primary differentiation of lymphocytes that occurs in ontogeny. In addition, although the mechanisms of tolerance to 'self' antigens are poorly understood studies on lymphocyte ontogeny may provide important clues. Lymphocytes, like other blood cells, belong to a renewal system and production of new lymphocytes is not confined to ontogeny. Hence, in discussing the primary differentiation of lymphocytes, sites of lymphocyte production in the adult must also be considered.
{"title":"Maturation of the immune system and immunodeficiency.","authors":"J J Owen","doi":"10.1136/jcp.s3-13.1.1","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.1","url":null,"abstract":"I will concentrate on recent work that has improved our understanding of the earliest phases of lymphocyte maturation, since this work provides a basis for the analysis of various forms of immunodeficiency. However, the reasons for interest in primary lymphocyte differentiation extend beyond a consideration of immunodeficiency. According to the clonal selection theory, which has received considerable support from experimental work, the broad range of foreign antigens which may enter the body are recognised by a repertoire of lymphocytes, each specific for a particular antigen. There is evidence that this repertoire of lymphocytes is acquired during the primary differentiation of lymphocytes that occurs in ontogeny. In addition, although the mechanisms of tolerance to 'self' antigens are poorly understood studies on lymphocyte ontogeny may provide important clues. Lymphocytes, like other blood cells, belong to a renewal system and production of new lymphocytes is not confined to ontogeny. Hence, in discussing the primary differentiation of lymphocytes, sites of lymphocyte production in the adult must also be considered.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11598741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The discovery of the LE cell phenomenon (Hargraves et al., 1948) has had particularly far-reaching effects beyond the immediate clinical field of rheumatology. It was, firstly, a timely spur urging research on the underlying causes of the systemic diseases of connective tissue into the then untrodden immunological paths that are now highways accommodating an ever-increasing army of investigators with ever-increasing expectations. It was also the seed (to change the metaphor) that engendered in the minds of those connected with laboratory investigation of patients the conviction that the more precisely the specificity of autoantibodies such as the LE cell factor can be defined the greater their discriminant value for diagnosis and prognosis and the better the chance of gaining insight into the underlying immunopathology, not to say aetiology. The extent to which these expectations about the role of anti-nuclear antibodies have been realised in the intervening decades is ripe for consideration.
{"title":"Antinucleic acid antibodies.","authors":"E J Holborow","doi":"10.1136/jcp.s3-13.1.107","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.107","url":null,"abstract":"The discovery of the LE cell phenomenon (Hargraves et al., 1948) has had particularly far-reaching effects beyond the immediate clinical field of rheumatology. It was, firstly, a timely spur urging research on the underlying causes of the systemic diseases of connective tissue into the then untrodden immunological paths that are now highways accommodating an ever-increasing army of investigators with ever-increasing expectations. It was also the seed (to change the metaphor) that engendered in the minds of those connected with laboratory investigation of patients the conviction that the more precisely the specificity of autoantibodies such as the LE cell factor can be defined the greater their discriminant value for diagnosis and prognosis and the better the chance of gaining insight into the underlying immunopathology, not to say aetiology. The extent to which these expectations about the role of anti-nuclear antibodies have been realised in the intervening decades is ripe for consideration.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"107-11"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11314356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Twenty years ago J. L. Gowans (1959) published rigorous evidence that lymphocytes circulate from blood to tissue to lymph in the rat. This suggested a definitive solution to a problem that had been clearly posed in 1885 by Walther Flemming, the discoverer of germinal centres. When he considered previous observations that the traffic of lymphocytes leaving a lymph node via the efferent lymphatic was much greater (by a factor of 10-20) than the traffic reaching the node via the afferent lymphatics it was clear to Flemming that the vigorous mitotic activity of lymphocytes within lymph nodes, both in germinal centres and elsewhere, was one factor that could account for the discrepancy between cell influx and cell efflux. More remarkably he perceived that the only alternative explanation was that lymphocytes leave the bloodstream within lymph nodes and recirculate back to the blood via efferent lymph. More than 70 years later it was shown, by exploiting tritiated thymidine, that lymphocytes recently produced by cell division within a resting lymph node could make only a minor contribution to the excess numbers leaving in the efferent lymph (Gowans, 1959; Hall and Morris, 1965a). The blood vessels from which lymphocytes entered the node in such large numbers were pinpointed by Gowans and Knight (1964) as specialised postcapillary venules in the thymus-dependent area of lymph nodes. In the 1920s histologists had been impressed by the plump endothelium of small veins in this situation. Zimmermann (1923) had tentatively suggested that the lymphocytes seen within the endothelial wall of these venules were migrating from the node into the blood. This view still has support based on the shape of lymphocyles as observed on histological sections. The direction in which the cells were moving before fixation has been inferred from their orientation in the vessel wall (for example, Norberg and Rydgren, 1978). The validity of this approach is questionable not just because of much other evidence in favour of the net migration of lymphocytes from the blood into the node (for example, Sedgley and Ford, 1976) but also because of contradictory results obtained by 63 other workers applying the same method (Anderson and Anderson, 1976). During the 1960s the astonishing diversity of the morphologically uniform small lymphocyte was gradually revealed. The diversity includes not only T and B populations but also several distinct maturational stages of each cell line. It also involves the production of clones or subsets of lymphocytes specific for each of the myriad antigens to which the body can respond. Not surprisingly, the migration of lymphocytes now seems much more complicated than could be conceived in 1959. Not only does each population show an individual migratory pattern but the migration of some lymphocytes from the blood into different organs is apparently due to distinguishable mechanisms.
{"title":"Lymphocytes. 3. Distribution. Distribution of lymphocytes in health.","authors":"W L Ford","doi":"10.1136/jcp.s3-13.1.63","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.63","url":null,"abstract":"Twenty years ago J. L. Gowans (1959) published rigorous evidence that lymphocytes circulate from blood to tissue to lymph in the rat. This suggested a definitive solution to a problem that had been clearly posed in 1885 by Walther Flemming, the discoverer of germinal centres. When he considered previous observations that the traffic of lymphocytes leaving a lymph node via the efferent lymphatic was much greater (by a factor of 10-20) than the traffic reaching the node via the afferent lymphatics it was clear to Flemming that the vigorous mitotic activity of lymphocytes within lymph nodes, both in germinal centres and elsewhere, was one factor that could account for the discrepancy between cell influx and cell efflux. More remarkably he perceived that the only alternative explanation was that lymphocytes leave the bloodstream within lymph nodes and recirculate back to the blood via efferent lymph. More than 70 years later it was shown, by exploiting tritiated thymidine, that lymphocytes recently produced by cell division within a resting lymph node could make only a minor contribution to the excess numbers leaving in the efferent lymph (Gowans, 1959; Hall and Morris, 1965a). The blood vessels from which lymphocytes entered the node in such large numbers were pinpointed by Gowans and Knight (1964) as specialised postcapillary venules in the thymus-dependent area of lymph nodes. In the 1920s histologists had been impressed by the plump endothelium of small veins in this situation. Zimmermann (1923) had tentatively suggested that the lymphocytes seen within the endothelial wall of these venules were migrating from the node into the blood. This view still has support based on the shape of lymphocyles as observed on histological sections. The direction in which the cells were moving before fixation has been inferred from their orientation in the vessel wall (for example, Norberg and Rydgren, 1978). The validity of this approach is questionable not just because of much other evidence in favour of the net migration of lymphocytes from the blood into the node (for example, Sedgley and Ford, 1976) but also because of contradictory results obtained by 63 other workers applying the same method (Anderson and Anderson, 1976). During the 1960s the astonishing diversity of the morphologically uniform small lymphocyte was gradually revealed. The diversity includes not only T and B populations but also several distinct maturational stages of each cell line. It also involves the production of clones or subsets of lymphocytes specific for each of the myriad antigens to which the body can respond. Not surprisingly, the migration of lymphocytes now seems much more complicated than could be conceived in 1959. Not only does each population show an individual migratory pattern but the migration of some lymphocytes from the blood into different organs is apparently due to distinguishable mechanisms.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"63-9"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.63","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11598745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The diversity of immunoglobulin (Ig) molecules and antigen-specific receptors on lymphoid cells, the activation processes during the immune response, the clonal propagation of cells stimulated by antigens, and the sophisticated control mechanisms in the immune system are unparalleled in other biological systems (see A. R. Williamson at page 76, and P. C. L. Beverley at page 59). The emergence of early lymphoid precursors is nevertheless likely to be governed by developmental programmes similar to those observed in haemopoietic precursors and other differentiating cell types. The primary purpose of this paper is to summarise some of the salient observations about the development of the earliest identifiable human lymphoid precursors.
{"title":"Lymphocytes. 2. Differentiation. Differentiation of lymphoid precursor cells.","authors":"G Janossy, G Pizzolo","doi":"10.1136/jcp.s3-13.1.48","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.48","url":null,"abstract":"The diversity of immunoglobulin (Ig) molecules and antigen-specific receptors on lymphoid cells, the activation processes during the immune response, the clonal propagation of cells stimulated by antigens, and the sophisticated control mechanisms in the immune system are unparalleled in other biological systems (see A. R. Williamson at page 76, and P. C. L. Beverley at page 59). The emergence of early lymphoid precursors is nevertheless likely to be governed by developmental programmes similar to those observed in haemopoietic precursors and other differentiating cell types. The primary purpose of this paper is to summarise some of the salient observations about the development of the earliest identifiable human lymphoid precursors.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"48-58"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11598744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I hope it is no longer old-fashioned to consider the immune system as being primarily concerned with defence against infection by micro-organisms. I intend to deal with the types of immunodeficiency listed in Table 1, except for the first two categories, and with particular emphasis on the commonest that we encounter-general immunodeficiency due to metabolic and nutritional abnormalities and druginduced depression of immune activity. We must consider the types of organism concerned, the consequence of an infection during a state of immune suppression, the few specific associations that exist between a particular state of depression and a particular organism, problems in the diagnosis of infection, its prevention, and, very briefly, treatment.
{"title":"Infection of immunosuppressed patients.","authors":"H E Kay","doi":"10.1136/jcp.s3-13.1.26","DOIUrl":"https://doi.org/10.1136/jcp.s3-13.1.26","url":null,"abstract":"I hope it is no longer old-fashioned to consider the immune system as being primarily concerned with defence against infection by micro-organisms. I intend to deal with the types of immunodeficiency listed in Table 1, except for the first two categories, and with particular emphasis on the commonest that we encounter-general immunodeficiency due to metabolic and nutritional abnormalities and druginduced depression of immune activity. We must consider the types of organism concerned, the consequence of an infection during a state of immune suppression, the few specific associations that exist between a particular state of depression and a particular organism, problems in the diagnosis of infection, its prevention, and, very briefly, treatment.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"13 ","pages":"26-9"},"PeriodicalIF":0.0,"publicationDate":"1979-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-13.1.26","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11444285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Replacement therapy in the mucopolysaccharidoses.","authors":"M F Dean","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"12 ","pages":"120-7"},"PeriodicalIF":0.0,"publicationDate":"1978-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1347130/pdf/jclinpath00432-0127.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11323585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The muscle cell.","authors":"J C Sloper, M C Barrett, T A Partridge","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"12 ","pages":"25-43"},"PeriodicalIF":0.0,"publicationDate":"1978-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1347121/pdf/jclinpath00432-0032.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11573765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lysosomes and the connective tissue diseases.","authors":"L Bitensky","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"12 ","pages":"105-16"},"PeriodicalIF":0.0,"publicationDate":"1978-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1347128/pdf/jclinpath00432-0112.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11254977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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