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Lymphoid tissue in the kidney of the musk shrew, Suncus murinus
Tissue & Cell, 1995 27 (4) 421-424 © 1995 Pearson Professional Ltd.
Lymphoid tissue in the kidney of the musk shrew, Suncus murinus H. H. Kerschbaum*, S. K. Singht, A. Hermann*
Abstract. We describe a lymphoid tissue in the kidney of the musk shrew, Suncus murinus. An anatomically well organised lymphoid tissue, resembling the mucosa-associated lymphoid tissue, is associated with the epithelium of the renal pelvis and the ureter, respectively. Lymphoid tissue distributed along the arcuate artery and arcuate vein is not structurally organised in centre and periphery. This tissue type is most prominently developed between blood vessels. Immunocytochemistry revealed S-100-immunoreactive dendritic cells in both, structurally organised and structurally non-organised lymphoid tissues. The lymphoid tissue is innervated by neurofilament-immunoreactive nerve fibres. Some of these nerve fibres are associated with glial fibrillary acidic protein-immunoreactive structures, indicating that they are myelinated. Keywords: Lymphoidtissue, insectivore,dendriticcells,S-100,calcium-bindingprotein
Introduction Anatomically well organised lymphoid tissues, in intimate contact with epithelia of the respiratory, the gastrointestinal tract, and the female urogenital system (Kraehenbuhl and Neutra, 1992; Kuper et al., 1992), constitute the mucosa-associated lymphoid tissue (MALT). Similar to primary and secondary lymphoid organs the MALT is innervated (Felten et al., 1988; Krammer and Kt~hnel, 1993; Pabst, 1992). Respiratory and gastrointestinal tracts are in frequent contact with a wide variety of antigenic material. Therefore, lymphoid tissues located in these organs are supposed to form the first immunological barrier against pathogenic antigens. In the kidney, which is also a target for pathogenic antigens entering the organ via urethra, bladder, and ureter, a structural organised lymphoid tissue has not been described. Investigations on the MALT have been performed on several species of placental mammals, but not on insectivores. Since these animals are at the evolutionary base of the mammals (Romer and Parsons, * Department of AnimaI-Physiology, Institute of Zoology, University of Salzburg, Hellbrunnerstr. 34, A-5020 Salzburg, Austria. "[" Department of Zoology, Banaras Hindu University, Varanasi, 221005, India. Received 11 November 1994 Accepted 28 February 1995 Correspondence to: Prof. Dr A. Hermann. Department of Animal-Physiology, Institute of Zoology, University of Salzburg, Hellbrunnerstr. 34, 5020 Salzburg, Austria. Tel: 0043-662-8044-5610, Fax: 0043-662-8044-5698.
1983) they are of particular interest in view of the development of the MALT. In this study we report on a newly identified lymphoid tissue in the kidney of the musk shrew, Suncus murinus.
Material and methods Male musk shrews (n=5) were trapped near Banaras, India. The animals were ~er~ific.~ed by cervical dislocation, and the kidneys were quickly removed and fixed in Bouin's solution. The organs were dehydrated in a graded series of ethanol solutions and embedded in parablast using xylene as an intermedium. Immunocytochemistry was performed on 7 gm thick parablast sections. For localisation of antigens a peroxidase anti-peroxidase (PAP) method according to Sternberger (1979) and an immunogold silver stain technique (Hacker, 1989) were used. The methods were described in detail previously (Hermann and Kerschbaum, 1994). Negative controls were performed using normal serum in place of the primary antiserum and by preabsorption of the primary antiserum with 1 pM of the appropriate antigen under liquid phase condition at 4°C for 24 h. Positive controls were performed on rat and human nervous tissue. A polyclonal antiserum to S-100 and to neurofilament protein, respectively, was obtained from Dakopatt, Denmark. 421
422
K E R S C H B A U M ET AL.
The polyclonal antiserum against glial fibrillary acidic protein (GFAP) was a gift from G. Hacker/LKH Salzburg.
Results Microscopical examination of musk shrew kidney and ureter at low magnification revealed lymphoid tissues in close association to the epithelium lining the renal pelvis and the ureter, respectively (Fig. la,b), as well as along the arcuate artery and arcuate vein (Fig. lc-e). The lymphoid tissues next to the epithelium are anatomically well organised in a periphery of densely packed cells and a centre of loosely associated cells. The difference in cell package density causes a darker appearance of the structure in the periphery than in the centre. The renal pelvis is lined with many units of the structurally organised lymphoid tissue. Each of them protrudes into the renal pelvis in a dome-like appearance (Fig. lb). At these dome-like structures the smooth muscle layer is reduced or even absent between the epithelium and the lymphoid tissue and, hence, lymphocytes are in close contact with the epithelium. Clusters of lymphoid tissues are also distributed along the arcuate artery and arcuate vein (Fig. lc-e). These lymphoid tissues are not structural organised but consist of diffusely distributed lymphocytes and dendritic cells. In a variety of cell types, including dendritic cells, S-100-1ike proteins are expressed (Donato, 1991; Gaillard et al., 1993; Matsuura et al., 1992; Sugimura et al., 1990; Uccini et al., 1986). Dendritic cells can be morphologically identified on hematoxylin/eosin stained sections as cells with spine-like arborizations. To further identify dendritic cells we used an antiserum to S-100. Dendritic cells, containing S-100-immunoreactive material, were found (1) confined to the centre of the lymphoid tissue situated next to the renal epithelium and the ureter (Fig. lb) and (2) distributed throughout the lymphoid aggregations along the arcuate artery and the arcuate vein. Tissues involved in the immune defence system, such as the spleen, the thymus, lymph nodes and the MALT, are innervated. We, therefore, used a polyclonal antiserum to neurofilament proteins and glial fibrillary acidic protein, respectively, in an attempt to identify nerve fibres and Schwann cells, in the lymphoid tissue of the kidney. Antiserum against neurofilament proteins revealed nerve fibres in the structurally organised lymphoid tissue located next to the renal pelvis and the ureter, as well as in the lymphoid aggregations along the arcuate artery and arcuate vein (Fig. ld,e). At least a subpopulation of these nerve fibres is associated with glial fibrillary acidic protein immunoreactivity (Fig. la,c), indicating that some nerve fibres are myelinated.
Discussion Structural organised aggregates of lymphocytes and accessory cells constitute the MALT in the respiratory and digestive tract of mammals (Kraehenbuhl and Neutra, 1992; Kuper et al., 1992). According to its location next to the epithelium, its composition of lymphocytes and dendritic cells, and its division into a central and peripheral area, the lymphoid aggregations in the kidney of Suncus murinus resemble MALT structures in other species (Roitt et al., 1987). To our knowledge this is the first report on a MALT-like tissue in the kidney. MALT-like structures contain antigen-presenting dendritic ceils (Abbas et al., 1994). In thymus, lymph nodes, and bronchus-associated lymphoid tissue dendritic cells exhibit S-100 immunoreactivity (Gaillard et al., 1993; Matsuura et al., 1992; Sugimura et al., 1990; Uccini et al., 1986), which is in accordance with our findings of dendritic cells in the MALT-like tissue in the musk shrew. Since extracellular S-100 is able to stimulate cell division and differentiation (Donato, 1991), it appears possible that S-100 plays a similar role in lymphocytes. However, the function and chemical identity of the S-100-1ike protein in dendritic cells remains to be elucidated. There are structural and physiological indications for an intimate communication between the central nervous system and the immune system (Rozsman and Brooks, 1988; Solomon, 1987). Evidence for innervation of the MALT has also been established for Peyer's patches (Felten et al., 1988; Krammer and Kahnel, 1993) and the bronchus associated lymphoid tissue (Pabst, 1992). In accordance with these findings our study shows that the MALT-like tissue in the kidney of the musk shrew is also innervated. At least a subpopulation of these nerve fibres is myelinated indicating a fast information transfer between the nervous system and lymphocytes. Despite the well-organised appearance of the lymphoid tissues of the MALT-like structures in the kidney of Suncus murinus it remains to be clarified, whether this structure is genuine or acquired by pathological infections of the kidney. In any case, our investigations indicate that the kidney of this insectivore is able to provide for a structural organised lymphoid tissue which most likely constitutes a first immunological barrier against invading pathogenic antigens.
ACKNOWLEDGEMENTS We like to thank A. Liaunigg and J. Thalhamer for discussions and W. Kaufmann for immunocytochemical localisation of neurofilament protein and GFAP. Supported by the Austrian Fonds zur Fdrderung der wissenschaftlichen Forschung, P-8050 and P-9247.
KIDNEY-ASSOCIATED LYMPHOID TISSUE
423
Fig. 1 Lymphoid tissue in the kidney. (a) Longitudinal section of the ureter originating from the kidney. The lymphoid tissue is embedded in adipose tissue. The section was treated with antiserum against glial fibrillary acidic protein. Arrow: immunoreactive Schwann cells in contact with the lymPhoid tissue; asterisk: artery; A: adipose tissue; L: lymphoid tissue; U: epithelium of the ureter, x 60. (b) Lymphoid tissue beneath the epithelium of the renal pelvis showing S-100-immunoreactive dendritic cells in its center. Lymphocytes which surround the center are in close contact with the epithelium of the renal pelvis and protrude in a dome-like structure into the renal pelvis. Epithelial cells exhibit weak labelling with antiserum against S-100. x 250. (c) Lymphoid tissue (arrowheads) between the renal cortex and the medulla located next to an artery (asterisk) contains glial fibrillary acidic pr°tein'immun°reactive fibers (arrow). x 390. (d) Lymphoid tissue (arrowheads) next to blood vessels (asterisks) in the renal cortex, adjacent to the medulla innervated by nerve fibers (arrow) immunostained with antiserum against neurofilament protein, x 130. (e) lymphoid tissue innervated by neurofilament-immunoreactive nerve fibres surrounded by blood vessels (asterisks). x 90. In a-e hematoxylin/eosin counterstaining.
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KERSCHBAUM ET AL.
REFERENCES Abbas, A.K., Lichtman, A.H. and Poper, J.S. 1994. Cellular and Molecular Immunology, Saunders, Philadelphia. Donato, R. 1991. Perspectives in S-100 protein biology. Cell Calcium, 12, 713-726. Felten, S.Y., Felten, D.L., Bellinger, D.L., Carlson, S.L., Ackermann, K.D., Madden, K.S., Olschowka, J.A. and Livnat, S. 1988. Noradrenergic sympathetic innervation of lymphoid organs, In: Neuroendocrinology (eds. J.E. Blalock and K.L. Bost), Karger, Basel, 14-36. Gaillard, V., Vivier, G., Barjhoux, L., Souchier, C., Touraine, J.L. and Blanc-Brunat, N. 1993. Image analysis of dendritic cells in the human fetal thymus. Thymus, 21, 75-91. Hacker, G.W. 1989. Silver-enhanced colloidal gold for light microscopy, In: Colloidal Gold-Principles, Methods and Applications (ed. M.A. Hayat), Academic Press, San Diego, 1, 297-321. Hermann, A. and Kerschbaum, H.H. 1994. Immunohistochemical, bioclfe-mical and physiological characterization of calciumbinding proteins, In: Modern Analytical Methods in Histology (eds. G.W. Hacker and J. Gu) Plenum Press, New York, 163-185. Kraehenbuhl, J-P. and Neutra, M.R. 1992. Molecular and cellular basis of immuno-protection of mucosal surfaces. Physiol Rev., 72, 853-879. Krammer, H.J. and Kghnel, W. 1993. Topography of the enteric nervous system in Peyer's patches of the porcine small intestine. Cell Tiss. Res., 272, 267-272. Kuper, C.F., Koornstra, P.J., Hameleers, D.M.H., Biewenga, J., Spit, BJ., Duijvestijn, A.M., van Breda Vriesman, P.J.C. and
Sminia, T. 1992. The role of nasopharyngeal lymphoid tissue. Immunology Today, 13, 219-224. Matsuura, Y., Matsuoka, T. and Fuse, Y. 1992. Ultrastructural and immunohistochemical studies on the ontogenetic development of bronchus-associated lymphoid tissue (BALT) in the rat: special reference to follicular dendritic cells. Eur. Res. J., 5, 824-828. Pabst, R. 1992. Is BALT a major component of the human lung immune system? Immunology Today, 13, 119-122. Roitt, I.M., Brostoff, J. and Male, D.K. 1987. Kurzes Lehrbuch der Immunologie. Thieme Verlag, Stuttgart. Romer, A.S. and Parsons, T.S. 1983. Vergleichende Anatomie der Wirbeltiere. Parey Verlag, Hamburg. Rozsman, T.L. and Brooks, W.H. 1988. Signaling pathways of the neuroendocrine-immunenetwork, In: Neuroendocrinology (eds. J.E. Blalock and K.L. Bost) Karger, Basel, 140-159. Solomon, G.F. 1987. Psychoimmunology: Interactions between central nervous system and immune system. J. Neurosci. Res., 18, 1-9. Sternberger, L.A. 1979. Immunocytochemistry, 2nd edn., Wiley, New York. Sugimura, M., Shirogane, D., Atoji, Y., Suzuki, Y., Ohshima, K., Kon, Y. and Hashimoto, Y. 1990. A comparative study on S-100 protein-immunoreactive cells in lymph nodes. Jpn. J. Vet. Sci., 52, 1015-1021. Uccini, S., Vitolo, D., Stoppacciaro, A., Paliotta, D., Cassano, A.M., Barsotti, P., Ruco, L.P. and Baroni, C.D. 1986. Immunoreactivity for S-100 protein in dendritic and in lymphocyte-like cells in human lymphoid tissues. Virchows Arch., 52, 129-141.
Lymphoid tissue in the kidney of the musk shrew, Suncus murinus H. H. Kerschbaum*, S. K. Singht, A. Hermann*
Abstract. We describe a lymphoid tissue in the kidney of the musk shrew, Suncus murinus. An anatomically well organised lymphoid tissue, resembling the mucosa-associated lymphoid tissue, is associated with the epithelium of the renal pelvis and the ureter, respectively. Lymphoid tissue distributed along the arcuate artery and arcuate vein is not structurally organised in centre and periphery. This tissue type is most prominently developed between blood vessels. Immunocytochemistry revealed S-100-immunoreactive dendritic cells in both, structurally organised and structurally non-organised lymphoid tissues. The lymphoid tissue is innervated by neurofilament-immunoreactive nerve fibres. Some of these nerve fibres are associated with glial fibrillary acidic protein-immunoreactive structures, indicating that they are myelinated. Keywords: Lymphoidtissue, insectivore,dendriticcells,S-100,calcium-bindingprotein
Introduction Anatomically well organised lymphoid tissues, in intimate contact with epithelia of the respiratory, the gastrointestinal tract, and the female urogenital system (Kraehenbuhl and Neutra, 1992; Kuper et al., 1992), constitute the mucosa-associated lymphoid tissue (MALT). Similar to primary and secondary lymphoid organs the MALT is innervated (Felten et al., 1988; Krammer and Kt~hnel, 1993; Pabst, 1992). Respiratory and gastrointestinal tracts are in frequent contact with a wide variety of antigenic material. Therefore, lymphoid tissues located in these organs are supposed to form the first immunological barrier against pathogenic antigens. In the kidney, which is also a target for pathogenic antigens entering the organ via urethra, bladder, and ureter, a structural organised lymphoid tissue has not been described. Investigations on the MALT have been performed on several species of placental mammals, but not on insectivores. Since these animals are at the evolutionary base of the mammals (Romer and Parsons, * Department of AnimaI-Physiology, Institute of Zoology, University of Salzburg, Hellbrunnerstr. 34, A-5020 Salzburg, Austria. "[" Department of Zoology, Banaras Hindu University, Varanasi, 221005, India. Received 11 November 1994 Accepted 28 February 1995 Correspondence to: Prof. Dr A. Hermann. Department of Animal-Physiology, Institute of Zoology, University of Salzburg, Hellbrunnerstr. 34, 5020 Salzburg, Austria. Tel: 0043-662-8044-5610, Fax: 0043-662-8044-5698.
1983) they are of particular interest in view of the development of the MALT. In this study we report on a newly identified lymphoid tissue in the kidney of the musk shrew, Suncus murinus.
Material and methods Male musk shrews (n=5) were trapped near Banaras, India. The animals were ~er~ific.~ed by cervical dislocation, and the kidneys were quickly removed and fixed in Bouin's solution. The organs were dehydrated in a graded series of ethanol solutions and embedded in parablast using xylene as an intermedium. Immunocytochemistry was performed on 7 gm thick parablast sections. For localisation of antigens a peroxidase anti-peroxidase (PAP) method according to Sternberger (1979) and an immunogold silver stain technique (Hacker, 1989) were used. The methods were described in detail previously (Hermann and Kerschbaum, 1994). Negative controls were performed using normal serum in place of the primary antiserum and by preabsorption of the primary antiserum with 1 pM of the appropriate antigen under liquid phase condition at 4°C for 24 h. Positive controls were performed on rat and human nervous tissue. A polyclonal antiserum to S-100 and to neurofilament protein, respectively, was obtained from Dakopatt, Denmark. 421
422
K E R S C H B A U M ET AL.
The polyclonal antiserum against glial fibrillary acidic protein (GFAP) was a gift from G. Hacker/LKH Salzburg.
Results Microscopical examination of musk shrew kidney and ureter at low magnification revealed lymphoid tissues in close association to the epithelium lining the renal pelvis and the ureter, respectively (Fig. la,b), as well as along the arcuate artery and arcuate vein (Fig. lc-e). The lymphoid tissues next to the epithelium are anatomically well organised in a periphery of densely packed cells and a centre of loosely associated cells. The difference in cell package density causes a darker appearance of the structure in the periphery than in the centre. The renal pelvis is lined with many units of the structurally organised lymphoid tissue. Each of them protrudes into the renal pelvis in a dome-like appearance (Fig. lb). At these dome-like structures the smooth muscle layer is reduced or even absent between the epithelium and the lymphoid tissue and, hence, lymphocytes are in close contact with the epithelium. Clusters of lymphoid tissues are also distributed along the arcuate artery and arcuate vein (Fig. lc-e). These lymphoid tissues are not structural organised but consist of diffusely distributed lymphocytes and dendritic cells. In a variety of cell types, including dendritic cells, S-100-1ike proteins are expressed (Donato, 1991; Gaillard et al., 1993; Matsuura et al., 1992; Sugimura et al., 1990; Uccini et al., 1986). Dendritic cells can be morphologically identified on hematoxylin/eosin stained sections as cells with spine-like arborizations. To further identify dendritic cells we used an antiserum to S-100. Dendritic cells, containing S-100-immunoreactive material, were found (1) confined to the centre of the lymphoid tissue situated next to the renal epithelium and the ureter (Fig. lb) and (2) distributed throughout the lymphoid aggregations along the arcuate artery and the arcuate vein. Tissues involved in the immune defence system, such as the spleen, the thymus, lymph nodes and the MALT, are innervated. We, therefore, used a polyclonal antiserum to neurofilament proteins and glial fibrillary acidic protein, respectively, in an attempt to identify nerve fibres and Schwann cells, in the lymphoid tissue of the kidney. Antiserum against neurofilament proteins revealed nerve fibres in the structurally organised lymphoid tissue located next to the renal pelvis and the ureter, as well as in the lymphoid aggregations along the arcuate artery and arcuate vein (Fig. ld,e). At least a subpopulation of these nerve fibres is associated with glial fibrillary acidic protein immunoreactivity (Fig. la,c), indicating that some nerve fibres are myelinated.
Discussion Structural organised aggregates of lymphocytes and accessory cells constitute the MALT in the respiratory and digestive tract of mammals (Kraehenbuhl and Neutra, 1992; Kuper et al., 1992). According to its location next to the epithelium, its composition of lymphocytes and dendritic cells, and its division into a central and peripheral area, the lymphoid aggregations in the kidney of Suncus murinus resemble MALT structures in other species (Roitt et al., 1987). To our knowledge this is the first report on a MALT-like tissue in the kidney. MALT-like structures contain antigen-presenting dendritic ceils (Abbas et al., 1994). In thymus, lymph nodes, and bronchus-associated lymphoid tissue dendritic cells exhibit S-100 immunoreactivity (Gaillard et al., 1993; Matsuura et al., 1992; Sugimura et al., 1990; Uccini et al., 1986), which is in accordance with our findings of dendritic cells in the MALT-like tissue in the musk shrew. Since extracellular S-100 is able to stimulate cell division and differentiation (Donato, 1991), it appears possible that S-100 plays a similar role in lymphocytes. However, the function and chemical identity of the S-100-1ike protein in dendritic cells remains to be elucidated. There are structural and physiological indications for an intimate communication between the central nervous system and the immune system (Rozsman and Brooks, 1988; Solomon, 1987). Evidence for innervation of the MALT has also been established for Peyer's patches (Felten et al., 1988; Krammer and Kahnel, 1993) and the bronchus associated lymphoid tissue (Pabst, 1992). In accordance with these findings our study shows that the MALT-like tissue in the kidney of the musk shrew is also innervated. At least a subpopulation of these nerve fibres is myelinated indicating a fast information transfer between the nervous system and lymphocytes. Despite the well-organised appearance of the lymphoid tissues of the MALT-like structures in the kidney of Suncus murinus it remains to be clarified, whether this structure is genuine or acquired by pathological infections of the kidney. In any case, our investigations indicate that the kidney of this insectivore is able to provide for a structural organised lymphoid tissue which most likely constitutes a first immunological barrier against invading pathogenic antigens.
ACKNOWLEDGEMENTS We like to thank A. Liaunigg and J. Thalhamer for discussions and W. Kaufmann for immunocytochemical localisation of neurofilament protein and GFAP. Supported by the Austrian Fonds zur Fdrderung der wissenschaftlichen Forschung, P-8050 and P-9247.
KIDNEY-ASSOCIATED LYMPHOID TISSUE
423
Fig. 1 Lymphoid tissue in the kidney. (a) Longitudinal section of the ureter originating from the kidney. The lymphoid tissue is embedded in adipose tissue. The section was treated with antiserum against glial fibrillary acidic protein. Arrow: immunoreactive Schwann cells in contact with the lymPhoid tissue; asterisk: artery; A: adipose tissue; L: lymphoid tissue; U: epithelium of the ureter, x 60. (b) Lymphoid tissue beneath the epithelium of the renal pelvis showing S-100-immunoreactive dendritic cells in its center. Lymphocytes which surround the center are in close contact with the epithelium of the renal pelvis and protrude in a dome-like structure into the renal pelvis. Epithelial cells exhibit weak labelling with antiserum against S-100. x 250. (c) Lymphoid tissue (arrowheads) between the renal cortex and the medulla located next to an artery (asterisk) contains glial fibrillary acidic pr°tein'immun°reactive fibers (arrow). x 390. (d) Lymphoid tissue (arrowheads) next to blood vessels (asterisks) in the renal cortex, adjacent to the medulla innervated by nerve fibers (arrow) immunostained with antiserum against neurofilament protein, x 130. (e) lymphoid tissue innervated by neurofilament-immunoreactive nerve fibres surrounded by blood vessels (asterisks). x 90. In a-e hematoxylin/eosin counterstaining.
424
KERSCHBAUM ET AL.
REFERENCES Abbas, A.K., Lichtman, A.H. and Poper, J.S. 1994. Cellular and Molecular Immunology, Saunders, Philadelphia. Donato, R. 1991. Perspectives in S-100 protein biology. Cell Calcium, 12, 713-726. Felten, S.Y., Felten, D.L., Bellinger, D.L., Carlson, S.L., Ackermann, K.D., Madden, K.S., Olschowka, J.A. and Livnat, S. 1988. Noradrenergic sympathetic innervation of lymphoid organs, In: Neuroendocrinology (eds. J.E. Blalock and K.L. Bost), Karger, Basel, 14-36. Gaillard, V., Vivier, G., Barjhoux, L., Souchier, C., Touraine, J.L. and Blanc-Brunat, N. 1993. Image analysis of dendritic cells in the human fetal thymus. Thymus, 21, 75-91. Hacker, G.W. 1989. Silver-enhanced colloidal gold for light microscopy, In: Colloidal Gold-Principles, Methods and Applications (ed. M.A. Hayat), Academic Press, San Diego, 1, 297-321. Hermann, A. and Kerschbaum, H.H. 1994. Immunohistochemical, bioclfe-mical and physiological characterization of calciumbinding proteins, In: Modern Analytical Methods in Histology (eds. G.W. Hacker and J. Gu) Plenum Press, New York, 163-185. Kraehenbuhl, J-P. and Neutra, M.R. 1992. Molecular and cellular basis of immuno-protection of mucosal surfaces. Physiol Rev., 72, 853-879. Krammer, H.J. and Kghnel, W. 1993. Topography of the enteric nervous system in Peyer's patches of the porcine small intestine. Cell Tiss. Res., 272, 267-272. Kuper, C.F., Koornstra, P.J., Hameleers, D.M.H., Biewenga, J., Spit, BJ., Duijvestijn, A.M., van Breda Vriesman, P.J.C. and
Sminia, T. 1992. The role of nasopharyngeal lymphoid tissue. Immunology Today, 13, 219-224. Matsuura, Y., Matsuoka, T. and Fuse, Y. 1992. Ultrastructural and immunohistochemical studies on the ontogenetic development of bronchus-associated lymphoid tissue (BALT) in the rat: special reference to follicular dendritic cells. Eur. Res. J., 5, 824-828. Pabst, R. 1992. Is BALT a major component of the human lung immune system? Immunology Today, 13, 119-122. Roitt, I.M., Brostoff, J. and Male, D.K. 1987. Kurzes Lehrbuch der Immunologie. Thieme Verlag, Stuttgart. Romer, A.S. and Parsons, T.S. 1983. Vergleichende Anatomie der Wirbeltiere. Parey Verlag, Hamburg. Rozsman, T.L. and Brooks, W.H. 1988. Signaling pathways of the neuroendocrine-immunenetwork, In: Neuroendocrinology (eds. J.E. Blalock and K.L. Bost) Karger, Basel, 140-159. Solomon, G.F. 1987. Psychoimmunology: Interactions between central nervous system and immune system. J. Neurosci. Res., 18, 1-9. Sternberger, L.A. 1979. Immunocytochemistry, 2nd edn., Wiley, New York. Sugimura, M., Shirogane, D., Atoji, Y., Suzuki, Y., Ohshima, K., Kon, Y. and Hashimoto, Y. 1990. A comparative study on S-100 protein-immunoreactive cells in lymph nodes. Jpn. J. Vet. Sci., 52, 1015-1021. Uccini, S., Vitolo, D., Stoppacciaro, A., Paliotta, D., Cassano, A.M., Barsotti, P., Ruco, L.P. and Baroni, C.D. 1986. Immunoreactivity for S-100 protein in dendritic and in lymphocyte-like cells in human lymphoid tissues. Virchows Arch., 52, 129-141.