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Immunological aspects of maxillary sinusitis
J. max.-fac. Surg. 2 (1974) 242-24or © Georg Thieme Verlag, Stuttgart
Immunological Aspects of Maxillary Sinusitis Barbara ~eromska
Department of Stomatological Surgery (Head: Doc. Joanna Krajnik, M.D.), Institute of Stomatology, Medical Academy, Poznar~,Poland
Summary Removed mucosa of surgical specimens from 20 cases of maxillary sinusitis was investigated for the presence of iramunoglobulin A and E producing cells by means of immunofluorescence. The same material was screened for mast cells, using toluidin blue metaehromatic reaction. Numerous IgA cells were found in 12 cases, while IgE cells were noted in 10 cases. Presence of the latter was usually accompanied by relatively large numbers of mast cells. A number of these mast cells have shown signs of degranulation. Significance of these findings is discussed.
Key-Words: Secretory immunological system; Immunoglobulins; Plasma cells; Immunofluorescence; Mast cells. Introduction In spite of progress in therapy, recurrent maxillary sinusitis has remained a troublesome problem, both for the oto-laryngologist and the dentist. The course of recurrent maxillary sinusitis, relapses and unclear relationship to the "focal process (Findeisen 1971)" has caused much controversy. The latter is still debatable, but it has been reported, that tile rSle of inflamed sinuses as a source of the focal process is significant in 20-70 per cent of the cases reviewed by Gaus (1970). Allergy of the host to microbial antigens seems to be an important factor in focal pathology (Taranta and Uhr 1971). However, the mechanisms of allergy, especially at the local level, have remained unclear. Routine histology does not provide a satisfactory explanation of remissions and exacerbations of chronic maxillary sinusitis. Typically chronic inflammation is characterized by a predominantly mononuclear cell infiltration. However, recent advances in immunology have provided convincing evidence, that tracts and channels lined with a mucosal surface possess their own mechanism of defence; this defence mechanism
is often called the secretory immunological system (Small et al. 1969). Immunity produced by this system is partially independent of systemic immunity (Small et al. 1969). Antibodies present in secretions have been shown to belong predominantly to the immunoglobulin A class (Heremans and Vaerman 1971). Further, it has been recently postulated that Immunoglobulin E can combine with IgA in mueosal defence mechanisms (Murray 1972). Both immunoglobulins have been shown to be produced locally in lamina propria plasma cells of the mucosal lining (Rossen et al. 1968, Tada and Ishizaha 1970). Local production of IgE is of special interest, for it is known that IgE is responsible for anaphylaxis and atopic diseases via vaso-active amine release from mast cells (Roitt 1971). Also maxillary sinusitis has been reported to initiate attacks of some atopic diseases, especially bronchial asthma (Findeisen 1971). Consequently, it seemed worthy of investigation to examine examples of inflamed sinus mucosa for the presence of IgA and IgE producing cells in association with the presence of mast cells. Hopefully, this study can provide some clue toward better understanding of the pathogenic role of sinusitis in systemic allergy.
Materials and Methods
Tissue source: 20 specimens of mucosae obtained from human maxillary sinuses were collected immediately after surgery from patients treated in the Clinic of Dental Surgery, Poznafl Medical Academy. They were handled and processed for immunofluorescent procedures in essentially the same way as described in a previous study (]arczewska et al. 1971). Tissue blocks were frozen at - 7 0 ° C and cryostat sections were subjected to immunofluorescent reactions. A portion of each
Immunological Aspects of Maxillary Sinusitis
Fig. 1 Immunoglobulin A in the cytoplasm of plasma cells in inflamed maxillary mucosa. R.a. lgA FITC. 240x.
243
Fig. 2 Specific fluorescence for secretory component in cells of glandular epithelium. R. a. SC-Ga, R. gamma FITC. 260x.
tissue specimen was processed in routine histological fashion; biopsy specimens were embedded in paraffin blocks. They were subjected to toluidine blue reaction and routine histological stains.
Immune globulins: Rabbit globulins anti-human IgA (R.a. IgA) were purchased from Sevac (Czechoslovakia) and from Behringwerke (West Germany) and rabbit anti-hmnan secretory component (R. a. SC) was obtained as a gift from Dr. L. Hanson (Goteburg), through the auspices of Prof. P. Perlmann (Stockholm). Sheep anti-human IgE (S. a. IgE), produced commercially, was aquired from Pharmacia (Uppsala).
Labelled
reagents:
Goat immune globulins against rabbit gamma globulins (G. a. R. gamma FITC) were the commercial reagent of Sevac. R. a. IgA FITC and S. a. IgE FITC were prepared in the laboratory, by conjugation of appropriate monovalent immune globulins with fluorescein isothiocyanate (FITC-Sigma, isomer I). This was aeomplished by utilizing the dialysis method of Clark and Shepard (1963), with the subsequent purification on G-25 Sephadex column and absorption on rat liver acetone tissue powder. The following reagents were prepared: R. a. IgA FITC (Optical Density-OD ratio 3.2 and 2.6), S.a. IgE FITC (OD ratio 1.6 and 1.9).
Immunofluorescent reactions: These reactions were accomplished in a manner similar to the technique described by ]arczewska et al. 1971. IgA and IgE were localized in the tissue by means of direct immunofluorescent reaction with appropriately labelled reagents. The secretory component was detected by indirect means, using
Fig. 3 Plasma ceils containing IgE. S.a. lgE FITC. 300x.
unlabelled R.a. SC reagent followed by G.a.R. gamma FITC. Control reactions included the blocking test with analogous unlabelled immunoglobulins, the reaction proper and finally the use of labelled reagents of like specificities from various manufacturers. Mast cell staining: Mast cells were detected by means of metachromatic reaction with toluidine blue when applied to paraffin sections (Culling 1963). Microscopy and microphotography: The research microscope Zetopan (Reichert) equipped with an Osram HBO 200 W burner, BG 12/2 barrier filter, OG1/OG9 ocular filters, dark field condenser and apochromatic objectives was used. Microphotographs were produced with an Exacta Varex (Zeiss, Jena) SL-camera on ORWO 27 DIN black and white film. Time of exposure varied from 1 to 5 minutes.
244
B. Zeromska
Fig, 4 Mast cells in vicinity of blood vessels. Toluidin blue rnetachromasia. 180x.
Fig. 5 Mast cells with signs of degranulation. Toluidin blue metachromasia. 300x.
Results
chromasia, were found in almost all inflamed sinus mucosae, but their number varied. On examination the mast cells were large cells, often present in the vicinity of blood vessels and contained many reddish granules in their cytoplasm (Figs. 4, 5). The mast cells were assessed semi-quantitatively by counting them in multiple fields, under high microscopic magnification (600x) and by calculation of the mean. Table 1 demonstrates the mast cell counts and presence of IgE and IgA cells in 10 random patients. It was also noted that numerous mast cells were usually accompanied by IgE producing plasma cells. Some mast cells have shown signs of degranulation exemplified by the presence of granules extracellularly.
Numerous IgA producing cells were detected in 12 cases or 60 per cent of the examined nmcosae. These cells were noted to be in single as well as cluster configurations which were visible in various sites of the lamina propria (Fig. 1). Reaction for the secretory component (SC) revealed its presence in tile cytoplasm of cells of glandular epithelium and in the lumen of serous glands (Fig. 2). I n the same areas IgA could be detected, which suggested a secretory characteristic. Presence of IgA cells was usually accompanied by a relatively mild clinical course of sinusitis. Plasma cells producing IgE were detected in I0 cases. They were also seen in mucosal stroma, but their fluorescence was weak (Fig. 3). Mast cells, visualized by means of toluidine blue rectaTable 1 Mast cell metachromasia and immunoglobulin producing cells in maxillary sinusitis. Patient
Number of mast cells per field of vision
DePlasma granulation cells IgE IgA
(600×) M.W. S.W. G.J. K.W. R.E. W.K. C.A. L.A. B.W. K. M,
1-2 2-5 6-10 16-18 2-6 2-4 14-16 0-3 3-6 10-14
+ + + +
+ + + ++ ~
+ ++ + + ++ + +
IgA producing plasma cells did not show any relationship to mast cell counts.
Discussion and Conclusion Results of this study indicate, that in the mucosa of a portion of the patients studied with maxillary sinusitis, there was present a considerable number of plasma cells which produced IgA and IgE. Therefore it may be postulated that numerous immunoglobulin producing cells are of some significance in the course of the disease. Demonstration of local immunoglobulin synthesis suggested, that an antigenic stimulus was functioning at the local level. This activity was probably related to antigenic products of inflammation. These findings are similar to these reported by Ishikav.,a et al. (1972), who noted an immunoglobulin response in secretory otitis media.
Immunological Aspects of Maxillary Sinusitis Explanation of increased immunoglobulin synthesis in sinusitis is a subject for speculation. Apparently secretory I g A has a beneficial effect, for it has been demonstrated that in cases runn~ ing a relatively mild clinical course abundant IgA plasma cells were present. Conversely tgA plasma cells were lacking or scarce in cases with frequent exacerbations. The direct bactericidal effect of I g A is debatable, for this immunoglobulin does not fix complement in the conventional way. However, it has been shown, that IgA can lyse bacteria in conjunction with lysosome and possess opsonizing and virus neutralizing properties (Heremans and Vaerman 1971). Thus, it seems probable that I g A constitutes one of the defence mechanisms in the course of sinusitis. The presence of IgE in involved sinus mucosa suggested the possibility of local formation of an anaphylactic-like, type I according to Roitt (1971), hypersensitivity in the course of sinusitis. IgE was
245
also demonstrated in few middle ear specimens, collected from children with otitis media (Ishikawa et al. 1972). Microbial antigens are apparently the most probable allergens. Even extremely small amounts of IgE elaborated by inflamed mucosa may be sufficient to elicit systemic anaphylactic effects (Ishizaka and Ishizaha 1971). It is known that reagins (homocytotropic anti~ bodies) can easily adhere to and coat mast cells due to a specific feature in the FC region (Ishizatea 1969). Large numbers of mast cells, some with signs of degranulation were found in this study. This might suggest the significance of maxillary sinus inflammation in the pathogenesis of atopic diseases. In conclusion it can be stated, that immunological studies during an attack of maxillary sinusitis may be significant in the assessment of this disease and its sequelae.
References
Clark, H. F., C. C. Shepard: A dialysis technique for preparing fluorescent antibody. Virology 20 (1963) 642 Culling, C. F. A.: Handbook of histopathological techniques. Butterwoths, London 1963, 195 Findeisen, D. G. R.: Allergic. VEB Volk Gesundheit, Berlin 1971, 126 Gaus, W.: Kieferh6hlenprozess und Herdforschung. Zahnfirztl. Prax. 21 (1970) 145 Heremans, J. F., ]. P. Vaerman: Biological significance of IgA antibodies in serum and secretions. In: Progress in Immunology. Ed. by B. Amos. Acad. Press, N.Y., London 1971, 875 lshikawa, T., J. Bernstein, R. E. Reisman, C. E. Arbesman: Secretory otitis media: Immunologic studies of middle ear secretions. J. Allergy Clin. Immunol. 50 (1972) 319 Ishizaka, K.: Characterization of human reaginic antibodies and immunoglobulin E. In: Cellular and humoral mechanisms in anaphylaxis and allergy. Ed. by H. Z. Movat. Karger, Basel 1969, 63 lshizaka, K., T. lshizaka: Immunoglobulin E and homocytotrople properties. In: Progress in Immunology. Ed. by B. Amos. Acad. Press, N.Y., London 1971, 859 ]arczewska, K., B. 2eromska, L. Lewandowski, M. G6rny: Immunofluorescent analysis of dental peri-
apical granulomas and radicular cysts. Ann. hmnunol. 3 (1971) 109 Murray, M.: Secretory antibody and local immunity. Proc. roy. Soc. Med. 65 (1972) 659 Roitt, I.: Essential Immunology. Bla&well, Oxford 1971, 109 Rossen, R. D., C. Morgan, K. C. Hsu, W. T. Butler, N. M. Rose: Localization of I1 S external secretory IgA by immunofluorenscence in tissues lining the oral and respiratory passages in man. J. hmnunol. 100 (1968) 706 Small, P. A., ]. H. Curry, R. H. Waldman: Characteristics of the secretory immunologic system. In: The Secretory Immunologic System. Ed. by D. H. Dayton, P. S. Small, R. M. Chano&, H. E. Kaufman, T. B. Thomasi. U.S. NIH, Bethesda 1969, 13 Tada, T., K. lshizaka: Distribution of y-E-forming cells in lymphoid tissues of the human and monkey. J. Immunol. 104 (1970) 377 Taranta, A., J. W. Uhr: Poststreptococcal diseases. In: Immunological Diseases. Ed. by M. Samter. Little Brown, Boston 1971, 601 B. Zeromska,M. D., Department of Stomatological Surgery, Medical Academy, Poznan, Poland
Immunological Aspects of Maxillary Sinusitis Barbara ~eromska
Department of Stomatological Surgery (Head: Doc. Joanna Krajnik, M.D.), Institute of Stomatology, Medical Academy, Poznar~,Poland
Summary Removed mucosa of surgical specimens from 20 cases of maxillary sinusitis was investigated for the presence of iramunoglobulin A and E producing cells by means of immunofluorescence. The same material was screened for mast cells, using toluidin blue metaehromatic reaction. Numerous IgA cells were found in 12 cases, while IgE cells were noted in 10 cases. Presence of the latter was usually accompanied by relatively large numbers of mast cells. A number of these mast cells have shown signs of degranulation. Significance of these findings is discussed.
Key-Words: Secretory immunological system; Immunoglobulins; Plasma cells; Immunofluorescence; Mast cells. Introduction In spite of progress in therapy, recurrent maxillary sinusitis has remained a troublesome problem, both for the oto-laryngologist and the dentist. The course of recurrent maxillary sinusitis, relapses and unclear relationship to the "focal process (Findeisen 1971)" has caused much controversy. The latter is still debatable, but it has been reported, that tile rSle of inflamed sinuses as a source of the focal process is significant in 20-70 per cent of the cases reviewed by Gaus (1970). Allergy of the host to microbial antigens seems to be an important factor in focal pathology (Taranta and Uhr 1971). However, the mechanisms of allergy, especially at the local level, have remained unclear. Routine histology does not provide a satisfactory explanation of remissions and exacerbations of chronic maxillary sinusitis. Typically chronic inflammation is characterized by a predominantly mononuclear cell infiltration. However, recent advances in immunology have provided convincing evidence, that tracts and channels lined with a mucosal surface possess their own mechanism of defence; this defence mechanism
is often called the secretory immunological system (Small et al. 1969). Immunity produced by this system is partially independent of systemic immunity (Small et al. 1969). Antibodies present in secretions have been shown to belong predominantly to the immunoglobulin A class (Heremans and Vaerman 1971). Further, it has been recently postulated that Immunoglobulin E can combine with IgA in mueosal defence mechanisms (Murray 1972). Both immunoglobulins have been shown to be produced locally in lamina propria plasma cells of the mucosal lining (Rossen et al. 1968, Tada and Ishizaha 1970). Local production of IgE is of special interest, for it is known that IgE is responsible for anaphylaxis and atopic diseases via vaso-active amine release from mast cells (Roitt 1971). Also maxillary sinusitis has been reported to initiate attacks of some atopic diseases, especially bronchial asthma (Findeisen 1971). Consequently, it seemed worthy of investigation to examine examples of inflamed sinus mucosa for the presence of IgA and IgE producing cells in association with the presence of mast cells. Hopefully, this study can provide some clue toward better understanding of the pathogenic role of sinusitis in systemic allergy.
Materials and Methods
Tissue source: 20 specimens of mucosae obtained from human maxillary sinuses were collected immediately after surgery from patients treated in the Clinic of Dental Surgery, Poznafl Medical Academy. They were handled and processed for immunofluorescent procedures in essentially the same way as described in a previous study (]arczewska et al. 1971). Tissue blocks were frozen at - 7 0 ° C and cryostat sections were subjected to immunofluorescent reactions. A portion of each
Immunological Aspects of Maxillary Sinusitis
Fig. 1 Immunoglobulin A in the cytoplasm of plasma cells in inflamed maxillary mucosa. R.a. lgA FITC. 240x.
243
Fig. 2 Specific fluorescence for secretory component in cells of glandular epithelium. R. a. SC-Ga, R. gamma FITC. 260x.
tissue specimen was processed in routine histological fashion; biopsy specimens were embedded in paraffin blocks. They were subjected to toluidine blue reaction and routine histological stains.
Immune globulins: Rabbit globulins anti-human IgA (R.a. IgA) were purchased from Sevac (Czechoslovakia) and from Behringwerke (West Germany) and rabbit anti-hmnan secretory component (R. a. SC) was obtained as a gift from Dr. L. Hanson (Goteburg), through the auspices of Prof. P. Perlmann (Stockholm). Sheep anti-human IgE (S. a. IgE), produced commercially, was aquired from Pharmacia (Uppsala).
Labelled
reagents:
Goat immune globulins against rabbit gamma globulins (G. a. R. gamma FITC) were the commercial reagent of Sevac. R. a. IgA FITC and S. a. IgE FITC were prepared in the laboratory, by conjugation of appropriate monovalent immune globulins with fluorescein isothiocyanate (FITC-Sigma, isomer I). This was aeomplished by utilizing the dialysis method of Clark and Shepard (1963), with the subsequent purification on G-25 Sephadex column and absorption on rat liver acetone tissue powder. The following reagents were prepared: R. a. IgA FITC (Optical Density-OD ratio 3.2 and 2.6), S.a. IgE FITC (OD ratio 1.6 and 1.9).
Immunofluorescent reactions: These reactions were accomplished in a manner similar to the technique described by ]arczewska et al. 1971. IgA and IgE were localized in the tissue by means of direct immunofluorescent reaction with appropriately labelled reagents. The secretory component was detected by indirect means, using
Fig. 3 Plasma ceils containing IgE. S.a. lgE FITC. 300x.
unlabelled R.a. SC reagent followed by G.a.R. gamma FITC. Control reactions included the blocking test with analogous unlabelled immunoglobulins, the reaction proper and finally the use of labelled reagents of like specificities from various manufacturers. Mast cell staining: Mast cells were detected by means of metachromatic reaction with toluidine blue when applied to paraffin sections (Culling 1963). Microscopy and microphotography: The research microscope Zetopan (Reichert) equipped with an Osram HBO 200 W burner, BG 12/2 barrier filter, OG1/OG9 ocular filters, dark field condenser and apochromatic objectives was used. Microphotographs were produced with an Exacta Varex (Zeiss, Jena) SL-camera on ORWO 27 DIN black and white film. Time of exposure varied from 1 to 5 minutes.
244
B. Zeromska
Fig, 4 Mast cells in vicinity of blood vessels. Toluidin blue rnetachromasia. 180x.
Fig. 5 Mast cells with signs of degranulation. Toluidin blue metachromasia. 300x.
Results
chromasia, were found in almost all inflamed sinus mucosae, but their number varied. On examination the mast cells were large cells, often present in the vicinity of blood vessels and contained many reddish granules in their cytoplasm (Figs. 4, 5). The mast cells were assessed semi-quantitatively by counting them in multiple fields, under high microscopic magnification (600x) and by calculation of the mean. Table 1 demonstrates the mast cell counts and presence of IgE and IgA cells in 10 random patients. It was also noted that numerous mast cells were usually accompanied by IgE producing plasma cells. Some mast cells have shown signs of degranulation exemplified by the presence of granules extracellularly.
Numerous IgA producing cells were detected in 12 cases or 60 per cent of the examined nmcosae. These cells were noted to be in single as well as cluster configurations which were visible in various sites of the lamina propria (Fig. 1). Reaction for the secretory component (SC) revealed its presence in tile cytoplasm of cells of glandular epithelium and in the lumen of serous glands (Fig. 2). I n the same areas IgA could be detected, which suggested a secretory characteristic. Presence of IgA cells was usually accompanied by a relatively mild clinical course of sinusitis. Plasma cells producing IgE were detected in I0 cases. They were also seen in mucosal stroma, but their fluorescence was weak (Fig. 3). Mast cells, visualized by means of toluidine blue rectaTable 1 Mast cell metachromasia and immunoglobulin producing cells in maxillary sinusitis. Patient
Number of mast cells per field of vision
DePlasma granulation cells IgE IgA
(600×) M.W. S.W. G.J. K.W. R.E. W.K. C.A. L.A. B.W. K. M,
1-2 2-5 6-10 16-18 2-6 2-4 14-16 0-3 3-6 10-14
+ + + +
+ + + ++ ~
+ ++ + + ++ + +
IgA producing plasma cells did not show any relationship to mast cell counts.
Discussion and Conclusion Results of this study indicate, that in the mucosa of a portion of the patients studied with maxillary sinusitis, there was present a considerable number of plasma cells which produced IgA and IgE. Therefore it may be postulated that numerous immunoglobulin producing cells are of some significance in the course of the disease. Demonstration of local immunoglobulin synthesis suggested, that an antigenic stimulus was functioning at the local level. This activity was probably related to antigenic products of inflammation. These findings are similar to these reported by Ishikav.,a et al. (1972), who noted an immunoglobulin response in secretory otitis media.
Immunological Aspects of Maxillary Sinusitis Explanation of increased immunoglobulin synthesis in sinusitis is a subject for speculation. Apparently secretory I g A has a beneficial effect, for it has been demonstrated that in cases runn~ ing a relatively mild clinical course abundant IgA plasma cells were present. Conversely tgA plasma cells were lacking or scarce in cases with frequent exacerbations. The direct bactericidal effect of I g A is debatable, for this immunoglobulin does not fix complement in the conventional way. However, it has been shown, that IgA can lyse bacteria in conjunction with lysosome and possess opsonizing and virus neutralizing properties (Heremans and Vaerman 1971). Thus, it seems probable that I g A constitutes one of the defence mechanisms in the course of sinusitis. The presence of IgE in involved sinus mucosa suggested the possibility of local formation of an anaphylactic-like, type I according to Roitt (1971), hypersensitivity in the course of sinusitis. IgE was
245
also demonstrated in few middle ear specimens, collected from children with otitis media (Ishikawa et al. 1972). Microbial antigens are apparently the most probable allergens. Even extremely small amounts of IgE elaborated by inflamed mucosa may be sufficient to elicit systemic anaphylactic effects (Ishizaka and Ishizaha 1971). It is known that reagins (homocytotropic anti~ bodies) can easily adhere to and coat mast cells due to a specific feature in the FC region (Ishizatea 1969). Large numbers of mast cells, some with signs of degranulation were found in this study. This might suggest the significance of maxillary sinus inflammation in the pathogenesis of atopic diseases. In conclusion it can be stated, that immunological studies during an attack of maxillary sinusitis may be significant in the assessment of this disease and its sequelae.
References
Clark, H. F., C. C. Shepard: A dialysis technique for preparing fluorescent antibody. Virology 20 (1963) 642 Culling, C. F. A.: Handbook of histopathological techniques. Butterwoths, London 1963, 195 Findeisen, D. G. R.: Allergic. VEB Volk Gesundheit, Berlin 1971, 126 Gaus, W.: Kieferh6hlenprozess und Herdforschung. Zahnfirztl. Prax. 21 (1970) 145 Heremans, J. F., ]. P. Vaerman: Biological significance of IgA antibodies in serum and secretions. In: Progress in Immunology. Ed. by B. Amos. Acad. Press, N.Y., London 1971, 875 lshikawa, T., J. Bernstein, R. E. Reisman, C. E. Arbesman: Secretory otitis media: Immunologic studies of middle ear secretions. J. Allergy Clin. Immunol. 50 (1972) 319 Ishizaka, K.: Characterization of human reaginic antibodies and immunoglobulin E. In: Cellular and humoral mechanisms in anaphylaxis and allergy. Ed. by H. Z. Movat. Karger, Basel 1969, 63 lshizaka, K., T. lshizaka: Immunoglobulin E and homocytotrople properties. In: Progress in Immunology. Ed. by B. Amos. Acad. Press, N.Y., London 1971, 859 ]arczewska, K., B. 2eromska, L. Lewandowski, M. G6rny: Immunofluorescent analysis of dental peri-
apical granulomas and radicular cysts. Ann. hmnunol. 3 (1971) 109 Murray, M.: Secretory antibody and local immunity. Proc. roy. Soc. Med. 65 (1972) 659 Roitt, I.: Essential Immunology. Bla&well, Oxford 1971, 109 Rossen, R. D., C. Morgan, K. C. Hsu, W. T. Butler, N. M. Rose: Localization of I1 S external secretory IgA by immunofluorenscence in tissues lining the oral and respiratory passages in man. J. hmnunol. 100 (1968) 706 Small, P. A., ]. H. Curry, R. H. Waldman: Characteristics of the secretory immunologic system. In: The Secretory Immunologic System. Ed. by D. H. Dayton, P. S. Small, R. M. Chano&, H. E. Kaufman, T. B. Thomasi. U.S. NIH, Bethesda 1969, 13 Tada, T., K. lshizaka: Distribution of y-E-forming cells in lymphoid tissues of the human and monkey. J. Immunol. 104 (1970) 377 Taranta, A., J. W. Uhr: Poststreptococcal diseases. In: Immunological Diseases. Ed. by M. Samter. Little Brown, Boston 1971, 601 B. Zeromska,M. D., Department of Stomatological Surgery, Medical Academy, Poznan, Poland