4
Pan American Health Organization PAHO/ACMR 15/6 Original: English
FIFTEENTH MEETING OF THE ADVISORY COMMITTEE ON MEDICAL RESEARCH
Brastlia, D.F., Brazil 14-17 June 1976
REVIEW OF THE ACTIVITIES OF THE PAHO/WHO IMMUNOLOGY
RESEARCH AND TRAINING CENTER IN SAO PAULO
The issue of this document does not constitute formal publication. It should not be reviewed, abstracted, or quoted without the consent of the Pan American Health Organization. The authors alone are responsible for statements expressed in signed papers. (1
REVIEW OF THE ACTIVITIES OF THE PAHO/WHO IMMUNOLOGY
RESEARCH AND TRAINING CENTER IN SAO PAULO*
The PAHO/WHO Immunology Research and Training Center (IRTC) in S. Paulo was established in 1966 in the De- partment of Microbiology, Immunology and Parasitology of the Escola Paulista de Medicina under the direction of Professor Otto G. Bier. In 1969, following on agreement between WHO, the Secretariat of Health of the
State of S. Paulo and the University of S. Paulo, the Center moved its headquarters to the Butantan Institute. The present staff of the Center is made up by Dr. Ivan Moto, Director, and Associate Professor of the University of S. Paulo, and three full-time immunologists, provided by Instituto Butantan in accordance with the agreement between WHO, the University of S. Paulo and the Secretariat of Health of the State of S. Paulo. The three immunologists ore: Dr. Mahasti S. de Macedo, Dr. Adenir Perini and Dr. Harumi Ando Takehara. At the twelfth meeting of the odvisory Committee on Medical Research in 1973 we reviewed the activities of the Center from 1970 to 1973. The present report summari ze the activities of the Center since it was established in 1966, with emphasis on the lost 3 years.
*Prepared by Dr. Ivan Mota, PAHO/WHO Immunology Research and Training Center, Butantan Institute, Sao Paulo, SP, Brazil (2
OBJECTIVES OF THE CENTER
The principal objective of the Center is to provide can- didates from Latin American countries with postgradodte teaching in basic Immunology and to carry on immunological research projects directly or indirectly related to health problems in the region.
TEACHING ACTIVITIES
COURSE ON BASIC IMMUNOLOGY. The S. Paulo IRTC holds annuolly a 4-month course on basic Immunology given by lo cal and invited visiting-professors. The course in given almost entirely in English and comprises approximately 140 hours of theoretical lectures, 105 hours of seminars and at least 320 hours of laboratory work. Up to the present time the S. Paulo IRTC has held 10 Courses on Basic Immuno logy. As con be seen in Table I most of the students who attended these Courses are presently working in the field of Immunology.
As a consequence of the Course on Basic Immunolo- gists many distinguished Immunologists have come to S. Paulo, as visiting professors to teach in the Course. During their stay in Brazil these immunologists have the opportunity of getting in contact with Brazilian immunolo- (3
giste in the state of S. Paulo as well as in other states.
In this way they exert a positive influence on many immuno logy centers beside the S. Paulo IRTC. The following
Visiting-Professors have given lectures in the S. Paulo IRTC: J. A. Andrade, Department of Endocrinology, Hospital
Tornú, Buenos Ayres, Argentina; Ruth Arnon, Weizman Institu te of Sciences, Rehovot, Israel; S. Avraseas, Institut of
Recherches Scientifiques Sur le Cancer, Villenuif, France;
E. L. Becker, Deportment of Pathology, The University of Connecticut School of Medicine, Farmington, Conn. U.S.A. ; E. H. Beutner, Department of Bacteriology and Immunology State University of New York, Buffalo, U.S.A.; Celso Bianco, The Rockfeller University, New York, N.Y., U.S.A.; R. Binaghi,
Collége de Fronce, Paris; G. Biozzi, Fondation Curie, Section of Biologie, Paris, France; Joseph Haimovich, Weizman lnstitu te of Science, Rehovot, Israel; W. L. Hale, Department of
Bacteriology and Immunology, State University of New York ,
Buffalo, U.S.A.; J. G. Howard, The Wellcome Research Labora- ratories Langley Court, Beckenham, Kent; E. A. Kabat, Columbia
College of Surgeons, New York, N.Y., U.S.A.; C. Moreno, The Wellcome Research Laboratories, Langley Court, Beckenham, Kent,
England; Victor Nussenzweig, Department of Pathology, New York,
University, New York, N.Y., U.S.A.; E. Potworowski, Institute Armand-Fropier, Universit¿ de Quebec, Quebec, Conada; A. Szenberg, Walter and Elisa Institute of Medical Research
Melbourne, Australia; Ivan Roitt, Department of Immunology, The Middlesex Hospital, London, England; J. L. Turk, Royal College of Surgeons, London, England; Nelson Voz, The National Asthma Center, Denver, Ca.; U.S.A.; G. Voisin, Centre of Recher- ches D'lnmuno-Pathologie, Hopital Saint Antoine, Paris , France; B. Waksman, Department of Pathology, Yale Univer- sity, Connecticut, U.S.A.. In addition to these foreigner immunologists the following distinguished Brazilion pro- fessors have collaborating with the IRTC by giving lectu- res: Willy Begak, Department of Genetica, Instituto Butan- tan, S. Paulo, Brazil; O. G. Bier, Director, Instituto Bu tantan, S. Paulo, Brazil; M6rio Camargo, Institute of Tro pical Medicine, University of S. Paulo, Sao Paulo, Brazil;
R. G. Ferri, Department of Microbiology and Immunology , Medical School, University of Sao Paulo, S. Paulo, Brazil;
S. F. Lara, Department of Biochemistry, Institute of Che- mistry, University of Sao Paulo, Brazil; A. de Oliveira
Lima, Laboratory of Immunology, Medical School, University of Rio de Janeiro, Brazil; C. Fava Neto, Department of Microbiology and Immunology, Medicol School, University of Sao Paulo, S. Paulo, Brazil; Benedito Oliveira, Department of Immunology, State University of Campinas, Campinas, S. Paulo, Brazil¡ S. Leal Prado, Department of Biochemistry,
Escola Paulista de Medicina, S. Paulo, Brazil; L. S. Prigenzi, Department of Immunology, State University of
Campinas, Campinas, S. Paulo, Brazil; W. Dios da Silva , Department of Immunobiology, Institute of Medical Sciences,
Belo Horizonte, MG, Brazil; Maria Siqueira, Division of Immunology, Instituto Biologico, S. Paulo, Brazil.
Beside the regular Course on Basic Immunology the
S. Paulo, IRTC offers occasional courses on local health problems. Thus, a Course on Chagas' diseoase will be hold (5
in July 1976 and a Course on "Lymphocyte transformation and macrophage cultivation for South Americon Research
Workers in Leprosy" was held in June, 1974. The following people porticipated in this Course: Dr. J. O. Almeida ,
Dept. of Microbiology and Immunology, Medical School of the University of S. Paulo, Ribeirao Preto, S. Paulo ,
Brazil; Dr. B. Beiguelman, Dept. of Medical Genetics, State University of Campinas, S. Paulo, Brazil; Dr. M. L. Brubaker, Pan American Health Organization; Dr. M. S. Cline, Boyer professor of Medical Oncology, Dept. of Medicine, Los Ange-
les, California; Dr. 5. Froland, Institute of Immunology and
Rheumatology, Oslo, Norway; Dr. T. Godal, Immunology, World Health Organization, Geneva, .Switzerland; Dr. Goihman Yahr,
Instituto Nacional de Dermatologia, Caracas, Vanezuela; Dr. R. C. Hastings, U. S. Public Health Service, Caville, Lousiona, U.S.A.; Dr. R. J. W. Rees, National Institute for
Medical Research, The Ridgeway, Mill Hill, London, England; Dr. H. Sansarricq, Leprosy Division of Communicable Diseases,
WHO; Dr. G. P. Walsh, Gulf South Research Institute and Dr. 1. Mota, PAHO/WHO Immunology Research and Troining Center, S. Paulo, Brazil. The following students attended the Course:
Dr. Edna Thomoas, Leprology Laboratory, Rio de Janeiro, Brazil; Dr. M. S. Damasco, Leprology Laboratory, Rio de Janeiro, Brazil; L. Liserre, WHO Referenoe Center for Serology of Leprosy, Ribeirao Preto, S. Paulo, Brazil; Dr. R. F. M. Lai A. Fat, Para Maribo, Suriname; Dr. R. Pisani, Dept. of Medical Genetics, State University of Campinas, S. Paulo, Brazil ; Dr. A. Corredor, Dept. of Microbiology and Immunology, Minis- terio de La Soalud Publica, Bogota, Colombia; Dr. P. Pagnano , (6
Medical School, Ribeirao Preto, S. Paulo, Brazil; Dr. Ises Abrahamsohn, Laboratory of Immunobiology, Instituto
Butantan, S. Paulo, Brazil; Dr. Sonia Jancar, Laboratory of Immunobiology, Instituto Butanton, S. Paulo, Brazil;
Dr. E. Fliess, Medical School, Del Salvador University , Buenos Ayres, Argentina; Dr. Maria Pinardi, Medical
School, National Institute of Dermatology, Caracas, Vene zuela and Dr. H. N. Cabrera, Dermatology Service, Hospi- tal F. J. Muniz, Buenos Ayres, Argentina.
POSTGRADUATED STUDENTS. Due to agreements with the Uni- versity of Sao Paulo, (Prof. Celeste Fava Neto) and the
Escolo Paulista de Medicina (Prof. Nelson Mendes) students on the posgraduate Course in Immunology of both the
University of Sao Paulo and of the Escola Paulista de Medi cina (a federal school) are accepted as fellows in the IRTC to carry on their research projects. These students work in the Center doing research for 2 to 3 years and are usually supported with a fellowship from FAPESP, CAPES, or
CNPq.. Since 1971 13 ,tudents have been accepted to work on their research projects in the IRTC. Four of these studente have concluded their stay satisfactorily and have presented the results of their investigations in their Master Degree Thesis. (7
RESEARCH ACTIVITIES
Although the S. Paulo IRTC has tackled many differents research problema since its establishment (see list of published papera), more recently the researches have been concentrated on problemsa of immediate hypersensitivity and Chagas' disease. For the atudy of experimental Chagas' disease a laboratory was set up in 1973 and is actively doing research on this problem. Dr. Harumi A. Takehara is the Head of this laboratory. The following research activities are in progress at the present time: a) Isolation and choracterization of the homocytotropic antibodies of the guinea pig. Work being done by Sergio Marangoni (fellow of FAPESP), Adenir Perini, Benedito de Oliveira Filho (Prof. of Immunology, State University of Campinas, S. Paulo) and I. Mota. b) Biological properties of the lymphocytosis promoting factor isolated from Bordetella pertussis. Work being done by Vilma Trindade (Postgraduate atudent working in the Center). (8
c) Role of macrophage in the production of homocytotropic
antibodies. Effect of an specific anti-macrophage serum. Work being done by Eugenia Lagus (Student, postgraduate Immunology Course, Escola Paulista de Medicina). d) Attempts ta vaccinate mice against T. cruzi with pre- treatment with Leptomos pessoai. Work being done by Harumi
Ando Takehara. The initial part of this work was made in collaboration with Dr. W. Dias do Silva, from the Laboratory of Immunobiology; Instituto Butantan.
e) Attempts to protect mice against T. cruzi with superna- tants of lymphoid cells obtained from mice chronically infected with T. cruzi. Work being done by Harumi Ando
Takehara and Maria Elisa Pupo (Biologist, voluntary assistant
in the IRTC.
f) Role of the mononyclear phagocytic system in experimental
Chagas' disease. It is known that the effect of many immu- nostimulanta; is directed partly upon the antigen processing by the macrophage, a cell that probably has a key role in the
imnunopathology of Chagas' disease. On the other hand it has been shown recently that druga capable of raising the levels of intracellular cyclic AMP inhibits phagocytosis whereas druga capable of reducing the level of the same enzi- me system are potent atimulatora of phagocytosis. Thus, it was decided to investigate whether such drugs has any (9
beneficial effect on the course of experimental Chagos' disease.
Work been done by A. Perini, Rodolfo P'ereira
Mendes and I. Mota.
g) Attempts to immunize mice against a letal dose of T. cruzi by pretreatment of the animals with L. pessoai plus adjuvants. Work been done by Mario Eliza Pinheiro and I. Mota.
PAPERS PUBLISHED BY THE S. PAULO IRTC.
L. R. Albuquerque, A. Perini and I. Moto. "Failure of
insoluble antigena to elicit onaphylactic reactions". Int.
Arch. Allergy Appl. Immunol. 41, 797 (1971).
E. H. Beutner, L. Prigenzi, W. Hale, C. A. Leme and O. G. Bier. "Immunofluorescent studies of autoantibodies to intercellular orea of epithelia in Brazilian pemphigus
folioceus". Proc. Soc. Biol. Med. 127, 81 (1971).
E. H. Beutner, G. W. Wood, T. P. Chrozelski, C. A. Lene and O. G. Bier. "Produgao de lesoes semelhantes aos do penfigo
foli6cio pela injeSao introdérmica em coelhos e macacos, de soro de doentes con titulo elevado de outoanticorpo. Mem. Inst. Butanton 35, 79 (1971). (lo
F. A. Braga. "Anafilaxia cutanea passiva homologa e hetero loga induzida pelos anticorpos homocitotropicos do camun- dongo". Mas-ter Degree Thesis, Escola Paulista de Medicina, 1975.
M. Gennari. "Estudo da aqao do veneno de Bothrops Jararoca sobre o complemento de cobaoio". Master Degree Thesis,
University of Sao Poulo, 1972.
P. D. Guercio, G. Torlone, F. Braga Andrade, G. Biozzi and
R. Binaghi. "Opsonic, cytophlic and agglutinoting activity of guinea pig 12 ond yM anti-Salmonella antibodies".
Immunology 16, 361 (1969).
Y. Kipnis. "Efeito da esplenectomia no produçoo de anticorpos homocitotropicos em cobaias e camundongos". Doctoral Degree
Thesis, University of Sao Paulo, 1972.
M. Sahihi de Macedo. "Mecanismo de reguladao da formacao de anticorpos da classe IgE". Moaster Degree Thesis, Escola
Paulista de Medicina, 1974.
M. Sahihi de Mocedo. "Studies on the regulatory mechanisms of homocytotropic antibody production in mice". Thesis presented in the Faculty of Science, University of Birmingham1 for the Degree of Master of Science, 1974-1975.
I. Mota and A. Perini. "A heat-labile mercaptbethanol (11
susceptible homocytotropic antibody in the guinea pig". Life Sec. 9, 923 1970.
I. Moto and A. Perini. "The effect of a synthetic double- atranded RNA on IgGl and IgE production by guinea pigs. A comparative study with lipopolysacchoride. Iomunology 29, 319 (1975).
I. Mota, A. Perini and V. S. Trindade. "The mechanism of the adjuvant effect of Bordetella pertussis: the substance responsible for the selective enhancement of IgE ontibody production". Int. Arch. Allergy Appl. Immunol. 47, 425
(1974).
H. Passos, M. Siqueira, 0. C. Martinez and 0. G. Bier. "Studies on the nephrotoxic activity of guinea pig gamma-l and gamma-2 antibodies". Immunology 26, 407 (1974).
A. Perini. "Estudos sobre o efeito adjuvonte de endotoxinas e dos ácidos nucleicos no produçao de anticorpos da classe IgE em cobaios. Doctoral Degree Thesis, University of Sao Paulo, Brazil, 1972.
A. Perini and 1. Mota. "Heterogeneity of guinea pig homocy- totropic antibodies". Immunology 22, 915 (1972).
A. Perini and I. Mota. "The production of IgE and IgGl antibodies in guinea pigs immunized with antigen and bacteriol lipopolysaoccharides". Immunology 25, 297 (1973). (12
H. Ando Takehara. "Doenga de Chagas experimental: tenta- tivoas de imunizaSao protetora por inoculaoao prévia co. flagelodos monox*nicos". Master Degree Thesis, Escola
Paulista de Medicina, 1975.
J. Uriel, M. Della Santina and E. Rizzo. "Characterization d'enzymes dans le venin óf Bothrops Jararaca por des méthodes dOimmunization". Bull. Soc. Chim. Biol. 50, 938
(1968).
PAPERS SUBMITTED FOR PUBLICATION.
F. A. Braga and I. Mota. "Homologous passive cutaneous anaphylaxia (PCA) in mice and heterologous PCA induced in rats with mouse IgE". Submitted for publication in
Immunologs.
M. Sahihi de Macedo, F. A. Braga and I. Moto. "Control of
IgE and IgGl antibody production in mice". Submitted for publication in Cellular Immunolagy.
H. Ando Takehara and W. D. da Silva. "Mechanism of resis- tance against T. cruzi in animalsvaccinated with L. peasoai".
To be published in the Proceedings of the PAHO Symposium on Trypanosomiasis. (13
INFLUENCE OF THE CENTER ON LOCAL IMMUNOLOGY
As a result of the establishoment of the IRTC in S. Paulo and of the stimulus provided by the visiting-professors a special interest in Immunology was generated with definite pratical consequences. As a result of the solid immunolo- gical background adquired in the Course on Basic Immunology many of the atudenta decisively focused their interest in immunology research and some of them were sent abroad for further training in high level laboratories, in Europe and the United States. (unfortunately many of these students did not return to their place of origin). In this way the
IRTC is accomplishing its rolo of selecting good candidates to become future first clasa researchers in the field of
Immunology. As a example of this let us quote one student of the 1968 Course (Dr. Celso Bianco) who is now a well known immunologist and has come for several years to give lectures on Cellular Immunology in the IRTC.
A further indication of the influence exerted by the IRTC in the developement of Immunology in S. Paulo is the strong group of immunologists now working a the Institu to Biologico in S. Paulo. In that Institution are being developed research projecta on immunogenetics and on immu- noglobulins of different animal species with the collabora- tion of two visiting-professors of the IRTC Immunology Course and of one former member of the permanent staff of the Center. (14
As further consequences of the establishment of the IRTC in S. Paulo it is atill possible to quote: a) The foundation of the Sociedode Brasileira de Imunologia,
SBI (Brazilion Society for Immunology), in 1972. The initi al idea, discussiona and deliberationa for the establishment of the SBI took place in the IRTC. Indeed, presently the
SBI has its headquartera provisorily located in the IRTC. With the support of the IRTC and the Brazilian Academy of
Sciences, the SBI was able to hold the first National Sympo- sium on Immunology in Rio de Janeiro, in 1973 and a second Symposium in 1974. b) The establishment of a new laboratory in Instituto Butan-
tan, the Laboratory for Immunobiology. The new laboratory has among its finalities to improve the preparation of immunobiological materials such as vaccines and antisera.
This laboratory is functioning in close association with the IRTC taking advantages of the facilities available at the
Center to modernize the Butantan Institute's methods of preparation of immunobiological reagents.
Thumathe Immunology Research and Training Center in
S. Paulo is accomplishing to the best of its ability the boals of training investigatora and atimulating immunology research in Latin American countries. a (i ·., o b a uO o .4 sc .4 4' O b C 3 e .4 .4 4' Y u .04 u ,4 m or .4 o ...I 1.4C u e eO u >. C 4 ce1 .4 .4 e Y .4 6 E .44 O o O a e 0r- e N -4 .lo0 . (:4 .41uo em o o b c 'O .. . 4 :-4 C a .4 o a e 0 b O . '-4 +4 w 3 c b > 3 ~, 14c 41 e o O o U:) -4-.4 e a 4' 4c C k Mi 0 5 4' *,4 a a O b' O .4 .-4 CU o a 4' Q-4 .,4 . o 4. m e -4 .*4 o O N .-I ',~ O ob &ni O'> O o o a. 0O 14 .4d 1C u 14 W. 140 Ue - ,.-,1 eQ. 4' SS 112 a iu0 4 w* C 50 C O o C' -4 Cce .4 O O 5 O> .40 b >4 o O ' o U. OCo o e-4 o So 0 . eC. . ,. e O -4 a · · O m *4 O3 o O ~4 -4 u ca e . O-4e. uc 14 a .4 = a. u> a aN e. 14334' CN aN {C orc Os 3- u> e U'a 14 ee *41-,4 * u> . 4 Co CL u. N o 1,4 a oa a 41t 04DOC Co U el >4 Co Ct O -4 4 Cm 0-4 .4 > 0 4-- OE 0 -4 4 ) .4> 3 .4. O 4' ·.4 :) 'O o., -4 e.,, C. ff, 4a. .4. ~ O o eeO 40Va. 6 -4 CO O 3 C O 4c .4 14 *- O oa oa .4") E CL o -4·C lo I 01 w 3 _--J¡ U,(n CL la cn --4 -4 o .4 .4 0.i'3- ea ao o-- ., b..., .4 i!1 -4 N N 3 r_ 4' N N z O 14 a c 0r a a a oZ O e o 14 b -4 .-4 4&ae U um m.1,4 C. >4 3 o O~ m e .4a o2 e c 01 3 14 N a +D C eo *rl a N O. 14 o U 3r o 14 ..4 4'o b e a c o b- O .e C u e 2 .4 u o o In o ea o .,4 14 0 u, Lc O 14 q- .4 e 14 14 b 4- da e u> o E
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