Modelo para la determinación de los marcadores genéticos de la respuesta inmunitaria en poblaciones colombianas


  • Edmond J. Yunis Dana-Farber Cancer Institute
  • Eduardo Egea Dana-Farber Cancer Institute

Palabras clave:

marcadores genéticos, respuesta inmunitaria, genética, inmunología, sistema inmunitario


Basados en nuestra experiencia, es posible estudiar factores genéticos del complejo mayor de histocompatibilidad (CMH) en varias enfermedades inmunológicas, o también factores genéticos que influyen en la falta de respuesta inmunitaria a vacunas como la hepatitis B. Los alelos de diferentes loci del CMH sirven por sí mismos para identificar riesgos para enfermedades o falta de respuesta a vacunas. El bloque de genes del CMH, que pueden existir al nivel de la población, en desequilibrio de enlace genético, es un mayor marcador para estudiar la susceptibilidad genética a enfermedades como las atopías así como también la falta de respuesta a vacunas. Nosotros proponemos que un estudio inmunogenético de poblaciones colombianas, podría utilizarse como control para identificar susceptibilidad genética para el desarrollo de atopías a los ácaros del polvo y a los hongos (mohos), que son alergenos comunes en Colombia. También, la existencia de una gran susceptibilidad para la hepatitis delta en la región norte de Colombia, indica que un estudio inmunogenético de identificación de haplotipos colombianos asociados con la falta de respuesta a la vacuna contra la hepatitis B serían muy útiles.

La identificación de individuos que no responden a vacunas comunes, sugeriría que ellos son más susceptibles a adquirir la hepatitis. En consecuencia, será necesario desarrollar otras vacunas con diferentes ntígenos para proteger a esa población.


Los datos de descargas todavía no están disponibles.

Biografía del autor/a

Edmond J. Yunis, Dana-Farber Cancer Institute

Profesor de Patologia Escuela de Medicina. Universidad de Harvard Boston, MA, U.S.A.
Jefe División de Inmuno-genética, Dana- Farber Cancer Institute. Miembro Honorario

Eduardo Egea, Dana-Farber Cancer Institute

Profesor Facultad de Medicina Universidad del Norte Barranquilla, Colombia. Research Fellow de la División de Inmunogenética, Dana-Farber Cancer Institute.

Referencias bibliográficas

Reinherz, E.L., and Schlossman, S. (1980). The differentiation and function of human T Iymphocytes. Cell 19:821-826.

Bronet, J.C. (1983). The origin of human B and ‘1’ cells from multipotent stem cells. A study of the TN syndrome. Eur. J. Immunology. 13:350-355.

Moller, G. (1981).Ontogeny of human Iymphocyte function. Immunology Rev. 57:1-10;

Rosenthal, A.S. (1978).Determinant selection and macrophage function in genetic control of the immune response. Immunological Rev. 40:136-152.

Geha, RS., Milgrom, H., Broff, M., Alpert, S., Martin, S., and Yunis, E.J. (1979). Effect of anti-HLA antisera on macrophage-T-cell interaction. Proc. Nat!. Acad. Sci. 76(8):4038-4041.

Cantor, H., and Boyse, E.A. (1975). Functional subclases of ‘1’Iymphocytes bearing different Ly antigens 11. Cooperation between subclasses of Ly and Ly + cells in the generation of killer activity. J. Exp. Med. 141:1390.

Nomenclature Committee IUIS/WHO (1984). Leukocyte differentiation antigens. In: Leukocyte Typing. pp 133, Barnard, A., Bounsell, L., et al. (Eds.) Springer-Veriag, Berlin.

Flomenberg, N., and Naito, K. (1983).AlIocytotoxic ‘1’cell clones: Both Leu 2+3 and Leu 2-3+ ‘1’cell recognize class I histocompatibility antigens. Eur. J. Immunol. 13:905-907.

Klein, J. (1982). The major histocompatibility complex. In: Immunology, the science of self and nonself discrimination. A. Wiley, Inter-Science Pub!., John Wiley and Sonso

Yunis, E.J., Dupont, B. (1987).The HLA system. In: Hematology of infancy and childhood. Nathan and Oski (Eds.). Saunders.

Schneider, P.M. (1986).Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. J. Clin. Invest. 78:650-657.

Cresswell, P., Springer, T., Strominger, J.L., Turner, M.J., Grey, H.M. and Kubo, R.T. (1974). Immunological identity of the small subunit of HLA-A antigens and B-2 microglobulin and its turnover on the cell membrane. Proc. Natl. Acad. Sci. USA. 71:2123-2127.

Tragardh, L., Wiman, K. R, and Peterson, P.A. (1979). Fragmentation of the human transplantation heavy chain by limited proteolysis, acid cleavage and cyanogen bromide treatment. Biochemistry. 18:1322-1328.

Terhorst, C., Parham, P., Mann, D.L., and Strominger, J.L. (1976). Structure of HLA antigens amino-acid and carbohydrate compositions and NH2-terminal sequence for four antigen preparations. Proc. Nat!. Acad. Sci. USA. 75:3390-3394.

Shackelford, D.A., Kaufman, A.J., and Strominger, J.L. (1982). HLA-DR antigens: Structure separation of subpopulations gene cloning and function. Immuno!. Rev. 66:133-137.

Reinsmoen, N., and Yunis, E. (1977). Inheritance of recombinant HLA-GLO haplotype suggesting the gene sequence. Nature. 267:276.

Thorsby, E., Albrechtssen, D.L., Hirschberg, H., Kaakinen, A., and Solheim, B.G. (1977).MLC-Activating HLAD detenninants; identification, Tissue Distribution and Significance. Transplantation Proceedings. 9:393-400.

Schwartz, B.D., and Cullen, S.E. (1978).Chemical characteristics of la antigens. Springer Sem. Immunopath. 185-190.

Finnegan, A., Smith, M., Smith, J., Berzofsky, J., Sachs, D., and Hodes, R (1986).The ‘1’cell repertoire for recognition of a phylogenetically distant protein antigen. Peptide specificity and MHC restriction of staphlococcal nuclease-specific ‘1’cell clones. J. Exp. Med. 164:897-910.

Schwartz, R, Fox, B.S., Fraga, E., Chen, C.H., and Singh, B. (1985). The ‘1’Iymphocyte response to cytochrome C. J. Immuno!. 135: 2598-2608.

Berkower, l., Matis, L.A., Buckenmeyer, G.K., Gurd Frank, RN., Longo, D.L., and Berzofksy, J.A. (1984). Identification of distinct predominant epitope recognized by myglobin-specific ‘1’cells under the control of different Ir genes and characterization of representative ‘1’cell clones. J. Immunol 132: 1370-1378.

Babbit, B.P., AlIen, P.M., Matsueda, G., Haber, E., and Unanue, E.R (1985). Binding of immunogenic peptides to la histocompatibility molecules. Nature. 317: 359•361.

Babbit, B.P., Matsueda, G., Haber, E., Unanue, E.R, and AlIen, P. (1986). Antigenic competition at the level of peptide-Ia binding. Proc. Nat!. Acad Sci. USA. 83: 4509-4513.

Buus, S., Colon, S., Smith, C., Freed, J.H., Miles, C., and Grey, H.M. (1986). Interaction between a “processed” ovalbumin peptide and la molecule. Proc. Nat!. Acad. Sci. USA. 83: 3968-3971.

Guillet, J., Ming-zong, L., Brinner, T.J., Buus, S., Sette Alexander Grey, H.M., Smith, J.A., and Gefter, M.L. (1986). Immunological self, nonself discrimination. 235: 865-870.

Alper, C.A., Awdeh, Z.L., and Yunis, E.J. (1986). Com- ‘plotypes, extended haplotypes, male segregation distortion and disease markers. Human Immunology. 15: 366-373.

Alper, C.A., Raum, D., Karp, S., Awdeh, Z.L., and Yunis, E.J. (1983). Serum complement “Supergenes” of the major histocompatibility complex in man (complotypes). Vox Sango 45: 62-67.

Alper, C.A., Awdeh, Z.L., Raum, D.D., and Yunis, E.J. (1985).Possible human analogs of the murine T/t complexo Exp!. Clin. Immunogenet. 2: 125-136.

Awdeh, Z.L., Raum, D., Yunis, E.J., and Alper, C.A. (1983a).Extended HLA complement allele haplotype: Evidence for T/t-like complex in mano Proc. Nat!. Acad. Sci.

USA. 80: 259-263.

Alper, C.A., Awdeh, Z.L., Raum, D.D., and Yunis, E.J. (1982). Extended major histocompatibility complex haplotypes in man: Role of allelos analogous to murine T mutants. Clin. Immunology and Immunopathol. 24: 276-285.

Bodmer, W.F., and Bodmer, J.G. (1978). The HLA system; Introduction. Br. Med. BuI!. 34: 309-316.

Amos, D.B., Pool, P., and Grier, J. (1980). HLA-A, HLAB, HLA-C and HLA-DR In: Manual of clinical immunology. Rose, N.R, Friedman, H. (Eds.). pp. 978. American Society for Microbiology.

McFarlane, 1.G. (1984). Autoimmunity in liver disease. Clin. Sci. 67: 569-578. 34. Craven, D.E., Kunches, L.M., Dienstag, J.L., Werner, B.C., Alper, C.A., Yunis, E.J., Awdeh, Z.L., Polk, B.F., Snydman, D.R, Platt, R., Crumpacker, C.S., and Grady, G.F. (1986).Non-responsiveness to hepatitis B vaccine in health care workers; results of revaccination and gene tic typings. An. Int. Med. 105: 356.

Vento, S. (1984).Antigen specific suppressor cell function in autoimmune chronic active hepatitis. Lancet. 1200-1204.

Walker, M.E., Szmuness, W., Stevens, C.E., and Rubinstein, P. (1981). Genetics of anti-HBs responsiveness: 1. HLA-DR7 and non-responsiveness to hepatitis vaccination (abstract). Transfusion. 21: 601.

Milich, D., Leroux-Roels, G.G., and Chisari, F.V. (1983). Genetic regulation of the immune response to hepatitis B surface antigen HBsAg; n. Qualitative characteristic of the humoral immune response to the A, D, and Y determinants of HBsAg. J. Immuno!. 130: 1395-1400.

Usonis, V., Kuhn!, P., Rede, H.D., and Doerr, H.W. (1986). Humoral immune response after hepatitis B-vaccination: Kinetics of anti-HBs antibodies and demonstration of HLA antigens. Zentra (b) Bacterio!. Microbio!. Hyg. (a). 262(3): 377-384.

Penichi, G., Cappellaccis, Mola, A., Morellini, M., Lulli, P., and Pescini, A. (1986). HLA and hyporesponsibility to anti-HBV vaccination (genetic study of non-responder subjects to anti•hepatitis B viral vaccine). Boll Inst. Sieroter Milan. 65(6): 459-463.

Gorzynski, T.J., and David, C.S. (1983). Immune response gene-associated antigens Ia/DR: structure and function in immunologically related diseases. Mayo Clin. Proc. 58: 457-466.

Cars, RM., and Anderson, R.R (1968).The disappearance rate of skinsensitivity antibody. J. Allergy. 42:29.

Ishizaka, K., and Ishizaka, T. (1978).Irnmunology of IgEmediated hypersensitivity in allergy-principles and practice. Vo!. 1. Middleton, Jr., Redd, C.H., and Ellis, Eds. pp. 52-78.

Bennich, H., and Johansson, S.G.O. (1971). Structure and function of human immunoglobulin E. Adv. Immuno!. 13:1.

Katz, D.H., and Marcelleti, J.F. (1983). Regulation of the IgE antibody system in human s and experimental animal. Progress in Immunology V. (Yamura and Tada, Eds.). V. Intern Congress of Immunology. pp. 465-482.

Scheleimer, RP., MacGlashan, D.W., Peters, S.P., Naderio, R., Proud, D., Adkinson, N.F. and Lichenstein, L.M. (1984).Inflammatory mediators and mechanism of release from puritied human basophils and mast cells. J. Allergy Clin. Immuno!. 4-473.

Smith, J.M. (1983). Epidemiology and natural history of asthma, allergic rhinitis and atopic dermatitis. In: Middleton, E., Reed, C., Ellis, E. (Eds.). Allergy; Principals and Practice. Sto Louis, C.V. Mosby company. pp. 771.

Blumenthal, M., Mendell, N., and Yunis, E. (1980). 1mmunogenetics of atopic diseases. J. All. Clin. Immunol. 65: 403-4G5.

Vaughn, W., and Black, J.H. (1954). Heredity in practice of allergy, 3rd ed. C.V. Mosby Co. pp. 74.

Deweck, A., Blumenthal, M., Yunis, E.J., and Jeannet, M. (1977). HLA and allergy. In: Dausset, J., Svejgaard, A, (Eds.). HLA and Disease, Baltimore. The Williams and Wilkins Company.

Blumenthal, M., Namboodiri, K., Mendell, N., Gleich, G., Elston, R.C., and Yunis, E. (1981). Genetic transmission of serum IgE levels. J. Med. Genet. 10: 219-228.

Hopp, R, Coleman, R., Bewerta, A., and Townley, R. (1984). Methacholine inhalation challenge as a potential genetic marker. American Academy of Pediatrics, section on allergy and immunology.

Levine, E., Stember, R, and Fotino, M. (1972).Ragweed, hay fever, genetic control and linkage to HLA-A haplotypes. Science. 178: 1201.

Blumenthal, M., Amos, D., Noreen, H., Mendell, N., and Yunis, E.J. (1974). Genetic mapping of Ir locus in mano Linkage to second locus of HLA. Science. 184: 1301.

Mendell, N.R, Blumenthal, M., Amos, D.B., Yunis, E.J., and EIston, R.C. (1978). Ragweed sensitivity. Segregation analysis and linkage to HLA-B. Cytogenetics. 22: 330-334.

Blumenthal, M.N., Yunis, E.J., Mendell, N.R, and Amos, D.B. (1977). HLA and ragweed allergy. Monographs in Allergy. 11: 83-88.

Marsh, D., Hsu, S.H., and Roebber, M. (1982). HLADw2- A genetic marker for human immune response to short ragweed allergen RA5 1 response resulting primarily from natural antigenic exposure. J. Exp. Med. 155: 1439-1451.

Marsh, D., Meyers, D., and Freidhoff, L. (1982). HLADw2- A genetic marker for human immune response to short ragweed allergen RA5; n response after ragweed immunotherapy. J. Exp. Med. 155: 1452-1463.




Cómo citar

Yunis, E.J. y Egea, E. 1988. Modelo para la determinación de los marcadores genéticos de la respuesta inmunitaria en poblaciones colombianas. Medicina. 10, 19 (ago. 1988), 18–30.



Artículos de Investigación