Veterinary Immunology and lmmunopathology, 30 ( 1991 ) 121-127
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Elsevier Science Publishers B.V., Amsterdam
Immunogenetics and the major histocompatibility complex* S.J. L a m o n t Department of Animal Science, Iowa State University, Ames, IA 50011, USA
ABSTRACT Lamont, S.J., 1991. Immunogenetics and the major histocompatibility complex. Vet. Immunol. Immunopathol., 30:121-127 The poultry immune system is a complex system involving many different cell types and soluble factors that must act in concert to give rise to an effective response to pathogenic challenge. The complexity of the immune system allows the opportunity for genetic regulation at many different levels. Cellular communication in the immune response, the production of soluble factors, and the rate of development of immune competency are all subject to genetic influences. The genes of the major histocompatibility complex (MHC) encode proteins which have a crucial role in the functioning of the immune system. The MHC antigens of chickens are cell surface glycoproteins of three different classes: Class I (B-F), Class II (B-L) and Class IV (B-G). The MHC antigens serve as essential elements in the regulation of cell-cell interactions. The MHC has been shown to influence immune response and resistance to autoimmune, viral, bacterial and parasitic disease in chickens. The MHC has been the primary set of genes identified with genetic control of immune response and disease resistance, but there are many lesser-characterized genes outside of the MHC that also regulate immunoresponsiveness. Polygenic control has been identified in selection experiments that have produced lines of chickens differing in antibody levels or kinetics of antibody production. These lines also differ in immunoresponsiveness and resistance to a variety of diseases. Understanding the genetic bases for differences in immunoresponsiveness allows the opportunity selectively to breed birds which are more resistant to disease. Indirect markers that can be used for this selection can include the MHC genes and immune response traits that have been associated with specific or general resistance to disease. ABBREVIATIONS McAb, monoclonal antibodies; MHC, major histocompatibility complex; REV, reticuloendotheliosis virus; SRBC, sheep red blood cells. *This article is Journal Paper No. J-14223 of the Iowa Agriculture and H o m e Economics Experiment Station, Ames, IA: Project No. 2237.
0165-2427/91/$03.50
© 1991 Elsevier Science Publishers B.V. All rights reserved.
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THE M A J O R H I S T O C O M P A T I B I L I T Y C O M P L E X IN C H I C K E N S
General organization The major histocompatibility complex ( M H C ) is a group of genes, first identified in the mouse, which was originally defined by its influence on tissue graft acceptance (Snell, 1953 ). The chicken was the second animal species in which the MHC was identified (Schierman and Nordskog, 1961 ). MHC genes and proteins have been divided into three classes in mammals: Class I, Class II and Class III. The Class III has not been identified in the chicken MHC, but the chicken possesses an additional unique class (Class IV) of MHC proteins expressed on erythrocytes and other cells. Because of its linkage with the B blood group (Briles et al., 1950) the chicken MHC has been designated as the B complex. Class I, II and IV genes of the chicken MHC are also designated as B-F, B-L and B-G, respectively. Gene structure Until the recent application of techniques of molecular genetics to the study of the chicken MHC, very little was known about the fine structure of the MHC genes. Now, Class I, II and IV genes of the chicken MHC have been cloned (Goto et al., 1988; Guillemot et al., 1988; Xu et al., 1989). The small size and close proximity of Class I and II genes on the chromosome may explain the very low frequency of recombinants between B-F and B-L. Uncharacterized genes identified within the MHC are hypothesized to be involved in disease resistance. Most important structural characteristics of the gene products, however, are conserved between the chicken and mammalian MHC. Antigen structure Class I, II and IV molecules are cell surface molecules. Class I (B-F) antigens are located on all cells. Class II (B-L) antigens are restricted to monocytes, macrophages, B cells and some T cells. Class I antigens consist of a single chain of three globular domains plus a noncovalently associated B2 microglobulin. Class II antigens consist of two dimorphic chains both with a transmembrane and cytoplasmic piece. Monoclonal antibodies (McAb) have been produced to antigens of each of the three subregions of the chicken MHC (B-G, Longenecker et al., 1979; Miller et al., 1982, 1984; B-F, Pink et al., 1985; B-L, Ewert et al., 1984; Guillemot et al., 1984; H~ila et al., 1984; Crone et al., 1985 ). These McAb have been extremely useful in isolating highly purified M H C antigens for biochemical characterization. The B-G antigens isolated from erythrocyte membranes by immunoprecipitation with McAb have seen shown to exist as polymers of a 47 kDa
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monomer (Salomonsen et al., 1987 ). Two-dimensional gel electrophoresis of B-G antigens revealed extensive polymorphism, hypothesized to be caused by multiple loci in the B-G region (Miller et al., 1984). McAb to Class I (BF) antigens precipitate a 40-45 kDa cell surface molecule along with a 12 kDafl2 microglobulin (Pink et al., 1985 ). Crone et al. ( 1985 ) used sequential immunoprecipitation by McAb of different specificities to demonstrate two distinct B-F products from B homozygous chickens, which indicated the existence of at least two Class I MHC gene products. Molecular analysis of Class II (B-L) antigens isolated with McAb showed a monomorphic a chain of 3234 kDa noncovalently bound to a polymorphic fl chain of approximately 2729 kDa (Ewert et al., 1984; Guillemot et al., 1986). Role in cellular interactions The Class I and Class II MHC molecules are the principal targets of alloreactive T cells responsible for rejection of histo-incompatible tissue grafts. Although this is important in human transplantation medicine, it has little relevance to poultry medicine. The more important function of the MHC antigens is that they serve as essential elements in cell-cell interactions of immunoregulation. The T cell-B cell interaction in the immune response of the chicken is MHC restricted (Vainio et al., 1987 ). That is, in order for effective antibody production to T-dependent antigens to take place, collaborating cells must be identical for at least one haplotype of Class II. Class II antigens also serve as restriction elements in antigen presentation by macrophages to T cells in the chicken. Recent studies have shown that MHC-restricted immunity may be important in cytotoxic T cell reactions to virus-infected or virus-transformed chicken cells (Maccubbin and Schierman, 1986; Weinstock and Schat, 1987). The MHC-restricted reactivity against reticuloendotheliosis virus (REV)-transformed chicken cells was shown to be directed against a virally induced antigen. Both in vitro and in vivo studies indicate that MHC restriction of cytotoxic T cells may also be important in immunity to Marek's disease virus (Schierman and Collins, 1987 ). I m m u n e response and genetic resistance to disease The major function of proteins encoded by the MHC is the regulation of immune response and disease resistance (Dorf, 1981 ). Examples of MHC control of immune response in chickens include the humoral response to simple chemically defined antigens and to complex native antigens (Benedict et al., 1975; Pevzner et al., 1978 ). There are numerous studies which confirm that genes in the chicken MHC influence resistance to disease, including autoimmune, viral, bacterial and parasitic disease (See reviews by Bacon ( 1987 ) and Lamont (1989 )). Certain MHC haplotypes have been associated with
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response to Marek's disease, Rous sarcomas, lymphoid leukosis, fowl cholera, coccidiosis and autoimmune thyroiditis. NON-MHC IMMUNOGENETICS
Selection experiments There are many examples of research in chickens that demonstrate that non-MHC, as well as MHC, genes influence disease resistance and immunoresponsiveness. Lines which have identical MHC types, but different background genes, may have different levels of response (Palladino et al., 1977; Erfet al., 1987; Steadham et al., 1987 ). The response to selection for antibody production to sheep red blood cells (SRBC) in chickens has been attributed to polygenic control (Siegel and Gross, 1980; van der Zijpp, 1983). Lines which differed for antibody production to SRBC also differed in response to disease challenge. Selection experiments have also been initiated which concentrate on factors other than antibodies to a single antigen. Studies focusing on early antibody production to multiple antigens and on selection for multiple traits of immune response are described in the following sections. Early immunocompetency selection Early development of immunocompetency is especially important to control disease in the vulnerable neonatal period and during the short time span of commercial broiler production. Selection of broilers for high early antibody production to E. coli and Newcastle disease virus vaccines has been successful (Pitcovski et al., 1987 a,b ). The selection also improved several other immune system parameters. The lines selected for high E. coli and NDV antibody response had a higher antibody response to SRBC (but not Brucella abortus), higher levels of IgG (but not total Ig), greater bursa weight, greater numbers of spleen plaque-forming cells to E. coli, higher delayed-type hypersensitivity response, higher T cell mitogenic response and more rapid clearance of bacteria from the circulatory system. Thus, the immune response kinetics can be shifted to an earlier age by using genetic selection. This may provide more protection to the young birds. Multi-trait selection In view of the delicate balance between the various components of the immune system that is necessary to ensure optimum immune function, a selection program based upon developing a balanced immune system might be recommended. Evaluating and selecting on several components of immune function might prevent immunosuppression caused by the over-emphasis of one facet of immunity at the expense of other essential functions. To apply this approach effectively, information is needed about genetic parameters of
IMMUNOGENETICS AND THE MAJOR HISTOCOMPATIBILITY COMPLEX
12 5
various i m m u n e system traits, such as heritabilities, genetic correlations between i m m u n e response traits and correlations with disease resistance and production traits. Several parameters were estimated in studies on selection for i m m u n e response in laying hens (Cheng and Lamont, 1988; Cheng, 1990). Heritabilities o f antibody response to different antigens ranged from 0.12 to 0.53. Heritability estimates o f cell-mediated i m m u n i t y and phagocytosis were lower, suggesting that greater environmental c o m p o n e n t s were present and selection progress will be slow. Correlations between traits were low, suggesting that selection for more than one facet o f i m m u n e response is possible and also desirable. Thus, to select for o p t i m u m immunity in a flock, an i m m u n o c o m petence profile that contains data on cell-mediated response, phagocytic activity, and perhaps M H C and lymphokines, as well as vaccine antibody response, should be considered. Monitoring a sample o f commercial birds for a broad i m m u n e trait profile could identify specific immunodeficiencies to be remedied at the breeder level. SUMMARY The complexity of the i m m u n e system of poultry - - involving several different cell types, m a n y soluble components, factors o f cell cooperation and rate o f d e v e l o p m e n t o f competency - - allows a multiplicity of levels at which genetic modulation o f i m m u n i t y can take place. The major histocompatibility complex genes have an important role in regulating i m m u n e function. Evaluation o f i m m u n e response traits can also be used in a program to improve i m m u n o c o m p e t e n c e in poultry.
REFERENCES Bacon, L.D., 1987. Influence of the MHC on disease resistance and productivity. Poult. Sci., 66:802-811. Benedict, A.A., Pollard, L.W., Morrow, P.R., Abplanalp, H.A., Maurer, P.H. and Briles, W.E., 1975. Genetic control of immune responses in chickens. I. Responses to a terpolymer ofpoly ( G l u 6° Ala 3° Tyr j°) associated with the major histocompatibility complex. Immunogenetics, 2:313-324. Briles, W.E., McGibbon, W.H. and Irwin, M.R., 1950. On multiple alleles affecting cellular antigens in the chicken. Genetics, 35: 633-652. Cheng, S., 1990. Genetic selection for immunocompetence in chickens. Ph.D. Dissertation. Iowa State University, Ames, IA, 137 pp. Cheng, S. and Lamont, S.J., 1988. Genetic analysis ofimmunocompetence measures in a White Leghorn chicken line. Poult. Sci., 67: 989-995. Crone, M., Simonsen, M., Skjodt, K., Linnet, K. and Olson, L., 1985. Mouse monoclonal antibodies to Class I and Class II antigens of the chicken MHC: evidence for at least two Class I products of the B complex. Immunogenetics, 21: 181-187.
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Doff, M.E. (Editor), 1981, The Role of the Major Histocompatibility Complex in Immunobiology. Garland Press, New York. Erf, G.W., Briles, W.E. and Marsh, J.A., 1987. Graft-versus-host response in sex-linked dwarf, autosomal dwarf and control K strain chickens. Dev. Comp. Immunol., 11: 769-779. Ewert, D.L., Munchus, M.S., Chen, C.-UH. and Cooper, M.D., 1984. Analysis of structural properties and cellular distribution of avian Ia antigen by using monoclonal antibody to monomorphic determinants. J. Immunol., 132: 2524-2530. Goto, R., Miyada, C.G., Young, S., Wallace, R.B., Abplanalp, H., Bloom, S.E., Briles, W.E. and Miller, M.M., 1988. Isolation of a cDNA clone from the B-G subregion of the chicken histocompatibitity (B) complex. Immunogenetics, 27:102-109. Guillemot, F.P., Oliver, P.D., Peault, B.M. and LeDouarin, N.M., 1984. Cells expressing Ia antigens in the avian thymus. J. Exp. Med., 160: 1803-1819. Guillemot, F., Turmel, P., Charron, D., LeDouarin, N. and Auffray, C., 1986. Structure, biosynthesis, and polymorphism of chicken MHC Class II (B-L) antigens and associated molecules. J. Immunol., 137:1251-1257. Guillemot, F., Billault, A., Pourquie, O., Behar, G., Chausse, A.-M., Zoorob, R., Kreibich, G. and Auffray, C., 1988. A molecular map of the chicken major histocompatibility complex: the class Ilfl genes are closely linked to the class I genes and the nucleolar organizer. EMBO J., 7: 2775-2785. Hfila, K., Wick, G., Boyd, R.L., Wolf, H., Bock, G. and Ewert, D.L., 1984. The B-L (Ia-like) antigens of the chicken. Lymphocyte plasma membrane distribution and tissue localization. Dev. Comp. Immunol., 8: 673-682. Lamont, S.J., 1989. The chicken major histocompatibility complex in disease resistance and poultry breeding. J. Dairy Sci., 72:1328-1333. Longenecker, B.M., Mosmann, T.R. and Shioyawa, C., 1979. A strong preferential response of mice to polymorphic antigenic determinants of the chicken MHC, analyzed with mouse hybridoma (monoclonal) antibodies. Immunogenetics, 9:137-147. Maccubbin, S.A. and Schierman, L.W., 1986. MHC-restricted cytotoxic response of chicken T cells; expression, augmentation, and clonal characterization. J. Immunol., 136:12-16. Miller, M.M., Goto, R and Clark, S.D., 1982. Structural characterization of developmentally expressed antigenic markers on chicken erythrocytes using monoclonal antibodies. Dev. Biol., 94: 400-414. Miller, M.M., Goto, R. and Abplanalp, H., 1984. Analysis of the B-G antigens of the chicken MHC by two-dimensional gel electrophoresis. Immunogenetics, 20: 373-385. Palladino, M.A., Gilmour, D.G., Scafuri, A.R., Stone, H.A. and Thorbecke, G.J., 1977. Immune response differences between two chicken lines identical at the major histocompatibility complex. Immunogenetics, 5: 523-529. Pevzner, I.Y., Trowbridge, C.L. and Nordskog, A.W., 1978. Recombination between genes coding for immune response and the serologically determined antigens in the chicken B system. Immunogenetics, 7: 25-33. Pink, J.R.L., Kieran. M.W., Rijnbeck, A.M. and Longenecker, B.M., 1985. A monoclonal antibody against chicken MHC class I (B-F) antigens. Immunogenetics, 21: 293-297. Pitcovski, J., Heller, E.D., Cahaner, A. and Peleg, B.A., 1987a. Selection for early responsiveness of chicks to Escherichia coli and Newcastle disease virus. Poult. Sci., 66: 1276-1282. Pitcovski, J., Heller, E.D., Cahaner, A., Peleg, B.A. and Drabkin, N., 1987b. Immunological traits of chicks selected for early and late immune response to E. coli and Newcastle disease virus. In: W.T. Weber and D.L. Ewert (Editors), Prog. Clin. Biol. Res., Avian Immunol., Alan R. Liss, New York, pp. 295-305. Salomonsen, J., Skjoedt, K., Crone M. and Simonsen, M., 1987. The chicken erythrocyte-specific MHC antigen. Characterization and purification of the B-G antigen by monoclonal antibodies. Immunogenetics, 25: 373-382.
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Schierman, L.W. and Collins, W.M., 1987. Influence of the major histocompatibility complex on tumor regression and immunity in chickens. Poult. Sci., 66:812-818. Schierman, L.W. and Nordskog, A.W., 1961. Relationship of blood type to histocompatibility in chickens. Science, 134: 1008-1009. Siegel. P.B. and Gross, W.B., 1980. Production and persistence of antibodies of experimental deep pectoral erythrocytes. 1. Directional selection. Poult. Sci., 59: 1-5. Snell, G.D., 1953. The genetics of transplantation. J. Natl. Cancer Inst., 14: 691-703. Steadham, E.M., Lamont, S.J., Kujdych, I. and Nordskog, A.W., 1987. Association of Marek's disease with Ea-B and immune response genes in subline and F2 populations of the Iowa State S1 Leghorn line. Poult. Sci., 66: 571-575. Vainio, O., Toivanen, P. and Toivanen, A., 1987. Major histocompatibility and cell cooperation. Poult. Sci., 66: 795-801. Van der Zijpp, A.J., 1983. The effect of genetic origin, source of antigen and dose of antigen on the immune response of cockerels. Poult. Sci., 62:205-211. Weinstock, D. and Schat, K.A., 1987. Virus specific syngeneic killing or reticuloendotheliosis virus transformed cell line target cells by spleen cells. In: W.T. Weber and D.L. Ewert (Editors), Avian Immunology II. Allan R. Liss, New York, NY, pp. 253-263. Xu, Y., Pitcovski, J., Peterson, L., Auffray, C., Bourlet, Y., Gerndt, B.M., Nordskog, A.W., Lamont, S.J. and Warner, C.M., 1989. Isolation and characterization of three class II major histocompatibility complex genomic clones from the chicken. J. Immunol., 142:2122-2132.
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Elsevier Science Publishers B.V., Amsterdam
Immunogenetics and the major histocompatibility complex* S.J. L a m o n t Department of Animal Science, Iowa State University, Ames, IA 50011, USA
ABSTRACT Lamont, S.J., 1991. Immunogenetics and the major histocompatibility complex. Vet. Immunol. Immunopathol., 30:121-127 The poultry immune system is a complex system involving many different cell types and soluble factors that must act in concert to give rise to an effective response to pathogenic challenge. The complexity of the immune system allows the opportunity for genetic regulation at many different levels. Cellular communication in the immune response, the production of soluble factors, and the rate of development of immune competency are all subject to genetic influences. The genes of the major histocompatibility complex (MHC) encode proteins which have a crucial role in the functioning of the immune system. The MHC antigens of chickens are cell surface glycoproteins of three different classes: Class I (B-F), Class II (B-L) and Class IV (B-G). The MHC antigens serve as essential elements in the regulation of cell-cell interactions. The MHC has been shown to influence immune response and resistance to autoimmune, viral, bacterial and parasitic disease in chickens. The MHC has been the primary set of genes identified with genetic control of immune response and disease resistance, but there are many lesser-characterized genes outside of the MHC that also regulate immunoresponsiveness. Polygenic control has been identified in selection experiments that have produced lines of chickens differing in antibody levels or kinetics of antibody production. These lines also differ in immunoresponsiveness and resistance to a variety of diseases. Understanding the genetic bases for differences in immunoresponsiveness allows the opportunity selectively to breed birds which are more resistant to disease. Indirect markers that can be used for this selection can include the MHC genes and immune response traits that have been associated with specific or general resistance to disease. ABBREVIATIONS McAb, monoclonal antibodies; MHC, major histocompatibility complex; REV, reticuloendotheliosis virus; SRBC, sheep red blood cells. *This article is Journal Paper No. J-14223 of the Iowa Agriculture and H o m e Economics Experiment Station, Ames, IA: Project No. 2237.
0165-2427/91/$03.50
© 1991 Elsevier Science Publishers B.V. All rights reserved.
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S.J. LAMONT
THE M A J O R H I S T O C O M P A T I B I L I T Y C O M P L E X IN C H I C K E N S
General organization The major histocompatibility complex ( M H C ) is a group of genes, first identified in the mouse, which was originally defined by its influence on tissue graft acceptance (Snell, 1953 ). The chicken was the second animal species in which the MHC was identified (Schierman and Nordskog, 1961 ). MHC genes and proteins have been divided into three classes in mammals: Class I, Class II and Class III. The Class III has not been identified in the chicken MHC, but the chicken possesses an additional unique class (Class IV) of MHC proteins expressed on erythrocytes and other cells. Because of its linkage with the B blood group (Briles et al., 1950) the chicken MHC has been designated as the B complex. Class I, II and IV genes of the chicken MHC are also designated as B-F, B-L and B-G, respectively. Gene structure Until the recent application of techniques of molecular genetics to the study of the chicken MHC, very little was known about the fine structure of the MHC genes. Now, Class I, II and IV genes of the chicken MHC have been cloned (Goto et al., 1988; Guillemot et al., 1988; Xu et al., 1989). The small size and close proximity of Class I and II genes on the chromosome may explain the very low frequency of recombinants between B-F and B-L. Uncharacterized genes identified within the MHC are hypothesized to be involved in disease resistance. Most important structural characteristics of the gene products, however, are conserved between the chicken and mammalian MHC. Antigen structure Class I, II and IV molecules are cell surface molecules. Class I (B-F) antigens are located on all cells. Class II (B-L) antigens are restricted to monocytes, macrophages, B cells and some T cells. Class I antigens consist of a single chain of three globular domains plus a noncovalently associated B2 microglobulin. Class II antigens consist of two dimorphic chains both with a transmembrane and cytoplasmic piece. Monoclonal antibodies (McAb) have been produced to antigens of each of the three subregions of the chicken MHC (B-G, Longenecker et al., 1979; Miller et al., 1982, 1984; B-F, Pink et al., 1985; B-L, Ewert et al., 1984; Guillemot et al., 1984; H~ila et al., 1984; Crone et al., 1985 ). These McAb have been extremely useful in isolating highly purified M H C antigens for biochemical characterization. The B-G antigens isolated from erythrocyte membranes by immunoprecipitation with McAb have seen shown to exist as polymers of a 47 kDa
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monomer (Salomonsen et al., 1987 ). Two-dimensional gel electrophoresis of B-G antigens revealed extensive polymorphism, hypothesized to be caused by multiple loci in the B-G region (Miller et al., 1984). McAb to Class I (BF) antigens precipitate a 40-45 kDa cell surface molecule along with a 12 kDafl2 microglobulin (Pink et al., 1985 ). Crone et al. ( 1985 ) used sequential immunoprecipitation by McAb of different specificities to demonstrate two distinct B-F products from B homozygous chickens, which indicated the existence of at least two Class I MHC gene products. Molecular analysis of Class II (B-L) antigens isolated with McAb showed a monomorphic a chain of 3234 kDa noncovalently bound to a polymorphic fl chain of approximately 2729 kDa (Ewert et al., 1984; Guillemot et al., 1986). Role in cellular interactions The Class I and Class II MHC molecules are the principal targets of alloreactive T cells responsible for rejection of histo-incompatible tissue grafts. Although this is important in human transplantation medicine, it has little relevance to poultry medicine. The more important function of the MHC antigens is that they serve as essential elements in cell-cell interactions of immunoregulation. The T cell-B cell interaction in the immune response of the chicken is MHC restricted (Vainio et al., 1987 ). That is, in order for effective antibody production to T-dependent antigens to take place, collaborating cells must be identical for at least one haplotype of Class II. Class II antigens also serve as restriction elements in antigen presentation by macrophages to T cells in the chicken. Recent studies have shown that MHC-restricted immunity may be important in cytotoxic T cell reactions to virus-infected or virus-transformed chicken cells (Maccubbin and Schierman, 1986; Weinstock and Schat, 1987). The MHC-restricted reactivity against reticuloendotheliosis virus (REV)-transformed chicken cells was shown to be directed against a virally induced antigen. Both in vitro and in vivo studies indicate that MHC restriction of cytotoxic T cells may also be important in immunity to Marek's disease virus (Schierman and Collins, 1987 ). I m m u n e response and genetic resistance to disease The major function of proteins encoded by the MHC is the regulation of immune response and disease resistance (Dorf, 1981 ). Examples of MHC control of immune response in chickens include the humoral response to simple chemically defined antigens and to complex native antigens (Benedict et al., 1975; Pevzner et al., 1978 ). There are numerous studies which confirm that genes in the chicken MHC influence resistance to disease, including autoimmune, viral, bacterial and parasitic disease (See reviews by Bacon ( 1987 ) and Lamont (1989 )). Certain MHC haplotypes have been associated with
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response to Marek's disease, Rous sarcomas, lymphoid leukosis, fowl cholera, coccidiosis and autoimmune thyroiditis. NON-MHC IMMUNOGENETICS
Selection experiments There are many examples of research in chickens that demonstrate that non-MHC, as well as MHC, genes influence disease resistance and immunoresponsiveness. Lines which have identical MHC types, but different background genes, may have different levels of response (Palladino et al., 1977; Erfet al., 1987; Steadham et al., 1987 ). The response to selection for antibody production to sheep red blood cells (SRBC) in chickens has been attributed to polygenic control (Siegel and Gross, 1980; van der Zijpp, 1983). Lines which differed for antibody production to SRBC also differed in response to disease challenge. Selection experiments have also been initiated which concentrate on factors other than antibodies to a single antigen. Studies focusing on early antibody production to multiple antigens and on selection for multiple traits of immune response are described in the following sections. Early immunocompetency selection Early development of immunocompetency is especially important to control disease in the vulnerable neonatal period and during the short time span of commercial broiler production. Selection of broilers for high early antibody production to E. coli and Newcastle disease virus vaccines has been successful (Pitcovski et al., 1987 a,b ). The selection also improved several other immune system parameters. The lines selected for high E. coli and NDV antibody response had a higher antibody response to SRBC (but not Brucella abortus), higher levels of IgG (but not total Ig), greater bursa weight, greater numbers of spleen plaque-forming cells to E. coli, higher delayed-type hypersensitivity response, higher T cell mitogenic response and more rapid clearance of bacteria from the circulatory system. Thus, the immune response kinetics can be shifted to an earlier age by using genetic selection. This may provide more protection to the young birds. Multi-trait selection In view of the delicate balance between the various components of the immune system that is necessary to ensure optimum immune function, a selection program based upon developing a balanced immune system might be recommended. Evaluating and selecting on several components of immune function might prevent immunosuppression caused by the over-emphasis of one facet of immunity at the expense of other essential functions. To apply this approach effectively, information is needed about genetic parameters of
IMMUNOGENETICS AND THE MAJOR HISTOCOMPATIBILITY COMPLEX
12 5
various i m m u n e system traits, such as heritabilities, genetic correlations between i m m u n e response traits and correlations with disease resistance and production traits. Several parameters were estimated in studies on selection for i m m u n e response in laying hens (Cheng and Lamont, 1988; Cheng, 1990). Heritabilities o f antibody response to different antigens ranged from 0.12 to 0.53. Heritability estimates o f cell-mediated i m m u n i t y and phagocytosis were lower, suggesting that greater environmental c o m p o n e n t s were present and selection progress will be slow. Correlations between traits were low, suggesting that selection for more than one facet o f i m m u n e response is possible and also desirable. Thus, to select for o p t i m u m immunity in a flock, an i m m u n o c o m petence profile that contains data on cell-mediated response, phagocytic activity, and perhaps M H C and lymphokines, as well as vaccine antibody response, should be considered. Monitoring a sample o f commercial birds for a broad i m m u n e trait profile could identify specific immunodeficiencies to be remedied at the breeder level. SUMMARY The complexity of the i m m u n e system of poultry - - involving several different cell types, m a n y soluble components, factors o f cell cooperation and rate o f d e v e l o p m e n t o f competency - - allows a multiplicity of levels at which genetic modulation o f i m m u n i t y can take place. The major histocompatibility complex genes have an important role in regulating i m m u n e function. Evaluation o f i m m u n e response traits can also be used in a program to improve i m m u n o c o m p e t e n c e in poultry.
REFERENCES Bacon, L.D., 1987. Influence of the MHC on disease resistance and productivity. Poult. Sci., 66:802-811. Benedict, A.A., Pollard, L.W., Morrow, P.R., Abplanalp, H.A., Maurer, P.H. and Briles, W.E., 1975. Genetic control of immune responses in chickens. I. Responses to a terpolymer ofpoly ( G l u 6° Ala 3° Tyr j°) associated with the major histocompatibility complex. Immunogenetics, 2:313-324. Briles, W.E., McGibbon, W.H. and Irwin, M.R., 1950. On multiple alleles affecting cellular antigens in the chicken. Genetics, 35: 633-652. Cheng, S., 1990. Genetic selection for immunocompetence in chickens. Ph.D. Dissertation. Iowa State University, Ames, IA, 137 pp. Cheng, S. and Lamont, S.J., 1988. Genetic analysis ofimmunocompetence measures in a White Leghorn chicken line. Poult. Sci., 67: 989-995. Crone, M., Simonsen, M., Skjodt, K., Linnet, K. and Olson, L., 1985. Mouse monoclonal antibodies to Class I and Class II antigens of the chicken MHC: evidence for at least two Class I products of the B complex. Immunogenetics, 21: 181-187.
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