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Pregnancy immunology

Published online by Cambridge University Press:  10 October 2008

Peter M Johnson*
Affiliation:
University of Liverpool, UK
Gordon H Ramsden
Affiliation:
Royal Liverpool University Hospital, UK
*
Peter M Johnson, Professor of Immunology, Department of Immunology, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK.

Extract

Immunology is a fast developing and intriguing biomedical science, which can give rise to specific considerations about the physiological process of both successful and unsuccessful vivparous pregnancy. It is normal in clinical organ transplantation for unmatched foreign tissues (allografts) to provoke immunological rejection by the host, unless there has been prior tissue matching (histocompatibility antigen tissue typing) or immunosuppressive therapy. Thus, it is still not fully clear how, after ‘random’ mating, haplo-nonidentical fetal tissue is able to survive in the potentially hostile immunocompetent maternal environment. The majority of pregnancies survive uninterrupted and there has now been much speculation and research regarding the immunological success of pregnancy (i.e. nature’s transplant). Medawar orginally offered four nonexclusive hypotheses to explain the enigmatic immunological survival of normal pregnancy:

1) the conceptus is not immunogenic and therefore does not evoke an immunological response;

2) pregnancy alters the maternal immune response;

3) the uterus is an immunologically privileged site;

4) the placenta is an immunological barrier between the mother and the as yet immunologically incompetent fetus.

Before discussing these, as well as some of the clinical immunological problems that may arise during pregnancy, it is necessary to outline some of the basic components of the normal immune system. This will lead to a description of current understanding of immunological events at the fetomaternal interface as well as the maternal immune response in human pregnancy.

Type
Articles
Copyright
Copyright © Cambridge University Press 1992

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References

1Medawar, PB. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp Soc Exp Biol 1953; 7: 320–38.Google Scholar
2Risk, JM, Johnson, PM. Genetic studies of the MHC region in human recurrent spontaneous abortion. In: Wegmann, TG, Gill, TJ, Nesbit-Brown, E eds. Molecular and cellular nature of maternal-fetal signalling. New York: Oxford University Press, 1991: 3957.Google Scholar
3Billington, WD. Maternal-fetal interactions in normal pregnancy. Baillieres Clin Immunol Allergy 1988; 2: 527–49.Google Scholar
4Johnson, PM. Immunology of pregnancy. In: Turnbull, AC, Chamberlain, GVP eds. Obstetrics. Edinburgh: Churchill Livingstone, 1989: 173–88.Google Scholar
5Bulmer, JN, Johnson, PM. Antigen expression by trophoblast populations in the human placenta and their immunobiological relevance. Placenta 1985; 6: 127–40.Google Scholar
6Johnson, PM, Ramsden, GH. Recurrent miscarriage. Baillieres Clin Immunol Allergy 1988; 2: 607–24.Google Scholar
7Risk, JM, Johnson, PM. Northern blot analysis of HLA-G expression by Be Wo human choriocarcinoma cells. J Reprod Immunol 1990; 18: 199203.Google Scholar
8Ellis, SA, Palmer, MS, McMichael, AJ. Human trophoblast and the choriocarcinoma cell line Be Wo express a truncated HLA class I molecule. J Immunol 1990; 144: 731–35.Google Scholar
9Kovats, S, Main, EK, Librach, C, Stubblebine, M, Fisher, SJ, DeMars, R. A class I antigen, HLA-G, expressed in human trophoblasts. Science 1990; 248: 220–23.Google Scholar
10Faulk, WP, Jeannet, M, Creighton, WD, Carbonara, A, Hay, F. Studies of the human placenta. II: Characterization of immunoglobulins on the trophoblastic basement membrane. J Reprod Fertil [Suppl] 1974; 21: 4357.Google Scholar
11Webb, PD, McLaughlin, PJ, Risk, JM, Johnson, PM. Indication of placental-type alkaline phosphatase associated with human syncytiotrophoblast membranes using monoclonal antibodies. Placenta 1986; 7: 405–15.Google Scholar
12Faulk, WP, McIntyre, JA. Immunological studies of human trophoblast: markers, subsets and function. Immunol Rev 1983; 75: 139–75.Google Scholar
13McIntyre, JA, Faulk, WP, Verhulst, SJ, Colliver, JA. Human trophoblast-lymphocyte cross-reactive (TLX) antigens defines a new alloantigen system. Science 1983; 222: 1135–37.CrossRefGoogle ScholarPubMed
14Johnson, PM. Immunobiology of trophoblast antigens in normal pregnancy and unexplained recurrent spontaneous abortion. In: Andreani, D, Bompiana, GD, Mario, DI, Faulk, WP, Galluzzo, A eds. Immunobiology of normal and diabetic pregnancy. Chichester: John Wiley, 1990: 187–95.Google Scholar
15Purcell, SFJ, McKenzie, IFC, Lublin, DM et al. The human cell surface glycoproteins HuLy-m5, membrane cofactor protein (MCP) of the complement system, and trophoblast-leucocyte common (TLX) antigen, are CD46. Immunology 1990; 70: 155–61.Google Scholar
16Lublin, DM, Liszewski, MK, Post, TW et al. Molecular cloning and chromosomal localization of human membrane cofactor protein (MCP). Evidence for inclusion in the multigene family of complement regulatory proteins. J Exp Med 1988; 168: 181–94.Google Scholar
17van Rood, JJ, van Leeuwen, A, Eerniese, JG. Leucocyte antibodies in sera from pregnant women. Nature 1985; 181: 1735–36.CrossRefGoogle Scholar
18Mowbray, JF, Gibbings, CR, Liddell, H, Reginald, PW, Underwood, JL, Beard, RW. Controlled trial of treatment of recurrent spontaneous abortion with paternal cells. Lancet 1985; i: 941–43.Google Scholar
19Johnson, PM, Chia, KV, Hart, CA, Griffith, HB, Francis, WJA. Trophoblast membrane infusion for unexplained recurrent miscarriage. Br J Obstet Gynaecol 1988; 95: 342–47.Google Scholar
20Beer, AE. New horizons in the diagnosis evaluation and therapy of recurrent spontaneous abortion. Clin Obstet Gynecol 1986; 13: 115–24.Google Scholar
21Lauritsen, JG, Kristensen, T, Grunnet, N. Depressed mixed lymphocyte culture reaction in mothers with recurrent spontaneous abortion. Am J Obstet Gynecol 1976; 125: 3539.CrossRefGoogle ScholarPubMed
22Power, DA, Catto, GRD, Mason, RJ, MacLeod, AM, Stewart, GM, Shewman, WG. The fetus as an allograft: evidence for protective antibodies to HLA-linked paternal antigens. Lancet 1983; ii: 701704.Google Scholar
23Stewart, GM, Mason, RJ, Thomason, MAR, MacLeod, AM, Catto, GRD. Non-cytotoxic antibodies to paternal antigens in paternal sera and placental eluates. Transplantation 1984; 38: 111.CrossRefGoogle Scholar
24Hole, N, Cheng, HM, Johnson, PM. Antibody reactivity against human trophoblast membrane in the context of normal pregnancy and unexplained recurrent miscarriage? INSERM Colloque 1987; 154: 213–23.Google Scholar
25Chia, KV, Johnson, PM. T-lymphocyte subsets in unexplained recurrent spontaneous abortion. Fertil Steril 1987; 48: 685–87.CrossRefGoogle ScholarPubMed
26Bulmer, JM. Immunopathology of pregnancy. Baillieres Clin Immunol Allergy 1988; 2: 697734.Google Scholar
27Clark, DA. Cytokines and pregnancy. Curr Opinions Immunol 1989; 1: 1148–52.CrossRefGoogle ScholarPubMed
28Daya, S, Clark, DA, Devlin, C, Jarrell, J, Chaput, A. Suppressor cells in human decidua. Am J Obstet Gynecol 1985; 151: 267–70.CrossRefGoogle ScholarPubMed
29Bulmer, JN, Johnson, PM. Macrophage populations in the human placenta and amniochorion. Clin Exp Immunol 1984; 57: 393403.Google ScholarPubMed
30Urbaniak, SJ. Rh(D) haemolytic disease of the newborn: the changing scene. Br Med J 1983; 291: 46.CrossRefGoogle Scholar
31Tovey, LAD. Haemolytic disease of the newborn – the changing scene. Br J Obstet Gynaecol 1986; 93: 960–66.CrossRefGoogle ScholarPubMed
32Laurell, AB, Nilsson, IM. Hypergamma-globulinaemia, circulating anticoagulant and biologic false positive Wasserman reaction. J Lab Clin Med 1957; 49: 694707.Google Scholar
33Lubbe, WF, Liggins, GC. Lupus anticoagulant and pregnancy. Am J Obstet Gynecol 1985; 153: 322–27.Google Scholar
34Scott, JR, Rote, NS, Branch, DW. Immunological aspects of recurrent abortion and fetal death. Obstet Gynecol 1987; 70: 645–56.Google ScholarPubMed
35Taylor, PV. Autoimmunity and pregnancy. Bailliere’s Clin Immunol Allergy 1988; 2: 665–96.Google Scholar
36Triplett, DA. Antiphospholipid antibodies and recurrent pregnancy loss. Am J Reprod Immunol 1989; 20: 5267.Google Scholar
37 Anonymous. Anticardiolipin antibodies: a risk factor for venous and arterial thrombosis [Editorial]. Lancet 1985; i: 912–13.Google Scholar
38Cosgriff, TM, Martin, BA. Low functional and high antigenic antithrombin III level in a patient with lupus anticoagulant and recurrent thrombosis. Arthritis Rheum 1981; 24: 9496.CrossRefGoogle Scholar
39Sanfellippo, MF, Drayna, CJ. Prekallikrein inhibition associated with lupus anticoagulant: mechanism of thrombosis. Am J Clin Pathol 1980; 136: 495–99.Google Scholar
40Carreras, LO, Vermylen, J, Spitz, B, van Assche, A. ‘Lupus’ anticoagulant and inhibition of prostacyclin formation in patients with repeated abortion, intrauterine growth retardation and intrauterine death. Br J Obstet Gynaecol 1981; 88: 890–94.CrossRefGoogle ScholarPubMed
41Wasserman, A, Neisser, A, Brock, C. Eine serodiagnostische Reaktion bei Syphylis. Dtsch Med Wochenschr 1906; 32: 745–46.Google Scholar
42Pangborn, MC. A new serologically active phospholipid from beef heart. Proc Soc Exp Biol Med 1941; 48: 484–86.Google Scholar
43Branch, WD. Immunologic disease and fetal death. Clin Obstet Gynecol 1987; 30: 295311.Google Scholar
44Harris, EN, Gharavi, AE, Boey, ML et al. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; ii: 1211–14.CrossRefGoogle Scholar
45Harris, EN, Loizou, S, Englert, H et al. Anticardiolipin antibodies and lupus anticoagulant. Lancet 1984; ii: 1099.Google Scholar
46Cowchock, S, Smith, J, Gocial, B. Antibodies to phospholipids and nuclear antigens in patients with repeated abortions. Am J Obstet Gynecol 1986; 155: 1002–10.CrossRefGoogle ScholarPubMed
47Unander, A, Norberg, R, Hahn, L, Afors, L. Anticardiolipin antibodies and complement in ninety-nine women with habitual abortion. Am J Obstet Gynecol 1987; 156: 114–19.Google Scholar
48Ramsden, GH, Johnson, PM. Unexplained recurrent miscarriage and the role of immunotherapy. Contemp Rev Obstet Gynaecol 1992; 4: 2935.Google Scholar
49Petri, M, Rheinschmidt, M, Whiting-O’Keefe, Q et al. The frequency of lupus anticoagulant in systemic lupus erythematosus. Ann Intern Med 1987; 106: 524–31.CrossRefGoogle ScholarPubMed
50Lockwood, CJ, Romero, R, Feinberg, RF, Clyne, LP, Coster, B, Hobbins, JC. The prevalence and biological significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. Am J Obstet Gynecol 1988; 161: 369–73.CrossRefGoogle Scholar
51Kajino, T. Polyclonal activation of IgM antibodies to phospholipids in patients with idiopathic fetal growth retardation. Am J Reprod Immunol 1991; 25: 2834.Google Scholar
52Reece, EA, Gabrielli, S, Cullen, MT, Zheng, XZ, Hobbins, JC, Harris, EN. Recurrent adverse pregnancy outcome and antiphospholipid antibodies to HLA-linked paternal antigens. Lancet 1990; 163: 162–69.Google Scholar
53Patton, PE, Coulam, CB, Bergstralth, E. The prevalence of autoantibodies in pregnant and nonpregnant women. Am J Obstet Gynecol 1987; 157: 1345–50.Google Scholar
54Cowchock, S, DeHoratius, RD, Wagner, FJ, Jackson, LG. Subclinical autoimmune disease and unexplained abortion. Am J Obstet Gynecol 1984; 150: 367–71.Google Scholar
55Harger, JH, Archer, DF, Marchese, SG, Muracca-Clemens, M, Garver, KL. Etiology of recurrent pregnancy losses and outcome of subsequent pregnancies. Obstet Gynecol 1983; 62: 574–81.Google Scholar
56Johnson, PM, Chia, KV, Risk, JM, Barnes, RMR, Woodrow, JC. Immunological and immunogenetic investigation of recurrent spontaneous abortion. Dis Markers 1988; 6: 163–71.Google Scholar
57Burrows, RF, Kelton, JG. Incidentally detected thrombocytopenia in healthy mothers and their infants. N Engl J Med 1988; 319: 142–45.Google Scholar
58Cines, DB, Dusak, B, Tomaski, A, Mennuti, M, Schreiber, AD. Immune thrombocytopenic purpura and pregnancy. N Engl J Med 1982; 306: 826–31.Google Scholar
59Lau, RJ. The current status of antiplatelet antibodies. Am J Reprod Immunol Microbiol 1987; 15: 7177.Google Scholar
60Hedge, UM. Immune thrombocytopenia in pregnancy and the newborn. Br J Obstet Gynaecol 1985; 92: 657–59.Google Scholar
61Kelton, JC. The prenatal prediction of thrombocytopenia in mothers with clinically diagnosed immune thrombocytopenia. Am J Obstet Gynecol 1982; 144: 449–54.Google Scholar
62Scott, JR, Cruikshank, DP, Kochehour, NK et al. Fetal platelet count in the obstetric management of immunologic thrombocytopenic purpura. Am J Obstet Gynecol 1980; 136: 495–99.CrossRefGoogle ScholarPubMed
63Letsky, EA. Coagulation defects in pregnancy. In: Turnbull, AC, Chamberlain, GVP eds. Obstetrics. Edinburgh: Churchill Livingstone, 1989; 557–84.Google Scholar
64Lavery, JP, Koontz, WL, Liu, YK, Howell, R. Immunologic thrombocytopenia in pregnancy; use of antenatal immunoglobulin therapy: case report and review. Blut 1985; 66 (suppl 3): 41S43S.Google Scholar
65Harlap, S, Shiono, PH, Ramcharan, S. A life table of spontaneous abortions and the effects of age, party and other variables. In: Porter, H, Hook, EB eds. Embryonic and fetal death. New York: Academic Press, 1980: 145–58.Google Scholar
66Miller, JF, Williamson, E, Glue, J, Gordon, YB, Grudzinskas, JG, Sykes, A. Fetal loss after implantation: a prospective study. Lancet 1980; ii: 554–56.Google Scholar
67Poland, BJ, Miller, JR, Harris, M, Livingstone, J. Spontaneous abortion. A study of 1961 women and their conceptuses. Acta Obstet Gynecol Scand [Suppl] 1981; 102: 132.Google Scholar
68Edmonds, KD. Lindsay, KS, Miller, JF, Williamson, E, Wood, PJ. Early embryonic mortality in women. Fertil Steril 1982; 38: 447–53.Google Scholar
69Regan, L. A prospective study of spontaneous abortion. In: Sharp, F, Beard, RW eds. Early pregnancy loss: mechanisms and treatment. London: Royal College of Obstetricians and Gynaecologists, 1988; 2327.CrossRefGoogle Scholar
70Wilcox, AJ, Weinberg, CR, O’Connor, JF et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189–94.Google Scholar
71Alberman, E. The epidemiology of repeated abortion. In: Sharp, F, Beard, RW eds. Early pregnancy loss: mechanisms and treatment. London: Royal College of Obstetricians and Gynaecologists, 1988; 917.Google Scholar
72Tho, PT, Byrd, JR, McDonough, PG. Etiologies and subsequent reproductive performance of 100 couples with recurrent abortion. Fertil Steril 1979; 32: 389–95.Google Scholar
73Stray-Pedersen, B, Stray-Pedersen, S. Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol 1984; 148: 140–46.Google Scholar
74Jones, GS. The luteal phase defect. Fertil Steril 1976; 27: 351–56.Google Scholar
75Tulppala, M, Viinikka, L, Ylikorkala, O. Thromboxane dominance and prostacyclin deficiency in habitual abortion. Lancet 1991; 337: 879– 81.CrossRefGoogle ScholarPubMed
76Johnson, PM, Davies, JM, Rand, J, Murphy, S, Cowchock, FS. Thrombocythaemia and recurrent miscarriage. Br J Obstet Gynaecol 1989; 96: 1231–32.Google Scholar
77Fox, H. Pathology of the placenta. London: WB Saunders, 1978; 1237.Google Scholar
78McIntyre, JA, Faulk, WP, Nichol-Johnson, VR, Taylor, CG. Immunologic testing and immunotherapy in recurrent spontaneous abortion. Obstet Gynecol 1986; 67: 169–75.Google Scholar
79Mowbray, JF. Immunization with paternal cells in the treatment of recurrent abortion. Fetal Med 1989; 1: 2646.Google Scholar
80Hill, JA. Immunological mechanisms of pregnancy maintenance and failure: a critique of theories and therapy. Am J Reprod Immunol 1990; 22: 3342.Google Scholar
81Unander, AM, Olding, LB. Habitual abortion: parental sharing of HLA antigens, absence of maternal blocking antibody and suppression of maternal lymphocytes. Am J Reprod Immunol 1983; 4: 171–78.Google Scholar
82Beer, AE, Semprini, AE, Xiaoyn, Z, Quebbeman, JF. Pregnancy outcome in human couples with recurrent spontaneous abortion: HLA antigen profiles, HLA antigen sharing, female serum MLR blocking factors and paternal leukocyte immunization. Exp Clin Immunogenet 1985; 2: 137–53.Google Scholar
83Coulam, CD, Moore, SB, O’Fallon, WM. Association between major histocompatibility antigen and reproductive performance. Am J Reprod Immunol Microbiol 1987; 14: 5458.Google Scholar
84Ober, C, Simpson, JL, Ward, M et al. Prenatal effects of maternal-fetal HLA compatibility. Am J Repord Immunol Microbiol 1987; 15: 141–49.Google Scholar
85Okensberg, JR, Persitz, E, Amar, A, Brautbar, C. Maternal-paternal histocompatibility: lack of association with habitual abortion. Fertil Steril 1984; 42: 389–95.Google Scholar
86Cauchi, MN, Koh, SH, Tait, B, Mraz, G, Kloss, M, Pepperell, RJ. Immunogenetic studies in habitual abortion. Aust N J Obstet Gynaecol 1987; 27: 5254.Google Scholar
87Reznikoff-Etievant, MF, Durieux, I, Huchet, J, Salmon, C, Netter, A. Human MHC antigens and paternal leucocyte injections in recurrent spontaneous abortions. In: Sharp, F, Beard, RW eds. Early pregnancy loss: mechanisms and treatment. London: Royal College of Obstetricians and Gynaecologists, 1988: 375–84.Google Scholar
88Jazwinska, EC, Kilpatrick, DC, Smart, GE, Liston, WA. Feto-maternal HLA compatibility does not have a major influence on human pregnancy except for lymphocytotoxin production. Clin Exp Immunol 1987; 68: 116–22.Google Scholar
89Beer, AE. Pregnancy outcome in couples with recurrent abortion following immunological evaluation and therapy. In: Beard, RW, Sharp, F eds. Early pregnancy loss: mechanisms and treatment. London: Royal College of Obstetricians and Gynaecologists, 1988: 337–49.Google Scholar
90Taylor, CG, Faulk, WP. Prevention of recurrent abortion with leucocyte transfusions. Lancet 1981; 1: 6870.CrossRefGoogle Scholar
91Carp, HJA, Toder, V, Gazit, E et al. Immunization by paternal leukocytes for prevention of primary habitual abortion: results of a matched controlled trial. Gynecol Obstet Invest 1990; 29: 1621.CrossRefGoogle ScholarPubMed
92Ho, HN, Gill, TJ, Hsieh, HJ, Jiang, JJ, Lee, TY, Hsieh, CY. Immunotherapy for recurrent spontaneous abortions in a Chinese population. Am J Reprod Immunol 1991; 25: 1015.Google Scholar
93Cauchi, MN, Lim, D, Young, DE, Kloss, M, Pepperell, RJ. The treatment of recurrent aborters by immunization with paternal cells-controlled trial. Am J Reprod Immunol 1991; 25: 1617.Google Scholar
94Johnson, PM, Ramsden, GH, Chia, KV, Hart, CA, Farquharson, RG, Francis, WJA. A combined randomised double-blind and open study of trophoblast membrane infusion (TMI) in unexplained recurrent miscarriage. INSERM Colloque 1991; 212: 272–84.Google Scholar
95Wallenberg, HCS, Dekker, GA, Makovitz, JW, Rotmans, P. Low dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae. Lancet 1986; 1: 13.Google Scholar
96Benigni, A, Gregorini, G, Frusca, T et al. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med 1989; 321: 357–62.Google Scholar
97Massorbio, M, Benedetto, C, Bertini, E, Tetta, C, Camussi, G. Immune complexes in pre-eclampsia and normal pregnancy. Am J Obstet Gynecol 1985; 152: 578–83.Google Scholar
98Hofmeyr, GJ, Wilkins, T, Redman, CWG. C4 and plasma protein in hypertension during pregnancy with and without proteinuria. Br Med J 1991; 302: 218.CrossRefGoogle ScholarPubMed
99Rosic, B, Sulovic, V, Juznik, N, Lazarevic, B, Vidanovic, M. The significance of complement and immunoglobulin determination in healthy pregnant women and patients with EPH gestosis. Clin Exp Obstet Gynecol 1988; 15: 157–60.Google Scholar
100Brosens, I, Robertson, WB, Dixon, HG. The role of the spiral arteries in the pathogenesis of preeclampsia. Obstet Gynecol Ann 1973; 1: 177–91.Google Scholar
101Robertson, WB, Khong, TY, Brosens, I et al. The placental bed biopsy: review from three European centers. Am J Obstet Gynecol 1986; 155: 401–12.CrossRefGoogle ScholarPubMed
102Khong, TY, Pearce, JM, Robertson, WB. Acute atherosis in pre-eclampsoa: maternal determinants and fetal outcome in the presence of the lesion. Am J Obstet Gynecol 1987; 157: 360–66.Google Scholar
103Sargent, IL, Redman, CWG, Stirrat, GM. Maternal cell mediated immunity in normal and pre-eclamptic pregnancy. Clin Exp Immunol 1982; 50: 601609.Google Scholar
104Alanen, A, Lassila, O. Cell-mediated immunity in normal pregnancy and pre-eclampsia. J Reprod Immunol 1982; 4: 349–54.CrossRefGoogle ScholarPubMed
105Chesley, LC, Cooper, DW. Genetics of hypertension in pregnancy: possible single gene control of pre-eclampsia and eclampsia in the descendants of eclamptic women. Br J Obstet Gynaecol 1986; 93: 898908.Google Scholar