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Both tumour and trophoblast produce an immunosuppressive protein which is believed to be a prostaglandin (PG) antagonist. Substances which digest this protein (protease) or enhance the synthesis of PG (levamisole) can reverse the immunodepression in cancer patients. The relevance of these observations to cancer immunotherapy is discussed.

In a study of 95 practically healthy humans and in experiments on 148 animals (dogs, rabbits, rats), an attempt was made at assessing seasonal effects on immunological reactivity. The content of IgM antibody-forming cells was determined as well as the activity of blood and lymphoid NK and K cells and number of E rosette-forming peripheral blood lymphocytes. The most pronounced changes were observed in the specific immune response (IgM antibodies and K cells), which was enhanced during autumn and winter. Seasonal fluctuations in E rosette-forming cells and IgE antibodies were less extensive. The activity of NK cells was found to be relatively stable.

The synthesis of gammaG, gammaA, gammaM, beta(1C)/beta(1A), C'1 esterase inhibitor, ceruloplasmin, transferrin, hemopexin, haptoglobin, fibrinogen, alpha(1)-antitrypsin, orosomucoid, beta-lipoprotein, alpha(2)-macroglobulin, and prealbumin was studied in 15 normal human embryos and fetuses of 29 days to 18 wk gestation and in the yolk sacs of four embryos from 5.5 to 11.5 wk gestation using tissue culture in (14)C-labeled amino acids followed by radioimmunoelectrophoresis. The human embryo as early as 29 day gestation synthesized beta(1C)/beta(1A), C'1 esterase inhibitor, transferrin, hemopexin, alpha(1)-antitrypsin, beta-lipoprotein, alpha(2)-macroglobulin, and prealbumin in culture. At 32 days gestation ceruloplasmin and orosomucoid were also synthesized, but synthesis of fibrinogen was not observed before 5.5 wk. Synthesis of gammaM occurred as early as 10.5 wk gestation, and gammaG synthesis was found in cultures as early as 12 wk gestation; gammaA synthesis was not detected in any of the tissue cultures. With the exception of the gamma-globulins, each of the proteins studied was synthesized by the liver, but additional sites of synthesis for some of these proteins were also found. Synthesis of gammaG and gammaM occurred primarily in the spleen, but other sites of synthesis were noted as well. Changes in the concentrations of most of these proteins and plasminogen in embryonic and fetal serum from 5.5 to 41 wk gestation, in amniotic fluid from 6.5 to 38 wk gestation, and in the sera of neonates during the 1st 3 wk postpartum are described. Although gammaA, gammaM, ceruloplasmin, or haptoglobin were not detectable in some of the embryonic and fetal sera, gammaA and ceruloplasmin were both present as early as 6.5 wk gestation, haptoglobin by 9.5 wk gestation, and gammaM by 17 wk gestation. Each of the other proteins were present in all of the sera examined.

Clonal cell strains have been isolated from normal human liver. These cells, while resembling fibroblasts morphologically, function as hepatocytes, as shown by their ability to synthesize and secrete an antigen identical to human serum albumin. Human diploid and aneuploid cell lines from nonliver sources do not exhibit this property. The spectrum of serum proteins synthesized varied from clone to clone and cell line to cell line.

A technique for the in vitro culture of rheumatoid synovial tissue with (14)C-amino acids and isolation and quantitation of the newly synthesized immunoglobulins has been developed. This technique has been used to compare immunoglobulin synthesis of 12 rheumatoid synovia with that of synovia from nonarthritic patients and with that of normal human lymph nodes and spleen. In addition, the spleen of a patient with Felty's syndrome has also been examined. Immunoglobulin synthesis in rheumatoid synovia has been shown to be quantitatively and qualitatively similar to that of normal human spleen and lymph nodes although somewhat less active than the Felty's syndrome spleen examined. 79% of the immunoglobulin produced in rheumatoid synovia was of the IgG type, whereas IgM comprised 10% and IgA, 11% of the total. Less than 10% of the IgM synthesized was found to be rheumatoid factor. A fraction containing approximately 90% of its radioactivity in the form of IgG has been obtained for further studies.