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Epstein–Barr virus and the nervous system
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Alexandros C. Tselis, Kumar Rajamani, Pratik Bhattacharya
Acute EBV infection is usually confirmed by the detection of heterophile antibodies. During the acute disease, agglutinating antibodies reactive against sheep erythrocytes are detectable. The precise nature of the antigen on sheep cells is unknown. Normal serum can contain small amounts of nonspecific sheep cell agglutinins, and these nonspecific antibodies (Forssman antibodies) must be absorbed out of the serum, leaving the EBV-specific heterophile antibodies behind. Accordingly, serum to be tested for heterophile antibodies is first incubated with guinea pig kidney, which contains the Forssman antigen (which has been identified as lipopolysaccharide–protein complexes present on cell surfaces of many different tissues, particularly in guinea pig kidney cells and horse red cells). If the resultant serum can still agglutinate sheep cells, then the serum contains EBV-specific heterophile antibodies, and acute EBV infection is confirmed. Heterophile antibodies are present only in the acute infection and fall to undetectable levels over a few weeks. The phenomenon of heterophile antibody production in infectious mononucleosis is the basis of the monospot test, which is performed on commercially available prepared slides.
Antibodies to Lipids and Lipid Membranes: Reactions with Phosphatidylcholine, Cholesterol, Liposomes and Bromelin-Treated Erythrocytes
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
Although Landsteiner performed many important experiments with antibodies to lipid antigens, particularly Forssman antigen (ceramide pentahexoside), a careful reading of his work makes it quite clear that he actually doubted, or was ambivalent to the concept, that any lipids or polysaccharides could be independent antigens. Despite abundant contemporary (1925 to 1936) evidence to the contrary (vide infraJ, he also apparently remained skeptical even to the concept that bona fide antibodies to phospholipids or cholesterol existed when lecithin and cholesterol were treated as if they were haptens.20
Therapeutic Circumvention of the Biologic Heterogeneity in Malignant Neoplasms by Tumoricidal Macrophages
Published in Gloria H. Heppner, Amy M. Fulton, Macrophages and Cancer, 2019
William E. Fogler, Isaiah J. Fidler
In conjunction with tumor cell specificity in macrophage-mediated cytolysis, the requirement for cell-to-cell contact implies a common neoplastic “recognition structure” responsible for their interaction with and subsequent destruction by activated mononuclear phagocytes. These sites are present on the tumor cell surface and are shared by tumors of disparate origins.98 However, the biochemical identities of the “recognition structures” have not been identified. The role of tumor cell surface carbohydrates in the binding and lysis of these cells by activated macrophages is under investigation.99 In this regard the monosaccharides, N-acetyl-D-galactosamine,100,101 D-galactose,101 L-fucose,101,102 and D-mannose,100 as well as removal of sialic acid residues103 have been reported to inhibit target cell recognition and destruction by macrophages. The spatial arrangement of simple membrane phospholipids has also been proposed as an important determinant in the binding and lysis of tumor cells by activated mononuclear phagocytes.97 Target cell characteristics important in macrophage-mediated cytotoxicity have also been investigated. The susceptibility of targets to destruction by tumoricidal rat and mouse macrophages was studied with virus-transformed cell lines in which various elements of the transformed phenotype are only expressed at specific temperatures.104 These studies demonstrated that the tumor cells were lysed by macrophages regardless of whether they expressed cell surface fibronectin protein or Forssman antigen, displayed surface changes which permit agglutination by low doses of plant lectins, expressed SV40 T antigen, had a low saturation density, or exhibited density-dependent inhibition of DNA synthesis. The susceptibility of tumor cells to destruction by tumoricidal macrophages appears to be independent of the in vitro biological behavior of the tumor cell. Melanoma-variant cell lines that have a low or high metastatic potential,89 that have invasive or non-invasive characteristics,89 that are either susceptible or resistant to lysis mediated by syngeneic T cells or natural killer (NK) cells,89 and that differ in differentiation markers105 (pigmentation and tryosinase activity) are all lysed in vitro by activated macrophages. Similarly, several cloned cell lines that were isolated from a murine fibrosarcoma induced by ultraviolet (UV) radiation and that vary in their degree of immunogenicity,106 sensitivity to the anthracycline antibiotic Adriamycin,107 or invasive and metastatic potential in vivo106,108 are all susceptible to destruction in vitro by lymphokine-activated macrophages. Not all investigators agree that macrophage-mediated destruction of tumor cells is independent of the metastatic potential of the cancer cell.109-112 These reports suggest an inverse relationship between the ability of a tumor cell to form metastases and its susceptibility to destruction by activated macrophages. Accordingly, it is only possible to conclude that the cytocidal activity of the activated mononuclear phagocyte is specific for the neoplastic phenotype.
ABO Blood Groups, Rh Factor, and Thyroid Cancer Risk: To ‘B’ or Not to ‘B’
Published in Endocrine Research, 2020
Abbas Ali Tam, Didem Özdemir, Sevgül Fakı, Muhammet Cüneyt Bilginer, Reyhan Ersoy, Bekir Çakır
The ABO blood groups are defined by carbohydrate moieties displayed on the surface of red blood cells and attached to a protein backbone, known as the H antigen. The blood group of an individual is determined by the ABO gene which is located on chromosome 9q34. Three variant alleles of this gene encode three glycosyltransferases with different substrate specificities.18 ABO antigens are expressed on red blood cells, epithelial and endothelial cells and various human tissues. The mechanisms underlying the association between ABO blood groups and some type of tumors were not clearly explained. However, some hypothesis was suggested. Hakomori et al.19 showed that the blood group antigens expressed on the surface of malignant cells were different from the antigens expressed on normal cells. This modified expression of blood group antigens on the surface of cancer cells may contribute to the development and progression of cancer by changing cell motility, sensitivity to apoptosis and immune escape.20 Another hypothesis is decreased tumor immune response due to the similar structure of certain tumor antigens with ABO antigens. One of the best known is Forssmann antigen. It is synthesized predominantly in gastric and colon tumors and is almost identical to the A antigen determinant structurally. This might cause inability of the immune system to recognize and attack tumor cells that express Forssmann antigen in subjects with blood group A.20 The host inflammatory response is another potential mechanism underlying the association between the ABO blood types and cancer. Inflammatory cells and mediators were reported to induce tumor development.21