[The main directions of studies in evolutionary immunology]. / Osnovnye napravleniia issledovanii v évoliutsionnoi immunologii.

The main directions in evolutionary immunology include: (1) study of phylogenetic relationships between nonspecific (hereditary) and specific (acquired, or adaptive) immunity; (2) study of the phenomena of graft rejection in a phylogenetic series; (3) study of occurrence and historical development of T- and B-systems of immunity; (4) study of phylogenesis of different cell types of the immunity system; and (5) study of historical development of the ability to specifically recognize foreign antigenic material. Because many problems of evolutionary immunology remain unsolved, studies in this field will be continued.

[Evolutionary development of the immunoglobulins super family]. / Evoliutsionnoe razvitie supersemeistva immunoglobulinov.

The origin of the ability of immunoglobulins (Igs) and T-cell receptors (TCRs) to specifically recognize antigens is related to the evolutionary development of proteins of the immunoglobulin superfamily (IgSF). The IgSF proteins are characterized by specific domain organization of molecules and statistically significant homology with known Igs. Four types of Ig domains (V1, V2, C1, and C2), differing from one another both in variations in their spatial organization and in the number of amino acid residues, have been distinguished. Immunoglobulin superfamily comprises Igs; TCRs; class I and II major histocompatibility complex (MHC) molecules; one-domain proteins of thymocytes and T-cells (Thy-1); myelin protein P0; beta 2-microglobulin; two-domain proteins--sponge receptor tyrosine kinase (RTK), sponge adhesive protein (SAP), Drosophila tyrosine-kinase receptor (DTKR), cortical-thymocyte receptors of Xenopus (CTX), human (CTH), etc.; and a large group of adhesins, coreceptors, and Ig receptors with varying number of domains. Evolutionary development of IgSF began with the origination of chaperones, Thy-1, and P0 of prokaryotes and unicellular eukaryotes. Mutations, duplications, and translocations of genes controlling both V and C domains yielded proteins differing in the number and combination of these domains. All IgSF proteins are divided into two groups. The first group includes the proteins with nonrearranging V2 domains and homophilic mode of interaction; the second, the proteins with rearranging V1 domains and heterophilic mode of interaction (Igs, TCRs). The acquisition of the capability of heterophilic antigen-binding mode of interaction was apparently related to the introduction of recombination-activating retroviral genes (RAG1 and RAG2) into the genome of Gnathostomata ancestors.

The functional transformation of cytotoxic lymphocytes into T-suppressors under the influence of two mediators.

A set of CTL-lines in the system differing in the whole H-2 complex, as well as in distinct subregions of H-2, was established. These lines were routinely tested in Cr51-release assay to insure that they retained lytic activity and antigen-specificity. The result of the interaction of CTL with H-2Kb-molecule and alpha1-thymosine was transition of CTL into a reversible state of anergy. A high concentration of alpha1-thymosine is necessary for this transition. Anergic CTL caused specific suppressor activity that is functional if transformation of CTL into T-suppressors took place.

The costimulatory and differentiating activity of soluble class I MHC antigens for an autologous thymocyte population.

Combined cultivation of macrophages with syngeneic thymocytes resulted in accumulation of soluble H-2Kk antigens in culture medium. Incubation of intact autologous thymocytes with these soluble class I MHC molecules was shown to induce functional maturation of thymocytes assayed in local graft-vs-host reaction. Similar thymocyte costimulating activity was detected for the papain-solubilized purified H-2Kk antigens. Soluble class I antigens were shown to costimulate IL2 production by thymocytes in response to submitogenic doses of exogenous IL2 and to increase PHA-induced thymocyte proliferation. Soluble class I molecules were shown to increase the level of expression of function-associated membrane antigens, H-2Kk, CD8 and CD4, and to trigger thymocyte differentiation. The expression of I-Ak antigens remained invariable. It was also shown that soluble autologous class I molecules may function as direct amplifiers of thymocyte proliferation in autologous, but not allogeneic, mixed leukocyte reactions. It is concluded that soluble MHC class I molecules are capable of triggering functional and phenotype differentiation of syngeneic thymocytes and acting as restricted coaccessory molecules when thymocyte activation is induced by a submitogenic dose of different stimuli.

[The effect of the antigenic fractions of the outer membrane of Francisella tularensis on the T-cell immunity indices]. / Vliianie antigennykh fraktsii vneshnei membrany Francisella tularensis na nekotorye pokazateli T-kletochnogo zvena immuniteta.

The immunological evaluation of the influence of individual gel-chromatographic antigenic fractions (GAF) of F. tularensis outer membrane on different forms of T-cell reactiveness, such as delayed hypersensitivity (DH), proliferation of lymphocytes in the reaction of blast transformation (RBT) and mixed lymphocyte culture (MLC), has been made. As revealed in this study, GAF isolated from F. tularensis produce a pronounced immunomodulating effect on the processes linked with polyclonal activation of T-lymphocytes. Thus, GAF II with a molecular weight of 85-200 kD inhibits the maturation and activity of T-effectors of DH, the proliferation of lymphocytes in RBT and MLC. On the contrary, GAF IV with a molecular weight of 15-35 kD produces a stimulating effect on T-cells in the immune system in all the parameters under study.

[Immunobiologic characteristics of hybrid proteins consisting of tumor necrosis factor alpha and thymosin alpha 1]. / Izuchenie immunobiologicheskikh svoistv gibridnykh belkov sostoiashchikh iz faktora nekroza opukholei alpha i timozina alpha 1.

The preparations of alpha 1-thymosin (T), alpha-tumor necrotic factor (TNF) and their based hybrid proteins: T-TNF, TNF-T, and T-TNF-T were studied by using a wide spectrum of immunobiological tests. In the L-929 cells, T-TNF preserved cytotoxicity unique to TNF; TNF-T preserved it 10 times less, and T-NTF-T was completely inactive. TNF-T inhibited the growth of Molt-4, Jm-9, Raji cells by 63 = 84%, and TNF suppressed only Raji cells by 50%. Hybrid proteins caused cell proliferation of the thymus, spleen, and lymph nodes; H-2K, CD4, and CD8 differently increased the expression of thymocytic antigens. The authors found the different effects of the drugs on phagocytosis, the production of antibody-forming cells, delayed reaction, and activation of natural killer cells. The protein T-TNF-T produced the most pronounced action.

[The effect of antigenic fractions of the outer membrane in Francisella tularensis on the functional activity of macrophages]. / Vliianie antigennykh fraktsii vneshnei membrany Francisella tularensis na funktsional'nuiu aktivnost' makrofagov.

The influence of different gel-chromatographic antigenic fractions (GAF) of the membrane of F. tularensis, strain A'Cole, on different forms of reactivity of mouse peritoneal macrophages, such as the adhesion, ingestion and presentation of antigen on the cell surface, has been immunologically evaluated. GAF isolated from F. tularensis have been shown to produce a pronounced modulating effect on all forms of macrophagal functional activity under study. Thus, GAF II with a molecular weight of 85-200 kD inhibits the adhesion, ingestion and presentation of antigens and, on the contrary, GAF IV with a molecular weight of 15-35 kD stimulates these functions.

Nonapeptide corresponding to the sequence 27-35 of the mature human IL-2 efficiently competes with rIL-2 for binding to thymocyte receptors [corrected].

Previously it was shown [1] that amino acid substitutions at the region of the first alpha-helix of IL-2 specifically inactivate its reactivity with the intermediate-affinity receptor p70, and mutations in the fifth alpha-helix specifically inactivate the binding to the low-affinity receptor p55. We have synthesized the peptides corresponding to the putative binding site of IL-2 with the intermediate-affinity receptor p70 and found that the nonapeptide corresponding to the sequence 27-35 of the mature IL-2 [2] effectively competes with human rIL-2 for binding to thymocyte receptors. Two types of nonapeptide receptors were revealed: those with Kd1 = 1.84 x 10(-8) M and Kd2 = 1.6 x 10(-7) M. The rIL-2 provides a 100% inhibitory effect on the binding of the 125I-labeled nonapeptide to thymocyte receptors, Ki = 3.5 x 10(-8) M. Low immunoproliferative activity of the peptide allows one to recommend it as a specific antiproliferation drug, IL-2 inhibitor [corrected].

[Macrophages and the functional differentiation of thymocytes (a review of the authors' own data)]. / Makrofagi i funktsional'naia differentsirovka timotsitov (obzor sobstvenennykh dannykh).

Cellular, humoral, and genetic mechanisms of induction of T-effectors of the transplant vs. host reaction (THR) have been studied in two-cell culture of phagocyte mononuclears and thymocytes. A direct physical contact and similarity of H-2K locus of major histocompatibility complex between the cooperating cells in culture is required for successful induction of T-effectors of THR. Contact interaction of macrophages with thymocytes leads to accumulation of a 67 KDa humoral factor in the culture medium. Incubation of intact thymocytes with this factor leads to functional transformation of immature thymocytes into corresponding effector cells. Similarity of H-2K locus of the factor producers and intact lymphocytes is also required for successful humoral induction of the T-effectors. The surface H-2K antigen is able to induce formation of THR t-effectors from non-reactive thymocytes. The H2-K-specific mediator, affinity-isolated from the supernatant of the macrophage-thymocyte culture can also cause this induction.

[The dependence of the functional activity of "immune" macrophages on T-cells]. / Zavisimost' funktsional'noi aktivnosti "immunnykh" makrofagov ot T-kletok.

The dependence of the functional activity of the peritoneal macrophages of mice immunized with Francisella tularensis vaccine strain on the presence of T-cells in the culture has been studied. The elimination of "immune" macrophages and sensitized T-lymphocytes by means of anti-Thy-1-2-serum has been shown to lead to a sharp decrease in both ingestive and digestive functions of the phagocytic mononuclears of peritoneal exudate to the level of the activity of macrophages isolated from intact animals.

The octapeptide corresponding to the region of the highest homology between alpha-interferon and thymosin-alpha 1 effectively competes with both cytokines for common high-affinity receptors on murine thymocytes.

The octapeptide corresponding to human interferon-alpha 2 (Hu IFN-alpha 2) sequence 131-138 has high affinity to murine thymocyte receptors (Kd = 4.2 x 10(-12) M, about 700 receptors per cell). The peptide receptor binding is inhibited by both Hu rIFN-alpha 2 (Ki = 8.6 x 10(-10) M) and thymosin-alpha 1 (TM-alpha 1) (Ki = 3 x 10(-7) M) as well as by the octapeptide homologous to the TM-alpha 1 sequence 16-23 (Ki = 4.5 x 10(-7) M). The peptide from IFN-alpha 2 (131-138) activates murine thymocyte blast transformation at a concentration of 10(-11) M in the presence of 2.5 micrograms/ml of concanavalin A.

[The comparative characteristics of the immunomodulating properties of protein A from Staphylococcus aureus of different origins]. / Sravnitel'naia kharakteristika immunomoduliruiushchikh svoistv belka A Staphylococcus aureus razlichnogo proiskhozhdeniia.

The immunomodulating properties of highly purified staphylococcal protein A and its analog obtained by gene engineering techniques have been compared with those of commercial preparations. The comparison has shown that the differences observed in this investigation may be explained by the presence of admixtures of staphylococcal nature in commercial preparations. The preparations of highly purified staphylococcal and recombinant protein A stimulate humoral immune response and the processes of phagocytosis and do not show mitogenic activity with respect to T cells. The conclusion on the identity of the immunomodulating activity of the preparations of natural and recombinant protein A has been made.

[The immunoregulatory properties of reaferon]. / Izuchenie immunoreguliatornykh svoistv reaferona.

The influence of human recombinant alpha-interferon (reaferon) on cell-mediated and humoral immune response has been studied. Experimental facts on the blast transformation of lymphocytes, humoral immune response and the reaction of delayed hypersensitivity are presented. The study has shown that reaferon possesses the main immunoregulatory properties, characteristic of natural human leukocytic alpha-interferon. Manifestation of these properties depends on the dose of preparation and the time of its use.

[Effect of recombinant human alpha-interferon (reaferon) on macrophage functional activity in mice]. / Vliianie rekombinantnogo al'fa-interferona cheloveka (reaferona) na funktsional'nuiu aktivnost' makrofagov myshei.

The influence of human recombinant alpha 2-interferon (reaferon) on the parameters of the phagocytic activity of mouse peritoneal macrophages (migration, spreading, adhesion and absorption of corpuscular antigen) has been studied. Reaferon in doses of 5-5 X 10(2) I. U./ml has been found to produce a stimulating effect on all parameters under study. The data obtained in this study suggest that a stimulating effect on the functional activity of macrophages is the same for recombinant (alpha 2) interferon and natural alpha-interferon.

[Changes in the expression of the surface antigens of thymocytes during their cultivation with macrophages]. / Izmenenie ékspressii poverkhnostnykh antigenov timotsitov v protsesse ikh kul'tivirovaniia s makrofagami.

The data on changes in expression of H-2 complex and Thy-1 antigens on cell surface of thymocytes resulting from their incubation with peritoneal macrophages has been presented. The process of joint cultivation of thymocytes with macrophages leads to significant decrease in number of cells with Thy-2-antigen and increase in that with H-2 complex antigens. An increase in H-2K+ cells in experimental thymocytes as compared to control ones was observed. No changes in H-2D expression was observed. A significant increase in Ia+ macrophages was observed after interaction with thymocytes as compared with intact mononuclear phagocytes.