Host-defense mechanism will be composed of nonspecific protective elements and antigen-specific immunity capable of participating in the elimination of foreign materials with or without non-self antigenic determinants, cancer cells with or without tumor-specific antigens, wasted or damaged self components and overproduced self components. Studies on the host defense have been reactivated recently to establish a new field in biological scinece. One of characteristics of such studies may be an elucidation of the sequential process in the contribution of varions protective elements to the elimination of foreign materials or unusual self components. Our group has performed studies to find out new protective elements or new regulatory systems as follows and to compose the sequential process on the basis of new findings.
1. Proposal of“primitive T cell response”as a new entity which shows several characteristics distinct from those of classical immunity of clonal nature and covers the time gap between the nonspecific resistance and clonal immunity.
2. Elucidation of T cell recruitment from the thymus in response to the requirement for host-defense which is involved continuously in the elimination of foreign materials.
3. Elucidation of local differentiation or activation of effectors by which host-defense mechanism can be expressed selectively at the site where foreign materials or unusual self components have to be eliminated.
Further studies in this field will be conducted to establish new simple therotetical backgrounds into which new findings of diversity can be incorporated.

View full abstract

Luminol-dependent chemiluminescence (CL) of human polymorphonuclear neutrophils (PMN) phagocytosing opsonized zymosan (OPZ) was studied. CL occurred immediately after addition of OPZ to PMN suspension, reached its peak in 15-20 min. and decreased gradually thereafter. The intensity of the peak CL was proportional to the number of PMN and the concentration of luminol. Increased amount of OPZ resulted in a shortened interval before the peak CL; its intensity, however, was not affected significantly by the amount investigated. Experiments using inhibitors of oxygen radicals such as superoxide dismutase, catalase, sodium benzoate, histidine and sodium azide revealed that histidine and sodium azide were most potent, which might suggest a direct perticipation in the emission of CL by singlet molecular oxygen generated in the myeloperoxidase-mediated reactions. CL emmited by PMN phagocytosing OPZ is easy to measure, and appears to reflect phagocytosis and killing action of PMN and also opsonic potential of the substance used to opso-nized zymosan if normal PMN are employed.

View full abstract

We showed the effects of supernatant of cultured human peripheral blood mononuclear cells (PBMC) enriched for Mφ or depleted of Mφ. Blastogenesis, NK activities of lymphocytes and opsonic activities, phagocytosis, bactericidal activities, chemiluminescence, chemotaxis of granulocytes were examined. Supernatant of PBMC depleted of Mφ did not enhance the chemotaxis. Complements were undetectable. And the enhancement of chemotaxis was heatstable. Therefore, we suspected that the soluble factors produced by Mp played the role in such phenomena.

View full abstract

Intravenous infusion of PGE₁is one of the most useful treatment of peripheral vascular diseases such as scleroderma, Buerger's disease and diabetic angiopathy. Since PGE₁is rapidly inactivated in the lungs, PGE₁must be administered into the obstructive artery or a large amount of it has to be given intravenously. The distribution of PGE₁to a whole body induces its systemic effects, diarrhea and hypotension. Moreover, PGE₁causes an irritation in the blood vessels near the site of injection. To avoid these therapeutic problems of PGE₁, we incorporated PGE₁in lipid microsphere (a small lipid particle) with an average particle size of 0.2 u, whose suspension is in widespread use for parenteral nutrition in man, and we compared its vasodilator property in man with that of commercially available PGE₁.

View full abstract

Effect of CCA on accessory cell activity was examined in immune response with recombination systems consisting of plastic adherent and G-10 passed murine splenocytes. CCA (1-10 μg/ml) showd no significant effect on those systems. In addition, treatment with CCA (1-10 μg/ml) and addition of plastic adherent cells resulted in no significant increase in Con A induced-plastformation of murine splenocytes. These findings suggests that macrophage is not involved in modulation of immune response by CCA.

View full abstract

Disodium 4-chloro-2, 2'-iminodibenzoate (CCA) markedly suppressed the PFC response of pokeweed mitogen (PWM) stimulated human peripheral lymphocytes. IgM-PFCs were clearly reduced in the concentration from 0.01 to 0.1 mcg/ml of CCA. Although IgG-PFCs were decreased gradually in higher concentration from 0.1 to 1.0 mcg/ml, the pattern of reduction was different from IgM-PFC reduction. CCA (0.1 mcg/ml) was added to the cultures at the various time after cultivation and PFCs were measured. The suppressive effect of CCA on IgM-PFC was observed in initial stage of the cultivation, in late stage, however, the suppressive effect was not observed. To study whether CCA inhibits directly B cell proliferation or not, purified B cells were cultivated in the presence of 0.1 mcg of CCA and helper factor as a substitute for T cell. The differentiation of B cells to immunoglobulin producing cells was not inhibited in this experimental system. These results suggest that the suppressive effect of CCA on B cell differentiation may be due to accerelate the suppressor T cells or decrease the helper function of T cells.

View full abstract