Delayed hypersensitivity and nonspecific cellular immunity. The conditions determining the maximally expressed immunity activity

In vivo experiments on the infection of mice with influenza A virus and Francisella tularensis and in vitro experiments on the bactericidal activity of macrophages have demonstrated the conditions leading to the maximally pronounced activation of immunity by means of preparations inducing delayed hypersensitivity (DH). The following conditions have been determined: the presence of pronounced DH previously to the injection of old tuberculin (OT) and staphylococcal phagolysate (SP) used as challenge antigens, the specificity and peculiar features of the antigenic structure of the challenge agent, the time of its administration after the course of multiple sensitizing injections of BCG and staphylococci, the dosage of OT and SP and the scheme of their administration, the desirability of their local use. The time of the maximum activation of cell-mediated immunity after the injection of OT and SP to sensitized animals with a high level of DH and the duration of such activation have been established.     

Delayed hypersensitivity and nonspecific cellular immunity. The cytotoxic activity of macrophages, natural and antibody-dependent killer cells

The experiment on (BALB/cXC57BL)F1 mice, showing a high level of delayed hypersensitivity (DH) when sensitized with BCG vaccine and Staphylococcus aureus strain B-243, has demonstrated the influence of such sensitization and DH reaction induced by the injection of a specific antigen (old tuberculin or staphylococcal phagolysate) into the sensitized animals on the cytotoxicity of macrophages, natural killers (NK) and antibody-dependent killers (ADK). Sensitization with BCG vaccine alone results in an insignificant rise in the activity of these effector cells, and sensitization with S. aureus produces no changes at all. The pronounced activation of the cytotoxicity of macrophages, NK and, to a lesser extent, ADK has been observed in DH reaction induced by the injection of a specific antigen into the sensitized mice. In the course of DH reaction a rise in the activity of NK and ADK not only against tumor target cells, but also against microbial ones (Candida albicans and S. aureus) has been found to occur.     

The mediator of cellular immunity. IV. Cooperation between lymphocytes and mononuclear phagocytes

Acquired resistance to an intravenous infection with Listeria monocytogenes involves the interaction of two cell types: specifically committed lymphocytes and monocyte-derived macrophages. This interaction was revealed in experiments using the polyfunctional alkylating agent, cyclophosphamide. Cyclophosphamide is toxic for both lymphocytes and blood monocyte antecedents. Rats treated with cyclophosphamide were immunized adoptively with cells obtained from the thoracic duct lymph of Listeria-immune donors. But such animals benefited from a lymphocyte injection only while they could assemble monocyte-derived macrophages in an inflammatory exudate. The results imply that blood monocytes provide an essential element to the host's defense mechanism against intracellular bacterial parasites, and that monocyte-derived macrophages are the instruments through which cellular resistance to infection is expressed.     

State of cellular immunity and phagocytes in guinea pigs infected with Mycoplasma pneumoniae

The work presents the results of the study of experimental Mycoplasma pneumoniae infection in guinea-pigs. A considerable increase in the engulfment of mycoplasmas and blood leukocytes was found to occur on days 14-28 after the infection. The correlation between the degree of the engulfment of mycoplasmas by macrophages and the activity of lymphocytes in the reaction of blast-cell transformation with phytohemagglutinin and Mycoplasma antigen was observed. The peculiarities of the course of infection in sensitized animals were revealed. Virulent Mycoplasma pneumoniae strains were found to have a toxic effect on the lymphocytes and macrophages of guinea-pigs. This effect was neutralized by specific antiserum. The importance of these facts for the pathogenesis of Mycoplasma infection is discussed.     

Experimental salmonellosis. VII. In vitro transfer of cellular immunity by ribosomal fraction of mouse mononuclear phagocytes

Sato, Ichiei (Gunma University, Maebashi, Japan), and Susumu Mitsuhashi. Experimental salmonellosis. VII. In vitro transfer of cellular immunity by ribosomal fraction of mouse mononuclear phagocytes. J. Bacteriol. 90:1194-1199. 1965.-The mononuclear phagocytes (termed monocytes) of mice hyperimmunized with live vaccine of Salmonella enteritidis inhibited the intracellular growth of virulent strain 116-54 of S. enteritidis. Also, the monocytes withstood the degeneration of cells caused by the phagocytosis of bacteria in the absence of immune serum in the tissue culture medium, termed cellular immunity. When the nonimmune monocytes were incubated with the ribosomal fraction of immune monocytes, obtained from the abdominal cavity of mice hyperimmunized with live vaccine of S. enteritidis, they acquired cellular immunity, but the monocytes did not acquire immunity when ribosomal fractions from normal mouse monocytes or from the monocytes of mice immunized with killed vaccine of S. enteritidis were used. The transfer agent present in the ribosomal fraction of immune monocytes was inactivated by treatment with ribonuclease but not with deoxyribonuclease or with trypsin.     

Delayed hypersensitivity during casein-induced murine amyloidosis.

Cellular immunity has been studied in mice at various times during the induction of amyloidosis following multiple injections of casein. The assay system used was one which measured delayed hypersensitivity (DH) in vivo, by injecting antigen into the left ear lobe of sensitized mice, followed by the intravenous administration of ¹²⁵I-deoxyuridine (¹²⁵I-UdR). The ears were then cut off and the $\text{L}\text{R}$¹²⁵I-UdR ratio provided a measure of DH. It was found that DH to casein appeared in pre-amyloidotic mice, remained through the stages of mild and moderate amyloidosis and disappeared in severely amyloidotic mice. DH to fowl IgG disappeared after three injections of casein and remained absent at all times thereafter, likely due to antigenic competition. In contrast, DH to DNFB persisted at all times, even in the face of severe amyloidosis. These results have been interpreted to indicate that, using this assay, DH is normal during casein-induced murine amyloidosis.     

Delayed type hypersensitivity reaction in the pathogenesis and formation of immunity in tularemia infections in mice

As a result of our studies, strain differences in the sensitivity of CBA and BALB/c mice to partially attenuated Francisella tularensis strain have been revealed. Relationship between the increased migration of lymphocytes to the liver and lymphoid organs and the intensive development of cell-mediated immunity reactions has been shown. An important role of local reactions (the skin at the site of the inoculation of F. tularessis + a regional lymph node) in the development of the pathological process and the formation of immunity to tularemia infection has been noted. A high level of resistance to F. tularensis strain used for inoculation in BALB/c mice seems to be greatly due to the fact that in these mice more intensive cell-mediated immunity reactions develop at the early stages of infection, than in CBA mice.     

Relationships between cell-mediated immunity and the IgE antibody response: II. Delayed hypersensitivity and antibody production to DNP-Ascaris conjugates

Rats of the W/F strain were immunized with DNP-Ascaris conjugates using complete Freund's adjuvant (CFA), Al(OH)₃ gel (alum), or B. pertussis vaccine as adjuvants. Cell-mediated immunity was assessed by lymphotoxin in vitro and by delayed hypersensitivity in vivo. IgE and IgG antibody determinations were made on serum pools obtained at various times during the primary and secondary responses. Although delayed hypersensitivity appeared earlier than lymphotoxin, these two parameters correlated during the primary but not during the secondary response. The discrepancies suggested that different cells may be responsible for these two phenomena. Antibody production was influenced by the adjuvant used. CFA led to IgG antibody responses to both hapten and carrier but not to IgE antibody production. The use of B. pertussis resulted in both IgE and IgG antibody production. In the case of alum, anti-hapten antibodies appeared during the primary response while anti-carrier antibodies of both IgE and IgG classes were detected after booster. The results indicated that cell-mediated immunity, IgE, and IgG antibodies appeared independently in an ordered, temporal sequence, and that these responses were not mutually exclusive but were under strong modulatory influences of the various adjuvants used.     

类花生酸在昆虫细胞免疫中的作用研究进展

类花生酸包括前列腺素类,凝血恶烷类和白细胞三烯类等,在高等动物中的作用研究较多,后来有许多学者发现类花生酸在昆虫的细胞免疫反应中发挥了重要作用。本文就类花生酸在昆虫清除细菌、真菌、寄生物及病毒等过程中发挥的作用进行了综述,并就深入研究方向进行了展望。     

Characteristics of bunyavirus- and togavirus-induced nonspecific suppressors inhibiting delayed hypersensitivity

Some properties and mechanisms of action of nonspecific suppressor cells, inhibiting delayed hypersensitivity to sheep red blood cells and activated in vivo in experimental tick-borne encephalitis and Tahyna virus infections in mice, have been studied. These nonspecific suppressor cells have been identified as T-lymphocytes in experiments with the use of antisera to T- and B-lymphocytes. The function of the suppressor cells can be realized without their proliferation and is mediated by a soluble factor whose formation requires the synthesis of protein. In respect to hydrocortisone, the above-mentioned suppressor cells are subdivided into 2 subpopulations: hydrocortisone-resistant in the thymus and hydrocortisone-sensitive in the spleen.     

Lymphocyte recruitment in delayed-type hypersensitivity. The role of IFN-gamma

Lymphocytes are recruited out of the blood into delayed-type hypersensitivity (DTH) reactions, but the factors controlling their migration are poorly understood. Our previous studies have shown that IFN-alpha/beta, its inducers, and T cell lymphokines can induce lymphocyte migration into the skin after intradermal injection. The present studies were designed to determine the effect of rIFN-gamma, IL-1, and anti-IFN-gamma on lymphocyte recruitment into DTH. Small peritoneal exudate lymphocytes, which preferentially migrate to inflammatory sites, were labelled with 111In and injected i.v. into rats. The intradermal injection of IFN-gamma stimulated the migration of these lymphocytes into the skin. IL-1 induced very little migration by itself, but enhanced the effect of IFN-gamma. Kinetic analysis demonstrated that the migration of lymphocytes to IFN-gamma was rapid, with a peak at 6 h, whereas migration into a DTH reaction was minimal for the first 8 h and reached a peak 24 h after intradermal injection. Polyclonal rabbit anti-IFN-gamma anti-serum, and a Mab to IFN-gamma, DB-2, could almost completely block lymphocyte migration induced by IFN-gamma. Furthermore, DB-2 inhibited lymphocyte recruitment into DTH reactions by 50 to 90%. This Mab did not affect migration in response to IFN-alpha/beta, although it partially inhibited the response to polyI:C. The effect of IFN-gamma on lymphocyte recruitment was not specific for small peritoneal exudate lymphocytes, because both spleen T cells and lymph node cells migrated in response to IFN-gamma and DB-2 inhibited the recruitment of splenic T cells to DTH. Thus, IFN-gamma is a potent stimulator of lymphocyte migration into the skin and a major mediator of lymphocyte recruitment into DTH.     

Multiple receptors mediate apoJ-dependent clearance of cellular debris into nonprofessional phagocytes.

Phagocytosis of apoptotic, senescent, and dying cells by macrophages is a well characterized process. More recently it has been shown that in addition to macrophages vital neighboring cells in the affected tissue participate in the cellular clearance. While scavenger receptors have been shown to mediate uptake into macrophages, it is poorly understood how cellular debris is internalized by nonprofessional phagocytes. We here analyze the endocytic activity of vital fibroblasts and epithelial cells exposed to cellular debris and membrane remnants. We show a mutual stimulation in the endocytosis of debris and apolipoproteinJ (clusterin) in these cells. Experiments using RAP (receptor-associated protein) to block ligand binding to LRP and megalin as well as studies in LRP- and megalin-deficient cells suggest that the uptake of apoJ and cellular debris is mediated by megalin, LRP, and yet unidentified internalization mechanisms.