Genetic control of the immune response to mammalian chymotrypsins in mice. II. The immune response to low doses of bovine alpha-chymotrypsin.

The immune response to the antigen bovine pancreatic alpha-chymotrypsin was investigated in ten recombinant strains of mice. Using a fixed antigen-percentage bound isotope technique, it was found that the quantity of antibody produced was related to the H-2 haplotype of the responding animal. A continuous distribution for the mean antibody responses was obtained for the ten strains of mice. High responsiveness was associated with the H-2 haplotype gamma2. The genetic control of the immune response to this immunogen was found to be both quantitative and qualitative.     

Genetics of antibody responsiveness to bovine serum albumin and rabbit gamma-globulin. II. Evidence for a partially common genetic regulation of response to bovine serum albumin and rabbit gamma-globulin

In order to measure the reciprocal nonspecific effect of the genetic regulation of antibody responsiveness to bovine serum albumin (BSA) and rabbit gamma-globulin (RGG), two independent bidirectional selective breedings for responses to these two antigens were carried out: selection V/BSA and selection V/RGG respectively. The total interline separation at selection limit (RT) was 5.3 log2 for selection V/BSA and 2.6 log2 for selection V/RGG. The sum of these two values (7.9 log2) is similar to the RT in selection V carried out by alternating these two antigens in consecutive generations. In selection V/BSA, the nonspecific effect for responsiveness to RGG was 72%. In selection V/RGG, the nonspecific effect for BSA responsiveness was 135%. The F1 hybrids between homologous lines of selection V/BSA and selection V/RGG presented a larger difference in antibody response to both antigens than their parental lines. This demonstrates an additive effect of the loci controlling the two responses.     

The immune response in the hamster. II. Studies on IgM

Hamster IgM has been isolated and characterized. The protein possessed unique antigenic determinants but also shared common determinants with the 7Sγ₁- and 7Sγ₂-globulin classes. These shared determinants were present on the F(ab′)₂ and Fab fragments of 7Sγ₂-globulin. The rapidly sedimenting (S_20,w = 20.7) IgM was dissociated into slowly sedimenting (≈ 7S) units after reduction and alkylation. Specific antibody formation in the IgM and IgG (7Sγ₁-globulin) classes appeared at similar times after immunization with protein antigens, although IgM antibody was only detectable for a short period. After immunization with antigen in Freund''s adjuvant, the serum concentration of IgM increased and remained at an elevated level even after disappearance of antibody to the immunizing antigen. Injection of adjuvant alone also increased the concentration of serum IgM, particularly after intraperitoneal administration of Freund''s incomplete adjuvant.     

Cell preparation in immune response by immune ribonucleic acid. II. Independence of T lymphocytes in immune response against T-independent antigens.

The immune response of congenitally athymic (nude) mice induced by immune ribonucleic acid (iRNA) to lipopolysaccharides of Escherichia coli 0-55 (LPS) was studied. The thymus-independent nature of the immune response of mice to LPS was confirmed and nude mice responded to LPS in a manner similar to normal mice. An iRNA preparation extracted from the spleen of nude mice immunized with LPS could induce the proliferation of rosette-forming cells (RFC) in nude mice. iRNA preparations were insensitive to treatment with deoxyribonuclease and pronase, but were inactivated by ribonuclease treatment. The active fraction of the iRNA preparation had sedimentation values in a sucrose density gradient between 7 and 16 S and comprised only a small fraction of the total RNA present in the spleen cells, thereby indicating that the active moiety was one or more species of RNA. The anamnestic response was induced by treatment with iRNA made from the spleen of nude mice immunized with LPS. An increase in the number of rosette-forming cells (RFC), plaque forming cells (PFC) and formation of humoral antibody to LPS was seen after injection with a small amount of LPS 4 weeks after iRNA treatment.     

The effects of oral D-penicillamine treatment on experimental arthritis and the associated immune response in rabbits. II. The effects on cellular parameters.

Prolonged oral treatment (up to 410 days) of rabbits with D-penicillamine at a dose of 15 mg/kg body weight commencing either before or after immunization and the onset of arthritis, diminished and eventually abolished the delayed hypersensitivity response to intradermally administered tuberculin PPD. The 48 h cutaneous hypersensitivity response to the immunizing antigen (ovalbumin) was also significantly reduced, as was the inhibition of leucotye migration by ovalbumin. Cutaneous Arthus reactivity to ovalbumin was unaffected by D-penicillamine treatment. D-penicillamine treatment of normal rabbits was also found to increase the phagocytic index of the reticuloendothelial system as measured by carbon clearance.     

Lymphoid procoagulant response to bacterial endotoxin in the rat.

A number of species respond to bacterial endotoxin (lipopolysaccharide [LPS]) wherein cells of the monocyte-macrophage lineage are rapidly induced either directly or via T-cell collaboration to initiate the extrinsic coagulation protease pathway. This results in fibrin formation and deposition as well as consumption of plasma coagulation proteins. It has been claimed that this cellular response, basic to the Shwartzman reaction, is lacking in rats and may account for the more limited severity of the Shwartzman reaction in this species. We examined the in vitro lymphoid procoagulant response in Fischer 344, Brown Norway, and Lewis rats. When peripheral blood mononuclear cells (PBM) were stimulated in vitro with LPS, a procoagulant activity (PCA) response was observed when assayed by acceleration of clotting of recalcified human or rat platelet-poor plasma. The response was rapid, with a maximum achieved at 4 h. PCA was not physically dissociated from viable PBM by 5 mM EDTA, which is consistent with the presence of an intrinsic plasma membrane initiator molecule rather than calcium-bound gamma-carboxylated glutamic acid-containing proteases. The induction of monocyte PCA was prevented by incubation of cells with cycloheximide or actinomycin D, implicating a new biosynthetic requirement. Cultivation of PBM with warfarin did not diminish the function of the effector PCA, nor did vitamin K augment the function of the endotoxin-induced PCA, indicating that the functional activity was not attributable to gamma-carboxylated glutamic acid-containing proteins. No inhibition of the cellular PCA molecule was produced by serine protease inhibitors. The LPS-induced PCA appeared to involve a tissue factor-like molecule since both factors X and VII were required in mediating PCA. Isolation of monocytes and T lymphocytes from LPS-stimulated PBM demonstrated that PCA was present in the monocyte-rich fraction. When isolated rat T lymphocytes and monocytes were separately exposed to LPS, PCA was not induced. In contrast, when the cells were combined, LPS induced PCA, indicating that the PCA response involved cellular collaboration between cells present in T lymphocyte and monocyte populations.     

Phylogenetic studies on the immune response: II. The immune response of the Australian echidna Tachyglossus aculeatus*

The immunological response of the primitive mammal Tachyglossus aculeatus has been studied. We have shown that this animal responds to flagella from Salmonella adelaide with production of mercaptoethanol-resistant antibodies during both primary and secondary responses. Although an anamnestic secondary response could be demonstrated, it was of much smaller magnitude than that of phylogenetically higher placental mammals. Serological investigations demonstrated the presence of a mercaptoethanol-sensitive antibody of high molecular weight and an antibody of lower molecular weight which was mercaptoethanol resistant. These two antibodies seem to be analogous to IgM and IgG antibodies of higher mammals.     

Genetic control of the immune response to mammalian chymotrypsins in mice. I. The immune response to high doses of bovine alpha-chymotrypsin.

The primary and secondary immune response to the antigen bovine pancreatic alpha-chymotrypsin was investigated in inbred mice. It was found that strain differences in the immune response only became apparent after secondary immunization. The genetic control of the immune response was investigated in twelve different strains of mice, F1, F2 and F1 backcross hybrids, following secondary immunization. A continuous distribution for the mean antibody responsiveness was obtained. High responsiveness was associated with both the H-2 haplotype and three non-H-2 loci. Furthermore the F1 hybrids produced a greater quantitative antibody response to chymotrypsin than either of the corresponding parental strains.     

Diverse effects of triamicinolone on the ocular response to circulating endotoxin.

The ocular response to circulating bacterial endotoxin (E coli 055:B5, 100 microgram/kg) can be either significantly reduced or made more servere by pretreatment with the synthetic glucocorticoid triamcinolone. A single injection (25 mg/kg) 3 hr prior to endotoxin sharply curtails the response. Daily injections for 3 days preceding endotoxin produces an enhanced response. With this regimen, an enhanced alteration in ocular vascular permeability is produced 4 hr following endotoxin if 5 mg of triamcinolone is injected daily; if larger quantities of steroid are employed (25 mg), there is a slight reduction in ocular vascular permeability, but an enhanced intravascular fibrin accumulation in ocular blood vessels as well as in capillaries of renal glomeruli (generalised Shwartzman reaction). Once the enhancement of the ocular response to endotoxin has been established by prior treatment with steroids, additional triamcinolone given 2--3 hr before endotoxin is no longer effective in protecting against ocular or renal changes. These divergent effects of steroid could be produced by either subcutaneous or intra-orbital injection, and the response was equal in both eyes following intra-orbital injection, suggesting that steroids probably do not exert their effects locally in this situation. Although different mechanisms of action of corticosteroids may be responsible for these diverse effects, it is suggested that a loss of responsiveness to steroids may be important in their ability to enhance the effects of endotoxinemia.     

Circannual rhythm in the effects of stress on the humoral immune response of the rat

Among the seasonal immunological changes that have been observed are increase in spring-summer and decrease in autum-winter humoral response, in unstressed subjects. In rats we show that, relative to controls, stress increased the antibody response to sheep red blood cells in July–August, and decreases it from September throughout February. We concluded, therefore, that stress reinforces the basic annual rhythm of this type of response.     

Cell participation in immune response by immune ribonucleic acid. I. The role of T lymphocytes in immune response by immune RNA against T-dependent antigens

T- and B-cell participation in the immune response induced by immune ribonucleic acid (iRNA) preparations against T-dependent antigens was studied using athymic nude, neonatally thymectomized (NT) and cyclophosphamide-treated (CY) mice. The iRNA(T + B) preparations were made from the spleen of BALB/c mice immunized with these antigens. Injection of the iRNA into nude or NT mice caused an increase in the number of specific rosette-forming cells (RFC) and of memory cells capable of responding to secondary stimulus with a small dose of the corresponding antigen. Injection with T-dependent antigens or with iRNA(T + B) did not cause any immune response in CY mice, suggesting depletion of the B-cell function. The iRNA(T) and iRNA(B) were prepared, respectively, from the thymuses of BALB/c mice and from the spleens of nude mice which had been immunized with T-dependent antigens. Injection of nude mice with both iRNA(T) and iRNA(B) caused an increase in the number of specific RFC and the secondary antibody formation response after boosting with a small dose of the corresponding antigen. Injection of iRNA(T) preparation into nude mice could induce the anamnestic response after boosting. However, neither of the iRNA(T) or iRNA(B) preparation could induce in nude mice the proliferation of the number of specific RFC. These results indicate the presence of at least two kinds of iRNA preparations against T-dependent antigens and that the cooperation of iRNA(T) and iRNA(B) was required for the induction of immune response against T-dependent antigens.     

头孢噻甲羧肟对肺炎大鼠免疫应答的调节作用

目的 初步探讨了头孢噻甲羧肟（ＣＡＺ）对肺炎大鼠的免疫调节作用。方法;雄性Ｗｉｓｔａｒ大鼠采用气管内注入感染法制备肺炎克雷伯氏杆菌性肺炎模型,注射治疗剂量ＣＡＺ７ｄ后测定免疫指标：结果ＣＡＺ增强巨噬细胞的吞噬功能及ＡＤＣＣ活性;降低ＣＤ４＾＋Ｔ淋巴细胞亚群,对脾小结发生中心Ｂ细胞密度,ＰＭＮ－ＣＬ及巨噬细胞ＡＣＰ活性无影响,结论：ＣＡＺ可增强肺炎大鼠巨噬细胞和抑制Ｔ淋巴细胞的免疫应答反应。     

Modulation of the immune response to transplantation antigens. II. The effects of heterologous antisera on the growth of tumour allografts in mice

The effects of heterologous antilymphocytic sera (ALS) and anti-tumour sera on the growth of allogeneic tumour grafts in mice have been examined. Some ALS were highly active in promoting tumour growth, whilst the antisera raised against the tumours were not. The ALS appeared to act by delaying the onset of the immune response, and although a full cytotoxic response developed later the tumour was by then too large to be rejected. No clear evidence could be obtained that immunological enhancement plays a role in the in vivo effects of the ALS.     

Studies on hepatic uptake of antigen. II. The effect of hepatotoxins on the immune response

Using the previously described animal model in which the effect of hepatic uptake of SRBC injected into the rat portal venous system was studied, the effect of two hepatotoxins—carbon tetrachloride and D-galactosamine—is described. Carbon tetrachloride results in an enhanced primary immune response to SRBC injection and the abolition of the difference in immune response to repeated injections via the portal vein and inferior vena cava. Radioactive labelling of SRBC shows that the enhanced primary response is accompanied by a significant reduction of hepatic uptake. No significant increase in splenic uptake was noted. In contrast, the production of galactosamine hepatitis did not affect the immune response to SRBC.These findings are considered in the light of the pathogenesis of the hyperglobulinaemia which is associated with liver disease.