Interaction between cytokines and 8-mercaptoguanosine in humoral immunity: synergy with interferon

In previous studies it has been demonstrated that a T cell-like differentiation signal is transmitted by C8-substituted guanine ribonucleosides such as 8-mercaptoguanosine (8MGuo) to antigen-stimulated B cells. A large subset of potentially reactive B cells remains unresponsive to antigen even in the presence of signals provided by these nucleosides except when this signal is preceded by a soluble activity present in mixed lymphocyte culture supernatants. Studies with purified preparations of interleukin (IL)-1, IL-2, IL-3, granulocyte-macrophage colony stimulating factor, B cell stimulatory factor 1 (IL-4), and B cell growth factor II (IL-5) indicated that none of these activities is capable of synergizing with 8MGuo to augment B cell responsiveness to antigen. Therefore, supernatants from a number of cloned cell lines were examined for activity that could synergize with 8MGuo, in order to determine the cellular source of this activity. Soluble products secreted by cloned 24/G1 T cells act synergistically with 8MGuo to evoke enhanced antibody responses to specific antigen in populations of purified B cells. Because concanavalin (Con) A-activated 24/G1 cells produce large quantities of interferon-gamma (IFN-gamma), the possibility that interferons might mediate synergy with 8MGuo was investigated. Purified murine IFN-gamma is unable to interact synergistically with 8MGuo; moreover, treatment of active 24/G1 supernatants with monoclonal anti-IFN-gamma antibodies or at pH 2 fails to abrogate their ability to synergize. In contrast to IFN-gamma, when B cells were supplemented with either IFN-alpha or IFN-beta, antigen-dependent synergy with 8MGuo was observed. However, abrogation of IFN-alpha and IFN-beta activity with specific antibodies fails to interfere with synergy between 8MGuo and mixed lymphocyte culture or Con A supernatants. Therefore, it appears that although IFN-alpha and IFN-beta are not responsible for the synergizing activity present in activated T cell supernatants, they nonetheless represent a previously unrecognized source of synergizing activity.     

Functionalization of magnetic nanowires by charged biopolymers

We report on a facile method for the preparation of biocompatible and bioactive magnetic nanowires. The method consists of the direct deposition of polysaccharides by layer-by-layer (LbL) assembly onto a brush of metallic nanowires obtained by electrodeposition of the metal within the nanopores of an alumina template supported on a silicon wafer. Carboxymethylpullulan (CMP) and chitosan (CHI) multilayers were grown on brushes of Ni nanowires; subsequent grafting of an enzyme was performed by conjugating free amine side groups of chitosan with carboxylic groups of the enzyme. The nanowires are finally released by a gentle ultrasonic treatment. Transmission electron microscopy, electron energy-dispersive loss spectroscopy, and x-ray photoelectron spectroscopy indicate the formation of an homogeneous coating onto the nickel nanowires when one, two, or three CMP/CHI bilayers are deposited. This easy and efficient route to the biochemical functionalization of magnetic nanowires could find widespread use for the preparation of a broad range of nanowires with tailored surface properties.     

NQO1 and NQO2 regulation of humoral immunity and autoimmunity

NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) are cytosolic enzymes that catalyze metabolic reduction of quinones and derivatives. NQO1-null and NQO2-null mice were generated that showed decreased lymphocytes in peripheral blood, myeloid hyperplasia, and increased sensitivity to skin carcinogenesis. In this report, we investigated the in vivo role of NQO1 and NQO2 in immune response and autoimmunity. Both NQO1-null and NQO2-null mice showed decreased B-cells in blood, lower germinal center response, altered B cell homing, and impaired primary and secondary immune responses. NQO1-null and NQO2-null mice also showed susceptibility to autoimmune disease as revealed by decreased apoptosis in thymocytes and pre-disposition to collagen-induced arthritis. Further experiments showed accumulation of NADH and NRH, cofactors for NQO1 and NQO2, indicating altered intracellular redox status. The studies also demonstrated decreased expression and lack of activation of immune-related factor NF-kappaB. Microarray analysis showed altered chemokines and chemokine receptors. These results suggest that the loss of NQO1 and NQO2 leads to altered intracellular redox status, decreased expression and activation of NF-kappaB, and altered chemokines. The results led to the conclusion that NQO1 and NQO2 are endogenous factors in the regulation of immune response and autoimmunity.     

Playing with cellular and humoral immunity

An interesting and easy game for the teaching of immunology was developed by the authors. Previously distributed figure cards are used by students that have to ask questions of each other. Most students considered the game to be interesting (97.7%) and declared that it helped them to understand the subject. The authors emphasise the importance of improving the quality of teaching using visual memory, fun and competition.     

Ineffective humoral immunity in the elderly

As individuals age, dysfunction of the immune system leads to an increased incidence of infectious disease. Due to the complex network of cellular interactions and the multi-factorial process of aging, numerous impairments in humoral immunity have been reported. Advances in technology have allowed scientists to begin to identify the molecular mechanisms behind the age-associated decline.     

脑梗死患者的细胞免疫与体液免疫的变化规律研究

目的探讨脑梗死患者的细胞免疫功能与体液免疫功能的变化规律。 方法2016年5月~ 2017年5月期间广东省佛山市禅城区中心医院收治的脑梗死患者120例设为观察组,观察组患者按照脑梗死的面积分为轻症组（大脑中动脉区域脑梗,脑梗范围的直径≤5 cm者,60例）和中重症组（大脑中动脉区域脑梗,脑梗范围的直径> 5 cm者,60例）;选择120例健康体检者设为对照组。采用流式细胞仪和速率散射免疫透射比浊法测定各组血免疫球蛋白IgA、IgM、IgG、补体C3、C4水平来反应体液免疫功能;用试剂盒、外周血中T淋巴细胞亚群CD3⁺、CD4⁺、CD8⁺、NK细胞、B细胞和CD4⁺/CD8⁺百分率水平的测定;对抗心磷脂抗体（ACA）浓度进行测定;通过ACA浓度反映的颈动脉粥样硬化（CAS）中生化指标的变化分析脑梗死患者的细胞免疫功能与体液免疫功能的关联。多组间比较采用单因素方差分析;患者性别比例采用χ²分析;通过直线相关分析细胞免疫与体液免疫的相关性。 结果脑梗死中重症组T淋巴细胞含量低于脑梗死轻症组和对照组,差异具有统计学意义（P < 0.05）,CD8⁺细胞百分率（27.91%±2.97%）T淋巴细胞含量高于脑梗死轻症组和对照组,CD4⁺/CD8⁺比值（1.98±0.03）水平高于脑梗死轻症组和对照组（P < 0.05）;与脑梗死轻症组和对照组比较,脑梗死中重症组NK细胞（12.29%±1.58%）和B细胞（12.76%±2.00%）均下降（P < 0.05）。与脑梗死轻症组和对照组比较,脑梗死中重症组血清中血球免疫球蛋白IgG（10.60±1.06）IU/ml水平降低（P < 0.05）;血球免疫球蛋白IgA（4.01±0.35）IU/ml、补体C3（2.13±0.04）IU/ml和补体C4（0.39±0.01）IU/ml的水平升高（P < 0.05）,而IgM（2.60±0.05）IU/ml无明显变化,差异无统计学意义（P > 0.05）。与脑梗死轻症组（14.11±2.09）PLU/ml和对照组（7.82±1.15）PLU/ml比较,脑梗死中重症组（16.88±2.50）PLU/ml血清ACA浓度提高,差异具有统计学意义（t = 9.153,P < 0.01）。与脑梗死轻症组和对照组比较,脑梗死中重症组总胆固醇[（1.75±0.03）mmol/L]和甘油三酯[（2.42±0.33）mmol/L]含量增加;高密度脂蛋白胆固醇[（0.41±0.03）mmol/L]含量降低;与对照组比较,脑梗死中重症组低密度脂蛋白胆固醇[（1.55±0.21）mmol/L]含量升高（P < 0.05）。通过细胞免疫参数与体液免疫参数之间的相关性分析显示呈负相关,且相关性曲线陡峭（P < 0.05）。 结论脑梗死患者的细胞免疫与体液免疫的变化规律可指导脑梗死治疗和预后。     

Immunization of salmonids against Yersinia ruckeri: significance of humoral immunity and cross protection between serotypes

Brook trout (Salvelinus fontinalis) were immunized with bacterins containing either Serotype 1 or 2 isolates of Yersinia ruckeri to determine the relative degree of cross-protection afforded when the fish were challenged with the homologous or heterologous serotype. While fish immunized with pH-lysed bacterins produced highly specific agglutinins that did not cross-react with antigens derived from a heterologous serotype of Y. ruckeri all fish were protected against experimental challenge, regardless of which serotype was used for bacterin production and experimental challenge. Other experiments indicated that brook trout injected intraperitoneally with highly specific antibodies could not be passively immunized against experimental challenge.     

Interaction of cholesterol-conjugated alkylating oligonucleotide derivatives with cellular biopolymers.

Interactions of oligonucleotide derivatives with mammalian cells and cellular biopolymers have been investigated. The derivatives were oligonucleotides bearing an alkylating 2-chloroethylamino group at the 3'-end and a cholesterol residue at the 5'-terminal phosphate. These compounds are readily taken up by cells and react with cellular DNA, RNA and some proteins which may play a role in delivery of the compounds into cells.     

Anti-malarial humoral immunity: the long and short of it

Humoral immunity is critical for limiting Plasmodium parasite infections and the severity of malaria. Naturally acquired immunity against malaria occurs inefficiently and protection is relatively short-lived. Here we review recent advances and explore emerging hypotheses regarding the molecular and cellular pathways that regulate Plasmodium parasite-specific B cell responses and durable anti-malarial humoral immunity.     

Interaction of protein with charged colloidal particles

The functional state of three proteins of different molecular weight (urease, lactate dehydrogenase, and hemoglobin) in the presence of the linear polyelectrolytes poly(allylamine hydrochloride) (PAA) and sodium poly(styrenesulfonate) (PSS) in the dissolved state and of the same polyelectrolytes bound to the surface of microspheres has been investigated. Microspheres were prepared by consecutive absorption of oppositely charged polyelectrolytes so that the outer layer of the shell was PAA for the acidic protein urease, and PSS for the alkaline proteins LDH and hemoglobin. It was shown that the dissolved polyelectrolyte completely inactivates all three proteins within one minute with a slight difference in the time constant. (By Hb inactivation are conventionally meant changes in the heme environment observed from the spectrum in the Soret band.) In the presence of microspheres, the proteins were adsorbed on their surface; in this case, more than 95% of the activity was retained within two hours. The proportion of the protein adsorbed on microspheres accounted for about 98% for urease, 72% for Hb, and 35% for LDH, as determined from the tryptophan fluorescence data. The interaction of hemoglobin with another type of charged colloidal particles, phospholipid vesicles, leads to the destruction of the tertiary structure of the protein, which made itself evident in the optical absorption spectra in the Soret band, as well as the spectra of tryptophan fluorescence and circular dichroism. In this case, according to circular dichroism, the percentage of α-helical structure of Hb was maintained. The differences in the physical and chemical mechanisms of interaction of proteins with these two types of charged colloidal particles that leads to differences in the degree of denaturing effects are discussed.     

Interaction of lactoperoxidase with enzymes and immunoglobulins in bovine milk

The interaction of lactoperoxidase with lysozyme and ribonuclease as well as immunoglobulins from cow milk has been investigated. As gel filtration and enzyme kinetics experiments have shown, the lactoperoxidase was slightly activated by complexing to lysozyme, while IgA and IgM were inhibitory for the peroxidase. Oh the other hand, IgG and ribonuclease had no effect on the enzyme activity although the latter did form a complex with the lactoperoxidase. The interaction between the lysozyme and lactoperoxidase appears to be rather specific since the alteration of the lactoperoxidase sugar moiety by periodate oxidation, prevented the formation of the lactoperoxidase-lysozyme complex.     

Intermolecular complexation and phase separation in aqueous solutions of oppositely charged biopolymers

Turbidity measurements performed at 450nm were used to follow the process of complex formation, and phase separation in gelatin-agar aqueous solutions. Acid (Type-A) and alkali (Type-B) processed gelatin (polyampholyte) and agar (anionic polyelectrolyte) solutions, both having concentration of 0.1% (w/v) were mixed in various proportions, and the mixture was titrated (with 0.01 M HCl or NaOH) to initiate associative complexation that led to coacervation. The titration profiles clearly established observable transitions in terms of the solution pH corresponding to the first occurrence of turbidity (pH(C), formation of soluble complexes), and a point of turbidity maximum (pH(phi), formation of insoluble complexes). Decreasing the pH beyond pH(phi) drove the system towards precipitation. The values of pH(C) and pH(phi) characterized the initiation of the formation of intermolecular charge neutralized soluble aggregates, and the subsequent formation of microscopic coacervate droplets. These aggregates were characterized by dynamic light scattering. It was found that Type-A and -B gelatin samples formed soluble intermolecular complexes (and coacervates) with agar molecules through electrostatic and patch-binding interactions, respectively.     

Phospholipids: “Greasing the wheels” of humoral immunity

Phospholipids are major structural components of all cellular membranes. In addition, certain phospholipids execute regulatory activities that affect cell behavior, function and fate in critically important physiological settings. The influence of phospholipids is especially obvious in the adaptive immune system, where these macromolecules mediate both intrinsic and extrinsic effects on B and T lymphocytes. This review article highlights the action of lysophospholipid sphingosine-1-phosphate as a lymphocyte chemoattractant, the function of phosphatidylinositol phosphates as signaling conduits in lymphocytes and the role of phospholipids as raw materials for membrane assembly and organelle biogenesis in activated B lymphocytes. Special emphasis is placed on the means by which these three processes push humoral immune responses forward. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism.     

T-cell regulation: with complements from innate immunity

The complement system was traditionally known as an effector arm of humoral immunity. Today we also recognize it as a main element of the innate immune system. In blood and other body fluids complement is a first line of defence against pathogens, because it becomes fully active within seconds. Active complement fragments attach to the invading pathogen to promote opsonization and lysis, triggering a local inflammatory response. This Review focuses on the evolving role of the complement system in the regulation of T-cell responses, from directing the initiation phase, through driving lineage commitment, to regulating the contraction phase.     

Dynamics of the humoral immunity indices in patients with subacute brucellosis being treated with levamisole

The dynamics of the main characteristics of humoral immunity in patients with subacute brucellosis, receiving levamisole and placebo, has been studied. Levamisole produced an immunomodulating effect manifested by an increase in the number of B-lymphocytes and a drop in the level of circulating immune complexes. Levamisole did not essentially influence the content of serum immunoglobulins and specific antibodies.     

Cellular and humoral aspects of innate immunity in the shark

Survival of many species depends, to a great extent, on their innate immunity. Innate immunity in the nurse shark (Ginglymostoma cirratum), a primitive elasmobranch, has been shown to consist of components, both humoral and cellular, which are in some respects similar to those found in mammals and other vertebrates. Innate immune factors present in the shark include complement (a complex system of serum proteins) and antibacterial proteins and enzymes, such as lysozyme. Shark complement, although opsonic and lytic in nature, differs from classical mammalian complement in the number of functionally distinct components involved in the activation sequence. Functional and structural analogues of several mammalian complement proteins have been isolated from the shark, and activation of shark serum by lipopolysaccharide or zymosan produces anaphylatoxin-like ligand(s) inducing mammalian smooth muscle contraction and chemotaxis of human leucocytes in vitro. Lysozyme activity has been recovered from shark leucocyte lysates, which also contain antibacterial peptides, distinct from lysozyme. The composition and antibacterial activity of shark leucocyte granules, the putative source of the activity, is under investigation. Cellular aspects of the inflammatory response which is an integral component of innate immunity, are leucocyte phagocytosis and chemotaxis. Both processes are functions of two distinct shark cell types, the granulocyte and the monocyte-macrophage. It should be noted that the innate resilience of the nurse shark is also augmented by a large pool of serum natural antibodies, which can account for as much as 45% of the total serum protein.