Complementary idiotypy in the regulation of the immune response.

A new concept is presented for the interactions of two complementary antibodies in the immune response. These antibodies bind to each other by means of their variable sequence determinants and therefore are designated as complementary idiotypes. Under certain conditions, both complementary idiotypes are produced by the same animal at the same time. An idiotype can drastically affect the expression of the complementary idiotype in the animal, inducing a peripheral quench effect of antibody-binding activity and a central effect on the immunocompetent cell, which produces the complementary idiotype. It is proposed that complementary idiotypes might be induced during every immune response, thus playing an essential role in the regulation of the immune response.     

Deubiquitylation and regulation of the immune response

Ubiquitylation is a fundamental mechanism of signal transduction that regulates immune responses and many other biological processes. Similar to phosphorylation, ubiquitylation is a reversible process that is counter-regulated by ubiquitylating enzymes and deubiquitylating enzymes (DUBs). Despite the identification of a large number of DUBs, our knowledge of the function and activities of this family of enzymes is just starting to accumulate. As described in this Review, recent studies of several DUBs, in particular CYLD and A20, show that deubiquitylation has an important role in the regulation of both innate and adaptive immune responses.     

Cannabinoid receptors and the regulation of immune response

Cannabinoid research underwent a tremendous increase during the last 10 years. This progress was made possible by the discovery of cannabinoid receptors and the endogenous ligands for these receptors. Cannabinoid research is developing in two major directions: neurobehavioral properties of cannabinoids and the impact of cannabinoids on the immune system. Recent studies characterized the cannabinoid-induced response as a very complex process because of the involvement of multiple signalling pathways linked to cannabinoid receptors or effects elicited by cannabinoids without receptor participation. The objective of this review is to present this complexity as it applies to immune response. The functional properties of cannabinoid receptors, signalling pathways linked to cannabinoid receptors and the modulation of immune response by cannabinoid receptor ligands are discussed. Special attention is given to 'endocannabinoids' as immunomodulatory molecules.     

Positive and negative regulation of the Drosophila immune response

Insects mount a robust innate immune response against a wide array of microbial pathogens. The hallmark of the Drosophila humoral immune response is the rapid production of antimicrobial peptides in the fat body and their release into the circulation. Two recognition and signaling cascades regulate expression of these antimicrobial peptide genes. The Toll pathway is activated by fungal and many Gram-positive bacterial infections, whereas the immune deficiency (IMD) pathway responds to Gram-negative bacteria. Recent work has shown that the intensity and duration of the Drosophila immune response is tightly regulated. As in mammals, hyperactivated immune responses are detrimental, and the proper down-modulation of immunity is critical for protective immunity and health. In order to keep the immune response properly modulated, the Toll and IMD pathways are controlled at multiple levels by a series of negative regulators. In this review, we focus on recent advances identifying and characterizing the negative regulators of these pathways.     

A dynamic continuum model for molecular regulation of the humoral immune response.

Based on current concepts of the nature of specific immunocompetent cell surface receptors, hematopoietic stem cell differentiation and membrane dynamics, a simple model is proposed by which the event of immunogen binding by cell surface receptors specifically stimulates a constitutive process. The concept that enhancement of process flows in two directions with time allows for correlation of recent experimental findings into a molecular theory for antibody induction. The Model helps explain antibody specificity, heterogeneity and affinity changes and rationalizes immune memory.     

Significance and mechanisms of cellular regulation of the immune response

The conditions known to favor the induction of delayed-type hypersensitivity (DTH), IgM and IgG antibody production, can be accounted for on the postulate that their precursors require the formation of different numbers of inductive complexes between their receptors, antigen, and the antigen-specific factor derived from helper T cells. The postulate that DTH precursors require the least, IgM B cells an intermediate number, and IgG precursors the most, accounts for the following facts: i) antigens with few foreign sites, for which there are relatively few helper T cell clones, induce only DTH; ii) medium doses of antigens that bear many foreign sites induce a humoral response; whereas iii) low doses that do not result in efficient collaboration induce DTH; and iv) high doses that partially block collaboration also lead to the induction of DTH. Furthermore, the conditions under which unresponsiveness can be induced at the humoral level in immunological competent animals are just those that give rise to the induction of DTH; the induction of a humoral response is also known to result in unresponsiveness at the DTH level. Therefore it seems very likely that these unresponsive states reflect the cellular regulation responsible for the exclusiveness between the induction of DTH and humoral immunity observed in the whole animal. Theoretically, this exclusiveness is due to the action of regulatory T cells. The biological significance of the way in which the induction of different classes is regulated is discussed. Experimental evidence is described that tests the following predictions: i) the class of response induced is due to the action of suppressor and repressor T cells, and ii) it is the number of inductive complexes formed that determines the class of response induced; DTH precursors require the least number and IgG precursors the most.     

The role of the immune response in helminth population regulation

In natural host-parasite relationships the immune response represents the most effective control against parasitism by those species adapted to life within the environment specified by the host genotype. The parasite population is regulated by immunologically-mediated, often density-dependent, responses which influence establishment, survival and fecundity. The mechanisms underlying such responses have been largely determined by experimental studies using laboratory infections in rodent hosts and are reviewed. The influence of genetic factors which enhance or depress antiparasite immune responses is discussed.     

白细胞介素1诱导激素对免疫应答的调节

在免疫应答中,由巨噬细胞产生的白细胞介素1(IL-1),不仅是介导免疫应答的一种重要因子,同时也是诱导激素对免疫应答进行反馈调节的一种重要媒介。胰岛素对免疫应答有促进作用,糖皮质激素对免疫应答有抑制作用;IL-1在低浓度时促进胰岛素分泌,在高浓度时则抑制胰岛素分泌,并诱导糖皮质激素产生。因此,不同浓度的IL-1可分别诱导激素对免疫应答的正负反馈调节,这种双向调节作用是维持免疫应答动态平衡的重要机制之一。     

Hormonal regulation of the immune response. I. Induction of an immune response in vitro with lymphoid cells from mice exposed to acute systemic stress

The effect of exposure of mice to stress, by acceleration and ether anesthesia, on in vitro immune responsiveness of their spleen or peritoneal cells, has been studied in different mouse strains. Stress 6, 16, or 24 hr prior to stimulation of explanted lymphoid cells with SRBC in vitro leads to suppression of immune reactivity, whereas a time interval of only 15 min resulted in impaired or normal or even enhanced production of PFC's.     

Multigenic regulation of the primary immune response to ovalbumin in mice

At least four genes regulate the primary immune response to ovalbumin in mice. The ability to be sensitized to transfer delayed type hypersensitivity to ovalbumin is controlled by two genes. One gene,OVA-, is linked to theH-2 complex and maps to the left ofI-E. The linkage of the other gene,OVA-Bg1, has not been determined, but it segregates independently of theLy M locus, of the heavy chain allotype genes and of certain genes controlling coat color. At least two genes regulate the ability to respond with a primary antiovalbumin antibody response. One gene,OVA-, is linked to theH-2 complex and maps to the right ofI-E. Discordance of the minimum dose of antigen needed to elicit delayed type hypersensitivity response and antibody suggests that non-H-2 gene(s) regulating the primary antibody response are different fromOVA-Bg1.Abbreviations used in this paper BSA bovine serum albumin - DTH delayed type hypersensitivity - H-2 major histocompatibility complex of mouse - Ir gene — immune response gene - OVA ovalbumin - SRBC sheep red blood cells     

Role of t lymphocytes in the humoral immune response. II. T cell-mediated regulation of antibody avidity.

The effect of activated T lymphocytes (ATC) on the avidity distribution of PFC in the secondary response was studied in normal mice. The total PFC response was not significantly changed for either direct or indirect PFC by administration of ATC before secondary antigen challenge. However, marked suppression occurred of indirect PFC that secreted high avidity antibody; no suppression was seen of high avidity direct PFC. At the same time, significant stimulation was seen of relative and absolute frequencies of indirect PFC that secreted middle and low avidity antibody. These effects were dependent on Thy 1-bearing, nylon nonadherent cells which demonstrated carrier specificity. In further characterization of these effects, it was found that increasing the number of ATC transferred produced progressive loss of high avidity PFC and compensatory increase in lower avidity PFC. Moreover, in these experiments, suppression of the high avidity response was inducible with the administration of ATC 5 weeks before to 3 days after the secondary immunization. Thus, it is likely that the avidity-modifying effects are dependent on T lymphocytes which influence the late stages of B lymphocyte maturation.