Imitating the humoral immune response

The immune system makes use of two distinct mechanisms to mount an efficient response against almost every foreign macromolecular substance. First, antibodies with their robust immunoglobulin domain architecture provide a rigid scaffold to support six hypervariable loops, capable of forming highly diverse binding sites. Second, an efficient genetic mechanism has evolved to create sequence diversity at the somatic level in a step-wise process, whereby random recombination of an inherited set of gene segments is followed by hypermutation events. Insight into the corresponding molecular mechanisms is developing rapidly and enables adaptation of the emerging principles to the creation of artificial binding proteins in vitro, using the techniques of combinatorial biotechnology. Thus, novel types of receptor molecules have been constructed from alternative scaffolds, including alpha-helical bundle and beta-barrel proteins. These may provide superior tools for the recognition, targeting or separation of a wide range of biomolecular structures or substances in biological research, technology, and even medicine.     

Ontogeny of the ferret humoral immune response.

Infant ferrets are born with nearly undetectable immunoglobulin levels, but by 9 days of age the infant ferret serum contains 77, 29, and 13% of adult mean serum levels of IgG, IgA, and IgM. Transmucosal uptake of IgG by the infant ferret occurred for the first 30 days of life. The specific anti-respiratory syncytial virus neutralizing titer of whole milk was 5.5 times higher than maternal serum despite a lower concentration of immunoglobulins in the milk.     

Assessment of the humoral immune response to cancer

One of the deadly hallmarks of cancer is its ability to prosper within the constraints of the host immune system. Recent advances in immunoproteomics and high-throughput technologies have lead to profiling of the antibody repertoire in cancer patients. This in turn has lead to the identification of tumour associated antigens/autoantibodies. Autoantibodies are extremely attractive and promising biomarker entities, however there has been relatively little discussion on how to interpret the humoral immune response. It may be that autoantibody profiles hold the key to ultimately uncovering neoplastic associated pathways and through the process of immunosculpting the tumour may have yielded an immune response in the early stages of malignant tumour development. The aim of this review is to discuss the utility of the autoantibody response that is elicited as a result of malignancy and discuss the advantages and limitations of autoantibody profiling. This article is part of a Special Issue entitled: Translational Proteomics.     

Durability of the humoral immune response in recovered COVID-19 patients

BackgroundThe immunological factors involved in protection against the disease caused by SARS-CoV-2 are insufficiently defined and understood. However, previous knowledge pertaining to the related SARS virus and other human coronaviruses may prove useful. Population-based serosurveys measuring anti-SARS-CoV-2 antibodies may provide a pattern for estimating infection degrees and observing the development of the epidemic. In this study, we aimed to investigate the persistence of antibody against the SARS-CoV-2 in recovered patients in Al Madinah region of Saudi Arabia.Materials and methodsA total of 150 recovered COVID-19 patients participated in this study. All the patients tested positive for the presence of SARS-CoV-2 RNA, using qualitative RT-PCR. An ELISA was used to measure anti-Spike (S) IgG antibodies in serum samples and screen for their persistence at various time points post-infection.ResultsThe patients were categorized as asymptomatic (27.3%), mild (28%) and moderate (44.7%) according to the disease severity. Amongst them, 35.3% were females (n = 53) and 64.7% were males (n = 97). Significant anti-S IgG antibody levels were observed among the different groups, with the patients in moderate group exhibiting the highest levels followed by the mild group; while the lowest levels were detected among the asymptomatic. There was a significant positive correlation between the patients’ age and anti-S IgG antibody concentrations (Pearson r = 0.45; p < 0.001).ConclusionOur findings provide a solid evidence to support the use of an anti-S IgG ELISA as a diagnostic tool to indicate SARS-CoV-2 infection. IgG seropositivity was sustained in recovered patients up to a hundred days' post-infection, the latest time point for antibody measurement in our study. Ours is the first report in Saudi Arabia to investigate the durability of humoral immune response in recovered COVID-19 patients.     

Modulation of humoral immune response through probiotic intake

Thirty healthy volunteers were randomised into three different treatment groups and consumed Lactobacillus GG, Lactococcus lactis or placebo (ethyl cellulose) for 7 days. On days 1, 3 and 5, an attenuated Salmonella typhi Ty21a oral vaccine was given to all subjects to mimic an enteropathogenic infection. All subjects responded well to the vaccine, but no significant differences were observed in numbers of IgA-, IgG- and IgM-secreting cells among the different groups. There was a trend towards a greater increase in specific IgA among the subjects receiving the vaccine in combination with Lactobacillus GG. Those receiving L. lactis with their vaccine evinced significantly higher CR3 receptor expression on neutrophils than those receiving either the placebo or Lactobacillus GG. These results indicate that probiotics may influence differently the immune response to oral S. typhi vaccine and that the immunomodulatory effect of probiotics is strain-dependent.     

A mathematical model of T-cell effects in the humoral immune response

Numerical simulations of several mathematical models are used to compare possible roles of T-helper and T-suppressor cells in the humoral immune response. These simulations suggest that T-helper cells must help T-suppressor cells, and T-suppressor cells exert inhibition on all T-helper cell subpopulations. The models display the well-known phenomenon of memory, low zone and high zone tolerance.     

Study of the phases of development of humoral immune response

In previously performed investigations to make clinical immunological diagnosis the principle of humoral immune response division into phases was put forward. The phases of humoral immune response were determined with lower content of immunoglobulins.     

Neonatal FcR overexpression boosts humoral immune response in transgenic mice

The neonatal FcR (FcRn) regulates IgG and albumin homeostasis, mediates maternal IgG transport, takes active part in phagocytosis, and delivers Ag for presentation. We have previously shown that overexpression of FcRn in transgenic (Tg) mice extends the half-life of mouse IgG by reducing its clearance. In this paper, we demonstrate that immunization of these mice with OVA and trinitrophenyl-conjugated human IgG results in a 3- to 10-fold increase of Ag-specific IgM and IgG in serum. The IgM increase was unexpected because FcRn does not bind IgM. Our results showed that the affinity of the Ag-specific IgG was at least as good in Tg mice as in the wild-type (wt) controls, implying appropriate affinity maturation in both groups. Influenza vaccination produced a 2-fold increase in the amount of virus-specific Ab in Tg animals, which proved twice as efficient in a hemagglutination inhibition assay as was the case in wt controls. After immunization, Tg mice displayed significantly larger spleens containing a higher number of Ag-specific B cells and plasma cells, as well as many more granulocytes and dendritic cells, analyzed by ELISPOT and flow cytometric studies. The neutrophils from these Tg mice expressed the Tg FcRn and phagocytosed IgG immune complexes more efficiently than did those from wt mice. These results show that FcRn overexpression not only extends the IgG half-life but also enhances the expansion of Ag-specific B cells and plasma cells. Although both effects increase the level of Ag-specific IgG, the increase in immune response and IgG production seems to be more prominent compared with the reduced IgG clearance.     

Functional activity of cells suppressing the humoral immune response in internal irradiation

In the adoptive transfer system of (CBA X C57BL/6)F1 mice, the estimation was made of the function of splenic cells, suppressors of the humoral immune response to sheep erythrocytes 1 and 6 months following the injection of 125I and 131I. Low absorbed doses of the radioactive isotopes were shown to stimulate the activity of the suppressors generated in mouse spleen.     

Analysis of the humoral immune response to influenza virus in vitro.

The induction of in vitro primary and secondary humoral immune responses to influenza virus in murine splenic explant culture is described. Anti-influenza antibody synthesized in vitro was detected and quantitated by a radioimmunoassay which utilized influenza coupled to bromoacetylcellulose. Both in vitro primary and secondary responses could be stimulated over a large range of virus doses. In vitro secondary responses were maximal when spleen donors had been immunized by the parenteral route although secondary type responses could be demonstrated as well after primary immunization by pulmonary infection. In vitro stimulation with influenza virus was relatively insensitive to inhibition at high antigen doses. The results are discussed in terms of the response of other antigens in spleen fragment culture.     

Intensity of the humoral immune response to herpesviruses as an indicator the body immune deficiency

The state of the local immunity system of the oral cavity was studied by the level of saliva immunoglobulins in patients with different processes on their mucous membranes: herpetic infection, respiratory allergosis and malignant tumors of the mouth cavity and the laryngopharynx. The suppression of the production of sIgA, was accompanied by the enhanced production of antibodies to the most widespread herpesviruses (herpes simplex virus, cytomegalovirus and Epstein-Barr virus). The maximum levels of serum IgG to herpesviruses were determined in patients with malignant tumors. The role of herpesviruses in the pathogenesis of immunodeficient states is discussed.     

Maturation of the humoral immune response as an optimization problem.

Efficient immune response often depends on the production of high affinity antibodies. We show analytically that the optimal strategy for a fast production of high affinity antibodies is to utilize a step-function mutation rate, i.e. a minimal mutation rate in early stages of the immune response, followed by a discontinuous switch to the maximal possible rate when the proliferating population of B-cells exceeds a threshold value. Our results are in accordance with the biological observations concerning the time of onset of the hypermutation process, and with the mutation rate during the later stages of the primary immune response. Indeed the hypermutation process plays a crucial role in responding to a prevailing pathogen at each round of immune response, and not only for coping with future infections. Moreover, as the effect of hypermutations is shown to be crucially dependent on the number of proliferating B-cells, its onset is not expected to depend on an external signal, but rather to be related to the clone's age. This suggests that the onset is host species specific, rather than pathogen specific. Another implication of the present results is that activation of hypermutations before the B-cell population has reached the critical size may impede the efficiency of the response.     

Role of helper T-lymphocytes in modulating the humoral immune response to cholera enterotoxin

The role of helper T-lymphocytes in the modulation of humoral immune response to sheep red blood cells with choleragen has been studied in vivo, the populations of cooperating marrow cells, formed in mice under the action of hydrocortisone being used as a model. In adoptive transfer marrow cells, taken from mice on day 12 after thymectomy and from mice previously treated with antithymocyte serum, have proved incapable of humoral immune response. Choleragen, similarly to theophylline, normalizes the humoral immune response of marrow cells in thymectomized mice, but inhibits this response in intact ones, while thymosin fraction 2 restores it again, thus abolishing the action of choleragen and theophylline. The opposite effects rendered by choleragen and theophylline on humoral immune response, depending on the hormonal status of the animals and the possibility of influencing these effects by means of thymosin fraction 2 indicate that the population of helper T-lymphocytes are selectively sensitive to changes in the concentration of intracellular cAMP. Their capacity for cooperative interaction in the immune process is regulated by thymic hormones and forms the basis of the mechanism permitting the modulation of humoral immune response with choleragen.     

The dynamics of the humoral immune response to mycobacterial antigens in mice]

The main regularities of humoral immune response to mycobacterial antigens have been studied in experiments on BALB/c mice immunized with live and thermoinactivated Mycobacterium tuberculosis, var. bovis. As shown in this study, the maximum level of serum antibodies to mycobacterial antigen is achieved in two weeks after immunization irrespective of the dose and viability or mycobacteria, then follows a decrease in the antibody level. The absence of uniformity in the dependence of primary immune response and the formation of immunological memory on the dose and viability of mycobacteria has been demonstrated.