TECHNIQUES FOR ELICITING MUCOSAL IMMUNE RESPONSE

1975 ◽  
Vol 80 (2_Suppl) ◽  
pp. S262-S280 ◽  
Author(s):  
R. H. Waldman ◽  
R. Ganguly
Keyword(s):  
Immune Response ◽  
Antibody Formation ◽  
Antigen Processing ◽  
Large Body ◽  
Vaccine Dose ◽  
Mucosal Immune Response ◽  
Secretory Iga ◽  
Cell Mediated Immunity ◽  
Mucosal Surfaces ◽  
Parenteral Immunization

ABSTRACT Development of techniques for eliciting an immune response on mucosal surfaces is a relatively new area of clinical research. With the recognition of the existence of secretory immunity, independent of the systemic system, there was renewed interest in re-examining the conventional approach for optimal immunization techniques. A large body of data indicate that the majority of the secretory immunoglobulins and antibody produced to antigenic stimulation of mucosal surfaces is locally produced. Thus, antibody to C. albicans in the cervical or vaginal mucus has been shown to be of local origin and it predominantly belongs to the secretory IgA immunoglobulin class. The mechanism of antigen processing by the secretory surface leading to antibody formation remains a mystery, but it might be determined by the selective localization of antigens in the reticuloendothelial cells of the lamina propria, bronchi or small intestine. Usually application of antigen topically to the mucosal surface elicits local antibody formation to a greater extent than does parenteral immunization. On the other hand, a more pronounced systemic immune response is seen when the antigen is administered systemically. However, a number of other factors determine the quality and quantity of the immune response, e. g., the physical state of the antigen, live vs killed vaccine, dose, adjuvant, previous exposure to similar or cross-reacting antigens, and site of application of the antigen. These factors are discussed in the review. Recent observations suggest that cell mediated immunity is a component of the secretory immune system, and like the humoral mechanism, also may be partially compartmentalized.

scholarly journals IMMUNE RESPONSE TO CHEMICALLY MODIFIED FLAGELLIN

1971 ◽  
Vol 134 (1) ◽  
pp. 21-47 ◽  
Author(s):  
C. R. Parish
Keyword(s):  
Immune Response ◽  
Antibody Formation ◽  
Delayed Type Hypersensitivity ◽  
Antigenic Determinants ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Adult Rats ◽  
Antigenic Activity ◽  
Cellular Immune ◽  
Derivatives Of

Flagellin (mol.wt. 40,000) from S. adelaide organisms and a series of acetoacetyl derivatives of flagellin were tested for their ability to induce humoral and cell-mediated immunity in adult rats. It was found that unmodified flagellin was an excellent inducer of antibody formation but a poor inducer of delayed-type hypersensitivity. In contrast, increasing acetoacetylation steadily destroyed the ability of flagellin to initiate antibody formation but enhanced the capacity of the molecule to induce flagellin-specific cell-mediated immunity and antibody tolerance. In fact, it appeared that in adult rats antibody formation and cell-mediated immunity may well be opposing immunological processes. Furthermore, the affinity of the acetoacetyl flagellins for anti-flagellin antibodies appeared to determine the type of immune response which predominated. High affinity antigen produced antibody formation whereas low affinity antigen induced cell-mediated immunity and antibody tolerance. The importance of affinity was further evidenced by the fact that a CNBr digest of flagellin induced humoral and cellular immune responses identical to an acetoacetylated flagellin of comparable antigenic activity. From these studies it was proposed that both humoral and cell-mediated immunity can be directed against the same antigenic determinants but that the specificity requirements for delayed hypersensitivity (and antibody tolerance) are less than those required for antibody formation. Some remarkable immunological features of the flagellin system were revealed. Flagellin induced comparable delayed-type hypersensitivity when injected in either saline or FCA. Furthermore, FCA only slightly enhanced the delayed responses induced by the acetoacetyl flagellins and in fact these preparations produced antibody tolerance whether injected in saline or adjuvant. Finally, in contrast to the adult tolerance induced by the acetoacetylated flagellins, which existed only at the antibody level, tolerance in neonatal rats existed at the level of both humoral and cell-mediated immunity. This finding is the first indication of a fundamental difference between neonatal and adult tolerance. The significance of these findings is discussed in the light of current immunological concepts and a hypothesis proposed to explain these phenomena.

scholarly journals REGULATION OF THE IMMUNE RESPONSE: SUPPRESSIVE AND ENHANCING EFFECTS OF PASSIVELY ADMINISTERED ANTIBODY

1971 ◽  
Vol 133 (5) ◽  
pp. 987-1003 ◽  
Author(s):  
Carolyn S. Pincus ◽  
Michael E. Lamm ◽  
Victor Nussenzweig
Keyword(s):  
Immune Response ◽  
Antibody Formation ◽  
Secretory Component ◽  
Secretory Iga ◽  
Antigenic Determinants ◽  
Antibody Synthesis ◽  
Serum Iga ◽  
Iga Antibody ◽  
Antigen Antibody

The ability of passively administered antibody to suppress the immune response against homologous antigenic determinants while concomitantly enhancing the response against other unrelated determinants of the same antigen molecule has been established in two distinct antigen-antibody systems: (a) guinea pig γ2-immunoglobulin + passive anti-F(ab')2 antibody, where suppression of anti-F(ab')2 antibody synthesis is accompanied by enhancement of the anti-Fc response; and (b) human secretory IgA + passive anti-serum IgA antibody, where suppression of antibody production against the α and L chains accompanies augmentation of the response to the secretory component. The mechanisms of the suppressive and enhancing effects are probably unrelated for the following reasons: (a) Enhancement of the response to certain determinants may be obtained without discernible suppression of the response to the homologous determinants; and (b) the F(ab')2 fragments of passive antibody can mediate immune suppression but were not observed to enhance the response against the unrelated determinants of the same antigen molecule. Also, the timing for achieving maximum suppression or enhancement of antibody formation is not the same; enhancement was obtained only at a later time. Both the enhancement and suppressive effects were obtained with the purified γG fraction of antisera. This finding rules out an exclusive role of γM antibody in the enhancement phenomenon.

scholarly journals Secretory immunoglobulin A of the respiratory system and COVID-19

2021 ◽  
Vol 31 (6) ◽  
pp. 792-798
Author(s):  
Nadezhda O. Kryukova ◽  
Ekaterina B. Rakunova ◽  
M. P. Kostinov ◽  
Irina A. Baranova ◽  
Oxana A. Svitich
Keyword(s):  
Immune Response ◽  
Respiratory Tract ◽  
Mucosal Immunity ◽  
Immunoglobulin A ◽  
Disease Diagnosis ◽  
Mucosal Immune Response ◽  
Secretory Iga ◽  
Published Data ◽  
Antibody Isotype ◽  
Treatment And Prevention

The main focus in the course of COVID-19 goes on assessing the overall immune response. The role of mucosal immunity in this disease has not been studied sufficiently.The study aimed to analyze published data about secretory IgA as a significant indicator of the mucosal immune response of the respiratory tract in the context of the COVID-19 pandemic.Methods. Articles were identified via PubMed bibliographic database. The time-span of research was two years (2020, 2021).Results. The search identified 54 articles. There is evidence that secretory IgA (sIgA) is the main antibody isotype of the mucosal immunity. It is produced in quantities significantly higher than those of all other isotypes of immunoglobulins combined. sIgA antibodies are effective against various pathogens, including the SARS-CoV-2 virus, due to mechanisms such as neutralization, suppression of adhesion to the mucosal surface and invasion of epithelial cells, agglutination and facilitating the removal of pathogenic microorganisms with the mucosal secretions. Virus-specific IgA antibodies in the blood serum are detected in patients with COVID-19 as early as two days after the first symptoms, while IgM or IgG class antibodies appear only after 5 days. We accessed the efficacy of intranasal immunization as to induction of predominant production of sIgA in the upper and lower respiratory tract.Conclusion. The current information on the local immune response of the respiratory mucosa is important for understanding the pathophysiological mechanisms of the disease, diagnosis, and development of new methods of treatment and prevention of COVID-19.

scholarly journals Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Alina S. Dzharullaeva ◽  
Amir I. Tukhvatulin ◽  
Alina S. Erokhova ◽  
Alina S. Bandelyuk ◽  
Nikita B. Polyakov ◽  
...  
Keyword(s):  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Mucosal Immune Response ◽  
Secretory Iga ◽  
Raw 264.7 Macrophages ◽  
Immune Reactions ◽  
Lectin Receptor ◽  
Effective Strategies ◽  
Parenteral Immunization

Induction of a robust and long-lived mucosal immune response during vaccination is critical to achieve protection against numerous pathogens. However, traditional injected vaccines are generally poor inducers of mucosal immunity. One of the effective strategies to improve vaccine efficacy is incorporation of adjuvant molecules that enhance and polarize adaptive immune reactions. Effects of Syk-coupled lectin receptor agonists as adjuvants to induce mucosal immune reactions during parenteral immunization are not fully studied. We now report that the agonists trehalose-6,6-dibehenate (TDB), curdlan, and furfurman, which stimulate Dectin-1, Dectin-2, and Mincle, respectively, activate transcription factors (NF-κB, NFAT, and AP-1) to various extents in murine RAW 264.7 macrophages, even though similar pathways are activated. The agonists also elicit differential expression of maturation markers in bone marrow-derived dendritic cells, as well as differential cytokine secretion from these cells and from splenic mononuclear cells. In vivo assays also show that agonists of Dectin-1 and Dectin-2, but not Mincle, induce heavy IgA secretion in intestinal mucosa even when delivered parenterally. Strikingly, this effect appears to be formulation-independent. Collectively, the data suggest that adjuvants based on Dectin-1 and Dectin-2 agonists may significantly improve the efficacy of parenteral vaccines by inducing robust local immune reactions in intestinal mucosa.

scholarly journals Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Michael W. Russell ◽  
Zina Moldoveanu ◽  
Pearay L. Ogra ◽  
Jiri Mestecky
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Mucosal Immunity ◽  
Cell Mediated Immunity ◽  
Upper Respiratory Tract ◽  
Critical Aspect ◽  
Mucosal Surfaces ◽  
Iga Antibodies ◽  
Upper Respiratory ◽  
Almost All

The mucosal immune system is the largest component of the entire immune system, having evolved to provide protection at the main sites of infectious threat: the mucosae. As SARS-CoV-2 initially infects the upper respiratory tract, its first interactions with the immune system must occur predominantly at the respiratory mucosal surfaces, during both inductive and effector phases of the response. However, almost all studies of the immune response in COVID-19 have focused exclusively on serum antibodies and systemic cell-mediated immunity including innate responses. This article proposes that there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19, and that it is important to elucidate this in order to comprehend especially the asymptomatic and mild states of the infection, which appear to account for the majority of cases. Moreover, it is possible that mucosal immunity can be exploited for beneficial diagnostic, therapeutic, or prophylactic purposes.

scholarly journals Transversal gene expression panel to evaluate intestinal health in broiler chickens in different challenging conditions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Criado-Mesas ◽  
N. Abdelli ◽  
A. Noce ◽  
M. Farré ◽  
J. F. Pérez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Barrier Function ◽  
Nutrient Transport ◽  
Gene Expression Pattern ◽  
Vaccine Dose ◽  
Special Focus ◽  
Intestinal Health ◽  
Barrier Failure ◽  
Expression Of Genes

AbstractThere is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.

Development of species-specific IgM antibodies and elevation of mucosal immune response in Labeo rohita using recombinant bicistronic nano DNA vaccine priming

2021 ◽  
Vol 113 ◽  
pp. 185-195
Author(s):  
Tasok Leya ◽  
Irshad Ahmad ◽  
Rajendran Kooloth Valappil ◽  
Pani Prasad Kurcheti ◽  
Gayatri Tripathi ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Vaccine ◽  
Labeo Rohita ◽  
Mucosal Immune Response ◽  
Igm Antibodies ◽  
Species Specific

scholarly journals Development of SARS-CoV-2 Specific IgG and Virus-Neutralizing Antibodies after Infection with Variants of Concern or Vaccination

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 700
Author(s):  
Franziska Neumann ◽  
Ruben Rose ◽  
Janine Römpke ◽  
Olaf Grobe ◽  
Thomas Lorentz ◽  
...  
Keyword(s):  
Immune Response ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Vaccine Dose ◽  
High Avidity ◽  
Receptor Binding Domain ◽  
Robust Immune Response ◽  
Specific Igg ◽  
Nucleoprotein N

The humoral immunity after SARS-CoV-2 infection or vaccination was examined. Convalescent sera after infection with variants of concern (VOCs: B.1.1.7, n = 10; B.1.351, n = 1) and sera from 100 vaccinees (Pfizer/BioNTech, BNT162b2, n = 33; Moderna, mRNA-1273, n = 11; AstraZeneca, ChAdOx1 nCoV-19/AZD1222, n = 56) were tested for the presence of immunoglobulin G (IgG) directed against the viral spike (S)-protein, its receptor-binding domain (RBD), the nucleoprotein (N) and for virus-neutralizing antibodies (VNA). For the latter, surrogate assays (sVNT) and a Vero-cell based neutralization test (cVNT) were used. Maturity of IgG was determined by measuring the avidity in an immunoblot (IB). Past VOC infection resulted in a broad reactivity of anti-S IgG (100%), anti-RBD IgG (100%), and anti-N IgG (91%), while latter were absent in 99% of vaccinees. Starting approximately two weeks after the first vaccine dose, anti-S IgG (75–100%) and particularly anti-RBD IgG (98–100%) were detectable. After the second dose, their titers increased and were higher than in the convalescents. The sVNT showed evidence of VNA in 91% of convalescents and in 80–100%/100% after first/second vaccine dose, respectively. After the second dose, an increase in VNA titer and IgGs of high avidity were demonstrated by cVNT and IB, respectively. Re-vaccination contributes to a more robust immune response.

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