scholarly journals ANTIGEN RECOGNITION AND THE IMMUNE RESPONSE

1972 ◽  
Vol 136 (6) ◽  
pp. 1478-1483 ◽  
Author(s):  
Maurice E. Bush ◽  
Sefik S. Alkan ◽  
Danute E. Nitecki ◽  
Joel W. Goodman

L-Tyrosine-p-azobenzenearsonate (RAT) induces cellular immunity without humoral antibody in guinea pigs. Asymmetric bifunctional antigens composed of one RAT moiety and one dinitrophenyl (DNP) group separated by flexible spacers induce anti-RAT cellular immunity and an anti-DNP humoral response. Symmetrical bifunctional antigens of similar design but comprised of two RAT determinants induce cellular immunity without demonstrable anti-RAT antibody. However, when the flexible spacer is replaced by a rigid decaproline chain, humoral anti-RAT responses are provoked. Since RAT contains both electropositive (azo) and electronegative (arsonate) centers, the failure of bifunctional RAT compounds with flexible spacers to induce humoral immunity might be ascribed either to intramolecular stacking, which compromises their bifunctional character, or to interaction of both determinants with receptors on the same cell surface, which would fail to satisfy the requirement for cooperation. In order to distinguish between these alternatives, symmetrical bifunctional antigens composed of two L-tyrosine-p-azophenyltrimethylammonium (TAT) determinants separated by flexible or rigid spacers were synthesized. TAT is immunogenic and does not cross-react with RAT. Furthermore, it contains only electropositive centers and consequently bifunctional molecules do not undergo intramolecular stacking. Immunization with either flexibly or rigidly spaced bifunctional TAT antigens raised anti-TAT antibody. These results conclusively demonstrate that "self-help," cooperation between bone marrow-derived and thymus-derived lymphocytes of identical or similar specificity, can occur, provided the determinants on the antigen are prevented from associating with each other.

1972 ◽  
Vol 135 (6) ◽  
pp. 1228-1246 ◽  
Author(s):  
Sefik S. Alkan ◽  
E. Brady Williams ◽  
Danute E. Nitecki ◽  
Joel W. Goodman

L-Tyrosine azobenzene-p-arsonate (RAT) induced cellular immunity without antibody production in guinea pigs. Bifunctional antigens were prepared consisting of one RAT carrier moiety linked either directly to a dinitrophenyl (DNP) haptenic determinant or through one or more 6-amino-caproyl (SAC) spacers. Each SAC unit has an extended span of 8 A. Guinea pigs immunized with these conjugates developed cellular immunity directed against the RAT determinant and antibody specific for the DNP determinant. The anti-DNP response was the same with one or three SAC spacers, but was significantly weaker when the two determinants were joined without a spacer. Animals immunized with either DNP-SAC-TYR or DNP-TYR developed neither cellular nor humoral immunity. Prior immunization with RAT potentiated the secondary anti-hapten response to DNP-SAC-RAT. Modification of RAT at either the arsonate or tyrosine positions showed that other charged groups (sulfonate and trimethylammonium) could substitute for arsonate without loss of immunogenicity. Removal of either the amino or carboxyl group from the side chain of tyrosine did not abolish immunogenicity, but immunogenicity was lost upon removal of both. Immunization with symmetrical bifunctional RAT-(SAC)n-RAT and cyclo-(L-RAT-D-RAT) antigens led to cellular immunity but no anti-arsonate antibody, suggesting a barrier to "self-help." These compounds were also ineffective in inducing a secondary anti-arsonate response in animals primed with arsonate-BSA conjugates and RAT.


2019 ◽  
Vol 6 (2) ◽  
pp. 51
Author(s):  
Jonathan E. Fogle ◽  
Jenna A. Scott ◽  
Glen W. Almond

Recent reports suggest that antibiotic therapy may either reduce or enhance the immune response to various porcine vaccines. Based upon these findings, we asked if antibiotic therapy alters immune cell populations, as measured by flow cytometry and/or vaccine-specific humoral immunity, as measured by sample to positive (S/P) antibody ratios. Here, we investigated the immuno-modulatory effects of enrofloxacin, ceftiofur, and tulathromycin on the immune response to a Mycoplasma hyopneumoniae (M. hyopneumoniae) and porcine circovirus type 2 (PCV-2) combination vaccine in weaned pigs. Maternal antibody likely interfered with the induction of immunity to M. hyopneumoniae. Antibiotic administration did not affect immune cell populations, as assessed by flow cytometry and did not affect the induction of humoral immunity to PCV-2.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3492-3492 ◽  
Author(s):  
Nikoletta Lendvai ◽  
Sacha Gnjatic ◽  
Erika Ritter ◽  
Yao-Tseng Chen ◽  
Christina Coughlin ◽  
...  

Abstract The type I Melanoma Antigen GEne (MAGE) proteins belong to the Cancer-Testis (CT) family of tumor-associated antigens and are widely expressed in solid and hematologic malignancies. They are immunogenic and frequently elicit spontaneous immune responses in patients with CT antigen-expressing tumors, particularly in malignant melanoma. In melanoma patients, there is high concordance between humoral and cellular immunity. Based on these findings, CT antigens are widely investigated as potential antigenic targets for tumor-specific therapeutic vaccines. We previously showed that the type I MAGE proteins CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A3 were commonly detected in primary myeloma specimens, and expression of CT7 and MAGE-A3 was correlated with abnormally elevated plasma cell proliferation. These findings suggest that type I MAGE may be rational targets for vaccine therapy in multiple myeloma. Therefore, it is important to determine if type I MAGE elicit cellular or humoral immune responses in myeloma patients. To investigate this hypothesis, we assessed cellular immunity against CT7 and humoral immunity against a broad panel of CT antigens. To quantify CT7-specific cellular immunity, expanded, polyclonal pools of T cells from the bone marrow, the tumor microenvironment, were co-cultured in interferon gamma (IFNγ) ELISpot assays with autologous antigen-presenting cells (APC) transduced with in vitro transcribed mRNA coding for CT7 or control antigens. CT antigen-specific humoral immunity was examined by ELISA assay using patient serum or plasma and recombinant CT antigens. This analysis demonstrated that 2/9 patients exhibited specific T cell immunity against CT7 in their bone marrow lymphocytes as measured by IFNγ secretion. These same two patients had positive titers for other CT antigens; one for MAGE-A1 (another type I MAGE), the other for SSX-1 (a structurally distinct CT antigen). Interestingly, neither patient had positive serology for CT7. Serum from 16 other myeloma patients did not have detectible antibody titers for a broad panel of CT antigens. These results show that CT antigens are immunogenic in myeloma patients, with cellular responses against CT7 and humoral responses against MAGE-A1 and SSX-1. However, unlike other types of cancer, there appears to be discordance between humoral and cellular immunity against CT7 in multiple myeloma. This may be due in part to the significant derangements of humoral immunity in this disease. These results support further investigation of immunologic therapies targeting type I MAGE in myeloma, especially therapeutic vaccine strategies.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Thiago Alvares da Costa ◽  
Marcos Vinicius Silva ◽  
Maria Tays Mendes ◽  
Tamires Marielem Carvalho-Costa ◽  
Lara Rocha Batista ◽  
...  

Dendritic cells (DCs) are major immune components, and depending on how these cells are modulated, the protective host immune response changes drastically.Trypanosoma cruziis a parasite with high genetic variability and modulates DCs by interfering with their capacity for antigen recognition, migration, and maturation. Despite recent efforts, the association between DCs andT. cruziI (TcI) and TcII populations is unknown. Herein, it was demonstrated that AQ1.7 and MUTUM TcI strains present low rates of invasion of bone marrow-derived DCs, whereas the 1849 and 2369 TcII strains present higher rates. Whereas the four strains similarly induced the expression of PD-L1, the production and expression of IL-10 and TLR-2, respectively, in DCs were differentially increased. The production of TNF-α, IL-12, IL-6, and CCL2 and the expression of CD40, CD80, MHC-II, CCR5, and CCR7 changed depending on the strain. The 2369 strain yielded the most remarkable results because greater invasion correlated with an increase in the levels of anti-inflammatory molecules IL-10 and PD-L1 but not with a change in the levels of TNF-α, MHC-II, or CD40 molecules. These results suggest thatT. cruzistrains belonging to different populations have evolved specific evasion strategies that subvert DCs and consequently the host response.


2019 ◽  
Vol 95 (11) ◽  
pp. 1058-1061
Author(s):  
Elena N. Kryuchkova ◽  
L. M. Saarkoppel ◽  
I. V. Yatsyna

There are considered features of disorders of the immune response in chronic exposure to dust aerosols. The detected changes of indices of the immune status of employees of the dust dangerous occupations and patients with chronic dust pathology of the lungs were unidirectional in the character, which is probably caused by manifestations of nonspecific response of the immune system to the dust factor. The deterioration of cellular immunity, humoral immunity and cytokine profile predisposes to the occurrence of immunopathologic states, contributing to the development of caused by both worksite and occupation pathology.


2021 ◽  
Vol 14 ◽  
pp. 175628642110128
Author(s):  
Anat Achiron ◽  
Mathilda Mandel ◽  
Sapir Dreyer-Alster ◽  
Gil Harari ◽  
David Magalashvili ◽  
...  

Background and Aims: The National Multiple Sclerosis Society and other expert organizations recommended that all patients with multiple sclerosis (MS) should be vaccinated against COVID-19. However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. We aimed to characterize humoral immunity in mRNA-COVID-19 MS vaccinees treated with high-efficacy DMTs. Methods: We measured SARS-CoV-2 IgG response using anti-spike protein-based serology (EUROIMMUN) in 125 MS patients vaccinated with BNT162b2-COVID-19 vaccine 1 month after the second dose. Patients were either untreated or under treatment with fingolimod, cladribine, or ocrelizumab. A group of healthy subjects similarly vaccinated served as control. The percent of subjects that developed protective antibodies, the titer, and the time from the last dosing were evaluated. Results: Protective humoral immunity of 97.9%, 100%, 100%, 22.7%, and 3.8%, was observed in COVID-19 vaccinated healthy subjects ( N = 47), untreated MS patients ( N = 32), and MS patients treated with cladribine ( N = 23), ocrelizumab ( N = 44), and fingolimod ( N = 26), respectively. SARS-CoV-2 IgG antibody titer was high in healthy subjects, untreated MS patients, and MS patients under cladribine treatment, within 29.5–55 days after the second vaccine dose. Only 22.7% of patients treated with ocrelizumab developed humoral IgG response irrespective to normal absolute lymphocyte count. Most fingolimod-treated MS patients had very low lymphocyte count and failed to develop SARS-COV-2 antibodies. Age, disease duration, and time from the last dosing did not affect humoral response to COVID-19 vaccination. Conclusions: Cladribine treatment does not impair humoral response to COVID-19 vaccination. We recommend postponing ocrelizumab treatment in MS patients willing to be vaccinated as a protective humoral response can be expected only in some. We do not recommend vaccinating MS patients treated with fingolimod as a protective humoral response is not expected.


2016 ◽  
Vol 5 (1) ◽  
pp. 1-4
Author(s):  
Jiacong You

Abstract Multiple studies elucidated the importance of cellular immune mechanisms for protection against Mycobacterium tuberculosis. However, recent studies showed that B lymphocytes play a role that is underestimated through various interactions with cellular immune response, forming an important aspect of host defense against M. tuberculosis bacteria. Therefore, the author hereby proposes a progressive perspective for immunology of tuberculosis, i.e., cellular immunity and humoral immunity are not necessarily mutually exclusive. The present study summarizes recent studies that support the important role of B lymphocytes in terms of M. tuberculosis infection.


2021 ◽  
Vol 1 (19) ◽  
pp. 174-176
Author(s):  
A.A. Grazhdantseva ◽  
D.V. Antonets ◽  
L.I. Karpenko ◽  
E.V. Starostina ◽  
M.B. Borgoyakova ◽  
...  

The constructed recombinant strain MVA-GP-VP40-MARV, in addition to the induction of humoral immunity, also forms specific cellular immunity to the Marburg virus, and therefore can be considered as a promising vaccine against Marburg fever.


2016 ◽  
Vol 89 (4) ◽  
pp. 493-498 ◽  
Author(s):  
Evelina Lesnic ◽  
Serghei Ghinda ◽  
Carmen Monica Pop

Background and aim. Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis complex, with an evolution and treatment outcome determined by the interaction between the mycobacterial and human genotypes. Various deficiencies of innate immune response starting from the first encounter of M. tuberculosis with lung cells endanger host infection control due to decreased triggering of cellular immune resistance and disturbed humoral immunity. Disturbed cell mediated immunity, known as the basic immune response in tuberculous infection, contributes to the deficient generation of central necrosis granuloma, consequently being responsible for severe clinical aspects and low final outcome. The tuberculosis patient’s immune assessment is important before treatment initiation, for establishing the risk reduction measures and increasing success rate.Material and methods. The immune study was conducted on 54 new pulmonary tuberculosis cases with treatment failure, 34 new pulmonary tuberculosis cases that successfully ended the treatment and 50 healthy group individuals. Immune assays performed were: blastic transformation of lymphocytes induced by different antigens, quantitatitve assessment of cellular immunity through CD4+ T cell and CD8+ T cell phenotyping, humoral immunity - through immunoglobulin isotyping, innate resistance – through phagocyte activity of neutrophils, the titter of anti-tuberculosis antibodies and the serum level of circulating immune complexes. Investigations were performed at the onset the treatment and at the end of intensive phase of the standard anti-tuberculosis treatment.Results. Immune disturbances evidenced in patients with treatment failure were: important deficiencies of cellular immunity, hyperactivity of humoral immunity and deficiencies of innate immunity. High predictive value for treatment failure showed the indices: deficiency of T lymphocytes count (OR=62.5) and T helper count (OR=12.5), high level of circulating immune complexes (OR=9.801), deficiency of innate resistance (decreased phagocytating index OR=2.875).Conclusions. For increasing the treatment success rate, the study of immune disturbances must be performed before of antituberculosis treatment initiation , especially of cellular immunity for the early start of immune adaptive treatment.


2002 ◽  
Vol 195 (6) ◽  
pp. 737-745 ◽  
Author(s):  
Brian P. O'Connor ◽  
Marilia Cascalho ◽  
Randolph J. Noelle

The contribution that long-lived bone marrow (BM) plasma cells (PCs) provide to enduring humoral immunity has been underscored by a number of recent studies. However, little is known about the immediate precursors that give rise to long-lived PCs in the BM of immune individuals. We have identified subsets of antigen-experienced B cells within the immune BM that are precursors to PCs. These PC precursors arise in the BM 14 days after immunization and persist for greater than 9 months. Phenotypically distinct subsets of PC precursors give rise to short-lived or long-lived PCs. The differentiation of PC precursors to PCs occurs in the absence of antigen and requires cell division. The functional significance of these newly identified PC precursors in the persistence and quality of the humoral immune response is discussed.


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