Local Immunity and Local Immune Responses

AbstractThe level of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative (TNBC) and HER2-positive breast cancers convey prognostic information. The importance of systemic immunity to local immunity is unknown in breast cancer. We previously demonstrated that histological alterations in axillary lymph nodes (LNs) carry clinical relevance. Here, we capture local immune responses by scoring TILs at the primary tumor and systemic immune responses by recording the formation of secondary follicles, also known as germinal centers, in 2,857 cancer-free and involved axillary LNs on haematoxylin and eosin (H&E) stained sections from a retrospective cohort of 161 LN-positive triple-negative and HER2-positive breast cancer patients. Our data demonstrate that the number of germinal center formations across all cancer-free LNs, similar to high levels of TILs, is associated with a good prognosis in low TILs TNBC. This highlights the importance of assessing both primary and LN immune responses for prognostication and for future breast cancer research.

Download Full-text

Mucosal Immunization with High-Mobility Group Box 1 in Chitosan Enhances DNA Vaccine-Induced Protection against Coxsackievirus B3-Induced Myocarditis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00466-13 ◽

2013 ◽

Vol 20 (11) ◽

pp. 1743-1751 ◽

Cited By ~ 13

Author(s):

Maowei Wang ◽

Yan Yue ◽

Chunsheng Dong ◽

Xiaoyun Li ◽

Wei Xu ◽

...

Keyword(s):

Immune Responses ◽

Dna Vaccine ◽

Myocardial Injury ◽

Flow Cytometric Analysis ◽

High Mobility ◽

Coxsackievirus B3 ◽

High Mobility Group ◽

Secretory Iga ◽

Adjuvant Effect ◽

Local Immunity

ABSTRACTCoxsackievirus B3 (CVB3), a small single-stranded RNA virus, belongs to thePicornaviridaefamily. Its infection is the most common cause of myocarditis, with no vaccine available. Gastrointestinal mucosa is the major entry port for CVB3; therefore, the induction of local immunity in mucosal tissues may help control initial viral infections and alleviate subsequent myocardial injury. Here we evaluated the ability of high-mobility group box 1 (HMGB1) encapsulated in chitosan particles to enhance the mucosal immune responses induced by the CVB3-specific mucosal DNA vaccine chitosan-pVP1. Mice were intranasally coimmunized with 4 doses of chitosan-pHMGB1 and chitosan-pVP1 plasmids, at 2-week intervals, and were challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 immunization alone, coimmunization with chitosan-pHMGB1 significantly (P< 0.05) enhanced CVB3-specific fecal secretory IgA levels and promoted mucosal T cell immune responses. In accordance, reduced severity of myocarditis was observed in coimmunized mice, as evidenced by significantly (P< 0.05) reduced viral loads, decreased myocardial injury, and increased survival rates. Flow cytometric analysis indicated that HMGB1 enhanced dendritic cell (DC) recruitment to mesenteric lymph nodes and promoted DC maturation, which might partly account for its mucosal adjuvant effect. This strategy may represent a promising approach to candidate vaccines against CVB3-induced myocarditis.

Download Full-text

Systemic immunosuppression by HIV infection influences HPV transcription and thus local immune responses in condyloma acuminatum

International Journal of STD & AIDS ◽

10.1258/0956462981922197 ◽

1998 ◽

Vol 9 (5) ◽

pp. 268-271 ◽

Cited By ~ 29

Author(s):

I Arany ◽

S K Tyring

Keyword(s):

Immune Responses ◽

Hiv Infection ◽

Hpv Infection ◽

Molecular Characteristics ◽

Immune Functions ◽

Local Immunity ◽

Immunodeficiency Virus ◽

Polymerase Chain ◽

Pcr Techniques ◽

Oncogenic Hpv

Summary: Human immunodeficiency virus (HIV) infection is considered to influence the pathogenesis of human papillomavirus (HPV)-associated diseases. It is not clear whether this occurs directly through molecular interactions between viral genes and/or indirectly through effects on the immune functions. In the present study we compared molecular characteristics of penile condylomas from immunocompetent and HIV-positive individuals. Using polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR techniques we determined some characteristics of local immune responses and transcriptional activity of both viruses. Our findings revealed that HIV-seropositivity was accompanied by multiple HPV infection and a CD4-count-dependent appearance of oncogenic HPV-types. HIV infection also changed the patterns of HPV transcription favouring transcription of early genes such as E7. Apparently, HIV infection influences local immunity by altering HPV transcription and by systemic immunodeficiency.

Download Full-text

Local Immunity and Local Immune Responses (Part 1 of 3)

Progress in Allergy Vol. 27 - Chemical Immunology and Allergy ◽

10.1159/000314479 ◽

1979 ◽

pp. 1-21

Author(s):

Rama Ganguly ◽

Robert H. Waldman

Keyword(s):

Immune Responses ◽

Local Immunity

Download Full-text

Local Immunity and Local Immune Responses (Part 2 of 3)

Progress in Allergy Vol. 27 - Chemical Immunology and Allergy ◽

10.1159/000314481 ◽

1979 ◽

pp. 22-42

Author(s):

Rama Ganguly ◽

Robert H. Waldman

Keyword(s):

Immune Responses ◽

Local Immunity

Download Full-text

Mucosal and Systemic Immune Responses in Humans after Primary and Booster Immunizations with Orally Administered Invasive and Noninvasive Live Attenuated Bacteria

Infection and Immunity ◽

10.1128/iai.67.7.3680-3685.1999 ◽

1999 ◽

Vol 67 (7) ◽

pp. 3680-3685 ◽

Cited By ~ 60

Author(s):

Jean-Francois Viret ◽

Didier Favre ◽

Bernhard Wegmüller ◽

Christian Herzog ◽

John U. Que ◽

...

Keyword(s):

Immune Responses ◽

Oral Vaccine ◽

Salmonella Typhi ◽

Primary Immunization ◽

Local Immunity ◽

Booster Immunization ◽

Antibody Secreting Cell ◽

Serum Igg ◽

Live Oral Vaccine ◽

Antibody Titers

ABSTRACT The mucosal and systemic immune responses after primary and booster immunizations with two attenuated live oral vaccine strains derived from a noninvasive (Vibrio cholerae) and an invasive (Salmonella typhi) enteric pathogen were comparatively evaluated. Vaccination with S. typhi Ty21a elicited antibody-secreting cell (ASC) responses specific for S. typhi O9, 12 lipopolysaccharide (LPS), as well as significant increases in levels of immunoglobulin G (IgG) and IgA antibodies to the same antigen in serum. A strong systemic CD4+ T-helper type 1 cell-mediated immune (CMI) response was also induced. In contrast to results with Ty21a, no evidence of a CMI response was obtained after primary immunization with V. cholerae CVD 103-HgR in spite of the good immunogenicity of the vaccine. Volunteers who received a single dose of CVD 103-HgR primarily developed an IgM ASC response against whole vaccine cells and purified V. cholerae Inaba LPS, and seroconversion of serum vibriocidal antibodies occurred in four of five subjects. Serum IgG anti-cholera toxin antibody titers were of lower magnitude. For both live vaccines, the volunteers still presented significant local immunity 14 months after primary immunization, as revealed by the elevated baseline antibody titers at the time of the booster immunization and the lower ASC, serum IgG, and vibriocidal antibody responses after the booster immunization. These results suggest that local immunity may interfere with colonization of the gut by both vaccine strains at least up to 14 months after basis immunization. Interestingly, despite a low secondary ASC response, Ty21a was able to boost both humoral (anti-LPS systemic IgG and IgA) and CMI responses. Evidence of a CMI response was also observed for one of three volunteers given a cholera vaccine booster dose. The direct comparison of results with two attenuated live oral vaccine strains in human volunteers clearly showed that the capacity of the vaccine strain to colonize specific body compartments conditions the pattern of vaccine-induced immune responses.

Download Full-text

Local sympathetic innervations modulate the lung innate immune responses

Science Advances ◽

10.1126/sciadv.aay1497 ◽

2020 ◽

Vol 6 (20) ◽

pp. eaay1497

Author(s):

Tingting Liu ◽

Lu Yang ◽

Xiangli Han ◽

Xiaofan Ding ◽

Jiali Li ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Adrenergic Receptor ◽

Innate Immune ◽

Surgical Removal ◽

Innate Immune Responses ◽

Neural Signals ◽

Critical Function ◽

Local Immunity ◽

Β2 Adrenergic Receptor

Local immunity of the lung needs to be under tight control. However, how efferent neural signals influence lung immunity remains incompletely understood. Here, we report the development of a modified iDISCO-based protocol, iDISCO(ace), for whole-tissue 3D assessment of neural innervations and immune reactions in intact, unsectioned lung tissues. We observed that genetic, pharmacologic, or surgical removal of local sympathetic innervations promoted LPS-elicited innate immune response in the lung. Also, sympathetic ablation enhanced IL-33–elicited type 2 innate immunity. We further show that the sympathetic neurotransmitter norepinephrine, or specific agonists of the β2-adrenergic receptor, can inhibit the LPS- or IL-33–elicited immune response in a cell-intrinsic manner. Moreover, genetic deletion of the β2-adrenergic receptor produced immunomodulatory effects similar to those observed with sympathetic ablation. Together, this study elucidates the critical function of local sympathetic innervations in negatively modulating the lung innate immune responses.

Download Full-text

Association of Toll-Like Cell Receptors TLR2 (p.Arg753GLN) and TLR4 (p.Asp299GLY) Polymorphisms with Indicators of General and Local Immunity in Patients with Atopic Dermatitis

Journal of Immunology Research ◽

10.1155/2017/8493545 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Yury A. Tyurin ◽

Anton F. Shamsutdinov ◽

Nikolay N. Kalinin ◽

Alsou A. Sharifullina ◽

Irina D. Reshetnikova

Keyword(s):

Atopic Dermatitis ◽

Immune Responses ◽

System Response ◽

Immunological Parameters ◽

Local Immunity ◽

Innate And Adaptive Immunity ◽

Immune System Response ◽

Relationship Of ◽

The Relationship ◽

Control Study

A whole group of polymorphisms of genes involved in the formation of the epidermal barrier, immune responses, and their regulation is important in the formation of atopic phenotype. The purpose of the study is to determine the relationship of polymorphisms of genes of Toll-like receptors TLR2 and TLR4 with clinical and immunological parameters in atopic dermatitis patients in a “case-control” study. Polymorphisms of genes TLR2 (p.Arg753Gln) and TLR4 (Asp299Gly) were detected by PCR. Parameters of the state of innate and adaptive immunity were assessed by the level of local production of sIgA, cytokine profile of blood serum for IL-4, IL-10, and IFN-γ. Biological samples from 50 people with allergic pathology, aged 4.5 to 35 years, and 100 healthy individuals (controls) were analyzed. Observed dysregulation of cytokine production (IL-4, IL-10) in patients with heterozygous polymorphic genotypes probably reflects an imbalance of Th1/Th2/Th17 regulation of immune system response in these individuals.

Download Full-text