Immune Responses to SARS-CoV2 Mirror Societal Responses to COVID-19: Identifying Factors Underlying a Successful Viral Response

The adaptive immune system was sculpted to protect individuals, societies, and species since its inception, developing effective strategies to cope with emerging pathogens. Here, we show that similar successful or failed dynamics govern personal and societal responses to a pathogen as SARS-CoV2. Understanding the self-similarity between the health-protective measures taken to protect the individual or the society, help identify critical factors underlying the effectiveness of societal response to a pathogenic challenge. These include (1) the quick employment of adaptive-like, pathogen-specific strategies to cope with the threat including the development of “memory-like responses”; (2) enabling productive coaction and interaction within the society by employing effective decision-making processes; and (3) the quick inhibition of positive feedback loops generated by hazardous or false information. Learning from adaptive anti-pathogen immune responses, policymakers and scientists could reduce the direct damages associated with COVID-19 and avert an avoidable “social cytokine storm” with its ensuing socioeconomic damage

A Highly Sensitive Flow Cytometric Approach to Detect Rare Antigen-Specific T Cells: Development and Comparison to Standard Monitoring Tools

Personalized vaccines against patient-unique tumor-associated antigens represent a promising new approach for cancer immunotherapy. Vaccine efficacy is assessed by quantification of changes in the frequency and/or the activity of antigen-specific T cells. Enzyme-linked immunosorbent spot (ELISpot) and flow cytometry (FCM) are methodologies frequently used for assessing vaccine efficacy. We tested these methodologies and found that both ELISpot and standard FCM [monitoring CD3/CD4/CD8/IFNγ/Viability+CD14+CD19 (dump)] demonstrate background IFNγ secretion, which, in many cases, was higher than the antigen-specific signal measured by the respective methodology (frequently ranging around 0.05–0.2%). To detect such weak T-cell responses, we developed an FCM panel that included two early activation markers, 4-1BB (CD137) and CD40L (CD154), in addition to the above-cited markers. These two activation markers have a close to zero background expression and are rapidly upregulated following antigen-specific activation. They enabled the quantification of rare T cells responding to antigens within the assay well. Background IFNγ-positive CD4 T cell frequencies decreased to 0.019% ± 0.028% and CD8 T cells to 0.009% ± 0.013%, which are 19 and 13 times lower, respectively, than without the use of these markers. The presented methodology enables highly sensitive monitoring of T-cell responses to tumor-associated antigens in the very low, but clinically relevant, frequencies

The mechanisms controlling NK cell autoreactivity in TAP2-deficient patients

The killing of natural killer (NK) cells is regulated by activating and inhibitory NK receptors that recognize mainly class I major histocompatibility complex (MHC) proteins. In transporter associated with antigen processing (TAP2)–deficient patients, killing of autologous cells by NK cells is therefore expected. However, none of the TAP2-deficient patients studied so far have suffered from immediate NK-mediated autoimmune manifestations. We have previously demonstrated the existence of a novel class I MHC–independent inhibitory mechanism of NK cell cytotoxicity mediated by the homophilic carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1) interactions. Here, we identified 3 new siblings suffering from TAP2 deficiency. NK cells derived from these patients express unusually high levels of the various killer cell inhibitory receptors (KIRs) and the CEACAM1 protein. Importantly, the patients' NK cells use the CEACAM1 protein to inhibit the killing of tumor and autologous cells. Finally, we show that the function of the main NK lysis receptor, NKp46, is impaired in these patients. These results indicate that NK cells in TAP2-deficient patients have developed unique mechanisms to reduce NK killing activity and to compensate for the lack of class I MHC–mediated inhibition. These mechanisms prevent the attack of self-cells by the autologous NK cells and explain why TAP2-deficient patients do not suffer from autoimmune manifestations in early stages of life. <br/

MOESM1 of A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells

Additional file 1: Figure S1. Grading of dissociation quality of all glial tumors. The three different parameters accounting for the dissociation cumulative grade-CG, i.e. Clumps, Remnants and Gooeyness, were graded following tumor dissociation using NP -2hr, dispase- 1hr, NP-ON and dispase-ON. The parameters were graded from 1 to 3, with 1 representing low dissociation quality and 3- high dissociation quality culture (see materials and methods). Statistics: Cell remnants following dissociation using NP-2hr to dispase-1hr (P < 0.03)