Immune cell activation and lymphocyte efficacy

The generation and regulation of an effective immune response depends on the orchestrated dynamics of various types of immune cells and molecular factors. Disturbances in the migration or the timing of individual processes can lead to ineffective responses. In a series of projects we are investigating how cell-cell interactions and local conditions influence the generation, efficacy and regulation of immune responses. Hereby, we are combining different types of measurements including single-cell and live-cell microscopy data with individual cell-based in order to reveal and decipher the processes that influence these dynamics.

Collaborators: Annette Oxenius (ETH Zurich), Christoph Scheiermann (University of Geneva), Jacqueline Marvel (CIRI, Lyon), Wolfgang Kastenmüller (Univ. Würzburg)

Publications: Oderbolz et al, bioRxiv 2021 (preprint)

Influence of prior immunity on novel immune responses

Immunological memory is subject to dynamical changes based on individual exposure histories. Analysing experimental and clinical data on influenza vaccination with different types of mathematical models and methods, we investigate how prior immunity and antigenic distances between viral strains affect the generation of novel responses and the composition of the memory cell population. Based on these analyses, we aim at revealing how existing immunity, e.g. against cross-reactive viral strains, can be efficiently exploited by vaccination to increase the protective capacity of immunological memory.

Collaborators: Samuel Wilks, Antonia Netzl, Derek Smith (Univ. of Cambridge), Jürgen Pahle (BioQuant, Heidelberg)

Optimizing vaccination regimens against Malaria infection

The project aims at determining optimal malaria vaccination regimens that rely on the use of attenuated parasites and the generation of CD8+ T cell responses. Combining mathematical models with experimental data that show the influence of variations in dosage, timing and frequency during prime-boost vaccination regimes in mice, we analyse and quantify the dynamics of memory T cell generation in various organs. Our analysis helps to reveal the interplay and importance of organ-specific T cell responses for the generation of protective, tissue-resident T cells in the liver.

Participants: Michael Gabel; Roland Frank, Ann-Kristin Mueller (Univ. Hospital HD)

Publication: Frank et al., Front Immunol 2018 

Memory CD8+ T cell dynamics during MCMV infection

Inflationary CD8+ T cell responses against Cytomegalovirus (CMV), a beta-herpesvirus that establishes life-long persistence in healthy individuals, are promising targets for the development of T cell based vaccines against various pathogens. These inflationary CD8+ T cells increase in numbers after resolution of acute infection and eventually stabilize at high frequencies with life-long persistence. In this project, we study the individual dynamics of inflationary and non-inflationary CD8+ T cell populations in response to murine CMV (MCMV) infection by combining mathematical models and experimental data to reveal the generation and maintenance of these immune responses.

Participants: Michael Gabel; Annette Oxenius (ETH Zurich)

Publication: Gabel et al., Front Immunol 2019