October 5th, 2010

Experimental Immunology

Loehning

Immunological memory protects the organism from pathogens it already defeated. This is achieved by a faster and more effective antigen-specific immune re­sponse. However, a misdirected, pathogenic immuno­logical memory can also trigger immunopathology or autoimmunity. Immunological memory is embodied in long-lived antibody-secreting plasma cells and memory T and B cells that differentiate from naive pre­cursors upon antigen exposure. An in-depth under­standing of immunological memory is crucial for the development of efficient vaccination strategies and cu­rative therapies of chronic immunopathology and au­toimmunity.

The main goal of the Lichtenberg group is a molecular understanding of the generation, maintenance and functional capacity of immunological memory. We study the differentiation pathways and inductive sig­nals of effector and memory cells. In addition, we ana­lyze the stability and flexibility of memory cells and their effector mechanisms as well as their functional activity in vivo during inflammation and viral or para­site infections. Here, we examine molecular factors that regulate the longevity and functional quality of memory cells. Our studies are performed at single-cell level: We assess individual lymphocytes to obtain in­sight into the quantitative regulation of the molecular switches that control lymphocyte cell fate decisions.

T helper (Th) cells secrete defined amounts of specific cytokines to determine not only the type of a particular immune response, but also its intensity. By single-cell analysis and mathematical modeling, we could show that during their initial activation, individual Th cells not only ‘learn’ which cytokines they should produce, but also in which quantity (see figure). This Quantita­tive Cytokine Memory is stably maintained in memory Th cells and recalled upon secondary antigen encoun­ter (Helmstetter et al., Immunity 2015). While analyz­ing the signals inducing quantitative programming of Th cells, we found that the alarmin interleukin (IL)-33 determines the intensity of Th type 1 (Th1) cell activa­tion upon viral infection. IL-33 enhances the clonal ex­pansion of Th1 cells and promotes their differentiation to potent, polyfunctional effector cells (Baumann et al., PNAS 2015). Moreover, we demonstrated a quantita­tive regulation of effector functions in individual Th cells via antagonizing key transcription factors. During parasite infections, hybrid Th1/Th2 cells are generated that stably co-express key Th1 and Th2 transcription factors. As these factors inhibit each other, a hybrid cell produces rather small amounts of Th1 and Th2 effec­tor molecules. Yet, hybrid cells support both Th1 and Th2 immune responses while inducing less immuno­pathologic damage than classic Th1 or Th2 cells (Peine et al., PLoS Biol. 2013).

 

Radbruch Prof. Dr. rer. nat. Andreas Radbruch Cell Biology Triantafyllopoulou_klein Dr. Antigoni Triantafyllopoulou Innate Immunity in Rheumatic Diseases Thurley Dr. Kevin Thurley Systems Biology of inflammation Ahmed Hegazy Prof. Dr. med. Dr. rer. nat. Ahmed N. Hegazy Inflammatory Mechanisms Polansky Dr. Julia Polansky-Biskup Immuno-Epigenetics Melchers Prof. Dr. Fritz Melchers Lymphocyte Development Farzin Mashreghi Dr. Mir-Farzin Mashreghi Therapeutic Gene Regulation Kruglov Dr. rer. nat. Andrey Kruglov Chronic Inflammation Loehning Prof. Dr. Max Löhning Pitzer Lab Osteoarthritis Research Kubagawa Prof. Dr. Hiromi Kubagawa Humoral Immune Regulation Hauser Prof. Dr. med. vet. Anja Erika Hauser Immune Dynamics Tokoyoda Dr. Koji Tokoyoda Osteoimmunology Scheffold Prof. Dr. rer. nat. Alexander Scheffold Cellular Immunology Niesner Dr. rer. nat. Raluca Niesner Biophysical Analytics Strangfeld Dr. med. Anja Strangfeld Pharmacoepidemiology Minden Prof. Dr. med. Kirsten Minden Paediatric Rheumatology Listing Dr. Joachim Listing Statistics & Clinical Studies Angela_Zink_230x230 Prof. Dr. Angela Zink Health Services Research Worm Prof. Dr. med. Margitta Worm Allergology Poddubnyy Prof. Dr. Denis Poddubnyy Spondyloarthritides Riemekasten Prof. Dr. med. Gabriela Riemekasten Cell Autoimmunity Hiepe Prof. Dr. med. Falk Hiepe Autoimmunology Hamann Prof. Dr. rer. nat. Alf Hamann Experimental Rheumatology Doerner Prof. Dr. med. Thomas Dörner B Cell Memory Buttgereit Prof. Dr. med. Frank Buttgereit Glucocorticoids & Bioenergetics Romagnani Prof. Dr. Chiara Romagnani Innate Immunity Hutloff Dr. rer. nat. Andreas Hutloff Chronic Immune Reactions Fillatreau Prof. Dr. rer. nat. Simon Fillatreau Immune Regulation Baumgrass Prof. Dr. Ria Baumgrass Signal Transduction Nedospasow Prof. Dr. Sergei Nedospasov Inflammation Biology