Helmholtz Immunology

How do multicellular organisms respond to foreign invaders? This is what Immunology, one of the branches of biomedical sciences, wants to understand. Many of the chronic diseases people suffer from are linked to the immune system. It interacts with bacteria, viruses, toxins and other environmental influences. But also malfunctions of the immune system lead to allergies or autoimmune diseases like diabetes 1.

The number of people suffering from chronic diseases has dramatically increased worldwide over recent decades, and diabetes and lung disease have become the leading cause of death globally. Comprehensive and interdisciplinary understanding of the mechanisms and sensitive timeframes involved when and how immunological factors contribute to diabetes and lung disease pathology is crucial to the development of suitable strategies for diagnosis and targeted therapies.

The teams in the Helmholtz Immunology community come from a broad range of scientific domains. By joining forces they aim to become a driving force for this cross-cutting topic of high relevance to many diseases. They aim to develop a vibrant, inspiring and internationally competitive research environment, promoting creativity and the generation and sharing of new ideas. Situated in an area of scientific excellence in Munich, the Helmholtz Immunology community also benefits from stimulating interactions with several of Germany’s top universities and research institutions such as LMU, TUM and the Max Planck Institute of biochemistry.

Type 1 Diabetes (T1D) is characterized by a breakdown of immunological self-tolerance to the insulin producing islet beta cells, and consequently their destruction by autoreactive T cells. We aim to dissect mechanisms of aberrant immune activation that can interfere with tolerance induction during islet autoimmunity and that promote progression from islet autoimmunity to clinical T1D. We strive to integrate our findings into understanding mechanisms of immune tolerance in diabetes with the future goal of developing innovative precision medicines.

Chronic obstructive pulmonary disease (COPD) is a major public health problem and its prevalence as well as morbidity and mortality are still rising. Innate inflammatory immune cells, i.e. neutrophils and macrophages, and CD8+ T cells have been described to be considerably involved in lung tissue damage in COPD. However, increasing evidence suggests that the inflammatory response of other specific immune cells, in particular CD4+ T and B cells present in the lungs of COPD patients, contributes to the pathogenesis of COPD.

During the last decade, it became obvious that distinct subsets of T cells exist that fulfill diverse tasks in our immune system. Our group is interested in understanding the contribution of the so-called T helper (Th) cells to the pathogenesis of allergic diseases. Here, our focus lies on allergic diseases of the skin such as atopic eczema (‘Neurodermitis’) and allergic contact dermatitis, but also on non-allergic inflammatory skin conditions such as psoriasis (‘Schuppenflechte’).

Type 2 immune responses confer protection against worm parasites (helminths), but also drive inflammation and immunopathology in allergy, asthma and nasal polyposis. The mission of the group is to explore regulatory mechanisms of type 2 immune responses to support the prevention and therapy of chronic inflammatory diseases.

We are interested in the establishment, maintenance and break of immunological tolerance in the intestinal system with a particular focus on prevention of allergic diseases. We believe that a better understanding of the multiple interactions between a healthy microbiota with the innate and adaptive immune system is mandatory for this task. The identification of novel mechanisms will contribute to our knowledge on how the intestinal homeostasis is maintained in general and how such mechanisms influence immune responses elsewhere in the body.

The research of The Institute of Allergy Research (IAF) is focused on the understanding of mechanisms involved in the development of allergies and allergen tolerance in the context of genetic predisposition, immune system and environmental factors. As part of the Center of Allergy & Environment (ZAUM) the IAF conducts applied, clinical and basic research. The aim of the research is to understand the mechanisms of allergic diseases, to assess risks for the onset of allergy as well as to develop novel strategies for prevention und therapy.

We investigate the molecular mechanisms of physiological and pathological immune responses such as the autoimmune diseases type 1 diabetes and lupus erythematosus. The goal of AMIR is to understand the molecular programs in T cells, which enable the distinction between self and foreign antigenic structures. The focus is on post-transcriptional gene regulations during T cell differntiation.

The pathogenesis of diabetes mellitus hinges on the loss of pancreatic islet beta cells which in type 1 diabetes is mediated by autoimmunity. We have studied how autoimmunity develops in the course of the disease in children, the target beta cell antigens and epitopes, and the factors that predispose to autoimmunity. We showed that autoimmunity develops most frequently around 1 to 2 years of age and that the proinsulin prohormone is a primary target antigen in this age period.

The Monoclonal Antibody Core Facillity at the Helmholtz Zentrum München (formerly GSF) was founded in 1990 by Dr. Elisabeth Kremmer and since then has established monoclonal antibodies against more than 2000 targets.

We collaborate with scientist at the Helmholtz Zentrum München and with national and international Universities and Research Centers to generate new antibodies and to develop new antibody-based technologies.

The Institute of Diabetes Research focuses on gaining knowledge about the development and the potential prevention of type 1 diabetes. Screenings enable early detection and we strive to delay or even prohibit the disease in the future. Our goal is a world without type 1 diabetes! Therefore, we study the molecular mechanisms of the pathogenesis, particularly the interaction of environment, genetics and the immune system. We aim to identify markers for early diagnosis and to develop therapies for the prevention and cure of type 1 diabetes.

The Research Unit Cellular Signal Integration (AZS) at the Institute of Molecular Toxicology and Pharmacology (TOXI) conducts research for a better understanding of cellular response pathways. In doing so, it focuses on the interaction of proteins complexes and the effects of posttranslational modifications. The aim of this research is to understand the faulty regulation of the signal complexes in the immune system in case of infectious diseases and the development of lymphoma, and to attack this pharmacologically.

We are strongly committed to advance our understanding of the pathogenesis of type 1 diabetes in order to move the field forward. Type 1 diabetes is an autoimmune disease in which clinical symptoms arise as a result of beta cell destruction and insulin deficiency. While genetic and environmental factors contribute to the disease, in recent years it has become increasingly evident that beta cells might be contributing to their own destruction and might have an active role in type 1 diabetes development.

The research of the Institute for Asthma and Allergy Prevention (IAP) at Helmholtz Zentrum München is focusing on the underlying mechanisms of asthma and allergies in childhood. The aim is to prevent the development and the manifestation of the disease. To this end, the scientists employ extensive international field and population studies as well as clinical studies and laboratory experiments. One prominent example is the so-called hygiene hypothesis, to which Erika von Mutius, director of IAP, and her team contributed robust evidence.

Tolerance to ”self” is a fundamental property of the immune system; its breakdown can lead to autoimmune diseases such as multiple sclerosis and diabetes. Selection processes in the thymus are essential for the generation of a self-tolerant T cell repertoire, either through removal of potentially dangerous T cells or through the induction of regulatory T cells. Our aim is to understand how the thymic microenvironment orchestrates these cell fate decisions.

Die Arbeitsgruppe Immunpharmakologie ist fokussiert auf Fragestellungen der Grundlagen- und angewandten Immunologie verschiedener Tumorerkrankungen. Unser Arbeitsgruppe bearbeitet dabei zwei zentrale Fragestellungen aus den Bereichen der Tumorimmunologie und Tumorimmuntherapie:

Our mission is to understand the basic principles of the blood and immune system by studying human patients with rare inherited disorders. Starting with the analysis of the patients’ phenotype, we unravel the genetic etiology of rare diseases using a variety of in vitro and in vivo model systems. We aim to develop novel therapeutic strategies with a particular focus on cell and gene therapy.

Inflammatory bowel diseases (IBD) comprise a heterogeneous group of chronic relapsing and remitting conditions defined as Crohn’s disease, ulcerative colitis, and other unclassified forms. The pathogenesis of IBD is multifactorial, encompassing environmental factors, imbalances of the microbial flora, epithelial barrier defects, immune dysfunctions, and genetics. Children with rare forms of very early onset IBD (VEO-IBD) show a distinct and severe phenotype refractory to standard medical and surgical treatment, suggesting that the pathogenesis is triggered mainly by inherited factors.

We are trying to understand what mechanisms are employed by the innate immune system to distinguish self from non-self or harmless from dangerous, respectively. Central to this complex task is a repertoire of pattern recognition receptors (PRRs) that have evolved to detect the presence of microorganisms. The ligands or targets of these PRRs are commonly referred to as microbe-associated molecular patterns (MAMPs).

We study circadian rhythms in the immune response using an interdisciplinary approach at the intersection of immunology, biochemistry and physiology. The recruitment of leukocytes to tissues and their localization within tissues plays a crucial role in the immune response. Recruitment of leukocytes to tissues underlies a circadian, i.e daily rhythm. This supports accumulating evidence for circadian oscillations in many components of the immune system with the potential to affect disease onset and therapies.

Human neutrophils are well known to play an important role in host defense and inflammation. Adhesion molecules of the ß2 integrin (CD11/CD18) family are critically involved in the recruitment and activation of neutrophils during inflammation by mediating e.g. firm adhesion, intraluminal crawling and phagocytosis of opsonized particles. Ligand binding of the ß2 integrins activates the non-receptor tyrosine kinase Syk which plays an important role for neutrophil activation in inflammatory settings. Our group focusses on Syk-mediated signalling events required for leukocyte activation at the molecular level using different techniques including real-time analysis of live cells. By integrating studies on the molecular and cellular level as well as animal studies, this project is intended to improve the understanding of the spatial and temporal dynamics of neutrophil activation in a (patho-) physiological context which may lead to the identification of new molecular targets for therapeutic intervention.

Our research is focussed on lymphocyte interactions in vivo. We are especially interested in Dendritic Cell (DC) biology and the immune responses resulting from interactions between DC and T lymphocytes. More precisely, we are studying the role of DCs in induction of immunity and tolerance. Here we exploit various animal models to analyze development, function and biology of DCs.

Development, plasticity and function of plasmacytoid dendritic cells Recognition of viral nucleic acids by dendritic cells Functional diversity of dendritic cell subsets in intestinal inflammation Regulation of cellular immune responses to yellow fever vaccination

My laboratory is interested in parameters of lymphocyte activation during an immune response in vivo. T cells are activated by antigen that is processed and presented by dendritic cells in lymphoid tissues. Dendritic cells mediate signals to T cells by way of a multitude of molecules and thereby critically influence their fate like apoptosis, proliferation, and effector and memory cell differentiation. The presentation of antigen as peptide-MHC complexes is the key factor in this process.

Unsere Forschung konzentriert sich auf normale und im Krankheitsfall deregulierte Signalprozesse im Immunsystem. Wir untersuchen zum einen, wie normale Immunzellen Pathogene erkennen und über welche molekularbiologischen Mechanismen diese Erkennung eine Aktivierung der Immunabwehr einleitet. Weiterhin möchten wir die Frage beantworten, wie pathologisch deregulierte Signale in Blutzellen zur bösartigen Transformation und damit zur Entstehung von Leukämien oder Lymphomen führen. Ziel ist, Grundlagen zur therapeutischen Manipulation des Immunsystems zu liefern.

T-Zellvermittelte Immunantworten bilden die Grundlage des immunologischen Schutzes gegen virale und viele bakterielle Krankheitserreger sowie gegen bösartige Tumore. Die Forschungs­aktivitäten von Prof. Zehn konzentrieren sich auf die Identifizierung neuer molekularer Mechanis­men, um T-Zellen für prophylaktische und therapeutische Zwecke effizienter zu nutzen. Ziel ist die Entwicklung neuer Behandlungsansätze für Menschen und Nutztiere. Einen weiteren Schwerpunkt bilden Untersuchungen, wie Immunzellen die Organphysiologie beeinflussen und zu pathophysio­logischen Prozessen in Nutztieren beitragen.

Our mission is to understand the basic principles of the blood and immune system by studying human patients with rare inherited disorders. Starting with the analysis of the patients’ phenotype, we unravel the genetic etiology of rare diseases using a variety of in vitro and in vivo model systems. We aim to develop novel therapeutic strategies with a particular focus on cell and gene therapy.

Up to 100 trillion microbes live in the human intestine. They are indispensable for health. However, changes in their relationship to the host have also been associated with diseases. Multiple sclerosis (MS) is one of these diseases, as Gurumoorthy Krishnamoorthy's work shows. With his research group "Neuroinflammation and Mucosal Immunology" he traces the responsible microbes. Using a specially developed transgenic MS mouse model, he was able to prove that these animals, which have an intact intestinal flora, show inflammatory reactions in the brain that are similar to those of multiple sclerosis in humans without external influences. In the following experiments on the mouse model, Krishnamoorthy's group was able to identify another important trigger: the cooperation of different cell types of the immune system.

Integrins are receptors on the cell surface that bind proteins of the extracellular matrix and connect them to the actin-myosin cytoskeleton. By orchestrating the gradual assembly of a gigantic signaling hub with hundreds of proteins, integrins can trigger biochemical signals and transmit and receive mechanical signals. Reinhard Fässler's Department "Molecular Medicine" is investigating how integrins assemble and disassemble their large and complex signaling hubs.

Immune reactions in the body are highly coordinated in order to fight infections with tailor-made defense reactions. Felix Meissner and his research group "Experimental Systems Immunology" are hoping to decipher how the immune system's task forces work together by elucidating their communication in molecular detail. Mass spectrometry makes it possible to identify hundreds or even thousands of different proteins in a mixture of molecules. For the first time, Meissner and his team were able to analyze the entirety of messengers emitted by immune cells. Communicating immune cells play a role in all inflammatory reactions in the body, including rheumatism, arteriosclerosis, diabetes, neurodegeneration and many other diseases.