Susceptibility to infection: What part does the immune system play?

Newborn babies and the elderly are particularly susceptible to bacterial and viral infection. But why is this? How can we predict who will contract an infection – and how can they be optimally treated? To find answers to these questions, the RESIST team is also conducting research on the immune system in these vulnerable groups.

The focus of research involving newborns is on the interaction with the microbiome (the entirety of the microorganisms that colonize the body) as it develops with the child. Why? These microorganisms ‘train’ the immune system and could potentially be used to promote immune maturation after birth so as to prevent severe infections that can result from bacteria and from life-threatening viral diseases.

Interaction between the immune system and the microbiome is also being studied in relation to another medical condition affecting adults. This is spondyloarthrosis, a class of rheumatic diseases that manifest as inflammation of the musculoskeletal system, and whose onset is triggered by an infection.
RESIST will investigate the influence the gut microbiome has on whether the patient recovers from this condition or whether it becomes chronic.

In elderly people, the RESIST team will look at factors such as their vulnerability to flu viruses or the chicken pox virus, which causes shingles. Another research focus in RESIST, where older people are involved, is vaccination. It is still not clear why vaccination of elderly individuals is often not as effective or completely useless. The development of new vaccines and innovative therapies are of interest in several RESIST projects dealing with hepatitis.

Projekte in area B (immune system)

B1

Which influence do intestinal bacteria have on the early development of the immune system and thus on susceptibility to infection?

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. The most important threats are infections. About a quarter of all infants born < 32 weeks of gestation develop a serious infection during infancy…

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B2

Arthritis triggers: Can intestinal bacteria trigger rheumatological diseases?

Spondyloarthritis (SpA) is a group of frequent chronic rheumatological diseases which start in young adults and lead to disability of the patients. Current therapies are not efficient enough in stopping the progressive impairment of the musculoskeletal system…

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B3

Maturation of the immune system: Which impact do intestinal bacteria and infections have on the fitness of immune cells?

Infections are one of the main risks leading to neonatal morbidity and mortality of preterm infants. There is little information on how the immune cell maturation and immune status of preterm babies differs from that of term infants. This project focuses on γδ T cells, αβ T cells and B cells…

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B4

Mechanisms of immune receptors: NLRs (nod-like receptors) initiate the defence against pathogens, but can also cause harm in humans. How can they be used for therapeutic puposes?

Nod-like receptors (NLRs) constitute a vital part of the innate immune system. These immune receptors recognize invading pathogens from within the cell and trigger an inflammatory reaction in the affected tissues via the activation and secretion of proinflammatory interleukines…

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B5

Herpes in elderly people: Do advanced age and allergies contribute to the reactivation of dormant herpes viruses?

Elderly individuals often show impaired adaptive immune responses towards vaccines. One underlying mechanism, called immune senescence, is a narrowing of the repertoire of immune receptors on white blood cells (B cell and T cell receptors), which reduces the flexibility of the immune system to respond to pathogens…

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B6

Cytomegaloviruses remain permanently in the body and stimulate continuously the immune system. Make this the course of atherosclerosis or diabetes worse?

Human Cytomegalovirus (HCMV) is an extremely common β-herpesvirus, persistently infecting the majority of the human population worldwide and inducing an unparalleled cellular immune response in the affected individuals. While HCMV infection reactivation from latency is well-known to cause severe disease…

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B7

Aging immune system: How is immune senescence characterised and does age have a general or specific effect on immune responses against viruses?

It is known that during aging, the functionality of the immune system declines. As a result, elderly persons are more prone to develop cancers and are more susceptible to infection with viral, bacterial and parasitic pathogens. Examples are the increased susceptibility to infections with influenza viruses…

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B8

Cure chronic hepatitis B: Why do some people recover spontaneously after therapy disruption?

Hepatitis B virus (HBV) is a global clinical challenge. Worldwide more than 250 million people are chronically infected with HBV with 650.000 HBV-related deaths annually. Current treatment options for chronic hepatitis B in industrialized countries are PEG-IFNα or nucleos(t)id-analoga (NA)…

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B9

Vaccination failure in hepatitis B: What causes vaccination failure and which new therapies are possible?

Hepatitis B Virus (HBV) infection often causes chronic infection, which may lead to liver cirrhosis that can progress to hepatocellular carcinoma. HBV vaccines are considered highly efficacious and are successfully applied worldwide. However, approximately 5% of HBV vaccinated individuals do not mount protective antibody responses after vaccination…

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B10

Hepatitis C vaccine: Which immune response is particularly efficient and can contribute to the development of a new vaccine?

Hepatitis C virus (HCV) has chronically infected ca. 71 million people worldwide. These patients are at risk of severe liver disease including hepatocellular carcinoma. The WHO has reported approximately 400.000 HCV-associated deaths for 2015…

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B11

Cholangitis – Which individual therapy approaches are possible?

Primary sclerosing cholangitis (PSC) is an autoimmune disease affecting the biliary tract. Chronic inflammation leads to a destruction of the biliary tract with recurrent bacterial Cholangitis…

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B12

Motor of immune reaction: So-called ubiquitins can play an important role during bacterial infections. Are they suitable for new therapeutic approach?

The risk and the course of serious bacterial infections are primarily determined by the interaction between the specific bacterium and the infected human. The susceptibility to infection is critically determined by individual host-specific factors including an underlying immunodeficiency, the age and the existence of implants…

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