Allergo Journal International

, Volume 27, Issue 3, pp 79–96 | Cite as

Respiratory virus-induced heterologous immunity

Part of the problem or part of the solution?
  • Emanuel Pusch
  • Harald Renz
  • Chrysanthi Skevaki



To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination.


A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratory-virus induced adaptive HI.


In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and influenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines which have the potential to provide protection against multiple virus strains are also discussed. Furthermore, respiratory viruses have been implicated in the development of autoimmune diseases, such as narcolepsy, Guillain–Barré syndrome, type 1 diabetes or myocarditis. Finally, we discuss the role of respiratory viruses in asthma and the hygiene hypothesis, and review our recent findings on HI between IV and allergens, which leads to protection from experimental asthma.


Respiratory-virus induced HI may have protective but also detrimental effects on the host. Respiratory viral infections contribute to asthma or autoimmune disease development, but on the other hand, a lack of microbial encounter is associated with an increasing number of allergic as well as autoimmune diseases. Future research might help identify the elements which determine a protective or detrimental outcome in HI-based mechanisms.


Respiratory virus Cross-reactivity Adaptive immunity Autoimmunity Asthma 







Acute disseminated encephalomyelitis


Antigen presenting cell


Bovine RSV


Celiac disease




Computationally optimized broadly reactive antigen


Chronic obstructive pulmonary disease




Coxsackie virus


Experimental autoimmune encephalomyelitis


Epstein–Barr virus


Anti-fusion protein


Anti-attachment glycoprotein


Guillain–Barré syndrome




Hepatitis C virus


HCV seronegative


House dust mite


Heterologous immunity


Human immunodeficiency virus


Human leukocyte antigen


Human metapneumovirus


Human papilloma viruses






Infectious mononucleosis


Influenza virus




Live attenuated influenza vaccine


Lower respiratory tract infections


Monoclonal antibody


Myelin basic protein


Middle East respiratory syndrome


Major histocompatibility complex


Myelin oligodendrocyte protein


Myosin heavy chain


natural killer T


Anti-N-methyl-D-aspartate receptor






Recombinant receptor binding-domain


Respiratory syncytial virus


Respiratory tract infections






Severe acute respiratory syndrome


Systemic lupus erythematosus


Sjögren’s syndrome


Type 1 diabetes mellitus




T effector memory cells


Toll-like receptor 2


T memory


Tribbles homolog 2


Tissue resident memory


Upper respiratory tract infections


Viral capsid proteins



The work was supported by the German Research Foundation, SFB 1021, Project C04 and the German Center for Lung Research (DZL).

Conflict of interest

C. Skevaki has received grants from the German Research Foundation, the German Center for Lung Research, Hycor and Mead Johnson Nutritional and consultancy fees by Hycor and Bencard. H. Renz has received a grant from the German Research Foundation and the German Center for Lung Research and payment for lectures from Allergopharma, Novartis, Thermo Fisher, Danone, Mead Johnson Nutritional, and Bencard and has received payment for research and development projects from Hycor, Mead Johnson, and Beckman Coulter. E. Pusch declares no relevant conflicts of interest.


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Copyright information

© Springer Medizin Verlag GmbH, a part of Springer Nature 2018

Authors and Affiliations

  • Emanuel Pusch
    • 1
  • Harald Renz
    • 1
  • Chrysanthi Skevaki
    • 1
  1. 1.Institute of Laboratory Medicine and Pathobiochemistry, Member of the German Center for Lung Research (DZL)Philipps University MarburgMarburgGermany

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