Innate lymphoid cells and asthma

The recent discovery of innate lymphoid cells (ILCs) has changed our understanding of immune regulation and uncovers the importance of innate immunity in the development of asthma. Historically, asthma was thought to be a Th2 mediated disease of the adaptive immune system but it has recently become clear that there are several different phenotypes of asthma some of which are non-allergic. In their review, Yu et al discuss the various roles of ILCs in the immune system specific to different asthma phenotypes and other allergic diseases (J Allergy Clin Immunol 2014; 133(4): 943-950).

ILCs are lymphocytes that produce a variety of cytokines similar to CD4+ T cells, but are antigen non-specific, which allows them to function independently of adaptive immunity.  The authors explain that ILC1s are similar to Th1 cells and have been shown to inhibit eosinophilic airway inflammation by promoting eosinophil apoptosis. Several studies show the likeness of ILC2s to Th2 cells in that they produce Th2 cytokines IL-4, IL-5, and IL-13.  ILC2s are found in the lungs of mice and humans with airway hyper responsiveness (AHR) and in the skin of atopic dermatitis patients. Similar to Th17 cells, ILC3s producing IL-17 have been found in the lung of some asthma patients and in the gut of colitis patients, and have been proposed to be implicated in obesity induced asthma, based on studies in mice. 

The authors conclude that at least two of the three types of ILCs are likely to be involved in human asthma, and in regulating both inflammation and homeostasis. The discovery of ILCs also suggests that innate immunity profoundly shapes allergic disease, in the presence or absence of adaptive immunity. For example, while the markers of ILC2s are not fully understood, the ability of ILC2s to interact with other Th2 associated cell types involved in allergy shows promise for asthma research that may lead to improved therapies.

Question for the authors:

Could you elaborate further on how ILCs managed to elude scientists for so long?  

ILCs eluded scientists in the past because they do not express cell surface markers associated with adaptive lymphocytes (e.g., T cells and B cells).  In our zeal to understand adaptive lymphocytes, we gated out other lymphocytes (including ILCs) during flow cytometric analyses.  In effect, we “threw out the baby with the bath water.”

Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts

Live vaccines and the growing neglect of adherence to routine immunizations can be life-threatening to immunodeficient patients.  This prompted the Medical Advisory Committee of the Immune Deficiency Foundation to issue recommendations based on the literature and the collective experience of the committee members. Shearer et al describe the relative risk for a child with severe immunodeficiency from close-contact spread of infectious diseases that are vaccine-preventable or from the shedding of live virus or bacteria from individuals who have received a live vaccine (J Allergy Clin Immunol 2014; 133(4): 961-966).  

The risk of acquiring an infection is well known to immediate family members of an immunodeficient child. However, relatives and non-family members who have not been vaccinated or have been vaccinated with live virus or bacteria pose a serious threat to these patients. Complacency is prevalent in society regarding pertussis, measles, mumps, and rubella vaccines. For example, the threat of pertussis to the pediatric population is alarming, especially for immunodeficient patients. This rise of preventable disease is associated with loss of the herd immunity in the general population along with parents avoiding vaccines out of fear of autism despite overwhelming evidence to the contrary. The immunosuppressed subject is at most risk of contracting these infections in crowded living conditions due to the ease of spread of disease by aerosol or oral-fecal route.  While avoidance of these diseases is ideal, the parent of an immunodeficient child must maintain a balance with the needs of a child to develop socially and educationally.

Vaccination for common infections represents a major advancement in the battle of communicable disease that threatens the welfare of humankind, especially the pediatric population. However, the alarming rise of non-immunized individuals could lead to a return of avoidable global epidemics.  Close contact with individuals recently vaccinated with live vaccines may cause the spread of infection to an immunodeficient child.  Shearer et al stress the importance of herd immunity, avoidance of live vaccines, and balancing the needs of this fragile population.

Questions for the authors:

What are the political implications of these findings?

There is no political agenda for those who have vaccine immunizations, only evidence-based science.

Could federal law mandate that all children and adults receive appropriate vaccinations?

That is most unlikely to happen.