What determines our susceptibility to infections?

From the page on applied immunology we have understood that our immune system plays a vital role in determining whether or not we are susceptible to infections. Yet other factors can play a role too, either by directly influencing susceptibility, or by influencing the immune system.

Genetics

An often described fact is how a genetic disorder called sickle cell anemia enhances susceptibility against malaria infections. This disorder is caused by a single mutation in the gene that produces hemoglobin, the protein in our red blood cells that transports oxygen. At a specific location in the hemoglobin gene, only one single change is made. Since we have two copies of each of our genes (one from our mother and one from our father), it could happen that only one of these genes have this mutation, while the other gene is still 'healthy'. When that occurs, this is called a heterozygous gene. When the mutation happens in both genes this is called homozygous. People who are homozygous for the sickle cell trait, cannot produce normal hemoglobin, which leads to a form of anemia where the red blood cells lose their round shape and turn to curved 'sickles'. People who are heterozygous have a high resistance to malaria infections (though not 100%).

Similarly, resistance against norovirus occurs when in the FUT2 gene a single nucleotide is mutated, where an amino acid guanine (G) is changed for adenine (A). In this case, you need to have the mutation on both copies of the gene (homozygous) in order to be resistant to norovirus. People who are heterozygous for this mutation, are not resistant to norovirus. The down side is that homozygous FUT2 mutations in this specific example probably lead to a higher susceptibility to influenza virus.

Microbiome

The huge amount of microbes that live with us in and on our body affects our ability to deal with infectious diseases. Recently the intensity of infection and the success of certain parasite strains have found to be influenced by the microbiome.

Nutrition

Since a long time we know that vitamin A affects our suscebtibility to infections. Vitamin A deficiency impairs innate immunity by impeding normal regeneration of mucosal barriers damaged by infection, and by diminishing the function of neutrophils, macrophages, and natural killer cells. Vitamin A is also required for adaptive immunity and plays a role in the development of T both-helper (Th) cells and B-cells. In particular, vitamin A deficiency diminishes antibody-mediated responses directed by Th2 cells, although some aspects of Th1-mediated immunity are also diminished.

Social influences

Recent studies suggest that social networks (family ties, friends, colleagues) have a positive effect on our susceptibility to infections. This is notwithstanding the fact that the proximity of many people (also in our networks) increase the chance to be exposed to pathogenic microbes. In addition, social support has a positive effect too, on our ability to deal with infections. Social support includes instrumental support, which is task-related help that we may receive, such as information and tangible resources to deal with problems or challenging situations. The other part of social support is emotional support; which refers to helping people to manage their feelings, including making someone feel loved or valued. These types of support have been found to enhance immune functions.

Stress is found to be associated with poor immune function. Stress reduces our immune functions through enhancing detrimental behavior such as smoking, excessive alcohol use and lack of sleep.

References:

• Stephensen CB. Vitamin A, infection, and immune function. Annu Rev Nutr. 2001;21:167-92.
• Epidemics - the Dynamics of Infectious Diseases by Dr. Marcel Salathé, Dr. Ottar N. Bjornstad, Dr. Rachel A. Smith, Dr. Mary L. Poss, Dr. David P. Hughes, Dr. Peter Hudson, Dr. Matthew Ferrari, Dr. Andrew Read.Coursera course by PennState university.