Our immune system is always at work over the course of our life from birth to death. We are exposed to microbes daily, some pathogenic, which results in an immune response. The humoral immune response leads to the production of antibodies that can fight off infection and provide long-term protection against future infection. Immune response to infection or vaccination may vary widely among individuals, but the factors behind this variability are currently unknown. Identification of these factors may lead to improved vaccination by optimizing vaccine-induced protection or to a better understanding of autoimmune disorders where antibody levels can correlate with disease severity.
The humoral immune response, also known as the antibody-mediated response, involves B cells that recognize antigens or pathogens circulating in the body. These antigens will bind to B cells, leading to B cell activation by T cells. B cells proliferate, produce plasma cells that bear the antibody matching the antigen, which circulate throughout the body and bind to the matching antigen. B cells will produce memory cells which provide future immunity; the memory cell can mount an immune response if the specific antigen appears in the body in the future. The intensity of this response to a given stimulation can be highly variable.
Previous studies have identified genetic variants that account for differences in susceptibility to pathogens in infectious phenotypes, but few studies have looked at this variability in healthy humans. A recent study published in Genome Medicine, from the lab of Dr. Jacque Fellay at École Polytechnique Fédérale de Lausanne, sought to identify specific determinants of this variability. The study took an integrative approach to investigate the role of age, sex, non-genetic, and genetic factors on humoral immunity in healthy individuals.
Looking at 1000 healthy individuals of stratified ages and gender, they characterized the serological response to 15 antigens from common human pathogens or vaccines. Total antibody levels of IgA, IgE, IgG, and IgM were measured by clinical-grade serological assays, as well as qualitative and quantitative IgG response to various viruses and bacteria such as measles, mumps, and influenza A virus or Helicobacter pylori and Toxoplasma gondii. A genome-wide genotyping was utilized to examine associations between 5 million genetic variants and antibody responses by a single marker and gene burden tests.
The results showed that age and sex were significant determinants of humoral immunity, with older individuals and women showing stronger responses to most antigens. The genetic studies showed that differences in response to viruses such as Epstein-Barr and rubella were associated with variation in human leucocyte antigen (HLA) gene region. This region encodes proteins involved in recognition of foreign antigens. Overall, the study provides evidence that age, sex, and host genetics contribute to the natural variation in humoral immunity in humans.
These associations could help improve vaccination and dissect pathogenic mechanisms implicated in human disease such as autoimmune disorders. "To combat infectious and autoimmune diseases, we need to better understand variation in the healthy immune response," says Jacques Fellay. "Our study is a necessary first step toward individualized healthcare in infection and immunity."
To learn more about the humoral immune response, as well as the role of antibodies and antigens in immunity watch the video below!