The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.

https://science.sciencemag.org/content/sci/296/5567/490.full.pdf

Allergy, Parasites, and the Hygiene Hypothesis

Haptoglobin is a hemoglobin-binding protein expressed by a genetic polymorphism as three major phenotypes: 1-1, 2-1, and 2-2. Most attention has been paid to determining haptoglobin phenotype as a genetic fingerprint used in forensic medicine. More recently, several functional differences between haptoglobin phenotypes have been demonstrated that appear to have important biological and clinical consequences. Haptoglobin polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases, including infections, atherosclerosis, and autoimmune disorders. These effects are explained by a phenotype-dependent modulation of oxidative stress and prostaglandin synthesis. Recent evidence is growing that haptoglobin is involved in the immune response as well. The strong genetic pressure favoring the 2-2 phenotype suggests an important role of haptoglobin in human pathology.

Biological and clinical significance of haptoglobin polymorphism in humans.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)61016-2.pdf

Epidemic meningitis, meningococcaemia, and Neisseria meningitidis.

https://mmbr.asm.org/content/mmbr/41/3/667.full.pdf

Serology, chemistry, and genetics of O and K antigens of Escherichia coli.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)61229-X.pdf

B.M. Greenwood

Papers

Immunosuppression in children with malaria

Impairment of the immune response to vaccination after acute malaria

Possible role of a B-cell mitogen in hypergammaglobulinaemia in malaria and trypanosomiasis.

Meningococcal disease and season in sub-Saharan Africa.

Mortality from pneumococcal meningitis.