Question

The lymphatic system includes our bodies' defenses against infections. AIDS, Leukemia, many autoimmune disorders, and allergies are all manifestations of a breakdown in the normal functioning of the lymphatic system. Find an online source that helps to explain how these diseases interact with the lymphatic system mechanisms. Provide the link and a brief summary of fewer than 250 words. Then, read at least two classmates' posts. What questions are you still wondering about after reading the summary they posted?

 

Answer 1

Roychoudhuri, et al., "Bach2 represses effector programmes to stabilize T_reg-mediated immune homeostasis" Nature 2013, 498, 506-510.

The HIV, the causative agent of AIDS, predominantly infects and destroys the helper T-cells (CD4⁺ cells). These CD4⁺ cells are the master regulators of adaptive immunity and can either suppress or escalate an immune response. Immune dysregulation is not only a central feature of diseases like allergy and autoimmune diseases, but also cancers like chronic lymphocytic leukemia (CLL). It is known that autoimmunity contributes to a variety of diseases like type I diabetes, SLE, Grave's disease, Crohn's disease, myasthenia gravis and Goodpasteur's syndrome.

An important discovery has been that a DNA-binding protein called BACH2, that is required for producing variations in antibodies (this diversity is required to combat various pathogens), plays an important role in autoimmunity and allergies. While it was previously thought to exist on B-lymphocytes only, it has now been found on CD4⁺ cells also. The study has discovered an expanded role for BACH2 as a broad regulator of immune activation that also stabilizes immunoregulatory capacity. It appears that BACH2 sets the threshold on immune system activation to determine the extent of immune response.

This study, carried out in mouse, showed that when the BACH2 gene was deleted, the mouse pups were born normal, but rapidly degenerated due to autoimmune diseases. When the gene was deleted from CD4⁺ cells, it lead to escalation of immune response into inflammation, even for simple scenario where protective regulatory cells form and reduce the immune activation. It is known that prolonged inflammation supports cancers. Previously, it was found using genome-wide analysis that in humans, genetic variations or SNPs (single nucleotide polymorphisms) in this BACH2 gene was associated with immune tolerance, as well as frequency of allergies and autoimmune diseases.

Thus, the BACH2 gene indeed appears to be at least one of the genes in the central role of the immune system, at the cross-roads of AIDS, leukemias, allergies and autoimmune diseases, by controlling the expression of other genes, but further studies are required to explore its roles in detail.