Transient autoantibodies to danger signals

Abstract

The Danger Model predicts that there are some molecules that no immune system can ever be fully tolerant of, namely proteins that are only transiently expressed during times of stress, infection, or injury. Among these are the danger/alarm signals themselves. Accordingly, a fleeting autoantibody response to danger signals is expected during times when they are released. Depending on context, these autoantibodies may serve beneficial “housekeeping” functions by removing surplus danger signals from the circulation or, conversely, create an immunodeficiency. Here, we will focus on the Type 1 Interferons as examples of foreseeable targets for a transient autoantibody response, but the principles outlined should hold for other danger-associated molecules as well.

Autoantibodies to Interferons in Infectious Diseases

“…Finally, it is important to remember the possibility that the production of aAbs can be limited in time and can stop when the triggering stimulus fails. For instance, while anti-IFN-I aAbs remained stable in patients with AIRE deficiency and thymic malignancies, anti-IFN-I aAbs with neutralizing activity peaked soon after COVID-19 onset and declined to undetectable levels during convalescence [ 187 ]. Therefore, depending on context, these aAbs may serve beneficial “housekeeping” functions through removing surplus danger signals from circulation or, conversely, induce disease emergence.…”

Tolerogenic dendritic cells in type 1 diabetes: no longer a concept

“…DC exist as a spectrum of phenotypes and immune actions between pro-inflammatory and anti-inflammatory cells at the population and single cell level (reviewed in ( 11 , 12 ) and Table 3 ). At one end of this spectrum, they are widely referred to as “mature” as a consequence of their response to entering inside, or being subjected to a building micro-environment of tissue “damage/danger” ( 74 – 82 ). Under such micro-environmental conditions, tissue-resident and/or migratory DC increase the expression of major histocompatibility complex (MHC) proteins loaded with peptides acquired from cells and proteins from their microenvironment, and upregulated the cell surface levels of co-stimulatory proteins like CD40, CD86, and a series of cell-cell adhesion molecules – some with signaling capacity into and inside from T-cells ( 83 – 86 ).…”