Innate and adaptive immunity responses often take the spotlight regarding the defense and protection against pathogens. Nevertheless, barrier tissues have proven to store inflammatory memory that allows them to protect us against pathogens. Indeed, this new insight of barrier memory provides a new perspective and positions our barrier tissues as a multifunctional structure balancing protection and metabolic function.
As a mammalian species, humans are a complex living entity that carries specialized immune cells and has a powerful physical barrier component to provide protection and defense. Indeed, epithelial barriers of the airways, skin, and intestine can modulate and respond to external and internal signals. Therefore, it has been proposed that barrier tissue can access and memorize information about previous pathogen encounters to provide a stronger and quicker response in future events.
Furthermore, immune memory information can be stored in locally accessible cell types that are residents and can maintain appropriate qualitative features. However, this storage mechanism can be compromised if these cells cannot store sufficient information or if there is excessive memory retrieval. Consequently, these two inappropriate memory settings will lead to increased infection or chronic inflammation, respectively.
This new barrier tissue memory term refers to a defined response to an initial trigger that is altering the environment and will persist until a secondary challenge.
Components of inflammatory memory
There are five inflammatory memory components. Each one cooperates among them.
|Specificity: the recognition of an initiating stimulus defines it. It can range from a unique receptor-activated recognition to a more context-specific cue.|
|Quantity: this refers to the amount or frequency of the responding cells.|
|Quality: describes the polarization of responding cells. This polarization is the response to the presence of genes or the activity of their products.|
|Durability: this measures the response time depending on the quantity and quality of the responding cells.|
|Distribution: the distribution encompasses the cell lineages, types, and subsets that show intrinsic alterations of the four aforementioned components.|
The recent findings on immunological memory can assure that it is a property found in all kingdoms of life. However, the information points towards the molecular and cellular mechanisms that can be classified as immunological memory. In fact, one of these mechanisms is the known reaction to a specific pathogen once there is a prior exposure.
Quantity and quality are the two main routes to memory storage by increasing the number of specific cells and altering these cells’ repose, respectively. Another component to consider is the durability and if this factor may be useful or detrimental for the immune response.
Besides, the quantitatively and qualitatively response can be found in multiple cell types. These cell types can be considered part of the innate immune response or the adaptative immune response. For example, lymphocytes can store memory of past immunological events and stay like “resident” tissue in a specific location for a long time.
Interestingly, macrophages can become “trained” too inflammatory responses. Another example is how other cells like endothelial cells and fibroblasts can change their structure and become primed as part of an inflammatory response. Besides, this can also be translated to the primming of microglia on the onset of neuroinflammation.
Immunological memory of epithelial cells
It is well-known that the skin, gut, and lungs’ epithelial barrier is the most important protective barrier we have. However, they are all specialized epithelial subsets with specific functions. High turnover epithelial cells are regulated at the level of multipotent epithelial progenitor and stem cells. Therefore, for these tissues to have their specific protective function, they need to “remember” immunological events. This particularity makes the progenitor compartment the best candidate for the memory storage unit.
This function is confirmed by multiple studies on the skin or gut epithelial surfaces. For instance, a study used a psoriasis-like inflammation on a particular site of a skin surface. Consequently, skin epithelial stem cells would accelerate the repair of the subsequent wound on that site.
Ketosis and the immune system:
It is clear that gut permeability and symbiosis with its microbiome its an important factor that contributes to the modulation of the immune response. The maintenance of ketosis is important for specific beneficial strains of bacteria, and now the measurement of ketone bodies can be easy with LEVL.
New findings on the relationship between inflammation and the immune response continue to rise. Nowadays, the permeability and damage of your epithelial barriers play a vital role in maintaining our health. Indeed, the participation of resident cells called to action by the innate immune response provides new insights towards different signals’ sensitization.
The immune response to pathogens has always been focused on immune cell activity. However, it is how these cells respond that provides a potent protective effect to our epithelial barriers. Nowadays, this new theory can join the term gut permeability while being supported by evidence-based studies that reaffirm the clear interaction between inflammation and immunity. – Ana Paola Rodríguez Arciniega, MS.
Ordovas-Montanes, Jose et al. “Distribution and storage of inflammatory memory in barrier tissues.” Nature reviews. Immunology vol. 20,5 (2020): 308-320. doi:10.1038/s41577-019-0263-z
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Dr. Alex Jimenez DC, MSACP, CCST, IFMCP*, CIFM*, CTG*
Licensed in Texas & New Mexico