Immunity

Ability of the organism to render harmless an agent recognized as foreign (such as bacteria, viruses, fungi or parasites) without a pathological reaction.

A distinction is made between:

• Innate immunity (various humoral and cellular defense mechanisms).
• Acquired or adaptive immunity (antigen-specific humoral and cellular mechanisms)
• Trained immunity

Innate immunity occurs in all multicellular organisms; it is immutable and not very specific. This enables the organism to react directly to pathogens.

The phylogenetically younger acquired (adaptive) immunity allows the pathogen to be recognized in the event of a new infection. This enables the organism to react selectively to the pathogen. Acquired immunity leads to immunological memory. The main difference between the two forms of reaction lies in the mechanism of pathogen recognition, whereby the cellular receptors involved are of particular importance.

Trained immunity" (TI) or "innate immune memory" is a term for a new concept that describes the ability of an organism to develop an increased responsiveness to secondary stimuli independently of adaptive immunity. Although the specificity of adaptive immune memory in vertebrates is provided by recombination of immunoglobulin family genes and clonal expansion, the basic mechanisms of non-specific enhanced responsiveness of innate immune cells are based on epigenetic, transcriptional and metabolic programs following transient stimulation. Changes in these programs lead to increased responsiveness to secondary challenges from a variety of stimuli. This phenomenon is referred to as "trained immunity" or "innate immune memory". On the one hand, trained immunity improves the response to infections and vaccinations by enabling a stronger innate immune response and improved protection against a variety of microbial stimuli. On the other hand, trained immunity may contribute to the pathophysiology of cardiovascular, autoinflammatory and neurodegenerative diseases. TI was first discovered in cells of the innate immune system, e.g. monocytes, macrophages and natural killer cells; however, these cells have a shorter lifespan in the bloodstream than the duration of TI. TI has also been found in cells with a long lifespan, such as stem cells and fibroblasts (Naik, S et al. 2017). Thus, it has been shown that epithelial stem cells (EpSCs) can develop a long-lasting memory for previous inflammatory stimuli, e.g. topical imiquimod treatment, enabling the skin to respond rapidly to subsequent damaging stimuli. After the initial stimulus, EpSCs retain chromosomal accessibility of several critical genes for the inflammatory response, enabling rapid transcription of AIM2 and its downstream effector genes upon a secondary stimulus, i.e. skin injury (Naik, S et al. 2017). This memory is mediated by the Aim2 gene encoding an activator of the inflammasome. The absence of the AIM2 protein or its downstream effectors, caspase-1 and interleukin-1beta, abolishes the memory of EpSCs for inflammation (Naik, S et al. 2017).

1. Averbeck M et al. (2007) Immunological basis of allergies. JDDG 5: 1015-1028

2. Naik, S et al. (2017) Inflammatory memory sensitizes skin epithelial stem cells to tissue damage. Nature 550: 475-480.

3. Piipponen M et al.(2020) The Immune Functions of Keratinocytes in Skin Wound Healing. Int J Mol Sci 21:8790.