Figure 1.

The cyclic “yin-yang” nature of the immune response. The immune response aligns with the yin-yang concept of complimentary forces. Yin represents a retractive or passive force, depicted as the immune contraction phase (5–8). Yang is the force that is active and expansive, as seen in the immune activation phase (1–4). Following repair of sites that were damaged by both pathogen and inflammatory processes, the immune system returns to a baseline and is poised to react to the next threat. 1. Upon encountering a pathogen, chemokine and cytokine gradients allow for recruitment of innate immune cells to the site of infection. 2. Innate immune cells secrete pro-inflammatory cytokines that cause further recruitment of immune cells, self and nearby immune cell activation, and the initiation of an inflammatory environment for further activation. 3. Stimulated from IFN-γ secretion from both self and other immune cells, macrophages differentiate into the pro-inflammatory M1 phenotype. This furthers the activation phase in the immune response. 4. Lymphocytes initiate the adaptive immune response, forming a more specific and targeted response to pathogens. This involves development, selection, activation, and differentiation into effector cells as lymphocytes enter the site of infection. 5. Successful elimination of the threat sets the stage for the contraction phase. Macrophages switch to the anti-inflammatory M2 phenotype, aiming to downregulate inflammatory processes from the activated phase. 6. Apoptosis of immune cells occurs, eliminating the excessive cells that were specifically recruited and activated for pathogen defense. This ensures the inflammatory and cytotoxic effector function of immune cells do not continue to persist. 7. Selected B and T lymphocytes undergo a complex process of differentiation into memory cells. Such memory lymphocytes residing in tissues or circulation for extended periods of time to serve as a record of past infection. This will allow for a faster and more robust response if the pathogen is encountered again. 8. Wound healing also occurs in steps 5-7, but its completion marks the end of the immune contraction phase. Following repair of sites that were damaged by both pathogen and inflammatory processes, the immune system returns to a baseline and is poised to react to the next threat. Created with BioRender.com.