Immune system via cell-cell contact and paracrine signaling

The term Immune system via cell-cell contact and paracrine signaling refers to the fundamental physiological processes by which immune cells communicate to coordinate a functional response, rather than a single molecular target (Janeway's Immunobiology, 9th ed.). Cell-cell contact, or juxtacrine signaling, involves direct physical interaction between membrane-bound molecules on adjacent cells, such as the binding of a T-cell receptor (TCR) to an antigen-presenting Major Histocompatibility Complex (MHC) or the interaction of checkpoint proteins like PD-1 and PD-L1 (Nature Reviews Immunology, 2018). Paracrine signaling involves the secretion of soluble mediators, such as cytokines (e.g., Interleukins, TNF) and chemokines, which act on nearby cells to alter their behavior, recruitment, or differentiation (NIH, National Institute of Allergy and Infectious Diseases). These processes are critical for maintaining self-tolerance and executing effector functions against pathogens; however, their dysregulation is a hallmark of many diseases, including cancer, where tumors hijack checkpoint pathways to evade immune detection, and autoimmune disorders, where excessive paracrine signaling leads to chronic inflammation (StatPearls, 2023). Because this entry describes a broad biological mechanism involving hundreds of distinct proteins, it is not considered a specific therapeutic target, although many drugs (e.g., Pembrolizumab, Infliximab) are designed to modulate specific components within these signaling frameworks (PubMed, PMC5820829).

Other names

Immune cell communicationJuxtacrine and paracrine immune signalingIntercellular immune signalingImmune cell-cell interaction

Modulation of immune cell interactions through the blockade or activation of surface receptors (cell-cell contact) or the neutralization/agonism of secreted signaling molecules such as cytokines and chemokines (paracrine signaling).