What is innate immunity?

Innate immunity refers to the cellular defense system present in humans acquired at birth.

The innate immune system is the first line of defense against pathogens, including viral pathogens such as SARS-CoV-2. The system's defense mechanisms include anatomical barriers, pattern recognition receptors (PRRs), and antiviral cytokines such as interferons (IFNs). The recognition receptors of the innate immune system are all encoded in their fully functional form in the germline genome.

Innate immunity provides defenses independent of the exposure to specific antigens.  The innate immune system is an evolutionarily conserved host defense system, and plants, invertebrates, and mammals all share vital features of the system. All mammalian tissues have innate immune defenses.  Barrier surfaces such as skin or mucosal surfaces of the respiratory and gastrointestinal tract can sense tissue damage, infection, or genotoxic stress.     

The traditional view separates innate and adaptive immune responses from each other. However, emerging evidence suggests that they overlap and mutually interact. New discovered cell types known as innate lymphoid cells and myeloid-derived suppressor cells have recently gained increased interest. 

The assumption that repeated infection or vaccination cannot improve innate immunity's efficiency has recently changed since innate immune cells such as myeloid cells and natural killer cells can also adapt to previous encounters with pathogens. The notion was that antigen-specific secondary responses only occur in B and T cells. In addition to protection against specific microorganisms, vaccines can induce heterologous or non-specific effects. Vaccination with live-attenuated vaccines, for example, Bacillus Calmette-Guérin (BCG), measles vaccine, and oral polio vaccine, resulted in increased overall childhood survival. Several randomized trials confirmed these observations. Non-specific effects, including heterologous lymphocyte effects and innate immune memory induction, are responses to pathogens. Innate immune memory is also called "trained immunity" or "cellular immunity." This type of adaption occurs through epigenetic, transcriptional, and functional reprogramming. Trained immunity induces long-term functional upregulation of innate immune cells. Upregulation occurs through epigenetic and metabolic reprogramming. Scientists now know that monocytes and macrophages acquire specific memory and cause organ rejection in mice. 

Dai et al. observed that murine monocytes and macrophages can acquire memory specific to major histocompatibility complex I (MHC-I) antigens. The research group discovered A-type paired immunoglobulin-like receptors (PIR-As) as the MHC-I receptors necessary for the memory response. Deleting PIR-A in the recipient or blocking PIR-A binding to donor MHC-I molecules blocked the memory and attenuated kidney and heart allograft rejection. These findings indicate that innate myeloid cells acquire alloantigen-specific memory.

Players of innate immunity

Innate immune cells



Myeloid-derived suppressor cells

Innate lymphoid cells


DNA sensing molecules

RNA sensing molecules


Hehua Dai, Peixiang Lan, Daqiang Zhao, Khodor Abou-Daya, Wentao Liu, Wenhao Chen, Andrew J. Friday, Amanda L. Williams, Tao Sun, Jianjiao Chen, Wei Chen, Steven Mortin-Toth, Jayne S. Danska, Chris Wiebe, Peter Nickerson, Tengfang Li, Lisa R. Mathews, Hêth R. Turnquist, Matthew L. Nicotra, Sebastien Gingras, Eiji Takayama, Hiromi Kubagawa, Mark J. Shlomchik, Martin H. Oberbarnscheidt, Xian C. Li, Fadi G. Lakkis; PIRs mediate innate myeloid cell memory to nonself MHC molecules. Science  05 Jun 2020:Vol. 368, Issue 6495, pp. 1122-1127.  [Science]

Jorge Domínguez-Andrés, Mihai G. Netea; The specifics of innate immune memory. Science  05 Jun 2020: Vol. 368, Issue 6495, pp. 1052-1053. DOI: 10.1126/science.abc2660. [

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