The innate immune system has evolved to protect against infection by detecting pathogen-associated molecular patterns (PAMPs), and triggering a complex set of responses collectively known as "inflammation".  Many cells express specific pattern recognition receptors (PRRs) for exogenous RNA including toll-like receptor 3,7,8 (TLR3, TLR7, TLR8), the RNA helicase RIG1 (RARRES3), protein kinase R (PKR, a.k.a. EIF2AK2), members of the oligoadenylate synthetase family of proteins (OAS1, OAS2, OAS3), and others.  All of these proteins can specifically bind to exogenous RNA molecules and trigger an immune response.
The specific chemical, structural or other characteristics of long RNA molecules that are required for recognition by PRRs remain largely unknown despite intense study.  At any given time, a typical mammalian cell may contain several hundred thousand mRNA and other, regulatory long RNA molecules.  How cells distinguish exogenous long RNA from the large amount of endogenous long RNA is an important open question in cell biology.  Several reports suggest that phosphorylation of the 5-end of a long RNA molecule can influence its immunogenicity, and specifically that 5-triphosphate RNA, which can be produced during viral infection, is more immunogenic than 5-diphosphate RNA, 5-monophosphate RNA or RNA containing no 5 phosphate. However, in vitro-transcribed (ivT) long RNA containing a 7-methylguanosine cap (present in eukaryotic mRNA) is also highly immunogenic despite having no 5 phosphate, suggesting that characteristics other than 5'-phosphorylation can influence the immunogenicity of an RNA molecule.
Eukaryotic mRNA contains chemically modified nucleotides such as N-methyladenosine, 5-methylcytidine, and 2'-O-methylated nucleotides.  Although only a very small number of these modified nucleotides are present in a typical mRNA molecule, they may help prevent mRNA from activating the innate immune system by disrupting secondary structure that would resemble double-stranded RNA (dsRNA), a type of RNA thought to be present in cells only during viral infection.
The immunogenicity of long RNA has been used to study both innate and adaptive immunity.