Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.
Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed mainly by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, as well as by epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.
In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the IFNG gene.
The innate, or nonspecific, immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.
Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons. Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the IRF-element (IRF-E) motifs, which is located upstream of the interferon genes. Some viruses have evolved defense mechanisms that regulate and interfere with IRF functions to escape the host immune system. For instance, the remaining parts of the interferon regulatory factor sequence vary depending on the precise function of the protein. The Kaposi sarcoma herpesvirus, KSHV, is a cancer virus that encodes four different IRF-like genes; including vIRF1, which is a transforming oncoprotein that inhibits type 1 interferon activity. In addition, the expression of IRF genes is under epigenetic regulation by promoter DNA methylation.
Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis can take place in immune cells and is also reported to occur in keratinocytes and some epithelial cells.
The type III interferon group is a group of anti-viral cytokines, that consists of four IFN-λ (lambda) molecules called IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4. They were discovered in 2003. Their function is similar to that of type I interferons, but is less intense and serves mostly as a first-line defense against viruses in the epithelium.
The interferon-α/β receptor (IFNAR) is a virtually ubiquitous membrane receptor which binds endogenous type I interferon (IFN) cytokines. Endogenous human type I IFNs include many subtypes, such as interferons-α, -β, -ε, -κ, -ω, and -ζ.
Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the STAT protein family, composed of STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6. STAT proteins are key activators of gene transcription which bind to DNA in response to cytokine gradient. STAT proteins are a common part of Janus kinase (JAK)- signalling pathways, activated by cytokines.STAT4 is required for the development of Th1 cells from naive CD4+ T cells and IFN-γ production in response to IL-12. There are two known STAT4 transcripts, STAT4α and STAT4β, differing in the levels of interferon-gamma production downstream.
Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). STAT2 sequence identity between mouse and human is only 68%.
Interferon-induced guanylate-binding protein 1 is a protein that in humans is encoded by the GBP1 gene. It belongs to the dynamin superfamily of large GTPases.
Interferon-induced guanylate-binding protein 2 is a protein that in humans is encoded by the GBP2 gene. GBP2 is a gene related to the superfamily of large GTPases which can be induced mainly by interferon gamma.
Interferon-inducible protein AIM2 also known as absent in melanoma 2 or simply AIM2 is a protein that in humans is encoded by the AIM2 gene.
Inflammasomes are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Activation and assembly of the inflammasome promotes proteolytic cleavage, maturation and secretion of pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as cleavage of gasdermin D. The N-terminal fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis, and is responsible for secretion of the mature cytokines, presumably through the formation of pores in the plasma membrane. Additionally, inflammasomes can be incorporated into larger cell death-inducing complexes called PANoptosomes, which drive another distinct form of pro-inflammatory cell death called PANoptosis.
NOD-like receptor family pyrin domain containing 11 is a protein that in humans is encoded by the NLRP11 gene located on the long arm of human chromosome 19q13.42. NLRP11 belongs to the NALP subfamily, part of a large subfamily of CATERPILLER. It is also known as NALP11, PYPAF6, NOD17, PAN10, and CLR19.6
Immunity Related Guanosine Triphosphatases or IRGs are proteins activated as part of an early immune response. IRGs have been described in various mammals but are most well characterized in mice. IRG activation in most cases is induced by an immune response and leads to clearance of certain pathogens.
Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a protein that in humans is encoded by the STING1 gene.
Murine caspase-11, and its human homologs caspase-4 and caspase-5, are mammalian intracellular receptor proteases activated by TLR4 and TLR3 signaling during the innate immune response. Caspase-11, also termed the non-canonical inflammasome, is activated by TLR3/TLR4-TRIF signaling and directly binds cytosolic lipopolysaccharide (LPS), a major structural element of Gram-negative bacterial cell walls. Activation of caspase-11 by LPS is known to cause the activation of other caspase proteins, leading to septic shock, pyroptosis, and often organismal death.
Jonathan C. Kagan is an American immunologist and the Marian R. Neutra, Ph.D. Professor of Pediatrics at Harvard Medical School. He is also the director of Basic Research and Shwachman Chair in Gastroenterology at Boston Children's Hospital. Kagan is a world leader in defining the molecular basis of innate immunity and inflammation.
