![]() In this article, we review the main features and biological activities of MIF. Mif-knockout mice were generated in 1999, and reported to be healthy and devoid of any apparent deficit 8. This intriguing observation indicated that MIF could be a mediator that links the endocrine and immune systems. In 1991, a search for new regulators of inflammation led to the re-discovery of MIF as a molecule released, similar to a hormone, by cells of the anterior pituitary gland after exposure to the endotoxin lipopolysaccharide (LPS) 7. However, authentic biological activities of MIF remained ambiguous until the cloning of human MIF complementary DNA in 1989 (Ref. However, dysregulated production of pro-inflammatory mediators might also become life-threatening, as shown in patients with severe sepsis or septic shock, indicating that tight regulation of cytokine production is required.ĭiscovered almost 40 years ago during studies of the DELAYED-TYPE HYPERSENSITIVITY reaction 4, 5, macrophage migration inhibitory factor ( MIF) was one of the first cytokines to be identified (Timeline). The increased susceptibility to infection of animals in which genes encoding cytokines or cytokine receptors are mutated or deleted is strong evidence to support a crucial role for cytokine- or cytokine-receptor-dependent signalling pathways in regulating antimicrobial host defences. Binding of conserved microbial molecular motifs, often known as pathogen-associated molecular patterns (PAMPs), to these receptors activates signal-transduction pathways and the transcription of immune genes, resulting in the release of numerous immunoregulatory molecules into the extracellular milieu and the expression of co-stimulatory molecules at the cell surface.Īmong these effector molecules, cytokines have an essential role as they initiate the host inflammatory response and coordinate the cellular and humoral responses, which lead, within minutes to a few hours, to either the eradication or the containment of the invasive pathogen. This process involves coordinated actions of the alternative and mannose-binding lectin pathways of complement, of acute-phase proteins and of germ-line-encoded pattern-recognition receptors, such as CD14 and TOLL-LIKE RECEPTORS (TLRs). ![]() The detection of pathogens is first carried out by sentinel cells of the innate immune system, such as macrophages and dendritic cells, located in tissues that are in contact with the host's natural environment, and then by circulating granulocytes and monocytes that are rapidly recruited to the site of infection. Natural host defences against microorganisms are mediated by the innate immune system - the most ancient of the two branches of the immune system 1, 2, 3. ![]() Genetic defects resulting in a failure to distinguish between self and non-self are life-threatening, as they predispose affected individuals to unrestricted microbial invasion and overwhelming infections. Sensing and eliminating invading microorganisms is required for the survival for all living creatures.
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