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The mannan-binding-lectin pathway of the innate immune response.

Dramatic progress has been achieved during the past year in our understanding of how the complement system is activated via the mannan-binding-lectin pathway. Surprising discoveries have changed our concepts of the complexes that are formed upon engagement of mannan-binding lectin with its serine proteases.

Animals↗

Scavenger receptors in innate immunity.

Scavenger receptors (SR) are expressed by myeloid cells (macrophages and dendritic cells) and certain endothelial cells. They play an important role in uptake and clearance of effete components, such as modified host molecules and apoptotic cells. They bind and internalise micro-organisms and their products including Gram-positive bacteria (lipoteichoic acid), Gram-negative bacteria (lipopolysaccharide), intracellular bacteria and CpG DNA. SR can alter cell morphology and their expression is affected by various cytokines. SR are involved in lipid metabolism and bind modified low-density lipoproteins.

Animals↗

Phagocytosis and innate immunity.

Phagocytosis is an evolutionarily conserved process utilized by many cells to ingest microbial pathogens, and apoptotic and necrotic corpses. Recent investigation has revealed a fundamental requirement for two co-ordinated cellular processes--cytoskeletal alterations and membrane trafficking--in the phagocytic event. Some elements of this machinery are co-opted by certain pathogens to gain entry into host cells.

Animals↗

Scavenger receptors in innate immunity.

Scavenger receptors are cell-surface proteins expressed by mammalian monocytes and macrophages and by invertebrate hemocytes, among other cell types. They exhibit distinctive ligand-binding properties, recognizing a wide range of ligands that include microbial surface constituents and intact microbes. The ligand-binding properties and expression patterns of these receptors suggest that they may function in one or more host-defense-related processes. Significant advances in scavenger receptor biology have recently been reported, including the identification of several new scavenger receptor genes.

Animals↗

The collectins in innate immunity.

The collectins are proteins with collagen tails and globular lectin domains that appear to play an important role in mammalian first line host defense. Recent insights have clarified the structural basis of ligand recognition, the interactions of collectins with complement cascades, and the association with disease susceptibility.

Animals↗

Innate immunity.

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Animals↗

Innate immunity.

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Animals↗

The role of IL-18 in innate immunity.

IL-18 - a novel cytokine with potent IFN-gamma-inducing activities - plays an important role in the Th1-mediated immune response in collaboration with IL-12. IL-18 is a member of the IL-1 family. The IL-18 receptor system and its signal transduction pathway are analogous to those of the IL-1 receptor. Mice deficient in IL-18 have demonstrated its critical role in natural killer cell activity and in vivo Th1 response.

Animals↗

Innate immunity.

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Animals↗

Recognition of gram-negative bacteria and endotoxin by the innate immune system.

Until about 10 years ago the exact mechanisms controlling cellular responses to the endotoxin - or lipopolysaccharide (LPS) - of Gram-negative bacteria were unknown. Now a considerable body of evidence supports a model where LPS or LPS-containing particles (including intact bacteria) form complexes with a serum protein known as LPS-binding protein; the LPS in this complex is subsequently transferred to another protein which binds LPS, CD14. The latter is found on the plasma membrane of most cell types of the myeloid lineage as well as in the serum in its soluble form; LPS binding to these two forms of CD14 results in the activation of cell types of myeloid and nonmyeloid lineages, respectively.

Acute-Phase Proteins↗

Lung surfactant proteins involved in innate immunity.

The two lung surfactant collectins, surfactant protein (SP)-A and SP-D, are involved in host defence against infectious and allergenic agents via enhancement of killing and clearance by macrophages and neutrophils. Recent gene-knockout, protein engineering and physiological studies have emphasised the roles that SP-A and SP-D play in acute inflammatory responses.

Animals↗

Innate immunity.

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Complement Activation↗

Transcriptome identification of putative genes involved in protein catabolism and innate immune response in human body louse (Pediculicidae: Pediculus humanus).

Genomics information relating to human body lice is surprisingly scarce, and this has constrained studies of their physiology, immunology and vector biology. To identify novel body louse genes, we used engorged adult lice to generate a cDNA library. Initially, 1152 clones were screened for inserts, edited for removal of vector sequences and base pairs of poor quality, and viewed for splicing variations, gene families and polymorphism. Computational methods identified 506 inferred open reading frames including the first predicted louse defensin. The inferred defensin aligns well with other insect defensins and has highly conserved cysteine residues, as are known for other defensin sequences. Two cysteine and five serine proteinases were categorized according to their inferred catalytic sites. We also discovered seven putative ubiquitin-pathway genes and four iron metabolizing deduced enzymes. Finally, glutathione-S-transferases and cytochrome P450 genes were among the detoxification enzymes found. Results from this first systematic effort to discover human body louse genes should promote further studies in Phthiraptera and lice.

Amino Acid Sequence↗

Is there a role for CEA in innate immunity in the colon?

Carcinoembryonic antigen (CEA) is a well known tumor marker associated with the progression of colorectal tumors. The CEA family of glycoproteins has been fully characterized and the function of some of its members is now beginning to be understood. Here, we advance the hypothesis that, rather than functioning in cell adhesion as has been suggested previously, CEA plays a role in protecting the colonic mucosa from microbial invasion. This hypothesis is based on new microscopic, molecular, phylogenetic and microbiological evidence.

Carcinoembryonic Antigen↗