Charles A. Janeway

Bio: Charles A. Janeway is an academic researcher from Yale University. The author has contributed to research in topics: T cell & Antigen. The author has an hindex of 86, co-authored 254 publications receiving 56217 citations. Previous affiliations of Charles A. Janeway include French Institute of Health and Medical Research & Massachusetts Institute of Technology.

Innate Immune Recognition

Abstract: ▪ Abstract The innate immune system is a universal and ancient form of host defense against infection. Innate immune recognition relies on a limited number of germline-encoded receptors. These receptors evolved to recognize conserved products of microbial metabolism produced by microbial pathogens, but not by the host. Recognition of these molecular structures allows the immune system to distinguish infectious nonself from noninfectious self. Toll-like receptors play a major role in pathogen recognition and initiation of inflammatory and immune responses. Stimulation of Toll-like receptors by microbial products leads to the activation of signaling pathways that result in the induction of antimicrobial genes and inflammatory cytokines. In addition, stimulation of Toll-like receptors triggers dendritic cell maturation and results in the induction of costimulatory molecules and increased antigen-presenting capacity. Thus, microbial recognition by Toll-like receptors helps to direct adaptive immune responses ...

A human homologue of the Drosophila Toll protein signals activation of adaptive immunity

Abstract: . Like Drosophila Toll, human Toll is a type I transmembrane protein with an extracellular domain consisting of a leucine-rich repeat (LRR) domain, and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin (IL)-1 receptor. Both Drosophila Toll and the IL-1 receptor are known to signal through the NF-kB pathway 5-7 . We show that a constitutively active mutant of human Toll transfected into human cell lines can induce the activation of NF-kB and the expression of NF-kB-controlled genes for the inflammatory cyto- kines IL-1, IL-6 and IL-8, as well as the expression of the co- stimulatory molecule B7.1, which is required for the activation of naive T cells. The Toll protein controls dorsal-ventral patterning in Drosophila embryos and activates the transcription factor Dorsal upon binding to its ligand Spatzle 8 . In adult Drosophila, the Toll/Dorsal signalling pathway participates in an anti-fungal immune response 2 . Signal- ling through Toll parallels the signalling pathway induced by the IL- 1 receptor (IL-1R) in mammalian cells: IL-1R signals through the NF-kB pathway, and Dorsal and its inhibitor Cactus are homo- logous to NF-kB and I-kB proteins, respectively 5,6 . Moreover, the cytoplasmic domain of Drosophila Toll is homologous to the cytoplasmic domain of IL-1R (ref. 9). Remarkably, the tobacco- virus-resistance gene that encodes N-protein is also similar to Toll in that it contains both a Toll signalling domain and an LRR domain 10 . It thus appears that the immune-response system mediated by Toll represents an ancient host defence mechanism 6 (Fig. 1). To inves- tigate the possibility that this pathway has been retained in the immune system of vertebrates, we used sequence and pattern searches 11 of the expressed-sequence tag (EST) database at the fragment was used to probe northern blots containing poly(A) + RNA from several organs. Most organs expressed two mRNA species: one of ,5 kilobases (kb) was predominant in most tissues except peripheral blood leukocytes (PBL), and corresponded to the length of the cDNA that we cloned. The lower band was ,4 kb long and this band was predominant in the PBL. The 4-kb band was not detectable in kidney, and liver did not contain any mRNA at all (Fig. 3). We also tested different mouse and human cell lines for expression of hToll mRNA by using PCR with reverse transcription (RT-PCR). We found mRNA for hToll in monocytes, macrophages, dendritic cells, g/d T cells, Th1 and Th2 a/b T cells, a small intestinal epithelial cell line, and a B-cell line (data not shown). The hToll gene is expressed most strongly in spleen and PBL (Fig. 3); its expression in other tissues may be due to the presence of macrophages and dendritic cells, in which it could act as an early-warning system for infection. Alternatively, hToll may be widely expressed because hToll signals through the conserved NF-kB pathway (see below) and NF- kB is a ubiquitous transcription factor. To characterize hToll functions and see whether it can induce transcription of immune response genes like dToll, we generated a dominant-positive mutant of hToll because the natural ligand of hToll is unknown. To produce a constitutively active mutant of hToll, we made use of genetic information from dToll: analysis of ventra- lizing mutants in Drosophila embryos had identified the function of the ectodomain C-flanking cysteine-rich region in dToll 16 as control- ling the activity of dToll in signal transduction. In three dominant

Immunobiology: The Immune System in Health and Disease

Abstract: Introductory immunology textbook for medical students, advanced undergraduates, and graduate students.

Phylogenetic Perspectives in Innate Immunity

Abstract: The concept of innate immunity refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms. Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity.

The Theory of Island Biogeography

Abstract: Preface to the Princeton Landmarks in Biology Edition vii Preface xi Symbols Used xiii 1. The Importance of Islands 3 2. Area and Number of Speicies 8 3. Further Explanations of the Area-Diversity Pattern 19 4. The Strategy of Colonization 68 5. Invasibility and the Variable Niche 94 6. Stepping Stones and Biotic Exchange 123 7. Evolutionary Changes Following Colonization 145 8. Prospect 181 Glossary 185 References 193 Index 201

Innate Immune Recognition

Abstract: ▪ Abstract The innate immune system is a universal and ancient form of host defense against infection. Innate immune recognition relies on a limited number of germline-encoded receptors. These receptors evolved to recognize conserved products of microbial metabolism produced by microbial pathogens, but not by the host. Recognition of these molecular structures allows the immune system to distinguish infectious nonself from noninfectious self. Toll-like receptors play a major role in pathogen recognition and initiation of inflammatory and immune responses. Stimulation of Toll-like receptors by microbial products leads to the activation of signaling pathways that result in the induction of antimicrobial genes and inflammatory cytokines. In addition, stimulation of Toll-like receptors triggers dendritic cell maturation and results in the induction of costimulatory molecules and increased antigen-presenting capacity. Thus, microbial recognition by Toll-like receptors helps to direct adaptive immune responses ...

Toll-like receptor signalling

Abstract: One of the mechanisms by which the innate immune system senses the invasion of pathogenic microorganisms is through the Toll-like receptors (TLRs), which recognize specific molecular patterns that are present in microbial components. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also instructs the development of antigen-specific acquired immunity. Here, we review the rapid progress that has recently improved our understanding of the molecular mechanisms that mediate TLR signalling.

TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.

Abstract: Effector functions in the immune system are carried out by a variety of cell types, and as our understanding of the complexity of the system expands, the number of recognized subdivisions of cell types also continues to increase. B lymphocytes, producing antibody, were initially distinguished from T lymphocytes, which provide help for B cells (1, 2). The T-cell population was further divided when surface markers allowed separation of helper cells from cytotoxic cells (3). Although there were persistent reports of heterogeneity in the helper T-cell compartment (reviewed below), only relatively recently were distinct types of helper cells resolved. In this review we describe the differences between two types of cloned helper T cells, defined primarily by differences in the pattern of lymphokines ynthesized, and we also discuss the different functions of the two types of cells and their lymphokines. Patterns of lymphokine synthesis are convenient and explicit markers to describe T-cell subclass differences, and evidence increases that many of the functions of helper T cells are predicted by the functions of the lymphokines that they synthesize after activation by antigen and presenting cells. The separation of many mouse helper T-cell clones into these two distinct types is now well established, but their origin in normal T-cell populations is still not clear. Further divisions of helper T cells may have to be recognized before a complete picture of helper T-cell function can be obtained.