B and T lymphocytes are the mediators of immunity, but their function is under the control of dendritic cells. Dendritic cells in the periphery capture and process antigens, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. They not only activate lymphocytes, they also tolerize T cells to antigens that are innate to the body (self-antigens), thereby minimizing autoimmune reactions. Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis. With knowledge comes the realization that these cells are a powerful tool for manipulating the immune system.

Dendritic cells and the control of immunity

Pathogen Recognition and Innate Immunity

The discovery of Toll-like receptors (TLRs) as components that recognize conserved structures in pathogens has greatly advanced understanding of how the body senses pathogen invasion, triggers innate immune responses and primes antigen-specific adaptive immunity. Although TLRs are critical for host defense, it has become apparent that loss of negative regulation of TLR signaling, as well as recognition of self molecules by TLRs, are strongly associated with the pathogenesis of inflammatory and autoimmune diseases. Furthermore, it is now clear that the interaction between TLRs and recently identified cytosolic innate immune sensors is crucial for mounting effective immune responses. Here we describe the recent advances that have been made by research into the role of TLR biology in host defense and disease.

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The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors

Pattern Recognition Receptors and Inflammation

The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

We recently showed that culture-derived metacyclic trypomastigotes (CMT), but not epimastigotes (Epi), of the Miranda 88 strain of Trypanosoma cruzi evade lysis by the human alternative complement pathway because of inefficient binding of factor B to complement component C3b on the parasite surface. These results suggested that CMT and tissue-culture-derived trypomastigotes (TCT), which also activate the alternative pathway poorly, might produce a molecule capable of interfering with factor B binding to C3b. We now demonstrate that CMT and TCT lysates, as well as molecules spontaneously shed from CMT and TCT but not Epi, accelerate decay of 125I-labeled factor Bb from the alternative-pathway C3 convertase (C3bBb) assembled on zymosan or Epi and also accelerate decay of the classical-pathway C3 convertase (C4b2a) on sheep erythrocytes. Parasites metabolically labeled with [35S]methionine spontaneously shed a limited number of radioactive components ranging in molecular mass from 86 to 155 kDa for trypomastigotes and 25 to 80 kDa for Epi. Decay-accelerating activity within supernatants is inactivated by papain and is coeluted with 35S-containing polypeptides on FPLC anion-exchange chromatography, suggesting that the active constituents are protein molecules. Molecules with decay-accelerating activity may explain the developmentally regulated resistance to complement-mediated lysis in infective and vertebrate stages of the T. cruzi life cycle.

Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases

Murine peritoneal exudate cells rich in cytolytic T lymphocytes (CTL) with specificity for alloantigens were found to adhere specifically to schistosomula, recovered from the lungs of mice, which bear alloantigens on their surface as a result of passive acquisition from the host. The presence of CTL in the adherent cell population was confirmed by a mixed killing reaction, in which it was shown that most of the cells that had adhered to the schistosomula were subsequently able to kill an appropriate tumor target cell. These CTL, however, failed to damage the schistosomula even after prolonged periods of culture (up to 66 hr) at high effector to target ratios. The same organisms were at least partially susceptible to complement-dependent damage by antibody with specificity for the same alloantigens. Furthermore, the same CTL preparations could artificially be induced to adhere to skin-stage schistosomula, which do not bear alloantigens on their surface, by using concanavalin A as a nonspecific binding agent to overcome the requirement for specific recognition of target antigens by the CTL. Such organisms were also insusceptible to CTL-mediated damage, even though they have previously been shown to be damaged by both eosinophils and neutrophils. Reasons for the lack of CTL damage are discussed, and it is emphasized that the adherence reaction provides a new model for examining the early stages of the interaction of CTL with their targets, and for studying the recognition by CTL of antigens that have been passively inserted into a target membrane.

Cytolytic T Lymphocytes Recognize Alloantigens on Schistosomula of Schistosoma Mansoni, but Fail to Induce Damage

Immunological involvement in the efficacy of praziquantel

Chitosan: An Adjuvant with an Unanticipated STING

Background
Interleukin-1β (IL-1β) is important for host resistance against Mycobacterium tuberculosis (Mtb) infections. The response of the dendritic cell inflammasome during Mtb infections has not been investigated in detail.

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Alan Sher

Papers

Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases

Cytolytic T Lymphocytes Recognize Alloantigens on Schistosomula of Schistosoma Mansoni, but Fail to Induce Damage

Immunological involvement in the efficacy of praziquantel

Chitosan: An Adjuvant with an Unanticipated STING

Mycobacterium tuberculosis infection of dendritic cells leads to partially caspase-1/11-independent IL-1β and IL-18 secretion but not to pyroptosis