Springer Seminars in Immunopathology 

About: Springer Seminars in Immunopathology is an academic journal. The journal publishes majorly in the area(s): Immune system & Antigen. It has an ISSN identifier of 0344-4325. Over the lifetime, 798 publications have been published receiving 27474 citations.

Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion

Abstract: Natural antibodies are produced at tightly regulated levels in the complete absence of external antigenic stimulation. They provide immediate, early and broad protection against pathogens, making them a crucial non-redundant component of the humoral immune system. These antibodies are produced mainly, if not exclusively, by a subset of long-lived, self-replenishing B cells termed B-1 cells. We argue here that the unique developmental pattern of these B-1 cells, which rests on positive selection by self antigens, ensures production of natural antibodies expressing evolutionarily important specificities that are required for the initial defense against invading pathogens. Positive selection for reactivity with self antigens could also result in the production of detrimental anti-self antibodies. However, B-1 cells have evolved a unique response pattern that minimizes the risk of autoimmunity. Although these cells respond rapidly and strongly to host-derived innate signals, such as cytokines, and to pathogen-encoded signals, such as lipopolysaccharide and phosphorylcholine, they respond very poorly to receptor-mediated activation. In addition, they rarely enter germinal centers and undergo affinity maturation. Thus, their potential for producing high-affinity antibodies with harmful anti-self specificity is highly restricted. The positive selection of B-1 cells occurs during the neonatal period, during which the long-lived self-renewing B-1 population is constituted. Many of these cells (B-1a) express CD5, although a smaller subset (B-1b) does not express this surface marker. Importantly, B-1a cells should not be confused with short-lived anergic B-2 cells, which originate in the bone marrow in adults and initiate CD5 expression and programmed cell death following self-antigen recognition. In summary, we argue here that the mechanisms that enable natural antibody production by B-1 cells reflect the humoral immune system, which has evolved in layers whose distinct developmental mechanisms generate complementary repertoires that collectively operate to maximize flexibility in responses to invading pathogens. B-2 cells, present in what may be the most highly evolved layer(s), express a repertoire that is explicitly selected against self recognition and directed towards the generation of high-affinity antibody response to external antigenic stimuli. B-1 cells, whose repertoire is selected by recognition of self antigen, belong to what may be earlier layer(s) and inherently maintain production of evolutionarily important antibody specificities that respond to pathogen-related, rather then antigen-specific signals.

Dendritic cell-mediated T cell polarization.

Abstract: Effective defense against diverse types of micro-organisms that invade our body requires specialized classes of antigen-specific immune responses initiated and maintained by distinct subsets of effector CD4(+) T helper (Th) cells. Excessive or detrimental (e.g., autoimmune) responses by effector T cells are controlled by regulatory T cells. The optimal balance in the development of the different types of effector and regulatory Th cells is orchestrated by dendritic cells (DC). This review discusses the way DC adapt the T cell response to the type of pathogen, focusing on the tools that DC use in this management of the T cell response.

Dendritic cell biology and regulation of dendritic cell trafficking by chemokines.

Abstract: DC (dendritic cells) represent an heterogeneous family of cells which function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. Then, following inflammatory stimuli, they leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. The key role of DC migration in their sentinel function led to the investigation of the chemokine responsiveness of DC populations during their development and maturation. These studies have shown that immature DC respond to many CC and CXC chemokines (MIP-lα, MIP-iβ, MIP-3α, MIP-5, MCP-3, MCP-4, RANTES, TECK and SDF-1) which are inducible upon inflammatory stimuli. Importantly, each immature DC population displays a unique spectrum of chemokine responsiveness. For examples, Langerhans cells migrate selectively to MIP-3α (via CCR6), blood CDllc+ DC to MCP chemokines (via CCR2), monocytes derived-DC respond to MIP-lα/β (via CCR1 and CCR5), while blood CDllc- DC precursors do not respond to any of these chemokines. All these chemokines are inducible upon inflammatory stimuli, in particular MIP-3α, which is only detected within inflamed epithelium, a site of antigen entry known to be infiltrated by immature DC. In contrast to immature DC, mature DC lose their responsiveness to most of these inflammatory chemokines through receptor down-regulation or desensitization, but acquire responsiveness to ELC/MIP-3β and SLCASCkine as a consequence of CCR7 up-regulation. ELC/MIP-3(3 and SLC/6Ckine are specifically expressed in the T-cell-rich areas where mature DC home to become interdigitating DC. Altogether, these observations suggest that the inflammatory chemokines secreted at the site of pathogen invasion will determine the DC subset recruited and will influence the class of the immune response initiated. In contrast, MIP-3β/6Ckine have a determinant role in the accumulation of antigen-loaded mature DC in T cell-rich areas of the draining lymph node, as illustrated by recent observations in mice deficient for CCR7 or SLC/6Ckine. A better understanding of the regulation of DC trafficking might offer new opportunities of therapeutic interventions to suppress, stimulate or deviate the immune response.

The Alternative Pathway of Complement

Abstract: The alternative pathway of complement activation provides the host with a humoral component of the natural defense mechanisms against infectious agents. The six plasma proteins involved in recognition and activation perform a continuous surveillance function that does not require specific antibody to recognize potential pathogens. Discrimination between host and foreign particles occurs because activation of the system is under strict control by regulatory plasma and membrane proteins of the host. Full activation only occurs when the function of these regulators is dampened on the surface of foreign particles. Organisms sensitive to attack by the alternative pathway include bacteria, fungi, certain viruses, virus-infected cells, some tumor cell lines, and human erythrocytes lacking the decay accelerating factor (DAF) in their membrane. Activation of the pathway on these particles results in the deposition of large numbers of C3b molecules and assembly of the cytolytic membrane attack complex. These events trigger, through a variety of mediators, several cellular responses including leukocyte chemotaxis, release of vasoactive amines, hydrolytic enzymes and of arachidonic acid metabolites, adhesion, and phagocytosis.

Monoclonal antibodies in cancer therapy

Abstract: A new perspective for monoclonal antibodies (mAbs) is their use in patients presenting with minimal cancer burden or micrometastatic disease, i.e. in secondary prevention of metastatic cancer disease. The first proof of efficacy of a mAb in minimal residual disease has recently been published with mAb 17-1A in patients with colorectal cancer stage III after complete resection of the primary tumour. After a median follow-up of 5 years, antibody therapy reduced overall death rate by 30% and decreased the recurrence rate by 27%. This result is similar to the benefit obtained with (radio)chemotherapy trials, however, with notably less toxicity.