Immunology

the impressions the cells of our immune system form when they first meet a new bacterium

Natural killer cells are the predominant innate lymphocyte subsets that mediate anti-tumor and anti-viral responses, and therefore possess promising clinical utilization. NK cells do not express polymorphic clonotypic receptors and utilize inhibitory receptors (KIR and Ly49) to develop, mature, and recognize ‘self’ from ‘non-self’. The essential roles of common gamma cytokines such as IL-2, IL-7, and IL-15 in the commitment and development of NK cells are well-established. However, the critical functions of proinflammatory cytokines IL-12, IL-18, IL-27, and IL-35 in the transcriptional-priming of NK cells are only starting to emerge. Recent studies have highlighted multiple shared characteristics between NK cells the adaptive immune lymphocytes. NK cells utilize unique signaling pathways that offer exclusive ways to genetically manipulate to improve their effector functions. Here, we summarize the recent advances made in the understanding of how NK cells develop, mature, and their potential translational use in the clinic.

PubMed comprises more than 29 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Besides mediating hemostatic functions, platelets are increasingly recognized as important players involved in inflammation. Data from experiments in mice and men revealed various points of intersection between thrombosis, hemostasis and inflammation, which are addressed and discussed in this review in detail. One such example is the intrinsic coagulation cascade that is initiated after platelet activation thereby further propagating and re-enforcing wound healing or thrombus formation, which contributes to the pathophysiology of severe diseases. FXII of the intrinsic pathway connects platelet activation with the coagulation cascade during immune reactions. It can activate the contact system thereby either creating an inflammatory state or accelerating inflammation. Recent insights into platelet biology could show that platelets are equipped with complement receptors. Platelets are important for tissue remodeling after injury has been inflicted to the endothelial barrier and to the subendothelial tissue. Thus, platelets are increasingly recognized as more than just cells relevant for bleeding arrest or thrombus formation, and further interesting insights into platelet biology are to be discovered. In the future this understanding will potentially offer novel opportunities for therapeutic intervention in diseases, where platelets are involved.

The clearance of apoptotic cells is essential for proper development, homeostasis and the termination of immune responses in multicellular organisms. Thus, the cellular and molecular players taking part in the sequential events of this process are of great interest. Research in the last 20 years has indicated that specific ligands and receptors take part in the attraction of immune cells toward apoptotic targets and in the interactions between apoptotic cells and professional as well as non-professional phagocytes that engulf them. Moreover, the phagocytosis of apoptotic cells (efferocytosis) leads to significant phenotypic changes in the engulfing cells that suggest it is a major fate-determining event for phagocytes. Particularly, efferocytosis has an important impact on the inflammation-resolution axis as well as embryonic development and tissue morphogenesis. Deficiencies in these processes can result in health threats, such as autoimmunity, atherosclerosis, bone loss, obesity, infertility, neurodegeneration, fibrosis and cancer. This Research Topic issue will cover a wide range of subjects in apoptotic cell clearance: 1. Apoptotic cell clearance in embryonic development and tissue morphogenesis.2. Apoptotic cell clearance in the maintenance of homeostatic physiology. 3. Apoptotic cell clearance in inflammation, developmental immunology and autoimmunity. 4. Apoptotic cell clearance in pathologies.5. Molecular pathways involved in apoptotic cell clearance and relate

Persistent and durable immunological memory forms the basis of any successful vaccination protocol. Generation of pre-existing memory B cell and T cell pools is thus the key for maintaining protective immunity to seasonal, pandemic and avian influenza viruses. Long-lived antibody secreting cells (ASCs) are responsible for maintaining antibody levels in peripheral blood. Generated with CD4+ T help after naïve B cell precursors encounter their cognate antigen, the linked processes of differentiation (including Ig class switching) and proliferation also give rise to memory B cells, which then can change rapidly to ASC status after subsequent influenza encounters. Given that influenza viruses evolve rapidly as a consequence of antibody-driven mutational change (antigenic drift), the current influenza vaccines need to be reformulated frequently and annual vaccination is recommended. Without that process of regular renewal, they provide little protection against “drifted” (particularly H3N2) variants and are mainly ineffective when a novel pandemic (2009 A/H1N1 “swine ‘flu) strain suddenly emerges. Such limitation of antibody-mediated protection might be circumvented, at least in part, by adding a novel vaccine component that promotes cross-reactive CD8+ T cells specific for conserved viral peptides, presented by widely distributed HLA types. Such “memory” cytotoxic T lymphocytes (CTLs) can rapidly be recalled to CTL effector status. Here, we review how B cells and follicular

PubMed comprises more than 29 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

T follicular helper cells and T follicular regulatory cells tightly control the production of (auto)antibodies by B cells. Understanding their phenotypes and how the function of these cells is dysregulated in rheumatic diseases will aid future therapeutic development.

PubMed comprises more than 29 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.