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Webinars - Immunology

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The most enigmatic blood circulation of our body:
3D models of splenic microvasculature based on immunostained serial sections

In vertebrates, a special secondary lymphatic organ, the spleen, is responsible for immunological survey of the blood. This task necessitates an astonishing solution for directly confronting T- and B-lymphocytes and macrophages with blood-borne materials: In humans and rodents, the arterial and the venous side of the splenic microcirculation are completely separated by a gap. This gap is filled by connective tissue of the splenic cords. Thus, blood leaves the open ends of the arterial capillary network, freely traverses the cords and then enters the venous sinuses from the outside via functional slits in their walls. On its way across the cords, the blood flows along the cell membranes of fibroblasts and of a large population of highly active macrophages without any barrier formed by endothelial cells. In humans, in addition to the sinuses, there is a second spleen-specific type of microvessel, the sheathed capillaries, which feed the capillary network.
We used Enzo chromogens in light microscopic triple staining of serial sections to definitively demonstrate that the arterial and the venous side of the human splenic microvasculature lack any connections. This was possible by detecting open capillary ends and by visualizing their unique morphology in 3D models viewed in virtual reality. Our method also permitted defining sheathed capillaries as post-arteriolar vessels surrounded by sheaths consisting of special stromal sheath cells, macrophages and recirculating B-lymphocytes. The sheaths most likely represent the splenic entry compartment for all types of antigens and particulate substances from the blood, because they are irrigated by open side branches of their capillary. Using 3D models based on immunohistology in transmitted light we are able to settle the 170-year-long debate of open versus closed circulation in the human spleen and provide previously unseen insight into the tissue microanatomy of the spleen.

Main Target Audience: Anatomists, Physiologists; Histologists; Clinical Laboratories; Hospitals; - Researchers interested in the following topics: Anatomy, The cardiovascular system, Immunohistochemistry (IHC), Histology, blood circulation, Immunology, Pathology

Why should you attend?: Whether you are a scientist, a student, a lab technician, or a curious citizen, this webinar will provide fascinating new anatomic insight into the architecture of the spleen and highlight captivating, state-of-the art digital visualization of immunohistochemistry results, a method which forms the pillar of our anatomical understanding since over a century.

Presented by: Prof. Dr. Birte Steiniger
Professor emeritus and head of Department of Immunobiology
Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Marburg

Prof. Dr. Oleg Lobachev
Professor for IT-Security and Artificial Intelligence
Leibniz University of Applied Sciences, Hannover

Topic: IHC, Immunology

Deciphering human B cells complexity in health and disease

B cells are responsible for the humoral immune response against pathogens. They mature with age in response to the environment, refining their antigen receptors. Their functions are extremely complex and go beyond the production of specific antibodies. Therefore, any glitch occurring in the sophisticated B cell machinery can lead to pathology, from immunodeficiency to autoimmunity. Understanding the different subpopulations of human B cells and their functions is key to unravel defects in B cells in patients with immunodeficiency and autoimmunity.
We investigated B cell functions in infancy and throughout childhood, through in vitro functional tests. We show that T-independent stimulation with CpG measures proliferation and the differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naive and memory B cells. The response to CD40L does not change with age. Finally, in patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Summary: I will report our experience on the study of B cell functions in infancy and throughout childhood and show how the proliferative potential, plasmablast differentiation and immunoglobulin secretion of B cell subsets can be reliably assessed in children through T-independent activation by the TLR9 agonist CpG. We also demonstrate how B cells respond to T-dependent co-stimulation. Finally, we show that in vitro functional tests can support physicians in assessing the state of the humoral immune system of patients with immune defects.

Main Target Audience: Anyone interested in human B cell biology. Research scientists in the academic and clinical field, at any career stage.

Why should you attend?: A clear and detailed description of in vitro B cell responses to different stimuli is crucial in order to design standardized and reproducible functional tests. Dr Marasco will talk about his experience on the study of B cell functions in children and young adults, providing an example of how in vitro functional tests could be conducted and interpreted in everyday clinical practice.

Presented by: Dr Emiliano Marasco, MD
Division of Rheumatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Topic: Immunology

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