MedArt

Mugwort (Artemisia vulgaris) is widely spread throughout the European temperate climate zone, North America and parts of Asia and is one of the main causes of hay fever in late summer and autumn. More than 95% of mugwort allergic patients are sensitized to Art v 1, the major allergen in mugwort pollen. Allergy or immediate hypersensitivity is one of the most powerful pathologic reaction of the immune system and is elicited by immunoglobulin E (IgE)-mediated stimulation of tissue mast cells. The typical sequences of events in immediate hypersensitivity consists of exposure to an antigen (e.g. Art v1), which stimulates TH2 cells specific for the antigen. Secreting Interleukins (IL) such as IL-4, this TH2 cells provoke B-cells to produce IgE Antibodies. IgE sensitizes/triggers mast cells by binding to FcεRI receptors (sensitation). Subsequent re-exposure to the allergens activates the mast cells to release the mediators (e.g. Histamine, proteases, prostaglandin D2, leukotriene and cytokines) that are responsible for the pathologic reactions. These mediators collectively causes increased vascular permeability, vasodilation, bronchial and visceral smooth muscle contraction, and local inflammation (e.g. Rhinitis, conjunctivitis). On the other hand mugwort is one of the unique essences of the fabulous Noilly Prat, originally a dry white vermouth from Marseillan. Joseph Noilly, a herbalist, developed the first formula in 1813. It was the first example of a dry vermouth and led to white vermouths being known as ‘French’. Noilly Prat is 18% alcohol by volume.

Ref: [1] Himly M et al., FASEB J. 2003 Jan;17(1):106-8. [2] Cellular and Molecular Immunolgy, A.Abbas, Saunders, Philadelphia; ISBN: 0-7216-0008-5

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Naïve T cells preferentially leave the blood and enter lymph nodes across the high endothelial venules (HEV). In the skin a network of immature dendritic cells called Langerhans cells, present in the epidermis serves to trap antigens. This professional antigen presenting cells (APCs) but also macrophages bearing antigen enter the lymph node through afferent lymphatic vessel. Also the mucosal immune system includes specialized collections of APCs organized to optimize encounters with environmental antigens introduced through the respiratory and gastrointestinal tracts. If the T cells recognize antigen presented in the lymph node by APCs, they are activated, and they return to the circulation through the efferent lymphatics and the thoracic duct, which empties into the superior vena cava, then into the heart, and ultimately into the arterial circulation. Effector and memory T cells preferentially leave the blood and enter peripheral tissue through venules at side of inflammation (e.g. skin or mucosa). This process of lymphocyte recirculation is regulated by adhesion molecule, called homing receptors, and their ligands on vascular endothelial cells, called addressins.

Ref: Cellular and Molecular Immunolgy, A.Abbas, Saunders, Philadelphia; ISBN: 0-7216-0008-5

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The thymus is a bilobed organ situated in the anterior mediastinum. It continues to grow between birth and puberty and then begins to atrophy (involution), a process directed by the high levels of circulating sex hormones. The lobe consists of an outer cortex and an inner medulla. The cortical portion is mainly composed of lymphocytes, supported by a network of finely-branched epithelial reticular cells, which is continuous with a similar network in the medullary portion. Scattered throughout the thymus are non-lymphoid cells, such as bone marrow-derived macrophages and dendritic cells. The cortex is the location of the earliest events in thymocyte development, where T cell receptor gene rearrangement and positive selection takes place. Precursors of T cells travel from the bone marrow through the blood to the thymic cortex and do not express a T cell receptor (TCR) or CD4 or CD8 (double-negative thymocytes). The ability of T cells to recognize foreign antigens is mediated by the TCR. Thus T cell receptor undergoes genetic rearrangement during thymocyte maturation, resulting in each T cell bearing a unique TCR. Selection processes promote survival of thymocytes whose TCRs bind self MHC molecules with low affinity (positive selection) and eliminate self–reactive thymocytes (negative selection). If these central tolerance mechanisms fail, autoimmunity may arise. At the next stage of T cell maturation, thymocytes express both CD4 and CD8 and are called double-positive thymocytes. Functional differentiation into CD4+CD8- and CD8+CD4- T cells (single-positive thymocytes) occurs in the medulla, and mature T cells are released into the circulation. Early maturation is characterized by cell proliferation induced by cytokines, mainly IL-7.

Ref: Cellular and Molecular Immunology, A.Abbas, Saunders, Philadelphia; ISBN: 0-7216-0008-5

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Immunoprecipitation is a technique in which an antigen is isolated by binding to a specific antibody attached to a sedimentable matrix. E.g. a particular protein antigen can be purified from a mixture of protein antigens in serum or other solutions by adding antibodies specific to the antigen, which are bound to insoluble beads. Unbound antigens are then washed away, and the desired antigen is recovered by changing the pH or ionic strength of the solution so that the affinity of antibody-antigen binding is lowered. Immunoprecipitation can be used as a means of purification, as a means of quantification, or as a means of identification of an antigen respectively protein. Antigens purified by immunoprecipitation are often analyzed by sodium dodecyl sulfatepolyacrylamid gel electrophoresis (SDS-Page) followed by Western blotting. Protein antigens, separated by SDS-Page and transferred to a membrane (blotting) can be labeled with radioactive or enzyme-coupled antibodies.

Ref: Cellular and Molecular Immunology, A.Abbas, Saunders, Philadelphia; ISBN: 0-7216-0008-5

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The spleen is the major site of immune responses to blood-borne antigen. Located in the left upper quadrant of the abdomen the spleen is organized as a ‘tree’ of branching arterial vessel, in which the smaller arterioles end in a venous sinusoidal system. The organ is surrounded by a capsule. The smaller branches of the arterial supply are sheathed by lymphoid tissue – T cell zone (PALS) and B cell zone (follicle and marginal zone) – which forms the white pulp. The specialized venous system has a unique capacity to filter blood and together with a large number of erythrocytes, dendritic cells (DC) and macrophages it constitute the red pulp. This splenic macrophages play an important role in (i) remove of older erythrocytes from the circulation, (ii) recycling of iron and (iii) recognition and up-take of blood-bone pathogens. This function, in combination with the highly organized lymphoid compartments makes the spleen the most important organ for antibacterial and antifungal immune reactivity. Individuals lacking a spleen are extremely susceptible to infections with encapsulated bacteria.

Ref: Reina E. Mebius, Georg Kraal, structure and function of the spleen, Nature Rev Immunol. 5, 606-616 (2005)

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Antibodies function as mediators of specific humoral immunity by engaging diverse molecular and cellular effector mechanisms that serve to eliminate the ... .... ..

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Microbes enter the body most often through the skin and the gastrointestinal and respiratory tracts. All these tissues are lined by epithelia that contains dendritic cells. The epithelia also contain numerous lymphatic capillaries that absorb the interstitial lymph. Dendritic cells capture microbial antigen from the site of infection and enter these lymphatic vessel. Lymph nodes, that are interposes along the lymphatic vessels acts as filters and are the organs in which adaptive immune responses to lymph-borne antigens are initiated. Thereby antigen presenting cells, such as the dendritic cells enter the lymph node through afferent lymphatic vessels and display the antigen to specific T cells to initiate these immune responses. In the lymph node the segregation of T cells (to the parafollicular cortex = T cell zone) and B lymphocytes (to the lymphoid follicle = B cell zone) is dependent on chemokines. The lymphocytes enter the lymph node through high endothelial venules (HEV), and are drawn to different areas of the node by chemokines that are produced in these areas and bind selectively to either cell type. Germinal centers develop in response to antigenic stimulation. They are the sites of B cell proliferation and selection of B cells producing specific antibodies.

Ref: Cellular and Molecular Immunolgy, A.Abbas, Saunders, Philadelphia; ISBN: 0-7216-0008-5

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