Lecture 8 2010.pptx

Steps in B cell development B cells develop in bone marrow and then migrate to secondary lymphoid tissues The early stages of B-cell development are dependent on bone marrow stromal cells Stages of B cell development are defined by the rearrangement and expression of the Ig genes Occurs in the bone marrow Binding to self-antigens in the bone marrow can lead to the deletion or inactivation of immature B cells . Replacement of light chains by receptor editing can change reactivity and rescue some self-reactive B cells 1 2 3 4 B cells encountering antigen in secondary lymphoid tissues form germinal centers and undergo differentiation to plasma cells B cells migrate from the bone marrow in the blood to lymph nodes and other secondary lymphoid tissues. If they do not encounter their specific antigen, the B cells pass through the primary follicles and leave the node in the efferent lymph, which eventually joins the blood at veins in the neck Germinal centers are formed when activated B cells enter lymphoid follicles Immune complexes bound to follicular dendritic cells form iccosomes, which are released and can be taken up by B cells in the germinal center. The interactions of helper T cells and B cells in lymphoid tissues Cross-linking of antigen receptors is the first step in B-cell activation Signals generated from the B-cell receptor and co-receptor synergize in B-cell activation B cell activation B-cell activation in response to thymus-dependent antigens also requires cognate T-cell help Important cytokines include IL-2, IL-4 and IL-5 Because of receptor-mediated endocytosis of Ig with bound antigen, B cells can process lots of antigen efficiently. Antigen-specific B cells are increased in number so a high density of specific antigen fragments can be presented While dendritic cells and macrophage present antigen early in the adaptive immune response, B cells are especially important APCs after antigen-specific B cells are expanded Antigen-specific B cells are increased in number. Because of receptor-mediated endocytosis of Ig with bound antigen, B cells can process lots of antigen efficiently. High density of specific antigen fragments can be presented Subsets of B cells Important cytokines for switch: IL-4- IgE, IgG IFN?- IgG TGF?- IgA T-dependent antigens elicit primary and secondary immune responses Eg. Bacterial LPS- develop in athymic individuals, do not require T cell help (cognate interaction), cannot function as APCs, no memory How do antibodies work? Neutralization by IgG antibodies protects cells from toxin action Viral and bacterial infection of cells can be blocked by neutralizing antibodies Clearance of pathogen via pathogen-specific Ig and FcR Receptors for the Fc regions of immunoglobulins are present on a variety of immune-system cells including: -neutrophils APCs -macrophages -dendritic cells -Langerhan?s cells -mast cells -eosinophils -basophils -B cells -FDC (follicular dendritic cells -NK cells Role of IgE FcR IgE cross-linking of mast cells leads to degranulation Eosinophils can attack larger parasites that can?t be phagocytosed via IgE/IgE FcR (Fc?RI) bridge Antibody-coated target cells can be killed by NK cells and ADCC Complement receptor- mediated clearance The classical pathway of complement activation is initiated by binding of C1q to antibody on a bacterial surface. Immune complexes bind to CR1 on erythrocytes, which transport them to the liver and spleen. Here they are removed by macrophages expressing receptors for Fc regions and for bound complement components Encapsulated bacteria are more efficiently engulfed by phagocytes when the bacteria are coated with antibody and C3b