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Adaptive immune development

Pro-B-cell stage (VJD) rearangement of Ig heavy chain
Pre-B-cell stage is defined when µ heavy chain is produced
Affinity maturation B cells Ig associated to antigens quicker with repeat exposure shown by lower Kd (dissociation constant), caused by point mutations in V regions
Location of Affinity maturation germinal centers in lymphoid follicles. Follicular dendritic cells display antigen and high - affinity B cells are selected to survive
Naïve B cell gets no CD40L signal produces IgM
Activation-induced cytidine deaminase (AID) a DNA-editing deaminase involved in somatic hypermutation, gene conversion, and class-switch recombination of immunoglobulin genes in B cells of the immune system.
B cell activation pathways 1. Cross linking by BCR antigen, 2. co-stimulation by complements, 3. co-stimulation by T helper cells
Naïve B cell binds to helper T cell and cytokines makes IgG , Ig M
B cell activation leads to mitosis colonal expansion
B cell activation leads to increased cytokine receptors increased response to HTcell cytokines
B cell activation leads to migration out of lymphoid follicles interacted with HTcell
B cell activation leads to secretion of low IgM Early humoral Immune response
BCR cross-linking (clustering) stimulates a signaling leading to changes in gene expression. multivalent arrays of the same epitope may activate the B cells strongly enough to stimulate their proliferation and differentiation without a requirement for T cell help.
ITAM: Immunoreceptor tyrosine-based activation motif are a defining feature of antigen-receptor complexes. TCR and BCR.  FcɛR1 on mast cells also have it. FcRγ chain, which is a signaling subunit containing one.
B cell co-stimulation of receptor by antigen co-receptor has 1) CR2 (complement receptor 2) recognizes C3d and iC3b, 2) CD19 3) CD81
B cell activation by costimulation with HTcells, 1)B cell acts as APC, costimulates with B7 2)TH cells express (CD40L) and secrete cytokines, activating Bcell
Follicular B cells Majority of B cells, reside in and circulate through follicles of lymphoid organs. make the bulk of T-dependent, class-switched, and high-affinity antibody responses to protein antigens. Give rise to long-lived plasma cells.
Marginal–zone B cells peripheral region of the splenic white pulp. Respond to blood-borne polysaccharide antigens. Express antigen receptors of limited diversity and make predominantly IgM responses.
B-1 cells Respond to non-protein antigens in the mucosal tissues and peritoneum. Express antigen receptors of limited diversity and make predominantly IgM responses. Lack features of T-dependent antibody responses to protein antigens.
Bcells in Spleen and lymph FBC and MBC
FBC respond in spleen and lymph to Protein antigen with Htcell and IgD IgM, leads to isotype or affinity switching or plasma cells
MBC respond to Lipids and polyssharides in lymph and spleen with IgM
MB1 respond to Lipids and polyssacharides in Mucosa with IgM
Thymus-independent (TI) antigens Polysaccharides, lipids, and other non-protein, Marginal-zone’ and ‘B-1’ cells respond
Thymus-dependent (TD) antigens globular protein antigens are processed by B cells so Tcells can respond. Follicular B cells play main role
initial antigen-specific T-B cell interaction consists of two phases 1. B cells process and present antigen to the T cells 2. previously activated helper T cells express CD40 ligand and secrete cytokines, which act on the B cells to initiate proliferation and differentiation to plasma cells
Initial T-B interaction, which occurs at the edge of lymphoid follicles (aka extra follicular foci.)
that CD28 on T cell surface protein that regulates an activation pathway, could mediate intercellular adhesion with activated B cells by interaction with the B7 antigen.
sequence of events following the first B-T tango Some B cells migrate back into the follicle accompanied by helper T cells --> form Follicular helper T (TFH) cells. Express high levels of the chemokine receptor CXCR5
CXCR5 receptor is CXCL13
T cells reach the lymph node paracortical region (T zone) via high endothelial venules (blood) or afferent lymphatics (peripheral tissues) in response to the CCR7-specific chemokines CCL19 and CCL21.
During contact with antigen-presenting DC, T cells become primed that includes induction of CXCR5 expression. Reduced CCR7 expression allows newly generated CXCR5+ T (TFH) cells to respond to follicular CXCL13 and relocate to B cell follicles where TFH-B cell interactions with receptors CD40, and cytokines IL-10, IL-21, initiate the germinal center reaction and the formation of plasma cells and memory B cells.
In response to signals from the TFH cells, B cells begin to proliferate, forming an organized structure called a germinal center, as well as formation of plasma cells (many of which migrate to the bone marrow) and memory B cells.
B cells recognize one epitope of the antigen and display different epitopes (peptides) for recognition by helper T cells
Once T cells are activated they secrete IL-2 and induce expression of IL-2Ralpha chains which make an IL-2complex and induce Tcell proliferation
T integrin TCR and CD4 binds to APC MHC2
T integrin CD 28 binds to APC B7, (CD80, CD86)
T integrin CD 152 (CLTA-4 ) binds to APC B7 (CD80, CD86)
Colonal expansion is exceptionally fast for for CD8+ T cells
CD1 is a Surface glycoprotein which can present lipids
CD 1 Can present to ab or gd T cells (CD1a,b,c), and NKT cells (CD1d).
Created by: splashgreen



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