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MUA M2B2 IDR 02
Adaptive immune development
Term | Definition |
---|---|
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). |