2/20/12

StudyBlue printing of 2/20/12 html, body, div, span, applet, object, iframe, h1, h2, h3, h4, h5, h6, p, blockquote, pre, a, abbr, acronym, address, big, cite, code, del, dfn, em, font, img, ins, kbd, q, s, samp, small, strike, strong, sub, sup, tt, var, b, u, i, center, fieldset, form, label, legend, table, caption, tbody, tfoot, thead, tr, th, td { margin: 0; padding: 0; border: 0; outline: 0; font-size: 100%; background: transparent; } body { line-height: 1; } blockquote, q { quotes: none; } blockquote:before, blockquote:after, q:before, q:after { content: ''; content: none; } /* remember to define focus styles! */ :focus { outline: 0; } /* remember to highlight inserts somehow! */ ins { text-decoration: none; } del { text-decoration: line-through; } /* tables still need 'cellspacing="0"' in the markup */ table { border-collapse: collapse; border-spacing: 0; } /* end RESET */ .header { min-width:800px; } .logo { padding:6px 20px 2px 20px; margin:0; font-size:25px; font-weight:bold; color:#808285; position:relative; border-bottom: 1px solid #c5c5c5; } .logo-blue { color:#70adc4; } .logo-desc { font-weight:normal; font-size:19px; color:#cccccc; margin-top:50px; position:absolute; display: none; } .back-button { position:absolute; top:20px; right:20px; font-size:13px; line-height:25px; color:rgb(0,175,225); font-weight:normal; } .back-button a { color:rgb(0,175,225); } .instructions { padding:0; margin:0; width:100%; position:relative; color:rgb(100,100,100); } .step-holder { border-left:1px solid #ededed; margin-left:20px; } .steps { padding:15px 0; float:left; width:24%; border-right:1px solid #ededed; text-align:center; } .steps-01 { } .steps-02 { } .steps-03 { } .steps-04 { } .label { padding:5px 10px; } .print-button { } .print-button a { background-color:rgb(0,175,225); color:white; line-height: 19px; padding:9px 8px 5px 30px; font-size:14px; text-decoration:none; background-image: url(images/printer.png); background-repeat: no-repeat; background-position: 7px 50%; -moz-border-radius: 5px; -webkit-border-radius: 5px; } .print-button a:hover { background-color:black; } .theNote .content { width: 8.0in !important; margin: 5px auto; padding:20px; background-color:white; } .theNote .header { border-bottom: 1px dashed #C8C8C8; font-size: 17px; padding: 0 0 10px; line-height: 19px; color: #00ADE1; min-width:500px; } .theNote .body { font-size: 14px; line-height: 19px; padding: 10px 0; } .theNote{ padding:6px 0; clear:both; background-color: rgb(200,200,200); } .theNote h3{ color: rgb(100,100,100); } .theNote h1, .theNote h3{ background-color:white; padding:2px 20px; width:8.0in !important; margin: 0 auto; font-size: 15px; } .theNote h1{ padding-top: 10px; font-size: 15px; } .theNote h1:first-child{ font-size: 20px; } .theNote h3 { font-size: 14px; font-weight: normal; } #options { border: 3px double #ccc; padding: 5px 12px; margin: 10px 50px 10px 20px; float: left; } #info { border-top: 1px solid #ccc; padding-top: 5px; font-style: italic; } li { margin: 5px 10px 5px 25px; } ul li { list-style: disc; } ol li { list-style: decimal; } img { border: 0; } table { clear: both; width: 100%; border: 1px solid #c5c5c5; border-width: 1px 0; margin: 0; page-break-after: always; } table#page { page-break-after: auto; } td { text-align: center; font-size: 12px; border-bottom: 1px dashed #c5c5c5; height: 1.75in; width: 50%; padding-left: 15px; } .leftside { border-right: 1px solid #cccccc; padding: 0 15px 0 0; } .bottom td { border-bottom: none; } .clearfix { clear:both; line-height:1px; height:1px; } img { max-width:80%; max-height:150px; margin:20px; } @media print {.header { display: none; } .content .header{ display:inherit; } table { border: 1px dashed #bbb; border-width: 1px 0; } .theNote{ background-color:white; } } B-cell life cycles: secondary lymphoid tissues primary follicles: start to see blast cells these are going to be the B cells that undergo affinity maturation and develop into plasma cells, undergo class switching activation-induced (cytidine) deaminase (AID) -- overwhelms DNA repair cytidine --> uridine seen as T or may become a null base site --> random base insertion AID is also involved in inducing class switching important during proliferative response of B cells Plasma cells migrate to the medullary cords or leave through efferent lymphatics (may migrate to bone marrow from here) How to Ig molecules transduce signals? Ig.alpha and Ig.beta are associated w/ immunoglobulin molecules Igs alone do not contain classic signaling motifs Ig.alpha and Ig.beta do contain ITAM (Immunoreceptor Tyrosine-based Activation Motifs) -- which are the targets of src family tyrosine kinases canonical ITAM sequences alpha and beta each have 1 ITAM each B cell receptor has a total of 4 ITAMs membrane-bound Src-family kinases Fyn, Blk, Lyn are associated w/ the B-cell receptor phosphorylate ITAMs Regulation of B-cell response phosphorylation of ITIMs -- negative regulation CD22 contains an ITIM - phospohrylation of this activates SHP-1, a deactivating phosphatase that deactivates the Ig-alpha/Ig-beta complex CD19, 21, TAPA-1 (81) coreceptors enhance signal transduction - form B-cell coreceptors >>association of co-receptor enhances antigen receptor signaling up to 1000x C3d or C3dg breakdown product of complement system binds to CD21 and may also bind to antigen, which will cross-link w/ mIgM --> leads to Src activation of ITAMs CD45 - a phosphatase activates lck kinase lck-kinase-P (inactive as phosphorylated) --> lck-kinase (active) cleaved by cD45 lck-kinase activates PLC phospholipase C (inactive) --> phospholipase C-P interacts w/ P-B cel linker protein (BLNK) - active >>>>leads to cellular activation Lck kinase phosphorylates PLC to generate diacylglycerol and IP3 Ig.beta is needed for B cell differentiation into Pre B cells Btk, a tyrosine kinase is necessary for B cell development an X-linked gene pre-B cells cannot develop into immature B cells females can be heterozygous and carry the disease while still producing B cells Ig.mu and lambda5 are needed for the differentiation of B cells into Pre-B cell II stage (large pre-B cell) w/o lambda5 B-cells will not make it to immature stage kappa chains rearranged before lambda chains kappa chain genes are providing signals that are necessary for the B-cell to develop even w/ functional lambda genes, w/o kappa B-cell cannot develop b/t pre-B II and immature B cell the cytoplasmic domain of Ig.alpha is needed for the final maturation of B cells truncating Ig-alpha eliminates ITAMs and only 1% of immature B cells leave the bone marrow as mature B cells Ig.alpha signal transduction is also needed for mature B cells to respond to LPS, a T-independent antigen Are T cells needed for B cell activation? most antigens are T-dependent (TIs are very specialized and unique w/ repeating units) T cells are needed for a secondary response Anti-Thy-1 targets thy-1 antigen on mouse T cells -- Anti-Thy-1 and complement eliminates T cells