| how do these cells bind to antibodies, B-cells,T-cells? | B-cells by membrane bond antibodies or B-cell receptors (BCR), T-cells by T-cell receptors (TCR) |
| how do TCR and BCR recognize antibodies? | BCR (Ig) ands soluble antibodies recognize wide set of antigens by attachment , TCR recognize antibodies by antigen presenting cells that have that have peptides presented by MHC molecules . |
| what's a variable region V? | antigen recognition |
| what's constant regions C? | interaction with down stream signaling (telling lymphocytes to differentiate or die) molecules recreating antibodies that are triggered by antigens binding to BCR and TCR receptors . |
| what's the constant region recreating antibodies? | interaction with receptors on phagocytes and complement proteins. |
| what are the types of antibodies of BCR (depending on their heavy chains)? | IgA(mucosal immunity ) , IgD( naive B-cell antigen receptor), IgE( defense against parasites), IgG(Opsonization),IgM(naive B-cell antigen). |
| what are the native B cells receptors ? | IgM and IgD |
| what the two types of light chains? | ⋋ and K |
| what's allelic exclusion ? | a process by which only one allele of a gene is expressed while the other allele is silenced. |
| what's affinity? | interaction of one antibody-antigen region (Kd= 10-6, 10-9) |
| what's avidity? | interaction of 2 or more antibody-antigen region, The measure of the total binding strength of an antibody is avidity,stronger as probability of repeated interaction. |
| what is the structure of T-cell receptors ? | 90% a and b chain,variable and constant regions variable regions recognize peptides presented on MHC.5-10% T-cells y and Ơ chains Recognize all kind of antigens do not require presentation on MHC.5% NK-T cells a and b chain variable regions do not show wide diversity, recognize lipid antigens presented by nonpolymorphic MHC . |
| what is positive and negative selection? | positive selection of T-cells only the T-cells that recognize MHC molecules will survive, others will die. negative selection B and T cells those who recognize self antigens will die. |
| the differences in antigen recognition between BCR Ig and TCR genes? | they contain multiple variable regions (V) and one or few constant regions (C).Between V and C regions are several short diversity (D) and joining (J) segments.Only Ig heavy chain and TCR b-chain contain D segment. |
| what is the maturation and selection chain of B-lymphocytes? | stem cell--> pro-B--> immature B--> mature B (follicular and memory) |
| what cells do not express Ig? | stem cells and and pro B . |
| what cells move on to become pre B cells? | only the cells that express the Igu heavy chain and other surrogate light chains survive and form the pre B cells. passing this check point releases survival signals.if the heavy chain is not made it will undergo apoptosis (cell death) . |
| what type of Ig are mature cells? | IgM and led they are mature B cells that can respond to antigens. |
| what is the maturation and selection chain of T-lymphocytes? | stem cells --> pro T--> pre T--> double positive T-cells--> single positive T-cells |
| what are pro T cells? | double negative T cells (CD4-, CD8-) that proliferate in response to IL7
In the thymus. If functional pre-TCR is not formed, cell will apoptose. |
| what are pre T cells? | in the thymus VDJ recombination takes place. TCR-b chains is expressed with invariant pre-Ta to form pre-TCR complex in pre-T cells. |
| what will pre-TCR will send signals to? | inhibit apoptosis ,inhibit VDJ recombination in the homologous chromosome (allelic exclusion); stimulate TCR-a gene recombination. |
| How do pre-TCR cells survive? | If no functional TCR-a gene is expressed cells will die. Surviving cells express complete abTCR and CD8, CD4 receptors. which are called double-positive T cells. |
| what is Positive selection regarding T-cells? | Low affinity interaction between abTCR and MHC molecules sends survival signal. These cells may recognize complexes of microbial antigens bond to MHC with higher affinity. Cell that cannot recognize MHC molecules will die. Cells that recognize class I MHC will retain CD8, and cells that recognize class II MHC will retain CD4. this will generate single-positive T cells. |
| what is Negative selection regarding T-cells? | Double positive T cells that bind MHC with high affinity will die by apoptosis. This process eliminates lymphocytes that may react to self antigens. |
| cell mediated immunity,T-cell functions? | 1- activation of phagocytes that ingest microbes. 2- killing cells infected with viruses and other parasites. 3- inflammatory response to fungi and helmiths. |
| what is the function of CD4 and CD8? | CD4 and CD8 recognize MHC molecules and activate downstream signals
Adhesion molecules facilitate binding of T-cell .CD4 activate phagocytes in tissues and activate B cells in lymphatic follicles, CD8 kill infected cells at the site of infection. |
| what are the molecules involved in T-lymphocyte activation? | CD3 (membrane associated molecules), ITAM ( Immunoreceptor Tyrosine based Activation Motif), ITIM ( Immunoreceptor Tyrosine based Inhibition Motif), B7 -CD29 (co-stimulator MHC with peptide is necessary but not sufficient without B7 expression) |
| what is the region of contact of immune cells called? | immune synapse where their is a high concentration of ligants and receptors. |
| what is the response to T-cell activation? | 1- CD69 involved in retention of lymphocytes in lymph nodes (down-regulates S1P1 receptor), 2- IL-2 stimulates survival and proliferation, 3- CD40 is an effector molecule, 4- CTLA-4 is an inhibitor of immune response . |
| how is the CD4 T-cell developed and what's the role of CD40L? | Effects are mediated by cytokines including CD40L that binds CD40 on macrophages, dendritic cells and B cells.CD40L and CD40 form positive self-amplification loop for activation of T cells by APCs. |
| what are memory T cells? | they are slowly proliferating supported by IL-7 and IL-15 produced by stromal cells in tissues. |
| what are central memory cells? | they reside in lymphoid organs |
| what are effector memory cells? | they reside in mucosal and other tissues. |
| what is migration controlled by? | integrins (receptors that bind to the extracellular matrix). , selectins (glycoproteins cell adhesion molecule) ,chemokines (signaling proteins secreted by cells). |
| what is rolling ? | TNF-a and IL-1 induce E-selectin expression on endothelial cells. Thrombin induces translocation of P-selectin to endothelial cell surface.Stable adhesion- chemokines secreted by macrophages and endothelial cells attach to endothelial cells and when bind to neutrophils increase affinity of integrins to integrin ligands on endothelial cells. Endothelial cells are stimulated by TNF-a and IL-1 to express ligands for integrins. |
| Naïve T cells role in cell migration? | do not express ligands for selectins or chemokines, and therefore do not migrate to infection site. Decline of the immune response. |
| how do Naïve T cells respond to infection? | During the response to the infection the survival and proliferation of effector T-cells is maintained by antigen, co-stimulatory signals from CD28 and cytokines like IL-2. |
| what happened in the absence of stimulation by antigen ? | lymphocytes die by apoptosis. |
| what happens to effector cells and memory cells after infection? | The number of effector cells subside within 1-2 weeks, when only memory T-cells remain to remember the antigen if another infection happens. |
| what is the first step in neutrophil migration to infection site? | (S1P) regulates exit of T-cells from lymph nodes. Blood has higher levels of S1P comparing to lymph node. |
| what is the second step in neutrophil migration ? | After clonal expansion is over L-selectin and CCRX7 receptor expression is lost and S1P receptor is re-expressed and guides lymphocytes out of lymph node. |
| what is the third step in neutrophil migration | Activated T cells express ligands for E and P-selectins, and integrins LFA-1 and VLA-4. Inflammatory cytokines TNF-a and IL-1 induce expression of E- and P-selectins and ligands for integrins ICAM-1 and VCAM-1. |
| what's the result of cell migration? | As a result effector T-cells roll, adhere and migrate through endothelium at the site of infection/inflammation. |
