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Biologic agents can block cell migration to sites of inflammation and reduce immune responses. Natalizumab is a humanized monoclonal antibody directed at the a4-integrin protein, a subunit of VLA-4, the binding partner of VCAM-1 expressed on endothelium in the central nervous system, and of a4b-integrin, the binding partner of MadCAM-1 expressed on endothelium in the gut. While natalizumab has had great success in alleviating the symptoms of autoimmune diseases such as multiple sclerosis and Crohn’s disease, a small number of patients have acquired life threatening infections of the neurotrophic virus, JC. Why are patients on natalizumab particularly susceptible to a virus infection of the central nervous system?
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- a. What are the number of total chromosomes that carries the genes encoding heavy and light chain polypeptides in a single B cell (in human)? b. From the total number of chromosomes carrying genes for immunoglobulin peptides from question a, how many encode the heavy and light chains actually expressed by a single B cell?arrow_forwardIn adoptive immunotherapy for melanoma, tumor-infiltrated lymphocytes(TILs) are expanded ex-vivo then reinfused into the patient together with IL-2. The rationale for the administration of IL-2 is that it serves as a growth factor for the TILs. Group of answer choices True Falsearrow_forwardNeutralizing antibodies are effective at preventing infection or toxicity mediated by pathogens or their toxic products. In fact, nearly all vaccines currently in use function by eliciting neutralizing antibodies. One example is the tetanus vaccine, in which neutralizing antibodies are generated against an inactivated form of the tetanus toxin (the tetanus toxoid). The most important feature of a neutralizing antibody is having high affinity for the antigen. being efficient at activating the complement cascade. having a high degree of multivalency, such as being a pentamer or hexamer of immunoglobulin monomers. being present at a high concentration in the circulation. 0 0 0 0arrow_forward
- To distinguish between two possible functions of CD8a+ dendritic cells, first function is that CD8a+ needed for the cross-presentation of antigens and then to be presented to the MHC I; and the second function is that the viral antigens are brought to the draining lymph nodes with the help CD8a+ dendritic cells. a set of wild-type and Batf3-/- mice are immunized with 100 PFU of WNV in the left footpad. At day 7 post-infection, the left popliteal LN are isolated from the mice, and the CD4 T cells in these LN populations are tested for responses to a WNV peptide bound to MHC class II (peptide Y). As a negative control, an MHC class II-binding peptide from ova is used. These results are shown in the figure below. Do these results rule in/out either of the two possible functions of CD8a+ dendritic cells indicated at the begining of this paragraph? Why or why not?arrow_forwardToll-like receptors represent an ancient pathogen-recognition system. The first pattern recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces: The synthesis of prostaglandins and leukotrienes The inflammatory response in Drosophila hemolymph vessels The production of antimicrobial peptides The recruitment of phagocytic cells to the site of infection The activation of Drosophila complementarrow_forwardFig. 1. AKAP11 and RIα are degraded by autophagy. (A) Brain lysates of Atg7F/F (Control) and Atg7F/F-SynCre (cKO) were subjected to immunoblottinganalysis with the indicated antibodies. (B) Quantification of protein levels in A. Unpaired Student’s t tests were used, and values are presented as mean ± SEM(n = 3 mice/genotype). **P < 0.01; ***P < 0.001; ns, not significant. (C) Brain lysates of Atg14F/F (Control) and Atg14F/F-SynCre (cKO) were subjected toimmunoblotting analysis with the indicated antibodies. (D) Quantification of protein levels in C. Unpaired Student’s t tests were used, and values are presented as mean ± SEM (n = 4 mice/genotype). **P < 0.01; ***P < 0.001; ns, not significant. (E) Atg7 WT and Atg7 KO MEF cells were nutrient starved by usingEBSS for the indicated times, and cells were assayed by immunoblotting analysis with the indicated antibodies. (F) Quantification of the protein levels from Ewas obtained by normalizing the level of proteins to Actin,…arrow_forward
- Why and how might antibodies againt IL-6 or IL-6 receptor be used for treating patients with life-threatening COVID? How to prepare Fabs from these antibodies?arrow_forwardDescribe the significance and need for receptor editing as a part of elimination of self-reactive B lymphocytes.arrow_forwardIDENTIFY THE METHOD. FIGURE 1. IL-1ẞ increases protein expression of PDGFRB and CD13 in cultured pericytes. The researchers used what method to generate the results in A? A PDGFR$ a-tubulin D CD13 B-actin p-AKT total AKT p-ERK total ERK GAPDH IL-18 0 5 10 50 IL-18 0 5 10 50 B E PDGFRB/a-tubulin p-/total AKT 1.5 1.0- 0.5- 0 1.5 1.0- 0.5- 0 0 5 10 IL-18 (ng/ml) 0 5 10 IL-18 (ng/ml) 50 50 C CD13/B-actin F p-/total ERK 2.01 1.5- 1.0- 0.5- 0 1.0- 0.5- 0 H 10 50 5 IL-18 (ng/ml) 0 5 10 IL-13 (ng/ml) 50arrow_forward
- Infants and young children with deficiencies in specific complement components present with recurrent respiratory infections caused by extracellular bacteria. The peak age of susceptibility is between 6 and 12 months after birth. At this time, as shown in figure below, maternal antibodies acquired by the child during fetal gestation are nearly gone, but the child is not yet generating robust antibody responses to new infections, as indicated by the low circulating levels of IgG and IgA. As children with this immunodeficiency get older, they outgrow this disease and show no further evidence of these recurrent infections. Based on this information, name one likely gene deficiency (in the complement system) that could cause this primary immunodeficiency, and the specific complement pathway likely to be affected. Explain your answer.arrow_forwardThere are several important mechanisms for generating diversity in immunoglobulin and T cell receptors. Explain the similarities and differences in mechanisms that generates diversity in these receptors.arrow_forwardIdentify some PAMPs that are recognized by PRRs.Which cells express PRRs? How do PRRs associate withPAMPs to promote innate immunity?arrow_forward
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