Passage
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic synovial (joint) inflammation. RA immunopathogenesis involves LFA-1, a surface receptor found on leukocytes that is composed of an α-chain (CD11a) and a β-chain (CD18) . The binding of LFA-1 to ICAM-1, an adhesion protein on the surface of B cells and endothelial cells, stimulates the migration of leukocytes to specific areas of inflammation. After successful LFA-1/ICAM-1 binding, CD18 is released into the plasma and synovial fluid (SF) , where it exists in soluble form (sCD18) . The levels of sCD18 in SF can be used as a marker for inflammation in RA.CD18 release has been shown to increase in response to tumor necrosis factor (TNF) , a pro-inflammatory cytokine involved in the inflammatory response of RA. In patients with newly diagnosed and untreated RA (eRA) , leukocytes produce adequate quantities of LFA-1 and plasma sCD18 levels are unchanged. However, over time there is dysregulation of LFA-1 synthesis and an increase in competition for ICAM-1 by other ligands, leading to a reduction in CD18 shedding. As a result, sCD18 is decreased in patients with chronic RA (cRA) .Experiment 1An immunofluorescence assay was used to measure plasma sCD18 levels in patients with eRA and cRA, and in age- and gender-matched healthy controls (HC) .
Figure 1 Baseline sCD18 measurements (Note: 50% of data points are below the median value; median = line inside the box.) Experiment 2Clinical assessments were performed in eRA patients to establish a baseline disease status. eRA patients were assigned DAS28CRP scores measured by RA-specific laboratory values. This was followed by treatment with anti-inflammatory drugs. DAS28CRP scores were calculated at 3-month intervals for 12 months, with lower scores indicating decreased RA severity (Figure 2) .
Figure 2 DAS28CRP scores in eRA patientsExperiment 3Heterogeneous populations of mononuclear cells were cultured from the synovial fluid (SFMC) and peripheral blood (PBMC) of eRA patients during an acute exacerbation of their symptoms. sCD18 levels were measured in SFMCs and PBMCs that were untreated, treated with TNF, or treated with monoclonal antibodies targeting TNF (anti-TNF) .
Adapted from Kragstrup TW, Jalilian B, Keller KK, et al. Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response. PLoS ONE. 2016;11(2) :e0148486.
-The antibodies used in Experiment 3 are composed of:

Question

Passage
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic synovial (joint) inflammation. RA immunopathogenesis involves LFA-1, a surface receptor found on leukocytes that is composed of an α-chain (CD11a) and a β-chain (CD18) . The binding of LFA-1 to ICAM-1, an adhesion protein on the surface of B cells and endothelial cells, stimulates the migration of leukocytes to specific areas of inflammation. After successful LFA-1/ICAM-1 binding, CD18 is released into the plasma and synovial fluid (SF) , where it exists in soluble form (sCD18) . The levels of sCD18 in SF can be used as a marker for inflammation in RA.CD18 release has been shown to increase in response to tumor necrosis factor (TNF) , a pro-inflammatory cytokine involved in the inflammatory response of RA. In patients with newly diagnosed and untreated RA (eRA) , leukocytes produce adequate quantities of LFA-1 and plasma sCD18 levels are unchanged. However, over time there is dysregulation of LFA-1 synthesis and an increase in competition for ICAM-1 by other ligands, leading to a reduction in CD18 shedding. As a result, sCD18 is decreased in patients with chronic RA (cRA) .Experiment 1An immunofluorescence assay was used to measure plasma sCD18 levels in patients with eRA and cRA, and in age- and gender-matched healthy controls (HC) .

Figure 1 Baseline sCD18 measurements (Note: 50% of data points are below the median value; median = line inside the box.) Experiment 2Clinical assessments were performed in eRA patients to establish a baseline disease status. eRA patients were assigned DAS28CRP scores measured by RA-specific laboratory values. This was followed by treatment with anti-inflammatory drugs. DAS28CRP scores were calculated at 3-month intervals for 12 months, with lower scores indicating decreased RA severity (Figure 2) .

Figure 2 DAS28CRP scores in eRA patientsExperiment 3Heterogeneous populations of mononuclear cells were cultured from the synovial fluid (SFMC) and peripheral blood (PBMC) of eRA patients during an acute exacerbation of their symptoms. sCD18 levels were measured in SFMCs and PBMCs that were untreated, treated with TNF, or treated with monoclonal antibodies targeting TNF (anti-TNF) .
Adapted from Kragstrup TW, Jalilian B, Keller KK, et al. Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response. PLoS ONE. 2016;11(2) :e0148486.
-The antibodies used in Experiment 3 are composed of:

Quizplus · Accepted Answer

11ecba2d_0f89_8c76_a3bf_6f7fc1828a13_MD0008_00 Antigens are foreign substances capable of triggering an adaptive immune response through antibody production. Antibodies are Y-shaped proteins that bind and neutralize these antigens in the blood and lymph, preventing their entry into host cells and marking them for destruction (eg, by phagocytosis/opsonization). Antibodies are produced and secreted by effector B cells (plasma cells), which are part of the adaptive immune system. The variable region of the antibody binds the antigen. A single antibody can bind only one type of antigen, and this specificity is determined by the unique amino acid structure of the antibody's variable region. Accordingly, antibodies that recognize different antigens have different variable regions. In this case, the variable region of the monoclonal antibody used in Experiment 3 was designed to specifically bind only TNF. (Choices A and B) Most antibodies are made up of four polypeptide chains that are held together by disulfide bonds and noncovalent interactions. Specifically, antibodies consist of two identical heavy polypeptide chains and two identical light polypeptide chains. Together, the light and heavy chains have a constant region at one end and a variable region at the other end. (Choice D) The constant region of antibodies does not bind antigens. Therefore, in this scenario, the antibody used in Experiment 3 does not bind TNF directly. Instead, the constant region determines antibody class and function by dictating which body cells and proteins the antibody can interact with in order to facilitate antigen destruction. The amino acid sequence of the constant region is largely conserved across all antibodies of the same class. Educational objective: Antibodies are synthesized and secreted by effector B cells, which are part of the adaptive immune system. Each antibody consists of two identical light chains, two identical heavy chains, a variable region that interacts with a specific antigen, and a constant region that interacts with the cells (eg, phagocytes) and proteins of the body to facilitate antigen destruction.