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group_2_presentation_3_-_lupus [2018/11/30 23:17] bhattj3 [Diagnosis] |
group_2_presentation_3_-_lupus [2018/11/30 23:31] (current) habibz |
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| In patients with Lupus the main cells affected within the innate immunity are Dendritic Cells (DC) and Neutrophils (Rahman & Isenberg, 2008). DCs serve to process antigens (foreign particles) and present them to T-cells. In Lupus patients DCs have been linked to an increase in the humoral response and expansion of autoreactive T-cells and B-cells (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). Neutrophils are granulocytes which aid in killing microbes by NETs (Neutrophil Extracellular Trap). This is a process in which DNA is released into the extracellular fluid and forms web structures that attach to pathogens preventing their mobility and spread. In Lupus these NETs undergo NETosis (apoptosis of the NETs) which results in a large accumulation of DNA which serves as autoantigens for DCs (Fortuna & Brennan, 2013). | In patients with Lupus the main cells affected within the innate immunity are Dendritic Cells (DC) and Neutrophils (Rahman & Isenberg, 2008). DCs serve to process antigens (foreign particles) and present them to T-cells. In Lupus patients DCs have been linked to an increase in the humoral response and expansion of autoreactive T-cells and B-cells (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). Neutrophils are granulocytes which aid in killing microbes by NETs (Neutrophil Extracellular Trap). This is a process in which DNA is released into the extracellular fluid and forms web structures that attach to pathogens preventing their mobility and spread. In Lupus these NETs undergo NETosis (apoptosis of the NETs) which results in a large accumulation of DNA which serves as autoantigens for DCs (Fortuna & Brennan, 2013). | ||
| - | {{:t_cell.jpeg?direct&300 | Interaction between T-cell and APC}}{{ :b_cell.jpeg?direct&300| B-cell complex with T-cell}} | + | {{:t_cell.jpeg?direct&300 |}}{{ :b_cell.jpeg?direct&300|}} |
| T-cell receptors (TCR) are located on the surface of T-cells. These receptors interact with the antigen that is presented by the APC (antigen presenting cell) or DC. The APC and T-cell form a complex with the TCR, and MHC and antigen (Rahman & Isenberg, 2008). However binding of the antigen-MHC complex does not result in a reaction. Instead binding of costimulatory ligands facilitate stimulation or inhibition. Stimulation results in recruitment of B-cells which form a new complex with the T-cell and antigen (Rahman & Isenberg, 2008). The cells stimulate the other in that binding of the B-cell CD40 to the CD40 ligand on the T-cell results in a release of cytokines from the T-cell. The cytokines stimulate B cell division, shift the antibody production from IgM to IgG, and allow for molecular changes in the antibody produced to increase affinity for the antigen (Rahman & Isenberg, 2008). The effect of the T-cell on the B-cell is based on its affinity to the antigen. Higher affinity of the T-cell to the antigen results in a greater response by the B cell. | T-cell receptors (TCR) are located on the surface of T-cells. These receptors interact with the antigen that is presented by the APC (antigen presenting cell) or DC. The APC and T-cell form a complex with the TCR, and MHC and antigen (Rahman & Isenberg, 2008). However binding of the antigen-MHC complex does not result in a reaction. Instead binding of costimulatory ligands facilitate stimulation or inhibition. Stimulation results in recruitment of B-cells which form a new complex with the T-cell and antigen (Rahman & Isenberg, 2008). The cells stimulate the other in that binding of the B-cell CD40 to the CD40 ligand on the T-cell results in a release of cytokines from the T-cell. The cytokines stimulate B cell division, shift the antibody production from IgM to IgG, and allow for molecular changes in the antibody produced to increase affinity for the antigen (Rahman & Isenberg, 2008). The effect of the T-cell on the B-cell is based on its affinity to the antigen. Higher affinity of the T-cell to the antigen results in a greater response by the B cell. | ||
| The antibodies that are produced by the B cell are known as autoantibodies because they bind to molecules that the body has in abundance such as DNA. The main antigen in Lupus patients is double stranded DNA (Rahman & Isenberg, 2008; Elkon & Casali, 2008; Fortuna & Brennan, 2013). Once the anti-DNA antibody binds to the antigen they form a antigen-antibody complex inducing inflammation at the tissue (Elkon & Casali, 2008; Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). It has been proposed that this complex migrates to the renal glomerular basement membrane and activates complement and promotes inflammation in kidneys which is characteristic of Lupus (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). Another theory suggests antibodies cross react with proteins in kidney thereby having an effect. Studies demonstrated that anti-DNA antibodies cross reacted with alpha actin which is a protein critical to maintaining function of renal podocytes (cells of the filtration barrier) (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). | The antibodies that are produced by the B cell are known as autoantibodies because they bind to molecules that the body has in abundance such as DNA. The main antigen in Lupus patients is double stranded DNA (Rahman & Isenberg, 2008; Elkon & Casali, 2008; Fortuna & Brennan, 2013). Once the anti-DNA antibody binds to the antigen they form a antigen-antibody complex inducing inflammation at the tissue (Elkon & Casali, 2008; Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). It has been proposed that this complex migrates to the renal glomerular basement membrane and activates complement and promotes inflammation in kidneys which is characteristic of Lupus (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). Another theory suggests antibodies cross react with proteins in kidney thereby having an effect. Studies demonstrated that anti-DNA antibodies cross reacted with alpha actin which is a protein critical to maintaining function of renal podocytes (cells of the filtration barrier) (Rahman & Isenberg, 2008; Fortuna & Brennan, 2013). | ||
| - | <box 50%| > {{ :total_lupus.jpeg?direct&300 |}} </box| Overview of immune response in Lupus > | + | <box 50%| > {{ :total_lupus.jpeg?direct&300 |}} </box| Overview of immune response in Lupus (https://www-nejm-org.libaccess.lib.mcmaster.ca/doi/full/10.1056/NEJMra071297) > |
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| === Blood tests for lupus === | === Blood tests for lupus === | ||
| - | <box 50%| > {{ :bloodtest.jpeg?direct&300 |}} </box| Overview of immune response in Lupus > | ||
| The normal immune system makes antibodies to help fight off foreign invaders (John Hopkins Lupus Center, 2018). In contrast, some immune systems produce antibodies that attack the body’s own cells mistaking them as invaders, causing inflammation and damage various body parts (John Hopkins Lupus Center, 2018). This type of antibodies is known as auto-antibodies, and is present in autoimmune diseases such as lupus (John Hopkins Lupus Center, 2018). Currently, many blood tests can be performed to identify specific auto-antibodies to assist the diagnosis of lupus (John Hopkins Lupus Center, 2018). A blood test confirming the presence of an auto-antibody cannot be conclusive, but combining many tests along with certain physical findings verifies the diagnosis (John Hopkins Lupus Center, 2018). Anti-nuclear antibody (ANA) tests are usually the first test conducted to test for the possible diagnosis of lupus, and in people with a positive result, more tests are performed to check for other antibodies that can help confirm the diagnosis (John Hopkins Lupus Center, 2018). These tests include anti-phospholipid antibody (APL), anti-double-stranded DNA antibody (anti-dsDNA), anti-Smith (anti-Sm), anti-U1RNP, anti-Ro/SSA, and anti-La/SSB. | The normal immune system makes antibodies to help fight off foreign invaders (John Hopkins Lupus Center, 2018). In contrast, some immune systems produce antibodies that attack the body’s own cells mistaking them as invaders, causing inflammation and damage various body parts (John Hopkins Lupus Center, 2018). This type of antibodies is known as auto-antibodies, and is present in autoimmune diseases such as lupus (John Hopkins Lupus Center, 2018). Currently, many blood tests can be performed to identify specific auto-antibodies to assist the diagnosis of lupus (John Hopkins Lupus Center, 2018). A blood test confirming the presence of an auto-antibody cannot be conclusive, but combining many tests along with certain physical findings verifies the diagnosis (John Hopkins Lupus Center, 2018). Anti-nuclear antibody (ANA) tests are usually the first test conducted to test for the possible diagnosis of lupus, and in people with a positive result, more tests are performed to check for other antibodies that can help confirm the diagnosis (John Hopkins Lupus Center, 2018). These tests include anti-phospholipid antibody (APL), anti-double-stranded DNA antibody (anti-dsDNA), anti-Smith (anti-Sm), anti-U1RNP, anti-Ro/SSA, and anti-La/SSB. | ||
