PSIO 431 Type II Immunopathology Single Antigen Multiple Organs Some Type II immunopathology mediated autoimmune diseases have manifestations in multiple different organs Discuss how antibodies to one single antigen can cause damage in multiple sites throughout the body Things you might discuss include but are not limited to where the antigen could be expressed how antibodies are made how they bind antigen where they circulate the ratios of antigen to antibody mechanisms of the immune system that result in cellular tissue damage or how immune system components can affect other organs You might also comment on what makes one antigen an attractive target rather than another Please do NOT comment on all the things listed above they are just to get you thinking If you are having trouble getting started it might help to think about a specific disease which affects multiple organs Good Luck Antibodies to one single antigen can cause damage in multiple sites throughout the body through Type II immunopathology where the actions of antibodies directed against a specific target tissue molecule or cell is a form of autoimmunity Autoimmunity can cause damage throughout multiple site of the body for example Systemic Lupus Erythematosus For lupus people make antibody to nuclear and nucleolar proteins DNA RNA red blood cells clotting factors platelets skin and T cells Antibody to dsDNA is pathogenic and can explain the wide range of symptoms and damage throughout the entire body One specific mechanism for antigen binding is foreign self hybrid antigen When a foreign protein couples to a self antigen it creates an anti self B cell The anti self B cell can bind and ingest self along with the foreign antigen This now allows foreign epitopes to be presented to a Tfh on a class II MHC and the B cell becomes activated because it would have received both necessary signals for activation from the MHC class II and the Tfh This is a problem because now the antibody that is made by the B cell is making antibodies against self Now that antibody is against self the Tfh signals the B cell to class switch in order to delete this autoantibody or it may proliferate and the autoantibodies will circulate through secondary lymphoid organs Because this autoantibody has become mobilized it may now cause cell damage or tissue damage through either 1 Complement mediated damage Tissues that are against which antibodies are made may be damaged by lysis by phagocytosis or by the release of the phagocytes lysosomal enzymes and ROS Or 2 Stimulatory hypersensitivity If the autoantibody is directed against a cell surface receptor it may potentially behave like an agonist that mimics whatever hormone or factor that usually works on that receptor To give an example of complement mediated damage we can look at the disease Autoimmune Hemolytic Anemia This is where red blood cells are being lysed due to the antigen binding with a foreign protein The result of this is complement being activated and destruction of the foreign protein which has become a part of the red blood cell This means that not only will the foreign protein be getting lysed but the red blood cell will also causing a mass amount of damage to cells in the body that are necessary to sustain life To give an example of stimulatory hypersensitivity we can look at hyperthyroidism or Grave s disease which is the most common cause of hyperthyroidism In Grave s disease IgG makes antibodies against thyroid stimulating hormone also known as TSH receptors on the thyroid The result of this is IgG mimics the effects of TSH binding causing the thyroid to release an abnormally high level of thyroid hormones Other mechanisms include emergence of a forbidden clone cross reaction between a foreign antigen and a self antigen passive antibody innocent bystander release of a sequestered antigen and failure of regulatory mechanisms Citations Cohen Z Fall 2015 Type II Immunopathology and Regulation In Immunology