Flashcards in TypeII Immunopathology Deck (17)
What is Type II immunopathology?
Type II immunopathology is due to IgG, IgM, or IgA antibodies causing harm to self. This typically refers to autoantibodies, but also includes auto reactive antibodies against cell surface receptors that stimulate (rather than damage) the cell.
What is a Type II mechanism of disease in muscle cells? Kidney cells?
Myasthenia gravis is a type II disorder where antibodies to the acetylcholine receptors on muscle cells. This leads to complement and neutrophil activation against the muscle cells. Goodpasture syndrome involves antibodies to the Type IV collagen in the basement membrane of kidney and lung cells. Immunoflorescent staining produces sharp lines as the antibodies line up along the BM, and not in clumps as in Type III immunopathology.
What is a type II mechanism of disease in heart cells? Lung cells?
Rheumatic heart disease is likely due to a cross-reaction of antibodies to Group A Strep M-protein and a structure on the heart's endothelial lining (likely laminin in the heart valves) and neutrophil-mediated destruction. (Dressler syndrome also affects the heart.) Goodpasture syndrome involves antibodies to the Type IV collagen in the basement membrane of lung and kidney cells.
What is a disease with a Type II mechanism affecting red cells? Platelets?
Autoimmune hemolytic anemia may be caused by viral infections, cancer, drug exposure, or another autoimmune disease. RBCs are opsonized and lysed by intra or extravascular hemolysis, depending on the specific type. Autoimmune thrombocytopenic purpura is similar, caused by similar processes, and leads to opsonization and lysis in the spleen. Results in bleeding.
What is a disease with a Type II mechanism affecting thyroid cells? Pancreatic islets?
Graves disease results from IgG attaching to the TSH receptor on thyroid cells, mimicking TSH and causing stimulation and hyperthyroidism. Type I diabetes has several antibodies that are islet-associated.
How are florescent antibodies used to diagnose Goodpasture syndrome?
With the patient's kidney biopsy, florescent anti-IgG antibodies are added and produce a sharp, linear image because the patient's IgG are all lined along the BM of the kidney. With a normal kidney biopsy, the patients' serum is added along with the anti-IgG florescent antibodies. The autoimmune antibodies in the patient's serum attach to the BM and the florescent antibodies attach to them, producing the same sharp, linear image.
What types of immunopathology do "lumpy-bumpy" and "linear" immunoflorescent patterns represent?
Lumpy-bumpy patterns represent Type III immunopathology, with immune complexes developing and depositing in the BM of blood vessels (and the kidney). Linear patterns represent Type II immunopathology because they show auto-antibodies attaching to antigens along tissues, whether they are cell tissues or BM or other tissues.
What sort of anti-antibodies would be most useful in detecting and distinguishing Type II and Type III immunopathology in a patient's kidney?
Florescent anti-IgG would be very useful, as it would detect both Type II (typically linear) and Type III (typically clumped) immunopathologies. The pattern would determine the type of immunopath (linear = Type II, clumped = Type III)
How can immunoflorescence delineate between Goodpasture syndrome and Systemic Lupus Erythematosus (SLE)?
Goodpasture syndrome is caused by antibodies to a specific antigen in the Collaged IV basement membrane in the kidney. SLE has a variety of causes, including many different antibodies. Immunoflorescence studies should show sharp, linear patterns in Goodpasture syndrome, and more diffuse patterns (due to varied antibodies) or lumpy patterns (Type III) in SLE.
How does antibody-mediated tissue damage result from the innocent bystander phenomenon?
There is damage to the normal tissue that happens to be associated with or infected by the foreign antigen. i.e., an RBC bound by an antigenic drug that results in lysis of the RBC.
How does antibody-mediated tissue damage result from cross-reaction of a foreign antigen with self?
If a self-antigen is sufficiently similar to a foreign antigen, infection by the foreign antigen may cause immune response to the cells expressing the self-antigen. May also lead to further damage due to the exposure of normally sequestered antigens in the damaged cells.
How does antibody-mediated tissue damage result from the coupling of self-antigen with a foreign antigen "carrier"?
If a B-cell producing an anti-self antigen escaped negative selection, and then encountered the "self" antigen bound to a foreign antigen, it would produce self and foreign epitopes on its MHC II, enabling Tfh cells to stimulate it to class switch and reproduce, producing an autoimmune clone.
How does antibody-mediated tissue damage result from exposure of a sequestered antigen?
The sequestered antigen cannot normally get out into the general system, and is not normally immunogenic. In the case of mumps, mumps may break down the blood/testis barrier and expose the sperm antigens to the immune system which would attack them as foreign, leading to sterility.
How does antibody-mediated tissue damage result from the inadequacies of T-cells?
If the precarious balance of Th1, 17, 2, fh, and Treg cells is not maintained, exaggerated responses and autoimmunity may follow.
What is Rheumatoid Factor?
RF is IgM anti-IgG ?????????????????????????
What is one condition where antibody stimulates rather than inhibits or harms its target cell?
Graves disease results from antibody specific for the TSH receptor on thyroid cells. Its binding results in over stimulation of the cell, as normal negative feedback systems don't work in this case. Causes hyperthyroidism.