BL.2.4: Type 2 Immunopathology, Platelet disorders Flashcards
Describe the molecular and cellular details of the immunologic mechanisms by which tissue damage occurs in a Type II reaction.
aka Cytotoxic antibody” reactionsSelf reactive antibodies attack your own tissue
Give an example of a Type II mechanism disease of muscle, kidney, heart, red cells, platelets, lung, thyroid, pancreatic islets.
Muscle:Myasthenia gravis: progressive muscle weakness. Ab to myosin and Ach receptorKidney: Goodpasture’s diseaseHeart: Rheumatic heart disease, from strep A cross reactivityRed cells: AIHAPlatelets: Autoimmune thrombocytopenic purpura (say that 3x fast). Platelets opsonized rapidly in spleen.Lung: Goodpasture’s diseaseThyroid: Grave’s disease, Hashimoto’sPancreatic islets: Diabetes
Describe the fluorescent antibody tests which would allow you to make the diagnosis of Goodpasture’s Syndrome, given: patient’s kidney biopsy, normal kidney biopsy, patient’s serum, and fluoresceinated goat antisera to human IgG and complement.
In Goodpasture’s the antibody is directed against the basement membrane, not trapped as clumps, so the staining by immunofluorescence is sharp and ‘linear,’ not ‘lumpy-bumpy’ as it is in Type III, immune complex conditions.Kidney biopsy: patient’s basement membrane would be ravaged by immune system, and evidence of glomerulonephritisThey would also have a glowing serum because the goat antisera would bind this person’s IgG and complement.
Distinguish between the “lumpy-bumpy” and “linear” immunofluorescent patterns in terms of the most probable immunopathologies they represent.
Type 2: sharp and linearType 3: lumpy bumpy
Describe how you could tell, using fluorescent antibodies and biopsies of patient’s kidney, if Type II or Type III immunopathology was involved. Name the antibodies you would use and the fluorescent patterns you would see.
Is it lumpy bumpy or is it sharp and linear??Lumpy bumpy = 3, Sharp linear = 2Were I looking for Goodpasture’s (Type 2), I would use anti-anti-basement membrane IgG tagged with pink sparkles and get sharp, linear, pink sparkles on the basement membrane of my kidney sample.If I was searching for a type 3 result, I would look for lumpy bumpy glowing immune complexes stuck in the kidney.
Given patient’s serum, fluorescent antibody to human immunoglobulins, and slices of normal kidney, describe how you could tell if the patient’s glomerulonephritis was due to Goodpasture’s disease or SLE.
Lupus: Check serum for antibodies for Nuclear proteins, DNA, RNA, erythrocytes, clotting factors, platelets, skin and T cells. If they have this, and large immune complexes have formed, they will have gotten stuck in the kidney. Apply the fluorescent antibody to the kidney, and observe a lumpy bumpy pattern.Goodpastures: is there a linear glowing pattern on the basement membrane?
Describe how antibody-mediated tissue damage could result from: The innocent bystander phenomenon.
Innocent bystander. A common mechanism, in which there is damage to normal tissue which happens to be associated with or infected by the antigen, which is truly foreign. Usually this is a result of the T cells calling in angry macrophages which end up damaging the regular tissue as an innocent bystander.
Describe how antibody-mediated tissue damage could result from: Cross-reaction of a foreign antigen with self.
Could be the case in Type 1 diabetes. Many patients are sick with a virus before diagnosis. The foreign antigen may look like an islet cell, and then the immune system goes after them!
Describe how antibody-mediated tissue damage could result from: Coupling self antigen with a foreign antigenic “carrier”.
Suppose you had anti-self B cells that hadn’t been aborted. They would not necessarily get you into trouble if the self antigens were T-dependent, and you did not have antiself T helper cells. Suppose that a foreign antigen were to couple to the self antigen. The anti-self B cell could bind and ingest self, and carry the foreign antigen along with it. Then foreign epitopes might be presented to a helper T cell on the B cell’s Class II MHC. The B cell would have received both necessary signals (from its receptor and from the T cell) and become activated.
Describe how antibody-mediated tissue damage could result from exposure of a sequestered antigen.
Note that in the special case of sequestered antigens, the antigen cannot get out into the general system, and therefore is not normally immunogenic.But if an immune response does get initiated, then the response can usually get into the place where the antigen was sequestered.Example: some men who get mumps end up sterile. It is thought that the mumps breaks down the blood/testis barrier, allowing immunization to sperm antigens.
Describe how antibody-mediated tissue damage could result from inadequacy of Treg cells.
A proper balance between Th1, Th2, and Treg activity usually assures that immune responses are appropriate.However, if that balance is perturbed one can imagine that too many Th1 cells might be stimulated, calling their friends, the angry macrophages. Those cats can’t be turned off → the tissue could easily be damaged in this situation.
Identify “Rheumatoid Factor” and describe its molecular nature.
IgM anti IgG
Name a condition in which antibody stimulates rather than inhibits or harms its target cell.
Grave’s disease.
Discuss how the Aire gene is involved in preventing autoimmune disease.
Amazingly, the Aire (autoimmune regulator) gene causes thymic stromal cells to express a wide variety of otherwise-inexplicable “out-of-place” peptides so that reactive T cells may be removed from the repertoire.In fact, Aire-deficient people develop multiple autoimmunities.
Discuss the idea that switching from Th1 to Th2 or Treg responses may be a way to treat autoimmune disease.
Remember that a proper balance between Th1, Th2, and Treg activity usually assures that immune responses are appropriate.Such balance is an area of intense speculation lately.Some recent experiments that cause major shifts in T cell balance look very promising as therapy, if they can make the translational jump from the lab or the Phase I trial into safe general use.
