Immunopathology Flashcards
Type I Immunopathology
Symptoms or pathology due to IgE antibody. Since the type of B-cell-helper Tfh cell that drives switching to IgE is closely related to the Th2 cell, Th2-mediated events are often seen along with those caused by IgE.
Type II Immunopathology
Pathology due to IgG, IgM, or IgA antibody causing harm to self. In most cases this refers to autoantibodies. Type V is now included in this category too: autoreactive antibody against surface receptors which happen to stimulate (rather than damage) the cell.
Type III Immunopathology
Formation of immune complexes which are trapped in the basement membranes of blood vessels and activate complement, leading to vasculitic inflammation. When Type III is chronic, T cell-mediated immunity becomes important.
Type IV Immunopathology
Pathologic outcomes of normal or abnormal (including autoimmune) T cell responses, including both helper and cytotoxic cells
Chronic Frustrated Immune Responses
Adaptive immune response to try to get rid of antigens that it never can–the antigen can be neither disposed of nor effectively walled off. E.g. normal gut flora (as in Crohn disease), skin flora (psoriasis), chemicals (as in chronic beryllium disease), or foods (gluten in celiac disease).
Mechanisms of Tissue Damage
Neutralization, e.g. IFN-gamma autoantibodies autoimmunity but manifests as immunodeficiency–associated with disseminated nontuberculous mycobacteria.
Complement-mediated damage, autoantibodies activate complement cascade directed at own tissue.
Stimulatory hypersensitivity, autoantibody is cell surface receptor agonist e.g. long-acting thyroid stimulator, IgG Ab to TSH-receptor results in hyperthyroidism or Graves disease
Myasthenia Gravis
Disease of progressive muscle weakness, because patients are making antibody to the acetylcholine receptor (AChR), activates complement, mediates destruction ACh receptors. Mutation in promotor that binds thymic transcription factor Aire, Th clones reactive with the AChR are not deleted by negative selection. Thymectomy and immunosuppression are effective.
Goodpasture Syndrome
Auto-Abs to lung and kidney basement membranes (BM) (specifically collagen IV) on which endothelial cells of capillaries sit. Persistent glomerulonephritis, and smokers risk pneumonitis with pulmonary hemorrhages. Staining by immunofluorescence of glomerulus is sharp and ‘linear’ because it’s type II. In Type III conditions you see clumps of immune complex stuck in the glomeruli i.e. lumpy & bumpy.
Dressler Syndrome
After heart attack, will make some autoantibody which reacts with heart. Persistent cardiac pain, fever, malaise, and pericardial effusion seen after heart attack (and more commonly after heart surgery) which is directly related to an immune response to pericardial or myocardial antigens. Treated with anti-inflammatory agents, gets better as heart heals.
Rheumatic Heart Disease
Heart disease after a Streptococcal infection, Cross reaction between a Group A Streptococcus M-protein antigen and a structure on the heart’s endothelial lining, probably laminin on heart valves, followed by neutrophil-mediated tissue destruction.
Rheumatic Fever
Same disease as rheumatic heart disease with more widespread manifestations, including in the skin and CNS. These are classic Type II conditions.
Poststreptococcal glomerulonephritis
Type III immunopathology, due to complexes between antibody and strep antigens trapped in the kidney.
Autoimmune Thrombocytopenic Purpura (ATP)
Bleeding abnormalities due to destruction of platelets (thrombocytes) by autoantibody, platelets are opsonized and destroyed in the spleen. Treatment: suppress the immune system and/or remove the spleen. ATP is often seen in young healthy people some weeks after a viral infection; in older people, in association with many other autoantibodies; and in people treated with certain drugs.
Graves Disease & Hashimoto Thyroid Disease
1 Disease with 2 Expressions (likely). Stimulatory autoimmunity to the TSH receptor on thyroid cells–Graves Disease is the leading cause of Hyperthyroidism. Autoimmunity to thyroglobulin (the molecule in which iodine is stored) and thyroid peroxidase in Hashimoto Disease leading to hypothyroidism–Pathological process is inflammatory and destructive (with both antibody and T cells involved). 75% of autoimmune thyroid disease (AITD) is genetic. 5 out of 6 in the US with Hashimoto are female.
Hybrid (foreign & self ) antigen formation
Foreign antigen were to couple to the self
antigen. The anti-self B-cell could bind to the self part and ingest it, carrying along the coupled foreign antigen. Then foreign epitopes might be presented to a Tfh cell on the B cell’s Class II MHC. The B cell would have received all necessary signals and become activated. Then it would make its antibody against self. It would also be instructed by the Tfh to class-switch.
