Immunopathology Type 2, Autoimmunity II Flashcards
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.
Add the fluorescent antibody to a preparation of normal kidney and patient serum. If the fluorescent antibodies fluoresced in a linear manner, one would think Type II and be leaning toward GoodPasture’s disease. If the fluorescent antibodies fluoresced in lumpy, bumpy fashion, one would be forced to think Type III and be leaning Systemic Lupus Erythematosus. This is essentially the application of the logic of learning objective #5 distinguishing between Type II and Type III fluorescence.
Describe how antibody-mediated tissue damage could result from the innocent bystander phenomenon
Example is TB – The infectious bacteria are localized in the lungs and thus the lung tissue is damaged as the body tries to rid itself of the infection. The immune system spares nothing in its quest to exterminate foreign beasts, not even itself. Thus, infected tissue can often be damaged as the body seeks to expunge the infective agent, but in doing so does major damage to different parts of the body.
Describe how antibody-mediated tissue damage could result from the cross-reaction of a foreign antigen with self
Example is Rheumatic Heart Disease. Antibody is produced against some devilish antigen and the antibody does a fine job of cleaning, destroying, and generally obliterating the antigen. However, the antibodies produced against the antigen also have some affinity for some self tissue (in the case of RHD, the heart valves). The antibody attacks the self-tissue, thinking it is “bad,” and all hell breaks loose as the body is being attacked by itself. It should be noted that by the time a patient develops clinical symptoms, the antigen that triggered everything may be long gone. The process is most likely being maintained by continued autoimmune responses to normally-sequestered antigens that are hemorrhaging from damaged cells.
Describe how antibody-mediated tissue damage could result from coupling self antigen with a foreign antigenic “carrier”
Fundamental Idea is that B-Cells and T-Cells can be switched on by different antigens
An anti-self B-cell escapes detection and binds a self protein that happens to have a foreign antigen attached. Normally, the self-protein would not cause Tfh cells to give the B-cell the go ahead to activated, but because the self-protein has foreign protein attached a problem arises. If the B-cell, which bound self, presents the foreign antigen on its surface, T-cells will indeed send the appropriate signals to activate the B-cell thinking that the B-cell has found something foreign. However, the B-cell has actually been activated against the self-protein it originally bound. Again, the fundamental idea is that B-cells don’t necessarily see or get excited about the same antigens/epitopes as T-cells and this can create trouble.
Describe how antibody-mediated tissue damage could result from exposure of a sequestered antigen
Example – Men who get mumps becoming sterile
Sequestered antigens are usually hidden nice and cozy inside the bellies of their sequestering beast cells. But, if they are somehow allowed to get out they can immunize cells and lead to an immune response. This usually happens when an immune response in initiated in the region where the antigen is sequestered. Damage to tissue where the cells that have sequestered antigens within reside can lead to the release of sequestered antigens and a further immune response.
Describe how antibody-mediated tissue damage could result from inadequacy of regulatory T cells.
It is currently being speculated that an appropriate balance of Th1, Th17, Tfh, Th2, and Treg activity is ESSENTIAL to an appropriate immune response. Some think that the balance can be perturbed so that self/non-self discrimination breaks down and the body starts attacking itself. Recent experiments that cause shifts in the T-cell balance show promise.
Identify “Rheumatoid Factor” and describe its molecular nature
Rheumatoid Factor (RF) provided the initial evidence that rheumatoid arthritis was autoimmune. RF can be detected by adding a patient’s serum to microscopic beads coated with normal human IgG. In the presence of RF, the beads agglutinate. Thus, RF is IgM anti-IgG. Although it is a useful biomarker, it may not cause much actual joint damage.
Name the condition in which antibody stimulates rather than inhibits or harms its target cell.
Graves’ Disease aka. Hyperthyroidism. Long-Acting Thyroid Stimulator: (LATS) is an IgG antibody that mimics TSH and binds the TSH receptor causing the cell to secrete thyroid hormones. The normal feedback controls that work on TSH have no effect on LATS and thus the thyroid is over-stimulated and hyperthyroidism results
Discuss how the Aire gene is involved in preventing autoimmune disease
The Aire gene is quite useful in that it causes thymic stromal genes to express a wide variety of otherwise-inexplicable “out-of-lace” peptides so that reactive T cells may be removed from the repertoire. These out of place peptides are ones that are produced and present in other parts of the body and are made in the thymus for the singular purpose of helping to negatively select anti-self T-cells. Aire is so important that Aire-deficient people develop several auto-immune diseases
